Effectiveness of a new non-hydrogen peroxide bleaching agent after single use - a double-blind placebo-controlled short-term study

Abstract Tooth whitening represents perhaps the most common aesthetic procedure in dentistry worldwide. The efficacy of bleaching depends on three aspects: bleaching agent, bleaching method, and tooth color. Objective: This in vivo study aimed to examine whitening effects on frontal teeth of the upper and lower jaws using an over-the-counter (OTC) non-hydrogen peroxide bleaching agent in comparison to a placebo after one single use. Material and methods: Forty subjects (25 female; 15 male) participated in this double-blind randomized placebo-controlled trial. The subjects were randomly allocated to two groups (n=20). The test group received the OTC product (iWhite Instant) and the placebo group received an identically composed product except for the active agents. Each subject was treated with a prefilled tray containing iWhite Instant or the placebo for 20 minutes. The tooth shade of the front teeth (upper and lower jaws) was assessed before (E_0), immediately after (E_1) and 24 h after treatment (E_2), using a shade guide (VITA classical). Statistical testing was accomplished using the Mann-Whitney U test (p<0.001). The dropout rate was 0%. Results: There were no significant differences at E_0 between placebo and test groups regarding the tooth color. Differences in tooth color changes immediately after (ΔE1_0) and 24 h after treatment (ΔE2_0) were calculated for both groups. The mean values (standard deviations) of tooth color changes for ΔE1_0 were 2.26 (0.92) in the test group and 0.01 (0.21) in the placebo group. The color changes for ΔE2_0 showed mean values of 2.15 (1.10) in the test group and 0.07 (0.35) in the placebo group. For ΔE1_0 and ΔE2_0 significant differences were found between the groups. Conclusion: In this short-term study, the results showed that a non-hydrogen peroxide bleaching agent has significant whitening effects immediately and 24 h after a single-use treatment.

Comparing the effects of small molecules BIX-01294, Bay K8644, RG-108 and valproic acid, and their different combinations on induction of pluripotency marker-genes by Oct4 in the mouse brain

Every cell type is characterized by a specific transcriptional profile together with a unique epigenetic landscape. Reprogramming factors such as Oct4, Klf4, Sox2 and c-Myc enable somatic cells to change their transcriptional profile and convert them to pluripotent cells. Small molecules such as BIX-01294, Bay K8644, RG-108 and valproic acid [VPA] are reported as effective molecules for enhancing induction of pluripotency in vitro, however, their effects during in vivo reprogramming are addressed in this experimental study. In this experimental study, Oct4 expressing lentiviral particles and small molecules BIX-01294, Bay K8644 and RG-108 were injected into the right ventricle of mice brain and VPA was systematically administered as oral gavages. Animals treated with different combinations of small molecules for 7 or 14 days in concomitant with Oct4 exogenous expression were compared for expression of pluripotency markers. Total RNA was isolated from the rims of the injected ventricle and quantitative polymerase chain reaction [PCR] was performed to evaluate the expression of endogenous Oct4, Nanog, c-Myc, klf4 and Sox2 as pluripotency markers, and Pax6 and Sox1 as neural stem cell [NSC] markers. Results showed that Oct4 exogenous expression for 7 days induced pluripotency slightly as it was detected by significant enhancement in expression of Nanog [p<0.05]. Combinatorial administration of Oct4 expressing vector and BIX-01294, Bay K8644 and RG-108 did not affect the expression of pluripotency and NSC markers, but VPA treatment along with Oct4 exogenous expression induced Nanog, Klf4 and c-Myc [p<0.001]. VPA treatment before the induction of exogenous Oct4 was more effective and significantly increased the expression of endogenous Oct4, Nanog, Klf4, c-Myc [p<0.01], Pax6 and Sox1 [p<0.001]. These results suggest VPA as the best enhancer of pluripotency among the chemicals tested, especially when applied prior to pluripotency induction by Oct4

