Eco-friendly sequential one-pot synthesis, molecular docking, and anticancer evaluation of arylidene-hydrazinyl-thiazole derivatives as CDK2 inhibitors.

One current approach in the treatment of cancer is the inhibition of cyclin dependent kinase (CDK) enzymes with small molecules. CDK are a class of enzymes, which catalyze the transfer of the terminal phosphate of a molecule of ATP to a protein that acts as a substrate. Among CDK enzymes, CDK2 has been implicated in a variety of cancers, supporting its potential as a novel target for cancer therapy across many tumor types. Here the discovery and development of arylidene-hydrazinyl-thiazole as a potentially CDK2 inhibitors is described, including details of the design and successful synthesis of the series analogs (27a-r) using one-pot approach under eco-friendly ultrasound and microwave conditions. Most of the newly synthesized compounds showed good growth inhibition when assayed for their in-vitro anti-proliferative activity against three cancer cell lines (HepG2, MCF-7 and HCT-116) compared to the reference drug roscovitine, with little toxicity on the normal fibroblast cell lines (WI-38). Furthermore, the compounds exhibiting the highest anti-proliferative activities were tested against a panel of kinase enzymes. These derivatives displayed an outstanding CDK2 inhibitory potential with varying degree of inhibition in the range of IC50 0.35-1.49 µM when compared with the standard inhibitor roscovitine having an IC50 value 0.71 µM. The most promising CDK2 inhibitor (27f) was selected for further studies to determine its effect on the cell cycle progression and apoptosis in HepG2 cell line. The results indicated that this compound implied inhibition in the G2/M phase of the cell cycle, and it is a good apoptotic agent. Finally, Molecular docking study was performed to identify the structural elements which involved in the inhibitory activity with the prospective target, CDK2, and to rationalize the structure-activity relationship (SAR).

Targeted nanocarriers based on iodinated-cyanine dyes as immunomodulators for synergistic phototherapy.

Photodynamic therapy (PDT), as one of the most powerful photo-therapeutic strategies for cancer treatment with minimum invasiveness, can effectively damage local tumor cells and significantly induce systemic antitumor immunity. However, current nanotechnology-assisted PDT-immunomodulators have either poor penetration for deep tumors or low singlet oxygen generation. Herein, we construct a novel theranostic nanocarrier (HA-PEG-CyI, HPC) by inducing the self-assembly of PEGylated CyI and attaching the ligand HA to its surface. The prepared HPC can be used as an ideal PDT-immunomodulator for synergistic cancer therapy. CyI is an iodinated-cyanine dye with enhanced singlet oxygen generation ability as well as excellent photo-to-photothermal and near-infrared fluorescence imaging properties. Under 808 nm laser irradiation, the prepared HPC can generate both reactive oxygen species (ROS) and elevate temperature which can subsequently result in apoptosis and necrosis at tumor sites. Moreover, the HPC-induced cell death can generate a series of acute inflammatory reactions, leading to systemic immunity induction and secondary death of tumor cells, which further results in reducing tumor recurrence. In vitro and in vivo results show that HPC can enhance the tumor targeting efficacy, generate ROS efficiently and exhibit a high temperature response under NIR irradiation, which working together can activate immune responses for synergistic phototherapy on tumor cells. Accordingly, the proposed multi-functional HPC nanocarriers represent an important advance in PDT and can be used as a superior cancer treatment strategy with great promise for clinical applications.

Iodinated Cyanine Dyes for Fast Near-Infrared-Guided Deep Tissue Synergistic Phototherapy.

Phototheranostics, which combines deep tissue imaging and phototherapy [photodynamic therapy (PDT) and/or photothermal therapy (PTT)] via light irradiation, is a promising strategy to treat tumors. Near-infrared (NIR) cyanine dyes are researched as potential phototheranostics reagents for their excellent photophysical properties. However, the low singlet oxygen generation efficiency of cyanine dyes often leads to inadequate therapeutic efficacy for tumors. Herein, we modified an indocyanine green derivative Cy7 with heavy atom iodine to form a novel NIR dye CyI to improve the reactive oxygen species (ROS) production and heat generation while, at the same time, maintain their fluorescence characteristics for in vivo noninvasive imaging. More importantly, in vitro and in vivo therapeutic results illustrated that CyI could quickly and simultaneously generate enhanced ROS and heat to induce more cancer cell apoptosis and higher inhibition rates in deep HepG2 tumors than other noniodinated NIR dyes upon NIR irradiation. Besides, low toxicity of the resulted iodinated NIR dyes was confirmed by in vivo biodistribution and acute toxicity. Results indicate that this low toxic NIR dye could be an ideal phototheranostics agent for deep tumor treatments. Our study presents a novel approach to achieve the fast-synergistic PDT/PTT treatment in deep tissues.

