La música como terapia en la escuela (estudio experimental de casos).

Cerciorarse de los encantos que la música produce en el niño y estudiar la influencia que esta tiene en el sujeto. Diez niños en edades comprendidas entre nueve y doce años, pertenecientes al aula de recuperación de quinto curso de EGB del Colegio Mixto de Pizarrales de Salamanca. Estudia los comienzos de la conducta musical en el hombre, su compromiso con la música, así como los efectos que la música produce en él, e intenta llevar los principios teóricos al terreno experimental, basándose, en los trabajos realizados por el Dr. Benenzon, de esta manera ha establecido un determinado tipo de reeducación en un grupo de niños con problemas psicomotores y motrices, a través de una serie de actividades. Prueba experimental. La experiencia consta de dos partes: una diagnóstica donde se propone conectar con los sujetos y de alguna manera conocerlos, mediante una comunicación no verbal y una segunda parte terapéutica, donde no se ha seguido ningún método determinado. 1)Un grupo de diez sujetos es bastante numeroso para poder observar a cada uno en particular; quizá el número ideal sea de cinco a seis. Al mismo tiempo, una duración de tres horas semanales en tres meses, es poco tiempo para poder determinar unos resultados precisos. 2) El ritmo y la imagen corporal se fueron desarrollando poco a poco, de forma muy lenta, al irse perfeccionado la percepción auditiva del ritmo musical y el uso rítmico en el tiempo y el espacio. 3) Poco a poco se logró una mayor sensibilidad a determinados tipos de música, en un principio nada atractivas, logrando captar determinados aspectos interesantes así como el adquirir un determinado gusto musical. 4) La responsabilidad creada a nivel de grupo e individual se fue acentuando, llegando a imponer ellos mismos el orden y el silencio. 5) La desinhibición y las barreras emocionales se expresaron en un compañerismo y en una conciencia de grupo bastante aceptable. 6) la atención prestada dio como resultado una mayor capacitación para el movimiento. 7) Adquirieron unos elementales conocimientos musicales relacionados fundamentalmente con los instrumentos. 8) La conclusión de las sesiones causó gran nerviosismo y tristeza.

Errores de inversión en la lectura oral.

Poner de manifiesto las características de los malos lectores para dar así una visión global del problema de la dislexia. 411 alumnos, 208 varones y 203 mujeres de segundo, tercer y cuarto nivel de E.G.B. pertenecientes a ocho centros de la zona de Castilla y León y Madrid; públicos y privados. El trabajo consta de dos partes: la teórica, basada principalmente en los niños con una manifiesta incapacidad para la realización del aprendizaje de la lecto-escritura, en el mismo periodo en que esto ocurre en la mayoría de sus compañeros, siempre que se encuentren dentro de unos límites establecidos y que no padezcan alteraciones psicopatológicas o neurológicas. Y una segunda parte práctica, que consiste en un trabajo de campo o experimental, que parte de una aplicación del test de Análisis de Lecto-Escritura (T.A.L.E.) a una muestra determinada de población, aplicando el subtest de lectura. Consta de unas pruebas comunes de series de palabras y sílabas; y otras de texto, siendo distintas estas últimas para cada nivel. La tesina se ha basado en un sólo tipo de error: Inversión, o lo que es lo mismo, la lectura de forma invertida del orden de colocación de letras o sílabas. 1) Es superior el número de errores de inversión en mujeres dentro de la prueba de sílabas, pero en la de palabras y texto es superior en varones, con lo que se corrobora la teoría de Debray y Melekian (el aumento es bastante notable). 2) El número de inversiones en sílabas es superior al que se da en palabras y textos. 3) Resulta llamativo que los errores más frecuentes se produzcan en palabras que no han tenido oportunidad de oír antes, como en el caso de los logátomos. 4) Las palabras con inversiones suelen tener más de tres sílabas por lo general, o menos pero con alguna sílaba compuesta, trabada o inversa. 5) Las sílabas con más errores de inversión son similares en los tres niveles: GLI, TAR, IB, OP, DRI, BOR, aunque se note cierto decrecimiento en el cuarto nivel, pero siempre dado por la lectura de sílabas de forma correcta. 6) Sería necesario tener una visión de conjunto, de todos los errores cometido (sustitución, repetición, omisión, adición,..) en las mismas pruebas, y así determinaríamos de forma más específica el peso que tiene la inversión en cada caso determinado.

