Antibacterial Polysiloxane Polymers and Coatings for Cochlear Implants.

Within this study, new materials were synthesized and characterized based on polysiloxane modified with different ratios of N-acetyl-l-cysteine (NAC) and crosslinked via UV-assisted thiol-ene addition, in order to obtain efficient membranes able to resist bacterial adherence and biofilm formation. These membranes were subjected to in vitro testing for microbial adherence against S. pneumoniae using standardized tests. WISTAR rats were implanted for 4 weeks with crosslinked siloxane samples without and with NAC. A set of physical characterization methods was employed to assess the chemical structure and morphological aspects of the new synthetized materials before and after contact with the microbiological medium.

Characterization and Mechanism for the Protection of Photolytic Decomposition of N-Halamine Siloxane Coatings by Titanium Dioxide.

N-Halamine antibacterial materials have superior inactivation activities due to oxidative chlorine species. However, N-Cl bonds and bonds between N-halamine and substrates often decompose rapidly under UV irradiation, leading to unrecoverable loss of antimicrobial activity. In this study, titanium dioxide was covalently bonded onto N-halamine siloxane poly[5,5-dimethyl-3-(3'-triethoxysilylpropyl)hydantoin] (PSPH) via a sol-gel process. Experimental testing of the chlorinated cotton fabrics treated with TiO2/PSPH demonstrated that the residual oxidative chlorine in cotton-TiO2/PSPH-Cl was still effective for inactivating bacteria after 50 washing cycles and under UV light irradiation for 24 h. Quantum mechanical calculations found that TiO2 improves the UV stability of the PSPH-Cl system by increasing the activation barrier of the C-Si scission reaction responsible for the loss of the biocidal hydantoin moiety. SEM, XPS and FTIR spectra were used to characterize the coated cotton samples. Cotton-TiO2/PSPH-Cl samples exhibited good antibacterial activity against Staphylococcus aureus (ATCC 6538) and Escherichia coli O157:H7 (ATCC 43895). The storage stability and washing stability of treated cotton fabrics were also investigated.

Dimensional stability of a novel polyvinyl siloxane impression technique

AIM: To introduce a modification of the reline impression technique (MRIT), and compare the dimensional changes of impressions obtained by MRIT and by conventional reline impression technique (CRIT). METHODS: An acrylic resin tablet was milled by a CAD-CAM system to simulate three abutments (A, B and C) with different distances among them. The abutments were molded using both impression techniques. For MRIT, before completing the putty silicone polymerization, the relieve procedure was made by compression and it was immediately repositioned to complete the polymerization. Impressions were stored dry at room temperature for different periods (immediately, 1 h, 2 days and 7 days). The distances were obtained by scanning. The differences between the impressions and their respective matrix reference measurements were calculated to determine the dimensional changes. Data were subjected to ANOVA and Tukey's test (p<0.05). RESULTS: For AB and BC distances, there was no statistically significant difference between CRIT and MRIT (p=0.0597 and p=0.2167, respectively). For AC, there was statistically significant difference between the techniques for the immediate storage time (p=0.006). In general, for CRIT the material showed expansion, while for MRIT it showed contraction. CONCLUSIONS: It was verified that the addition silicon impressions obtained by both impression techniques showed dimensional stability, except for the immediate time-point...

Effects of two disiloxanes ALIS-409 and ALIS-421 on chemoprevention in model experiments.

Morpholino-disiloxane (ALIS-409) and piperazino-disiloxane (ALIS-421) compounds were developed as inhibitors of multidrug resistance of various types of cancer cells. In the present study, the effects of ALIS-409 and ALIS-421 compounds were investigated on cancer promotion and on co-existence of tumor and normal cells. The two compounds were evaluated for their inhibitory effects on Epstein-Barr virus immediate-early antigen (EBV-EA) expression induced by tetradecanoyl-phorbol-acetate (TPA) in Raji cell cultures. The method is known as a primary screening test for antitumor effect, below the (IC50) concentration. ALIS-409 was more effective in inhibiting EBV-EA (100 µg/ml) and tumor promotion, than ALIS-421, in the concentration range up to 1000 µg/ml. However, neither of the compounds were able to reduce tumor promotion significantly, expressed as inhibition of TPA-induced tumor antigen activation. Based on the in vitro results, the two disiloxanes were investigated in vivo for their effects on mouse skin tumors in a two-stage mouse skin carcinogenesis study. The application of dimethyl-benzanthracene (DMBA; 390 nmol) as a tumor initiator was followed by exposure to TPA (1.7 nmol/l) as a tumor promoter. The experiments showed that ALIS-409 at a concentration of 85 nmol/l had a weak EBV-EA inhibitory effect in vitro and a moderate antitumor activity, compared to the positive control of DMBA plus TPA-treated mice. Flow cytometry by differential staining demonstrated interactions in co-cultures of MCF7 breast cancer and MRC5 human lung fibroblasts. The growth rate of tumor cells in mixed populations of MCF7 breast cancer and MRC5 normal fibroblast cells was reduced in the presence of ALIS-409, as compared to the control non-treated cell populations. The two disiloxanes were moderately-effective in chemoprevention in DMBA-induced and TPA-promoted in vivo tumor formation. Authors suggest that the inhibition of tumor cell and fibroblast interaction by ALIS409 might have some perspective in the development of anti-stromal therapy.