Synthesis, Photochemical and In Vitro Cytotoxic Evaluation of New Iodinated Aminosquaraines as Potential Sensitizers for Photodynamic Therapy.

In this work, several benzothiazole-based aminosquaraine dyes, displaying strong absorption within the so-called phototherapeutic window (650⁻800 nm), were synthesized. The ability, of all the new dyes, to generate singlet oxygen was assessed by determining the correspondent phosphorescence emission and through the comparison with a standard. The quantum yields of singlet oxygen generation were determined and exhibited to be strongly dependent on the nature of the amino substituents introduced in the squaric ring. The photodynamic activity of the synthesized dyes was tested against four human tumor cell lines: breast (MCF-7), lung (NCI-H460), cervical (HeLa) and hepatocellular (HepG2) carcinomas; and a non-tumor porcine liver primary cell culture (PLP2). All the compounds synthesized were found to be able to inhibit tumor cells growth upon irradiation more than in the dark, in most of the cases, very significantly. Considering the photodynamic activity exhibited and the low toxicity displayed for the non-tumor cells, some of the synthetized dyes can be regarded as potential candidates as photosensitizers for PDT.

Time Intervals Between Prior Cervical Conization and Posterior Hysterectomy Influence Postoperative Infection in Patients with Cervical Intraepithelial Neoplasia or Cancer.

BACKGROUND This study was conducted to observe the influence of different time intervals between prior cervical conization and posterior hysterectomy on postoperative infection in female patients with cervical intraepithelial neoplasia or cancer. MATERIAL AND METHODS Medical records of 170 patients who underwent hysterectomy following cervical conization between November 2010 and September 2016 at the Zhenjiang 4th Hospital were reviewed. According to the interval between hysterectomy and cervical conization, patients were classified into 1-2-week, 4-5-week, and 6-week groups. The outcomes of 46 patients who underwent conization with iodoform gauze inside the vagina were observed. RESULTS The total postoperative infection rate after hysterectomy was 25.3% (43/170). The expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1) in the cervical secretions and tissues were found to gradually increase, peaking at 2 weeks after conization, then significantly decreasing 3-6 weeks onwards. Compared with the 1-2-week group, the 4-5-week and 6-week groups exhibited significantly lower infection rates (2/42, 4.8%, 4-5-week group; 0%, 0/33, 6-week group; vs. 41/95, 43.2%, 1-2-week group; p<0.001). In the 1-2-week group in particular, the postoperative infection rate after laparoscopic hysterectomy was significantly higher than the rate after abdominal hysterectomy (21/35, 60% vs. 20/60, 33%, p=0.0177). In addition, the vaginal and cervical wound infection rates after conization in patients treated with iodoform were significantly lower than the rates in those without iodoform treatment (p<0.05). CONCLUSIONS Hysterectomy should be performed at least 4 weeks after conization. Treatment with iodoform would be beneficial.

Nonsurgical Clinical Management of Periapical Lesions Using Calcium Hydroxide-Iodoform-Silicon-Oil Paste.