Estudio experimental de la comprensión de las pasivas.

Estudiar la comprensión de las oraciones pasivas. 300 sujetos, distribuidos en diez grupos de edad de 30 sujetos cada uno. Las edades oscilan entre los 4 y los 14 años. Estudio que pretende concluir a qué edad se comprenden las oraciones pasivas, puesto que sobre este particular se han realizado pocas investigaciones y la mayoría de los casos a niños de habla inglesa, para después generalizar los resultados a todos los idiomas. Para llevar a cabo la investigación, se realizaron dos tipos de pruebas: una de forma escrita (mejor `leída´) y otra de forma manipulativa. LA prueba escrita es del tipo `objetiva de elección múltiple´, y la manipulativa es una especie de entrevista de estructura cerrada, puesto que el experimentador siempre realiza las mismas preguntas, en el mismo orden y, es cerrada porque el entrevistado no puede salirse de lo que se le pide. La prueba objetiva de elección múltiple se compone de 36 ítems en cada uno de los cuales se propone una oración modelo y debajo se incluyen tres opciones, para elegir la que se corresponde con la del modelo. La estructura de la prueba es de la siguiente forma: los cinco primeros ítems, son oraciones pasivas afirmativas. Dentro de las cuales dos son reversibles y tres, no reversibles. Los cinco ítems siguientes son oraciones activas afirmativas, también distribuidas en tres no reversibles y dos reversibles. Esas mismas diez oraciones se transforman después en negativas e interrogativas. Entre ambas se incluyeron seis oraciones nuevas en la forma impresional, de las cuales, tres eran afirmativas y tres negativas. La prueba manipulativa, como ya se ha dicho, consistía en una entrevista de estructura cerrada, que consta de cuatro oraciones, cada una de ellas expresada en forma activa y en forma pasiva, con el objetivo de estimular una acción determinada. Después de cada una de las oraciones se hacía siempre la misma pregunta, pero cambiando el verbo de la acción. La primera parte de esta prueba consistió en que los sujetos realizaran la acción indicada en la oración, para ello se les dejaban los objetos necesarios. La segunda parte de la prueba consistió en una respuesta verbal. 1) La comprensión de las oraciones pasivas se desarrolla con la edad en una secuencia progresiva de forma regular.2) Los resultados concluyen que la comprensión de las oraciones pasivas se adquiere después de los 14 años. Esa conclusión es discordante, con respecto a los estudios realizados sobre el tema por diversos autores especialistas en la materia, para los cuales la comprensión de las oraciones pasivas se adquieren como edad límite a los 10 años. Esta discrepancia puede deberse a que estos autores han generalizado los resultados obtenidos con niños de habla inglesa.3) En la revisión de la información sobre pasivas no se ha encontrado ninguna investigación que incluyera frases pasivas en sus distintas formas de expresión, solo se utilizaron oraciones afirmativas.4) Se consiguen con bastante diferencia antes las pasivas no reversibles que las reversibles. Esto puede ser debido a que las pasivas no reversibles no admiten más que una interpretación, pero con las reversibles pueden formar los niños dos enunciados plausibles aunque cambien el sujeto por el objeto o viceversa.5) En cuanto a la edad de comprensión, su en las oraciones no reversibles se admite como válida la obtenida en la prueba manipulativa desechando por completo la obtenida en la prueba escrita, prácticamente se coincide con los resultados obtenidos por otros investigadores.6) Se puede apreciar que la misma diferencia de edad que existe entre la comprensión de pasiva no reversibles y reversibles, en sus distintas modalidades, se da entre pasivas no reversibles y reversibles afirmativas y negativas; en cambio, en las interrogativas la edad de comprensión es la misma en un tipo que en otro.7) Se confirma que la pasiva se entiende mejor cuando la prueba es de forma manipulativa y oral, que cuando es escrita.

