SEM and EDS study of TotalFill BC Sealer and GuttaFlow Bioseal root canal sealers.

BACKGROUND: Recently, a new generation of calcium silicate-based root canal sealers has been developed. These new types of sealers have the ability to set in wet environment, have high alkalinity and present potential antimicrobial activity. OBJECTIVES: The aim of this study was to determine the chemical composition and microstructure of 2 novel calcium silicate-containing root canal sealers - TotalFill® BC Sealer and GuttaFlow® Bioseal. MATERIAL AND METHODS: The tested sealers were prepared according to the manufacturers' instructions. Sixteen cylindrical dishes (inner diameter: 4 mm; height: 3 mm) were placed on a glass Petri dish and packed with the materials. The Petri dish was transferred to an incubator. After the sealers set, excess material was removed with diamond discs and polishing paste. The materials were assessed using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) X­ray microanalysis. RESULTS: Both TotalFill BC Sealer and GuttaFlow Bioseal contained calcium, zirconium, oxygen, carbon, silicon, and a trace of sodium. In the case of TotalFill BC Sealer, trace amounts of copper and technetium were also present, and for GuttaFlow Bioseal, iron, zinc, and a trace of magnesium and hafnium were noted. No bismuth was found. Both of the assessed sealers contained fine particles embedded in the matrix; however, GuttaFlow Bioseal also had larger particles with a diameter of 2-10 µm. CONCLUSIONS: TotalFill BC Sealer represents a higher degree of purity in comparison with GuttaFlow Bioseal. The clinical implications of heavy metals present in GuttaFlow Bioseal need to be investigated. Both materials have a fine particle structure, which is desirable for root canal sealers.

Structure-activity relationships of novel heteroaryl-acrylonitriles as cytotoxic and antibacterial agents.

Eighteen new 2,6-disubstituted acrylonitriles and two new (benzimidazol-1-yl)-acetamide derivatives were prepared and screened for antibacterial and cytotoxic activities on 12 human cancer cell lines. Based on the lead structure 2-(benzimidazol-2-yl)-3-(5-nitrothiophen-2-yl) acrylonitrile it was found that placement of methyl groups at the 5,6 positions of the benzimidazole ring lead to a 3-fold increase in overall cytotoxic activity. Replacing the nitrothiophene for pyridine reduced cytotoxic activity as did replacing the nitro group for a methoxy group. Cytotoxic activity was only slightly reduced when the benzimidazole ring was replaced by a imidazo[4,5-b]pyridine or a benzthiazole ring but replacement by benzoxazole led to a substantial decrease in activity. Moving the acrylonitrile group from position 2 to position 1 of the benzimidazole ring also resulted in moderately active compounds. (Benzimidazol-1-yl)acetamides showed only modest activity. The structure-activity relationships found in the cytotoxicity studies are mirrored in the results of the antibacterial experiments.

Synthesis and biological activity of new 2-amino-8-chloro-5,5-dioxo[1,2,4]triazolo[2,3-b][1,4,2]benzodithiazines.

Two series of 1-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)-4-arylsemicarbazides 6-17 and 2-arylamino-8-chloro-5,5-dioxo[1,2,4]triazolo[2,3-b][1,4,2]benzodithiazines 18-26 were prepared in order to evaluate their biological activity. Compounds 6 and 18-26 were tested for their in vitro cytotoxic potency against 12 human cancer cell lines. The compounds 6 and 19 were inactive, whereas triazolobenzodithiazines 18, 20-26 possess tumor growth inhibitory properties. The prominent methyl 8-chloro-2-(4-chlorophenylamino)-5,5-dioxo[1,2,4]triazolo[2,3-b][1,4,2]benzodithiazine-7-carboxylate (21) exhibited potency higher or comparable to cisplatin. Moreover, compounds 6, 9, 19 and 23-25 with structure similar to other chemotherapeutic agents were tested for their antibacterial activity and exhibited MIC and MBC against Staphylococcus aureus (3.9-31.5 microg ml).

Traumatic cartilage lesions of the knee in the own material.