BACKGROUND: The study aim is to avoid tooth extraction by nonsurgical treatment of periapical lesion. It assesses healing progress in response to calcium hydroxide-iodoform-silicon oil paste (CHISP). Numeric Pain Rating Scale was used to validate the approach. Furthermore, CHISP was used to treat cystic lesions secondary to posttraumatic avulsion of permanent teeth. MATERIALS AND METHODS: Over 200 patients with radicular cysts were treated with CHISP through the root canal. Radiographs were used to verify lesion size and position, ensure correct delivery to the site, and monitor the progress of bone healing in the lesion area. Ten males and 10 females were randomly selected for statistical assessment. RESULTS: No severe pain, complications, or failure in cyst healing was reported. Complete healing was achieved in an average of 75 days. Furthermore, healing of radicular cyst secondary to posttraumatic tooth avulsion was successful. CONCLUSION: CHISP indicated an antiseptic effect, which enhanced and shortened healing time of periapical lesions. The less invasive procedure avoids tooth extraction and reduces bone resorption. Cyst management with CHISP can remedy failed root canal treatments. The results show a bone regenerative capacity of CHISP suggested in first rapid phase and a second slow phase.

Five Easy Pieces. The Total Synthesis of Phosphoiodyn A (and Placotylene A).

The convergent total synthesis of the marine natural product phosphoiodyn A, a nanomolar agonist of human peroxisome proliferator-activated receptor delta (hPPARδ), was achieved in five steps total from commercially available and inexpensive starting materials. The synthesis relies on the unprecedented regioselective hydrozirconation of a terminal acetylene in the presence of a conjugated 1,3-diyne and on ammonolysis of a ß-chlorophosphonic acid monoester. The scheme also provides the newly isolated placotylene A, an inhibitor of bone marrow-derived macrophage (BMM) differentiation.

Synthesis of novel 17-(5'-iodo)triazolyl-3-methoxyestrane epimers via Cu(I)-catalyzed azide-alkyne cycloadditon, and an evaluation of their cytotoxic activity in vitro.

The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of 3-methoxyestrane 17α- and 17ß-azide epimers (3 and 5) with different terminal alkynes afforded novel 1,4-substituted triazolyl derivatives (8a-f and 11a-f). If the Ph3P in the classical CuAAC process was replaced by Et3N, the formation of small quantities of 5-iodotriazoles (9a-f and 11a-f) was observed. For the preparation of 5-iodo-1,2,3-triazoles (9a-f and 11a-f), an improved method was developed, directly from steroidal azides and terminal alkynes, in reactions mediated by CuI and ICl as iodinating agents. The antiproliferative activities of the structurally related triazoles were determined in vitro with the microculture tetrazolium assay on six malignant human cell lines of gynecological origin (HeLa, A2780, MCF7, MDA-MB-231, MDA-MB-361 and T47D). X-ray analysis revealed the presence of the iodo substituent on the 1,2,3-triazole ring.

Characterization and anti-inflammatory effects of iodinated acetylenic acids isolated from the marine sponges Suberites mammilaris and Suberites japonicus.

The previously unknown compounds 1-4, acetylenic acids with one or two iodine atom(s), were isolated from the marine sponges Suberites mammilaris and Suberites japonicus. Their complete structures were determined using NMR and mass spectrometry. The methylated compounds 1a and 2a exhibited a strong NO inhibitory effect on RAW264.7 cells, while methylated 3a and 4a were inactive in RAW264.7 cells, but highly active in BV2 microglia cells.

Phosphoiodyns A and B, unique phosphorus-containing iodinated polyacetylenes from a Korean sponge Placospongia sp.

Two unprecedented phosphorus-containing iodinated polyacetylenes, phosphoiodyns A and B (1-2), were isolated from a Korean marine sponge Placospongia sp. Their structures were elucidated by spectroscopic data analysis. Phosphoiodyn A exhibited potent agonistic activity on human peroxisome proliferator-activated receptor delta (hPPARδ) with an EC(50) of 23.7 nM.

Effects of depletion of glutathione on abscisic acid- and methyl jasmonate-induced stomatal closure in Arabidopsis thaliana.

Glutathione (GSH) is involved in abscisic acid (ABA)- and methyl jasmonate (MeJA)-induced stomatal closure in Arabidopsis thaliana. In this study, we examined the effects of GSH-decreasing chemicals, p-nitrobenzyl chloride (PNBC), iodomethane (IDM), and ethacrynic acid (EA), on ABA- and MeJA-induced stomatal closure in Arabidopsis. Treatments with PNBC, IDM, and EA decreased GSH contents in guard cells. Depletion of GSH by PNBC and IDM enhanced ABA- and MeJA-induced stomatal closure and inhibition of light-induced stomatal opening by ABA, whereas EA did not enhance either ABA- and MeJA-induced stomatal closure or inhibition of light-induced stomatal opening by ABA. Depletion of GSH did not significantly increase the production of the reactive oxygen species (ROS), cytosolic alkalization, or cytosolic Ca(2+) oscillation induced by ABA and MeJA. These results indicate that depletion of GSH enhances ABA- and MeJA-induced stomatal closure without affecting ROS production, cytosolic alkalization, or cytosolic Ca(2+) oscillation in guard cells of Arabidopsis.