Efeito do composto ftalimídico LASSBio-468 sobre a fibrose pulmonar induzida por sílica em camundongos / Effect of compound ftalimídico LASSBio-468 on the silica-induced lung fibrosis in mice

A silicose é uma doença ocupacional causada pela inalação de sílica em sua forma livre e cristalina. A inflamação e fibrose pulmonar constituem as principais características da patologia, que envolve uma variedade de mediadores inflamatórios, como o TNF-(alfa), um mediador de ações amplas e que exerce seus efeitos em um grande número de tipos celulares. LASSBio-468 é um análogo da talidomida já descrito como capaz de modular a produção de TNF-(alfa) e inibir o choque endotóxico e artrite reumatóide em modelos animais. Neste estudo, nós investigamos o potencial efeito do LASSBio -468 em modelo de silicose experimental emcamundongos. Animais Swiss-webster machos (18 – 20g) foram instilados intranasalmente com uma suspensão de sílica (10 mg/50 µL) e veículo (salina). O tratamento consistiu na administração por via oral de LASSBio-468 (12,5 – 100 mg/kg) e talidomida (50 mg/Kg) durante 7 dias consecutivos, do vigésimo primeiro ao vigésimo oitavo dia após a instilação de sílica. Foram analisadas a função pulmonar (resistência e elastância) e hiperreatividade das vias aéreas à aerolização de metacolina (3 – 27 mg/mL), através de pletismógrafo invasivo de corpo inteiro (Finepoint, Buxco System), além de análises morfológicas e morfométricas do tecido pulmonar. A produção de colágeno tecidual foi acessada pelo método de sircol, enquanto que a quantificação de citocinas/quimiocinas foi realizada pelo ensaio de ELISA. A técnica de imunohistoquímica permitiu a identificação da população de miofibroblastos no pulmão. Através de uma digestão mecânica e enzimática do tecido pulmonar, obtivemos uma cultura primária de miofibroblastos que, assim como macrófagos alveolares AMJ2C11 e células epiteliais A549, foram pré-tratados com diferentes concentrações de LASSBio-468 e talidomida, estimulados com IL-13 ou sílica e avaliados quanto a proliferação celular, viabilidade e produção de mediadores inflamatórios in vitro. Demonstramos que animais silicóticos apresentaram níveis basais elevados de resistência pulmonar e elastância, bem como hiperreatividade frente à aerolização de metacolina. Resposta inflamatória tecidual, extensiva deposição de colágeno, formação de granuloma e produção de quimiocinas (KC and MCP -1) e citocinas (TNF-(alfa)and TGF-(beta)) também foram detectadas em pulmões de animais silicóticos, assim co mo o aumento do número de miofibroblastos no tecido. O tratamento com LASSBio-468 reduziu o comprometimento da função pulmonar e hiperreatividade, formação de granulomas, expressão de miofibroblastos e deposição de colágeno no tecido pulmonar de animais doentes.Miofibroblastos oriundos de animais silicóticos apresentaram basal de proliferação superior, sendo responsivos também ao estímulo mitogênico da IL-13, que foi atenuado frente ao pré-tratamento com LASSBio-468. A estimulação de macrófagos alveolares e células epiteliais com sílica promoveu a liberação de TNF-(alfa) e IL-8, respectivamente, sendo o LASSBio-468 capaz de inibir de forma significativa esta produção. Em conjunto, nossos resultados mostraram que o tratamento com LASSBio-468 foi capaz de reduzir de forma curativa o comprometimento da função pulmonar e resposta granulomatosa, através de ações sobre células específicas, indicando que o composto em questão parece constituir uma promissora ferramenta para o tratamento de doenças pulmonares fibróticas crônicas como a silicose.