Background. The knee joint cartilage is vulnerable to traumatic injury, which may lead to osteoarthritis and may result in restrictions of normal knee function and negatively influence the physical activity. The purpose of this study was the epidemiologic and statistical analysis of traumatic cartilage lesions. Material and methods. From 1998 to 2003, 5233 arthroscopies of the knee joint were performed in 5114 patients. The diagnosis of the cartilage lesion based on arthroscopy was a criterion for the inclusion to the study group. The retrospective analysis of patients' data was performed with the use of questionnaire adapted from IKDC (International Knee Documentation Committee) questionnaire and ICRS (International Cartilage Repair Society) questionnaire. Results. Traumatic cartilage lesions were found in 81.9% of all diagnosed cartilage lesions. Traumatic non-contact onset was the most common mechanism of injury and it was usually connected with sports participation and day living activity. Grade II according to ICRS classification was the most frequent grade of the traumatic cartilage lesion. The medial femoral condyle and patellar articular surface were the most common locations of the traumatic lesions. Conclusions. Our study confirms that traumatic cartilage lesions of the knee joint are common and occur in wide group of patients. In many cases they may lead to osteoarthritis.

A Comparative Chemical Study of Calcium Silicate-Containing and Epoxy Resin-Based Root Canal Sealers.

Objective. The present study assessed the chemical elements in two novel calcium silicate-containing root canal sealers, BioRoot RCS and Well-Root ST, compared to a calcium silicate-containing root canal sealer that has been on the market for several years, MTA Fillapex, and epoxy resin-based sealer AHPlus. Material and Methods. The sealers were mixed and manipulated according to the manufacturers' instructions. Twelve cylindrical molds (inner diameter 4 mm; height 3 mm) were placed on a glass petri dish and packed with the materials. The dish was transferred to an incubator. After 72 h the molds were examined by scanning electron microscopy and energy dispersive X-ray microanalysis. Results. BioRoot RCS and Well-Root ST had high peaks of calcium, zirconium, oxygen, carbon, silicon, and chlorine. Well-Root ST also had sodium, magnesium, aluminum, and titanium peaks. MTA Fillapex and AHPlus had carbon, oxygen, calcium, titanium, and bismuth peaks. A silicon peak was also observed for MTA Fillapex, and zirconium and tungsten peaks for AHPlus. Conclusion. BioRoot RSC had the highest degree of purity. The clinical implication of metals contained in the other sealers needs to be investigated.

Synthesis, X-ray crystal structures, stabilities, and in vitro cytotoxic activities of new heteroarylacrylonitriles.

Twenty-three acrylonitriles, substituted at position 2 with either triazoles or benzimidazoles and at position 3 with various substituted furan, thiophene, or phenyl rings, were prepared by Knoevenagel condensation and tested for in vitro cytotoxic potency on 11 human cancer cell lines. X-ray crystal analysis of two representative compounds showed that the olfenic bond is E-configured. Structure-activity-relationships (SAR) indicated that position 2 is flexible for substituents with various nitrogen heterocyclics while position 3 is very sensitive to change; the most potent compounds contained a 5-nitrothiophen-2-yl ring at position 3 and either benzimidazol-2-yl (11) or a 5-benzyl-1H-[1,2,4]-triazol-3-yl (7) group at position 2 of acrylonitrile. SARs for the thiophen-2-yl-benzimidazoles show the following trend for position 5: NO2 >> H > Cl = CH3. Compound 11 was on average 10- and 3-fold more potent than cisplatin and etoposide, respectively. However, the acrylonitrile functionality is not an absolute requirement for cytotoxic activity because replacement of the nitrile group for either a hydrogen or a methyl group also gave active compounds. The acrylonitriles caused delayed cell death characterized by giant cells with multilobed nuclei. Compound 11 was found to bring about the increase in the activities of caspases 3 and 9 in the HL-60 cell line in a manner similar to etoposide, strongly indicating that apoptosis is the mechanism of cell death. The selectivity of various compounds toward cancer cells was estimated by comparing the IC50 values obtained from a noncancerous epithelial cell line, h-TERT-RPE1, with the average IC50 value from the cancer cell lines; 11 showed an average 1.7-fold greater activity toward cancer cells. The stabilities of the new compounds under cell culture conditions, estimated by HPLC, indicated that a major fraction of the compounds were lost from the medium over the first 24 h.

Synthesis and anticancer activity of novel 2-amino-4-(4-phenylpiperazino)- 1,3,5-triazine derivatives.

The synthesis and anticancer activity of novel 2-amino-4-(4-phenylpiperazino)-1,3,5-triazine derivatives 4a-b and 5a-f are described. Compounds 4a, 5a,c and 5f were evaluated by in vitro assays of growth inhibition against several human tumor cell lines. The vitro cytotoxic activity was found for 2-{2-amino-4-[4-(2-chlorophenyl)piperazino]- 1,3,5-triazin-6-yl}-3-(4-nitrophenyl)acrylonitrile (5f) (IC50 = 0.45 microM - 1.66 microM), whilst other tested compounds were inactive. Some of the molecular orbital calculations for the tested derivatives were also presented.