Antineoplastic agents. 548. Synthesis of iodo- and diiodocombstatin phosphate prodrugs.

Toward the objective of designing a structurally modified analogue of the combretastatin A-4 phosphate prodrug (1b) with the potential for increased specificity toward thyroid carcinoma, synthesis of a series of iodocombstatin phosphate (11a-h) and diiodocombstatin phosphate prodrugs (12a-h) has been accomplished. The diiodo series was obtained via 8a and 9c from condensation of 4 and 6, and the iodo sequence involved a parallel pathway. Both series of iodocombstatins were found to display significant to powerful inhibition of the growth of a panel of human cancer cell lines and of the murine P388 lymphocytic leukemia cell line. Of the diiodo series, 12a was also found to markedly inhibit growth of pediatric neuroblastoma, and monoiodocombstatin 9a strongly inhibited HUVEC growth. Overall, the strongest activity was found against the breast, CNS, leukemia, lung, and prostate cancer cell lines and the least activity against the pancreas and colon lines. Parallel biological investigations of tubulin interaction, antiangiogenesis, and antimicrobial effects were also conducted.

Histological evaluation of bone response to pediatric endodontic pastes: an experimental study in guinea pig.

This study aimed to evaluate by the intra-osseous implant technique the most commonly used materials for pulp therapy in pediatric dentistry: calcium hydroxide (CH), Guedes Pinto paste and CTZ paste, according to FDI (1980) and ANSI/ADA (1982) recommendations. Thirty guinea pigs, 10 for each material, divided into experimental periods of 4 and 12 weeks received one implant on each side of the lower jaw symphysis. The external lateral tube wall served as control for the technique. At the end of the observation periods, the animals were euthanized and specimens were prepared for routine histological examination. It was observed that CH and CTZ paste induced severe inflammation, a large amount of necrotic tissue, lymphocytes, foreign body cells and bone resorption, while Guedes Pinto Paste induced little or no inflammation in the 4-week observation period. After 12 weeks, the reactions to CH and Guedes Pinto paste were also absent/mild, presenting a general pattern of replacement by recently formed bone tissue while a moderate to severe inflammatory response was observed with CTZ paste. Guedes Pinto paste presented acceptable biocompatibility levels in both analyzed periods; CH only showed acceptable biocompatibility in the 12-week period while CTZ paste showed no biocompatibility in both periods. Among the tested materials, only Guedes Pinto paste presented an acceptable biocompatibility.

Histological evaluation of bone response to pediatric endodontic pastes: an experimental study in guinea pig

This study aimed to evaluate by the intra-osseous implant technique the most commonly used materials for pulp therapy in pediatric dentistry: calcium hydroxide (CH), Guedes Pinto paste and CTZ paste, according to FDI (1980) and ANSI/ADA (1982) recommendations. Thirty guinea pigs, 10 for each material, divided into experimental periods of 4 and 12 weeks received one implant on each side of the lower jaw symphysis. The external lateral tube wall served as control for the technique. At the end of the observation periods, the animals were euthanized and specimens were prepared for routine histological examination. It was observed that CH and CTZ paste induced severe inflammation, a large amount of necrotic tissue, lymphocytes, foreign body cells and bone resorption, while Guedes Pinto Paste induced little or no inflammation in the 4-week observation period. After 12 weeks, the reactions to CH and Guedes Pinto paste were also absent/mild, presenting a general pattern of replacement by recently formed bone tissue while a moderate to severe inflammatory response was observed with CTZ paste. Guedes Pinto paste presented acceptable biocompatibility levels in both analyzed periods; CH only showed acceptable biocompatibility in the 12-week period while CTZ paste showed no biocompatibility in both periods. Among the tested materials, only Guedes Pinto paste presented an acceptable biocompatibility.