Design and synthesis of some phthalimide derivatives for antihyperlipidemic activity

To synthesize, explore the pharmacophore and evaluate the Structural Activity Relationship [SAR] of some reported and new N-phthaloylamides and N-phthaloylesters of some amino acids [namely, glycine. 1-alanirie, beta-alanine and y-aminobutyrie acids] aiming to find more effective antihyperlipidemic compounds using molecular overlay studies as a modern technique for drug design. The N-phthaloylamides and esters were synthesized using mixed anhydride method in good to escellent yields. The mixed anhydride method have represented a better and an efficient way for synthesizing such amides and esters than the old procedures. Twenty four of the newly synthesized compounds la-i, IIa-i, IIIa, and IVa were tested for their antihyperlipidemic activity against Triton WR- 1339-induced hyperlipidemia in rats. Triton WR-1339 [Tyloxapol, Sigma] was used to induce the suitable hyperlipidemia within 24 hours. Carboxymethylcellulose sodium [CMC-Na, Sigma] was used as a suspending agent. Male waster rats [6-7 week-old, 210-230 g body weight] were used as experimental animals. Spekol - 11 apparatus [Germany] was used to measure the total triglycerides and total cholesterol in the serum. Centrifuge [UK] was used to prepare the blood serum samples. The test compounds were suspended in carboxymethylcellulose sodium solution in 0.5% in normal saline to give 6% concentrations. Triton was dissolved in normal saline to give 12% solution. One hundred thirty five rats were arranged in 27 groups [5 animals each] and were deprived of food but were allowed free to access to drinking water. Each animal in all groups was injected in the tail vein with a volume of Triton solution equivalent to 300 mg/kg boy weight. The animals of one group were orally administered 1 ml of CMC-Na solution and kept as a control group. Animals in the remaining groups were orally given the test compounds at a dose level of 150 mg/kg boy weight. Alter 24 hours, blood was taken from each animal and centrifuged to obtain the serum. The plasma total cholesterol [TC] and total triglyceride [TG] levels were measured and the rates of decrease [%] were calculated using the following equation: Rate of decrease [%] = [I -Vt/Vc] x 100. Where Vt and Vc are the value of TC or TG for the test groups and control group, respectively. The preliminary evaluation of the antihyperlipidemic activity of [1-24] against Triton WR 1339-induced hyperlipidemia in rats showed that several derivatives have demonstrated significant lowering of serum total cholesterol and triglyceride levels comparing to clofibrate. Most of the compounds have shown good to excellent activities. The test compounds have also shown more antitriglyceridimic than anticholestrolemic activities

Kinetics of oxidation of [N-isopropylidene - hydrazine-s-methyldithiocarboxylate] cobalt [II] complex by N-bromosuccinimide and N-bromophthalimide in non polar solvent

The kinetics of oxidation of [N-isopropylidene - hydrazine-s-methyldithio-carboxylate] cobalt [II] complex by N-bromosuccinimide [NBS] and N-bromophthalimide [NBP] in benzene solvent were studied spectrophotometrically at lambda = 300 - 310 nm and at 281-297 K for a range of complex and oxidant concentrations. The reaction exhibited a first order dependence on both reactants. The detection of the initial cobalt [III] products which are slowly converted to the final cobalt [III] supports an inner-sphere mechanism for the oxidation of the complex by both oxidants. Under identical experimental conditions, the extent of oxidation using the oxidizing agents is in the order: NBS > NBP. GC-MS analysis for the reaction mixture after completion of the oxidation reaction indicates the presence of both succinimide and phthalimide as side products of the oxidation process

Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance), histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber) were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9), mice were immunized with 10 æg ovalbumin (OVA, ip) on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 æg OVA at 3-day intervals. Control mice (N = 8) received saline under the same protocol. In the dexamethasone (N = 8) and LASSBio596 (N = 8) groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip) or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip) 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76 percent, respectively) compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

Microondas doméstico na síntese de derivados ftalimídicos / Use of domestic microwave oven in the synthesis of phthalimide derivatives