Postoperative treatment and rehabilitation after total knee arthroplasty.

Total arthroplasty is the primary surgical method used in patients with extensive deformations of the knee joint in the course of osteoarthritis or rheumatoid arthritis. Good outcome after arthroplasty depends on the proper identification of indications, good surgical technique, and the proper postoperative treatment and rehabilitation. In postoperative treatment appropriate conditions should be provided for healing of the damaged tissues and prevention of early and late complications. The aim of rehabilitation is to restore mobility in the highest possible range and full muscular control of the operated knee, i.e. to rebuild correct static and dynamic function of the joint and the entire lower limb. This study present a model of postoperative management and rehabilitation after total knee arthroplasty based on current literature and clinical experience from 597 arthroplasties performed in 530 patients between the years 1995 and 2002.

Synthesis, enzymatic evaluation, and docking studies of fluorogenic caspase 8 tetrapeptide substrates.

The synthesis, enzymatic evaluation, and molecular modeling studies of new fluorogenic tetrapeptide-based substrates selective for caspase 8, having the general structure Ac-IETD-AXX, are described. Various fluorescent reporter groups (AXX), i.e., 3- and 4-substituted coumarins and quinolin-2(1H)-ones were synthesized by von Pechmann condensation. They were subsequently coupled with the caspase-8-selective tetrapeptide Ac-IETD-OH under newly developed synthetic conditions to give the desired substrates in good yields and in high enantiomeric purity. Based on K(M) and V(max) values, the new compounds proved to be excellent substrates for recombinant human caspase 8. In contrast, the K(M) values for the same compounds as substrates for human caspase 3 were approximately 10-20-fold higher. Molecular modeling studies based on the X-ray crystal structures of both human caspases 3 and 8 revealed that there is sufficient room within both active sites to accommodate substrates with moderately bulky substituents in the 3- and 4-positions of the fluorogenic coumarins and quinolin-2(1H)-ones. Automated docking of the substrates into the active sites of both human caspases 3 and 8 with the program AutoDock 3 gave structures similar to the published crystallographic structures for the same tetrapeptide bound to caspase 8 in the form of an irreversible inhibitor. The calculated binding energies for the new substrates to either caspase 3 or 8 showed little difference between the substrates, consistent with the K(M) data. In addition, the calculated binding energies (DeltaG) to caspase 8 were considerably more negative than those to caspase 3, also consistent with the K(M) data. A possible molecular interaction that might explain the selectivity of the IETD tetrapeptide motif for caspase 8 over caspase 3 is discussed.

Synthesis and cytotoxicity testing of novel 2-(3-substituted-6-chloro-1,1-dioxo-1,4,2-benzodithiazin-7-yl)-3-phenyl-4(3H)-quinazolinones.

A new series of thirteen 2-[3-(substituted amino)-6-chloro-1,1-dioxo-1,4,2-benzodithiazin-7-yl]-3-phenyl-4(3H)-quinazolinones 4-16 were prepared in order to evaluate their cytotoxic activity against 12 human cancer cell lines. The bioassay indicated that the quinazolinone derivatives 5, 8-12, 15, and 16 possess cancer-cell growth-inhibitory properties. Compounds 5 and 12 showed a high level of selectivity for certain cell lines. The most active compounds 9, 10, 15, and 16 showed moderate antiproliferative activity and were approximately 4-fold less potent than cisplatin.

[(2-Phenylindol-3-yl)methylene]propanedinitriles inhibit the growth of breast cancer cells by cell cycle arrest in G(2)/M phase and apoptosis.

Cell cycle arrest of malignant cells is an important option for cancer treatment. In this study, we modified the structure of antimitotic 2-phenylindole-3-carbaldehydes by condensation with malononitrile. The resulting methylene propanedinitriles inhibited the growth of MDA-MB 231 and MCF-7 breast cancer cells with IC(50) values below 100 nM. Though they exhibited similar structure-activity relationships as the aldehydes, they did not inhibit tubulin polymerization but were capable of blocking the cell cycle in G(2)/M phase. The cell cycle arrest was accompanied by apoptosis as demonstrated by the activation of caspases 3 and 9. Since the new 2-phenylindole derivatives also inhibited the growth of transplanted MXT mouse mammary tumors, they are interesting candidates for further development.