Orthographic facilitation in oral vocabulary acquisition

An experiment investigated whether exposure to orthography facilitates oral vocabulary learning. A total of 58 typically developing children aged 8-9 years were taught 12 nonwords. Children were trained to associate novel phonological forms with pictures of novel objects. Pictures were used as referents to represent novel word meanings. For half of the nonwords children were additionally exposed to orthography, although they were not alerted to its presence, nor were they instructed to use it. After this training phase a nonword-picture matching posttest was used to assess learning of nonword meaning, and a spelling posttest was used to assess learning of nonword orthography. Children showed robust learning for novel spelling patterns after incidental exposure to orthography. Further, we observed stronger learning for nonword-referent pairings trained with orthography. The degree of orthographic facilitation observed in posttests was related to children's reading levels, with more advanced readers showing more benefit from the presence of orthography.

Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model

Gastrointestinal (GI) models that mimic physiological conditions in vitro are important tools for developing and optimizing biopharmaceutical formulations. Oral administration of live attenuated bacterial vaccines (LBV) can safely and effectively promote mucosal immunity but new formulations are required that provide controlled release of optimal numbers of viable bacterial cells, which must survive gastrointestinal transit overcoming various antimicrobial barriers. Here, we use a gastro-small intestine gut model of human GI conditions to study the survival and release kinetics of two oral LBV formulations: the licensed typhoid fever vaccine Vivotif comprising enteric coated capsules; and an experimental formulation of the model vaccine Salmonella Typhimurium SL3261 dried directly onto cast enteric polymer films and laminated to form a polymer film laminate (PFL). Neither formulation released significant numbers of viable cells when tested in the complete gastro-small intestine model. The poor performance in delivering viable cells could be attributed to a combination of acid and bile toxicity plus incomplete release of cells for Vivotif capsules, and to bile toxicity alone for PFL. To achieve effective protection from intestinal bile in addition to effective acid resistance, bile adsorbent resins were incorporated into the PFL to produce a new formulation, termed BR-PFL. Efficient and complete release of 4.4x107 live cells per dose was achieved from BR-PFL at distal intestinal pH, with release kinetics controlled by the composition of the enteric polymer film, and no loss in viability observed in any stage of the GI model. Use of this in vitro GI model thereby allowed rational design of an oral LBV formulation to maximize viable cell release.

Hard tissue formation adjacent to implants of various size and configuration immediately placed into extraction sockets: an experimental study in dogs

Objectives To evaluate the influence of implant size and configuration on osseointegration in implants immediately placed into extraction sockets. Material and methods Implants were installed immediately into extraction sockets in the mandibles of six Labrador dogs. In the control sites, cylindrical transmucosal implants (3.3 mm diameter) were installed, while in the test sites, larger and conical (root formed, 5 mm diameter) implants were installed. After 4 months of healing, the resorptive patterns of the alveolar crest were evaluated histomorphometrically. Results With one exception, all implants were integrated in mineralized bone, mainly composed of mature lamellar bone. The alveolar crest underwent resorption at the control as well as at the test implants. This resorption was more pronounced at the buccal aspects and significantly greater at the test (2.7 +/- 0.4 mm) than at the control implants (1.5 +/- 0.6 mm). However, the control implants were associated with residual defects that were deeper at the lingual than at the buccal aspects, while these defects were virtually absent at test implants. Conclusions The installment of root formed wide implants immediately into extraction sockets will not prevent the resorption of the alveolar crest. In contrast, this resorption is more marked both at the buccal and lingual aspects of root formed wide than at standard cylindrical implants. To cite this article:Caneva M, Salata LA, de Souza SS, Bressan E, Botticelli D, Lang NP. Hard tissue formation adjacent to implants of various size and configuration immediately placed into extraction sockets: an experimental study in dogs.Clin. Oral Impl. Res. 21, 2010; 885-895.doi: 10.1111/j.1600-0501.2010.01931.x.