Microondas são utilizadas na síntese orgânica desde 1986, e mostra-se vantajosa em diversos aspectos como possibilidade de maiores rendimentos, maior seletividade e menor decomposição térmica. A ftalimida e derivados, constituem-se em uma importante classe de compostos utilizados na química orgânica sintética, e do ponto de vista da Química Farmacêutica e Medicinal, é considerada um importante bióforo constituindo subunidade estrutural de caráter farmacofórico para uma série de compostos com diferentes atividades farmacológicas, entre elas, a anemia falciforme. O objetivo deste trabalho foi desenvolver metodologia alternativa na síntese de derivados ftalimídicos explorando a condensação de anidrido ftálico com aminas funcionalizadas sob radiação de microondas doméstico. Os resultados mostraram que os compostos ftalímidicos sintetizados podem ser obtidos em menores tempos reacionais (5-10 minutos) e maiores rendimentos(60-89%) quando comparados ao aquecimento convencional (refluxo), demonstrando o potencial da utilização do microondas na obtenção destas moléculas...

Synthesis and pharmacological evaluation of carboxamides

Some carboxamide derivatives with potential anti-inflammatory and analgesic properties were synthesized from the reaction of phthalimido alkyl acids with benzylamine at room temperature. All the compounds synthesized were unequivocally confirmed by means of Infrared, Nuclear Magnetic Resonance [1H and 13C], Mass spectrophotometer, and elemental analyses. The carboxamides were evaluated pharmacologically for their in vivo anti-inflammatory and analgesic activities by carrageenan-induced rat paw oedema and acetic acid-induced writhing test respectively. All the investigated compounds exhibited significant anti-inflammatory activity in the range of 45 to 70% in comparison to control. They showed promising analgesic activity at the dose used. 3-Benzamido-propionic acid -2-[N-benzyl]-carboxamide [4] exhibited the highest anti-inflammatory and analgesic activities and the effects were dose-dependent

Experimental studies of the effects of ZnPcS2P2-based-photodynamic therapy on bone marrow purging / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>An effective purging technique plays an important role in autologous hematopoietic stem cells transplantation. Photodynamic therapy (PDT) provides a novel approach for this purpose. This study dealt with the purging effects of di-sulfo-di-phthalimidomethyl phthalolcyanine zinc (ZnPcS2P2)-based photodynamic therapy (ZnPc-PDT).</p><p><b>METHODS</b>Fluorescence intensity of cell extracts was measured using a fluorescence spectrophotometry. The proliferative potency of K562 cells and HL60 cells was detected using MTT colorimetric assay, Typan blue dye exclusion method, colony formation test. The proliferative potency of normal hematopoietic cells was evaluated using mixture colony-forming unit (CFU-Mix), granulocyte-macrophage colony-forming unit (CFU-GM), and erythrocyte colony-forming unit (CFU-E) assays. K562 cells were mixed with normal mononuclear cells (MNCs) at ratios of 1:100 and 1:1000 for creating the model of simulated remission bone marrow. Colony formation test and nested-RT-PCR were carried out to detect the residual K562 cells in cell mixture.</p><p><b>RESULTS</b>After a 5-hour incubation with ZnPcS2P2, the content of ZnPcS2P2 in normal MNCs was the lowest value. At the same time, the content in K562 cells and HL60 cells was very high. Therefore, the time point was selected as the optimal one for irradiating the cell suspensions. ZnPc-PDT could significantly kill proliferative K562 cells and HL60 cells in a dose-dependent manner. At the concentration of 1.0 microg/ml, the inhibitory rate of ZnPc-PDT on the colony formation was 100% for K562 cells, 89.7% for HL60 cells. 0.25 microg/ml ZnPc-PDT could completely photoinactivate residual K562 cells in the simulated remission bone marrow. Under an identical condition, the inhibitory rates of CFU-Mix, CFU-GM, CFU-E were 18.0%, 18.6%, and 17.8% respectively.</p><p><b>CONCLUSION</b>ZnPc-PDT appears to be a promising approach for bone marrow purging.</p>