A pesquisa teve como objetivo avaliar a biocompatibilidade através da técnica de implantes intra-ósseos dos materiais utilizados em odontopediatria para tratamento pulpar: hidróxido de cálcio, pastas Guedes Pinto e CTZ, de acordo com as recomendações da FDI (1980) e ANSI/ADA(1982). Trinta guinea pigs, dez para cada material, divididos em períodos experimentais de 4 e 12 semanas receberam um implante em cada lado da sínfise mandibular. A parede lateral externa do copo serviu como controle para a técnica. No final dos períodos experimentais, os animais foram sacrificados e os espécimes preparados para o exame histológico de rotina. Observou-se que o hidróxido de cálcio e a pasta CTZ mostraram reação inflamatória severa, grande quantidade de tecido necrosado, linfócitos, células de corpo estranho e reabsorção óssea; enquanto a pasta Guedes Pinto induziu pouca ou nenhuma inflamação no período de 4 semanas. Após 12 semanas as reações para o hidróxido de cálcio e pasta Guedes Pinto foram ausentes/suaves apresentando um padrão geral de substituição por tecido ósseo neoformado, enquanto uma resposta inflamatória de moderada a severa foi observada para a pasta CTZ. A pasta Guedes Pinto apresentou níveis aceitáveis de biocompatibilidade nos dois períodos analisados; hidróxido de cálcio apresentou biocompatibilidade aceitável somente no período de 12 semanas e a pasta CTZ não mostrou biocompatibilidade em ambos os períodos. Entre estes, apenas a pasta Guedes Pinto apresentou níveis de biocompatibilidade nos dois períodos analisados.

Iodination of verapamil for a stronger induction of death, through GSH efflux, of cancer cells overexpressing MRP1.

The multidrug resistance protein 1 (MRP1), involved in multidrug resistance (MDR) of cancer cells, was found to be modulated by verapamil, through stimulation of GSH transport, leading to apoptosis of MRP1-overexpressing cells. In this study, various iodinated derivatives of verapamil were synthesized, including iodination on the B ring, known to be involved in verapamil cardiotoxicity, and assayed for the stimulation of GSH efflux by MRP1. The iodination, for nearly all compounds, led to a higher stimulation of GSH efflux. However, determination of concomitant cytotoxicity is also important for selecting the best compound, which was found to be 10-fold more potent than verapamil. This will then allow us to design original anti-cancer compounds which could specifically kill the resistant cancer cells.

In vitro glutathione conjugation of methyl iodide in rat, rabbit, and human blood and tissues.

Methyl iodide (MeI) is an intermediate in the manufacture of some pesticides and pharmaceuticals, and is under review for US registration as a non-ozone depleting alternative for methyl bromide for pre-plant soil fumigation. MeI is primarily metabolized via conjugation with glutathione (GSH), with further metabolism to S-methyl cysteine and methanethiol. To facilitate extrapolations of animal pharmacokinetic data to humans, rate constants for the GSH metabolism of MeI were determined in cytosols prepared from the liver and kidneys of rats, human donors, female rabbits, and rabbit fetuses, from rabbit olfactory and respiratory epithelium, and from rabbit and rat blood using a headspace vial equilibration technique and two-compartment mathematical model. MeI was metabolized in liver and kidney from adults of all three species, but metabolism was not detectable in fetal rabbit kidney. Maximal metabolic rates (V(max)) were similar in liver from rat and human donors (approximately 40 and 47 nmol/min/mg, respectively) whereas the V(max) rates in kidney cytosols varied approximately three-fold between the three species. No difference was observed in the loss of MeI from active and inactive whole blood from either rats or rabbits. The metabolism in olfactory and respiratory epithelial cytosol had Michaelis-Menten constant (K(m)) values that were several times higher than for any other tissue, suggesting essentially first-order metabolism in the nose. The metabolism of MeI in human liver cytosol prepared from five individual donors indicated two potential populations, one high affinity/low capacity and one with a lower affinity but higher capacity.

Effects of co-substrates and inhibitors on the anaerobic O-demethylation of methyl tert-butyl ether (MTBE).