Influence of lateral pressure to the implant bed on osseointegration: an experimental study in dogs

Aim To study osseointegration and bone-level changes at implants installed using either a standard or a reduced diameter bur for implant bed preparation. Material and methods In six Labrador dogs, the first and second premolars were extracted bilaterally. Subsequently, mesial roots of the first molars were endodontically treated and distal roots, including the corresponding part of the crown, were extracted. After 3 months of healing, flaps were elevated and recipient sites were prepared in all experimental sites. The control site was prepared using a standard procedure, while the test site was prepared using a drill with a 0.2 mm reduced diameter than the standard one used in the contra-lateral side. After 4 months of healing, the animals were euthanized and biopsies were obtained for histological processing and evaluation. Results With the exception of one implant that was lost, all implants were integrated in mineralized bone. The alveolar crest underwent resorption at control as well as at test sites (buccal aspect similar to 1 mm). The most coronal contact of bone-to-implant was located between 1.2 and 1.6 mm at the test and between 1.3 and 1.7 mm at the control sites. Bone-to-implant contact percentage was between 49% and 67%. No statistically significant differences were found for any of the outcome variables. Conclusions After 4 months of healing, lateral pressure to the implant bed as reflected by higher insertion torques (36 vs. 15 N cm in the premolar and 19 vs. 7 N cm in the molar regions) did not affect the bone-to-implant contact. To cite this article:Pantani F, Botticelli D, Garcia IR Jr., Salata LA, Borges GJ, Lang NP. Influence of lateral pressure to the implant bed on osseointegration: an experimental study in dogs.Clin. Oral Impl. Res. 21, 2010; 1264-1270.doi: 10.1111/j.1600-0501.2009.01941.x.

In vitro antibacterial action of Tetraclean, MTAD and five experimental irrigation solutions

P>Aim To investigate the antibacterial effect of Tetraclean, MTAD and five experimental irrigants using both direct exposure test with planktonic cultures and mixed-species in vitro biofilm model. Methodology Tetraclean, MTAD and five experimental solutions that were modifications of existing formulae including MTAD + 0.01% cetrimide (CTR), MTAD + 0.1% CTR, MTAC-1 (Tween 80 replaced by 0.01% CTR in MTAD), MTAC-2 (Tween 80 replaced by 0.1% CTR) and MTAD-D (MTAD without the Tween 80 and no CTR added) were used as disinfectants in the experiments. In the direct exposure test, a suspension of Enterococcus faecalis was mixed with each of the solutions. After 0.5, 1, 3 and 10 min, an inactivator was added and the number of surviving bacteria was calculated. A mixed-species biofilm from subgingival plaque bacteria was grown in brain heart infusion broth in anaerobic conditions on synthetic hydroxyapatite discs. Two-week-old biofilms were exposed to the solutions for 0.5, 1 and 3 min. The samples were observed by confocal laser scanning microscopy after bacterial viability staining. The scans were quantitatively analysed, and the volume of killed cells of all cells was calculated for each medicament. Results Tetraclean and MTAC-2 (0.1% CTR) killed planktonic E. faecalis in < 30 s. Complete killing of bacteria required 1 min by MTAC-1, 3 min by MTAD + 0.1% CTR and 10 min by MTAD, MTAD-D and MTAD + 0.01% CTR. In the biofilm test, there were significant differences in microbial killing between the different solutions and times of exposure (P < 0.005). MTAC-2 showed the best performance, killing 71% of the biofilm bacteria in 3 min, followed by MTAC-1 and Tetraclean. MTAD and the three MTAD modifications demonstrated the lowest antibacterial activity. Conclusion Tetraclean was more effective than MTAD against E. faecalis in planktonic culture and in mixed-species in vitro biofilm. CTR improved the antimicrobial properties of the solutions, whereas Tween 80 seemed to have a neutral or negative impact on their antimicrobial effectiveness.

Effects of Early Functional Loading on Maintenance of Free Autogenous Bone Graft and Implant Osseointegration: An Experimental Study in Dogs