Gelatin-siloxane hybrid scaffolds with vascular endothelial growth factor induces brain tissue regeneration.

In the brain after infarction or trauma, the tissue becomes pannecrotic and forms a cavity. In such situation, a scaffold is necessary to produce new tissue. In this study, we implanted a new porous gelatin-siloxane hybrid derived from gelatin and 3-(glycidoxypropyl) trimethoxysilane (gelatin-GPTMS) scaffolds into a brain defect, and investigated whether it makes a new brain tissue. In addition, vascular endothelial growth factor (VEGF) was added on gelatin-GPTMS scaffolds and its effect on tissue regeneration was examined. At 30 days after the implantation, the marginal territory of the scaffolds became occupied by newly formed tissue. Immunohistochemical analysis revealed that the new tissue was constituted by endothelial, astroglial and microglial cells, some of which were labeled for bromodeoxyuridine (BrdU). Addition of VEGF promoted numbers of these cells. Thus, combination of gelatin-GPTMS scaffolds and VEGF is preferable for brain regeneration.

[Current methods of treatment and prevention of pathologic scars]. / A kóros hegek kezelésének és megelozésének lehetoségei napjainkban.

The aetiology of pathologic scarring is unknown today regarding the keloids. The authors have analyzed the literature and own experience retrospectively according to the evidence based treatments and prevention of the hypertrophic and keloid scars. The corticosteroids have been used intralesionally since the beginning of the 1960-ies. It was followed by the pressure garment therapy in order to treat the widespread burns scars in the early 1970-ies. The silicone gel sheeting is being used since the 1980-ies. The basic treatment of keloids changed, radiotherapy was combined with the above mentioned methods because of its high recurrence rate. Newer methods, cryosurgery as well as lasers were used to treat keloids. The number of effective topical agents was increased. The researchers have been looking for other, intralesionally usable medicine and genetic causes for more than ten years. The clinicians have had the standard protocols of the adjunct and alternative methods too. After having the standard and internationally accepted scar assessment system (Vancouver-scar scale and score), the controlled, randomized trials were practicable. The prospective evaluation of the efficacy of different protocols with adequate follow-up became performable. The comparison of different methods is difficult because of the lack of its standard outcome.

Effect of SILA-409, a new organosilicon multidrug resistance modifier, on human pancreatic cancer xenografts.

BACKGROUND: Failure of cancer chemotherapy is largely caused by multidrug resistance in tumor cells, mediated by ABC transporters that pump many cytostatics out from the cells. Thus, inhibition of the activity of P-glycoprotein efflux pumps can improve the therapeutic results. Disiloxanes are synthetic resistance modifiers that suppressed not only the multidrug resistance gene but also MRP in various cancer cell lines. Among these compounds, SILA-409 [1,3-dimethyl-1,3-bis(4-fluorophenyl)-1, 3-bis(3-morpholino-propyl)-disiloxanedihydro chloride] showed a remarkable antiproliferative effect and markedly inhibited the P-glycoprotein-mediated efflux mechanism in vitro. The efficacy of this organosilicon drug was investigated in vivo, in a xenograft system. MATERIALS AND METHODS: Human pancreatic cancer xenografts (PZX-40/19G) were treated s.c. with 10 mg/kg b.w. SILA-409 every second day for 34 days. Tumor volume changes were recorded every week. At the end of the experiment, a complete autopsy was performed and all the vital organs were evaluated histologically. The apoptotic and mitotic rates were counted and evaluated by morphometric methods, and the immunohistochemical expression of P-glycoprotein was determined using a monoclonal anti-p170 antibody. RESULTS: This large dose of the organosilicon compound did not result in histologically observable toxic effects, and some tumor growth delay was noted. SILA-409 did not affect the mitotic activity, but the number of apoptotic cells per mm2 was significantly increased. In the untreated tumors, 60% of the cells displayed p170-positivity, while in the treated group, P-glycoprotein was expressed in just 26% of the carcinoma cells. CONCLUSION: The multidrug reversal effect of SILA-409 was demonstrated in vivo without any apparent toxicity. In addition, it increased the apoptotic activity, exhibited some tumor growth delay, but did not affect the mitotic rate. This new organosilicon compound deserves further attention with a combination of multidrug-resistant substrate chemotherapeutic agents, especially in multidrug-resistant tumors.