Methyl tert-butyl ether (MTBE) contamination is widespread in aquifers near urban areas around the world. Since this synthetic fuel oxygenate is resistant to most physical methods of treating fuel-contaminated water, biodegradation may be a useful means of remediation. Currently, information on anaerobic MTBE degradation is scarce. Depletion has been observed in soil and sediment microcosms from a variety of locations and under several redox conditions, but the responsible organisms are unknown. We are studying anaerobic consortia, enriched from contaminated sediments for MTBE-utilizing microorganisms for over a decade. MTBE degradation occurred in the presence of other fuel components and was not affected by toluene, benzene, ethanol, methanol, or gasoline. Many aryl O-methyl ethers, such as syringic acid, that are O-demethylated by acetogenic bacteria, were also O-demethylated by the MTBE-utilizing enrichment cultures. The addition of these compounds as co-substrates increased the rate of MTBE degradation, offering a potentially useful method of stimulating the MTBE degradation rate in situ. Propyl iodide caused light-reversible inhibition of MTBE degradation, suggesting that the MTBE degradation process is corrinoid dependent. The anaerobic MTBE degradation process was not directly coupled to methanogenesis or sulfidogenesis and was inhibited by the bactericidal antibiotic, rifampicin. These results suggest that MTBE degradation is mediated by acetogenic bacteria.

Antimicrobial effect and pH of chlorhexidine gel and calcium hydroxide alone and associated with other materials

The purposes of this study were to evaluate the effectiveness of 2 percent chlorhexidine (CHX) gluconate gel, calcium hydroxide [Ca(OH)2] and their combination with iodoform and zinc oxide powder as intracanal medications against select microorganisms, and to measure the pH changes caused by these medications. Antimicrobial activity was determined by the agar diffusion method. The zones of growth inhibition were measured and the results were analyzed statistically by Kruskal-Wallis test (p<0.05). The pH of the pastes was measured right after preparation, after 24 h and 1 week later. The largest mean zones of microbial inhibition were produced by 2 percent CHX gel, followed by Ca(OH)2 + 2 percent CHX gel + iodoform, Ca(OH)2 + 2 percent CHX gel, Ca(OH)2 + 2 percent CHX gel + zinc oxide, and Ca(OH)2 + water. The mean pH of all medications stayed above 12.0 during the whole experiment, except for CHX gel (pH=7.0). The results of this study showed that all medications had antimicrobial activity, but the most effective against the tested microorganisms were 2 percent CHX gel, followed by its combination with Ca(OH)2 and iodoform.

O objetivo do estudo foi avaliar, in vitro, a efetividade antimicrobiana da clorexidina gel 2 por cento (CHX) e hidróxido de cálcio, isoladamente e associados com iodofórmio e pó de óxido de zinco como medicamentos intracanais frente a microrganismos e medidos pHs das diferentes medicações. A atividade antimicrobiana foi determinada pelo método de difusão em ágar. As áreas de inibição de crescimento foram medidas e os resultados estatisticamente analisados utilizando-se o teste de Kruskal-Wallis (p<0,05). O pH das pastas foi mensurado após a manipulação, após 24 h e após uma semana. Os resultados mostraram que a maior zona de inibição foi da CHX gel 2 por cento, seguida pelo Ca(OH)2 + 2 por cento CHX gel, Ca(OH)2 + 2 por cento CHX gel + iodofórmio, Ca(OH)2 + 2 por cento CHX gel +óxido de zinco, Ca(OH)2 + água. A média de pH de todos os medicamentos intracanais foi de 12 durante todo o experimento, exceto com CHX gel 2 por cento (pH=7,0). Estes resultados permitiram concluir que todos os medicamentos tiveram atividade antimicrobiana, no entanto, a maior foi da CHX gel 2 por cento, seguido da associação com o Ca(OH)2. e iodofórmio.