Purpose: The aim of the present study was to investigate the healing, integration, and maintenance of autogenous onlay bone grafts and implant osseointegration either loaded in the early or the delayed stages. Materials and Methods: A total of 5 male clogs received bilateral blocks of onlay bone grafts harvested from the contralateral alveolar ridge of the mandible. On one side, the bone block was secured by 3 dental implants (3.5 mm x 13.0 mm, Osseospeed; Astra Tech AB, Molndal, Sweden). Two implants at the extremities of the graft were loaded 2 clays after installation by abutment connection and prosthesis (simultaneous implant placement group); the implant in the middle remained unloaded and served as the control. On the other side, the block was fixed with 2 fixation screws inserted in the extremities of the graft. Four weeks later, the fixation screws were replaced with 3 dental implants. The loading procedure (delayed implant placement group) was performed 2 clays later, as described for the simultaneous implant placement sites. The animals were sacrificed 12 weeks after the grafting procedure. Implant stability was measured through resonance frequency analysis. The bone volume and density were assessed on computed tomography. The bone to implant contact and bone area in a region of interest were evaluated on histologic slides. Results: The implant stability quotient showed statistical significance in favor of the delayed loaded grafts (P=.001). The bone-to-implant contact (P=.008) and bone area in a region of interest (P=0.005) were significantly greater in the delayed group. Nevertheless, no difference was found in terms of graft volume and density between the early loaded and delayed-loaded approaches. Conclusions: The protocol in which the implant and bone graft were given delayed loading allows for effective quality of implant osseointegration and stabilization, with healing and remodeling occurring in areas near the implant resulting in denser bone architecture. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Sing 68:825-832, 2010

Reduced venous endothelial responsiveness after oral lipid overload in healthy volunteers

The aim of this study was to investigate endothelial venous function, mflammatory markers, and systemic oxidative stress after an oral lipid overload (OLO). We studied 18 healthy adults (9 men; age, 29.2 +/- 0.9 years; body mass index, 22.3 +/- 0.4 kg/m(2)). Blood samples were collected in the fasting state and 3, 4, and 5 hour after the OLO (1000 kcal, 58% fat) for metabolic variables, oxidative stress, inflammatory markers, adiponectin, and resistin. Changes in vein diameter to phenylephrine, acetylcholine, and sodium nitroprusside (dorsal hand vein technique) were measured before and after the OLO. Oral lipid overload increased triglycerides (61 +/- 6 vs 134 +/- 17 mg/dL, P <.001), insulin (7.2 +/- 0.8 vs 10.7 +/- 1.3 mu U/mL, P <.05), and resistin (5.38 +/- 0.5 vs 6.81 +/- 0.7 ng/mL, P <.05) and reduced antioxidant capacity (plasma total antioxidant capacity: 186.7 +/- 56 vs 161.8 +/- 50 U Trolox per microliter plasma, P <.01), vascular reactivity (171.3 +/- 85 vs 894.4 +/- 301 ng/mL, P <.001), and maximum acetylcholine venodilation (105.9% +/- 9% vs 61.0% +/- 7%, P <.05). No changes were observed for sodium nitroprusside. Post-OLO triglycerides were positively correlated with phenylephrine dose (rho = 0.38, P <.05) and resistin (rho = 0.43, P <.01) and negatively correlated with the maximum acetylcholine venodilation (rho = -0.36, P <.05). In conclusion, an OLO impaired venoconstriction responsiveness in healthy subjects, probably because of a reduction in the antioxidant capacity. (C) 2008 Elsevier Inc. All rights reserved.

A light and scanning electron microscopy study of bone healing following inferior alveolar nerve lateralization: An experimental study in rabbits

Purpose: The purpose of this study was to evaluate the bone healing kinetics around commercially pure titanium implants following inferior alveolar nerve (IAN) lateralization in a rabbit model. Materials and Methods: Inferior alveolar nerve lateralization was performed in 16 adult female rabbits (Oryctolagus cuniculus). During the nerve lateralization procedure, 1 implant was placed through the mandibular canal, and the IAN was replaced in direct contact with the implant. During the 8-week healing period, various bone labels were administered for fluorescent microscopy analysis. The animals were euthanized by anesthesia overdose, and the mandibular blocks were exposed by sharp dissection. Nondecalcified samples were prepared for optical light and scanning electron microscopy (SEM) evaluation. Results: SEM evaluation showed bone modeling/remodeling between the IAN and implant surface. Fluorochrome area fraction labeling at different times during the healing period showed that bone apposition mainly occurred during the first 2 weeks after implantation. Conclusions: The results obtained showed that bone healing/deposition occurred between the alveolar nerves in contact with a commercially pure titanium implant. No interaction between the nerve and the implant was detected after the 8-week healing period. Appositional bone healing occurred around the nerve bundle structure, restoring the mandibular canal integrity and morphology.