Polyvinylsiloxane dental impression material used to support the pinna after severe injury.

This case illustrates the simple, cheap and immediate provision of a splint for the pinna after severe injury using dental polyvinylsiloxane impression material.

Transient adhesion of platelets in pump-oxygenator systems: influence of SMA and nitric oxide treatments.

We employed gamma scintigraphy to quantify the transient accumulations of platelets in pump-oxygenator systems employed in cardiopulmonary bypass (CPB). A flat sheet microporous polypropylene membrane oxygenator (Cobe Duo) was employed, with and without siloxane/caprolactone oligomer coating (SMA) (n = 8 each). The effect of nitric oxide gas infusion on platelet deposition was also evaluated for the uncoated Cobe Duo system (n = 10 each). Scintigraphic images of radiolabelled cells were obtained and converted to numbers of all platelets, labeled and unlabeled, adhering to the pump and oxygenator surfaces. These numbers were compared, by study group, for a 90-min period of normothermic CPB in the adult pig, employing standard prime and anticoagulation regimens. Platelets adhered in large numbers to control oxygenators, reaching maxima (> 20% of the circulating platelet mass) 30 min following institution of CPB, and decreasing for the duration of CPB. SMA treatment significantly decreased platelet adhesion following a 5-10-min transient accumulation period. Nitric oxide infusion significantly reduced platelet adhesion throughout the CPB period. Platelet accumulations on the high fluid shear centrifugal pump surfaces increased monotonically to maxima at about the same time as for the oxygenators, but did not decrease thereafter. Higher platelet surface densities were observed on the centrifugal pump surfaces than on the oxygenator surfaces. CPB with the untreated circuit tended to reduce circulating platelet counts vs theoretical values based on hemodilution alone. In contrast, SMA significantly increased the circulating platelet count versus the untreated control group. These results indicate that platelet adherence to the foreign surfaces of CPB equipment are influenced in characteristic ways by time and fluid shear. SMA treatment and nitric oxide infusion both reduce platelet adhesion to oxygenator surfaces. SMA treatment spares these cells for the circulation.

Sobredentaduras retenidas por ataches esféricos de implantes oseointegrados mediante la aplicación de un compuesto polixilano vinílico / Osseointegrated implant overdenture retained by ball attachments through the application of a vinyl-siloxane compound

Se describe un estudio clínico radiológico lineal en 15 pacientes donde se usaron esferas retentivas ("bola atache") para soportar prótesis completas inferiores y un compuesto polisiloxano vinílico para su fijación y retención. El plazo de seguimiento fue hasta de 5 años, correspondiendo: sexo: 6 masculinos, 9 femeninos; edad: 40 a 70 años. Los resultados muestran características satisfactorias ya que la reabsorción ósea controlada radiográficamente y corroborada por sonda roma de plástico, se presenta próxima a 1 mm. Fuerzas traumáticas pueden determinar algún fenómeno más pronunciado obedeciendo a circunstancias esencialmente locales y en relación a un sector del implante. La edad permite resultados muy satisfactorios en personas jóvenes, y el sexo no marcó diferencias significativas. Se describen las modificaciones de la técnica clásica en la aplicación de retenedores esféricos en forma directa y la utilización de un elastómero de consistencia fluida (polisiloxano vinílico de impresión de corrección) para lograr la fijación y retención de esta prótesis a los retenedores ("bola atache"), calculada por dinamómetro en 400 a 450 grs. Su aplicación en forma directa permite una adecuada oclusión que compensa el esfuerzo masticatorio y la resiliencia de la mucosa. El estudio clínico radiológico y el diagnóstico implantoprotético son condiciones fundamentales para determinar el número, diámetro y ubicación de los implantes con sus respectivas esferas retentivas

Cisobitan in treatment of prostatic cancer. A prospective controlled multicentre study.