Antimicrobial analysis of different root canal filling pastes used in pediatric dentistry by two experimental methods

The objective of this study was to compare, by two experimental methods, the antimicrobial efficacy of different root canal fillingpastes used in pediatric dentistry. The tested materials were: Guedes-Pinto paste (GPP), zinc oxide-eugenol paste (OZEP), calcium hydroxide paste (CHP), chloramphenicol + tetracycline + zinc oxide and eugenol paste (CTZP) and Vitapex®. Fiven microbial strains (S. aureus, E. faecalis, P. aeruginosa, B. subtilis and C. albicans) obtained from the American Type Culture Collection were inoculated in Brain Heart Infusion (BHI) and incubated at 37°C for 24 h. For the direct exposure test (DET), 72 paper points were contaminated with the standard microbial suspensions and exposed to the root canal filling pastes for 1, 24, 48 and 72 h. The points were immersed in Letheen Broth (LB), followed by incubation at 37°C for 48 h. An inoculum of 0.1 mL obtained from LB was then transferred to 7 mL of BHI, under identical incubations conditions and the microbial growth was evaluated. The pastes showed activity between 1 and 24 h, depending on the material. For the agar diffusion test (ADT), 30 Petri plates with 20 mL of BHI agar were inoculated with 0.1 mL of the microbial suspension, using sterile swabs that were spread on the medium. Three cavities were made in each agar plate (total = 90) and completely filled with one of the filling root canal pastes. The plates were pre-incubated for 1 h at room temperature and then incubated at 37°C for 24 to 48 h. The inhibition zone around each well was recorded in mm. The complete antimicrobial effect in the direct exposure test was observed after 24 h on all microbial indicators. All root canal filling materials induced the formation of inhibition zones, except for Vitapex® (range, 6.0-39.0 mm).

O objetivo do presente estudo foi comparar o efeito antimicrobiano de diferentes pastas obturadoras do canal radicular usadas na Odontopediatria, por dois métodos experimentais. Os materiais testados foram: pasta Guedes Pinto, pasta de óxido de zinco e eugenol, pasta de hidróxido de cálcio, pasta CTZ e Vitapex®, sobre cinco microrganismos (S. aureus, E. faecalis, P. aeruginosa, B. subtilis e C. albicans) obtidos do American Type Culture Collection. As cepas foram inoculadas no Brain Heart Infusion (BHI) e incubadas a 37°C por 24 h. Para o teste de contato direto, 72 pontas de papel foram contaminadas com suspensões padrão dos microrganismos e expostas às pastas obturadoras por 1, 24, 48 e 72 h. As pontas foram imersas em Letheen Broth (LB), seguido de incubação a 37°C por 48 h. Um inóculo de 0,1 mL obtido do LB foi transferido para 7 mL de BHI, sobre condições idênticas de incubação e o crescimento microbiano foi avaliado. As pastas mostraram ação entre 1 e 24 h, dependendo da pasta testada. Para o teste de difusão em ágar, 30 placas de Petri com 20 mL de agar BHI foi inoculada com 0,1 mL da suspensão microbiana, utilizando-se de swab esterilizado, semeado de modo confluente no meio. Três cavidades foram feitas em cada placa de ágar (total = 90) e completamente preenchidas com uma das pastas obturadoras. As placas foram pré-incubadas por 1 h em temperatura ambiente e então incubadas a 37°C por 48 h. As zonas de inibição em torno das cavidades foram mensuradas. O efeito antimicrobiano completo obtido pelas pastas analisadas, por meio do teste por contato direto, foi observado após 24 h em todos os microrganismos. No teste por difusão em ágar, todos os materiais induziram a formação de zonas de inibição, exceto o Vitapex® (variando de 6,0 - 39,0 mm).

Iodinated nitroimidazoles as radiosensitizers.

Four different nitroimidazole derivatives, with up to two iodine atoms on the imidazole ring, were investigated for their radiosensitizing potency under hypoxic conditions, in order to test whether the introduction of iodine atoms increases the radiosensitizing potency of nitroimidazoles. Misonidazole and metronidazole were used as controls. Human colonic adenocarcinoma cells were incubated with the drugs at different concentrations and for different time-periods. Photon energies of 50 kV, 60 kV and 20 MV and total radiation doses of up to 20 Gy were used. The introduction of additional iodine atoms into the nitroimidazole derivatives resulted in a strong increase in cytotoxicity of the compounds. In parallel, there were indications that the radiosensitizing potency was also increased.