Cisobitan, an organosilicon compound with estrogenic and antigonadotropic properties has been evaluated clinically in comparison with an estrogen preparation. In a multicenter study a total of 140 patients with well and moderately well differentiated prostatic cancer were randomly allocated to treatment with Cisobitan or Estradurin/Etivex, 70 to each group. Of 34 patients with poorly differentiated prostatic cancer 18 were given Cisobitan--and 16 were given Estracyt-treatment. Among the patients with well and moderately well differentiated prostatic cancer there were, disregarding mortality, no major differences in subjective, objective or laboratory response to the two kinds of treatment. The pattern of side effects was similar, but oedema requiring diuretics occurred more often in the estrogen treated group. There was a significant difference in mortality at 12 months between the groups, two in the Cisobitan group and ten in the estrogen treated group. Cancer was the cause of death in two patients in the estrogen treated group. All other patients succumbed in cardiovascular diseases. At 24 months the difference in mortality rate was less pronounced: Another ten patients had died in the Cisobitan treated group and seven among the estrogen treated patients. Cancer was responsible for the deaths in seven of the Cisobitan patients compared to four of the estrogen treated patients. Within three years one more patient in both groups had died. Of the 34 patients with poorly differentiated cancer, twelve were alive at the 24 months' follow up, six in the Cisobitan group and six in the Estracyt group.

Clinical trial of a new antigonadotropic substance, 2,6-cis-diphenylhexamethylcyclotetrasiloxane, in cancer of the prostate. A pilot study.

An organic siloxane compound, 2,6-cis-diphenylhexamethylcyclotetrasiloxane, (Cisobitan) has been shown to possess antigonadotropic properties. In this study it has been tried in prostatic cancer. 9 patients received the drug in the dose of 4-5 mg/kg body weight. General condition and subjective response, cytologic changes and semiquantitative scintigraphic changes of metastases were recorded, as well as common laboratory data. In this limited trial, Cisobitan was not adequate for tumour palliation. In a few instances subsequent oestrogen treatment was more effective. No side effects of Cisobitan were noted for periods up to 6 months. Further studies may be of value, perhaps using a higher dose.

Clinical experimental randomized study of 2.6-cis-diphenylhexamethylcyclotetrasiloxane and estramustine-17-phosphate in the treatment of prostatic carcinoma.

Patients with poorly differentiated prostatic carcinoma and skeletal metastases were randomized to treatment with 2.6-cis-diphenylhexamethylcyclotetrasiloxane (2.6-cis) and estramustine-17-phosphate (estramustine). Parallel with the clinical study a group of non-randomized patients were treated with 2.6-cis. Cytological regression of the tumor could be registered in half of the estramustine group but not in the 2.6-cis group. There were no drug-related changes in blood chemistry, kidney function tests, hematology or liver enzymes. There was in increase in acid and alkaline phosphatase in both groups but more pronounced in the 2.6-cis group. In both groups follicle-stimulating and luteinizing hormone values were depressed. Testicular and penis atrophy was observed in the 2.6-cis group. Relief of pain and marked improvement of conditions occurred in the majority of the cases in both groups. In general, no tumor regression was observed during administration of 300 mg. 2.6-cis daily for at least 3 months. Some tumor regression was noted during 600 mg. estramustine therapy daily.

Blood coagulation studies in patients with advanced carcinoma of the prostate treated with 2,6-cis-diphenylhexamethylcyclotetrasiloxane or estramustine-17-phosphate.

Two drugs, 2,6-cis-diphenylhexamethylcyclotetrasiloxane (Cisobitan) and estramustine-17-phosphate (Estracyt) were given to patients with poorly differentiated metastatic carcinoma of the prostate. The effect of the drugs on blood coagulation was investigated. Some parameters showed changes during the treatment: Antithrombin III decreased in the Estracyt treated patients to a level which might imply a thrombogenic effect. Fibrinogen decreased, whereas factor VIII showed no consistent change. Normotest changes appeared to correlate with liver damage whereas antithrombin III showed no change. Increased levels of fibrinogen degradation products and fibrinopeptide A (FPA) were more frequent in the group of deteriorating patients. However, the number of FPA analyses were too small for any definite conclusions regarding possible disseminated intravascular coagulation.

Prostatic carcinoma treated with 2,6-cis-diphenylhexamethylcyclotetrasiloxane (Cisobitan).

Thirteen patients with stage III or IV carcinoma of the prostate were treated with 2,6-cis-Diphenylhexamethylcyclotetrasiloxane (Cisobitan, a new organosilicon compound. The drug proved to be a strong antiandrogen and exerted all the known effects of estrogens, including feminization and cardiovascular complications. It is therefore doubtful whether Cisobitan will be a reasonable alternative to estrogens in the treatment of patients with advanced prostatic cancer.