Evaluation of Experimental Autoimmune Uveitis in Mice Treated with FTY720

PURPOSE. FTY720 (fingolimod) is an immunomodulatory drug capable of preventing T-cell migration to inflammatory sites by binding to and subsequently downregulating the expression of sphingosine-1 phosphate receptor 1 (S1P(1)) leading in turn to T-cell retention in lymphoid organs. Additional effects of FTY720 by increasing functional activity of regulatory T cells have recently been demonstrated, raising the conversion of conventional T cells into regulatory T cells and affecting the sequestration of regulatory T cells in normal mice. In this study, the action of FTY720 in the ocular autoimmune model in mice was investigated. METHODS. Mice were immunized with 161-180 peptide and pertussis toxin and were treated with 1 mg/kg/d FTY720 by gavage (7-21 days postimmunization [dpi]) or left untreated. Spleen cells, harvested 21 dpi, were cultured and assayed for cytokine production. Draining lymph node, spleen, and eye cells 21 dpi were assayed for quantification of T-cell populations. Disease severity was evaluated by histologic examination of the enucleated eyes at 21 and 49 dpi. In addition, anti-IRBP antibodies were analyzed by ELISA. RESULTS. FTY720 was effective in suppressing the experimental autoimmune uveitis score. Although there was a reduction in the number of eye-infiltrating cells, FTY did not prevent Treg accumulation at this site. FTY720 leads to a significant increase of CD4(+)IFN-gamma(+) and CD4(+)Foxp3(+) cell percentages in lymph nodes, suggesting that this site could be the source of Treg cells found in the eye. CONCLUSIONS. The data showed that treatment in vivo with FTY720 was able to suppress EAU in mice. These results are indicative of the possible therapeutic use of FTY720 in ocular autoimmune processes. (Invest Ophthalmol Vis Sci. 2010;51:2568-2574) DOI:10.1167/iovs.09-4769

Functional interferences in host inflammatory immune response by airway allergic inflammation restrain experimental periodontitis development in mice

Aims Periodontal disease (PD) and airway allergic inflammation (AL) present opposing inflammatory immunological features and clinically present an inverse correlation. However, the putative mechanisms underlying such opposite association are unknown. Material and Methods Balb/C mice were submitted to the co-induction of experimental PD (induced by Actinobacillus actinomycetemcomitans oral inoculation) and AL [induced by sensitization with ovalbumin (OVA) and the subsequent OVA challenges], and evaluated regarding PD and AL severity, immune response [cytokine production at periodontal tissues, and T-helper transcription factors in submandibular lymph nodes (LNs)] and infection parameters. Results PD/AL co-induction decreased PD alveolar bone loss and periodontal inflammation while experimental AL parameters were unaltered. An active functional interference was verified, because independent OVA sensitization and challenge not modulate PD outcome. PD+AL group presented decreased tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, -gamma, IL-17A, receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand and matrix metalloproteinase (MMP)-13 levels in periodontal tissues, while IL-4 and IL-10 levels were unaltered by AL co-induction. AL co-induction also resulted in upregulated T-bet and related orphan receptor gamma and downregulated GATA3 levels expression in submandibular LNs when compared with PD group. Conclusion Our results demonstrate that the interaction between experimental periodontitis and allergy involves functional immunological interferences, which restrains experimental periodontitis development by means of a skewed immune response.

CCR2 Deficiency Results in Increased Osteolysis in Experimental Periapical Lesions in Mice

Introduction: Periapical lesions are chronic inflammatory disorders of periradicular tissues caused by etiologic agents of endodontic origin. The inflammatory chemokines are thought to be involved in the latter observed osteolysis. With a murine model of experimental periapical lesion, the objective of this study was to evaluate the role of the chemokine receptor CCR2 in the lesion progression, osteoclast differentiation and activation, and expression of inflammatory osteolysis-related mediators. Methods: For lesion induction, right mandibular first molars were opened surgically with a (1)/(4) carbine bur, and 4 bacterial strains were inoculated in the exposed dental pulp; left mandibular first molars were used as controls. Animals were killed at 3, 7, 14, and 21 days after surgeries to evaluate the kinetics of lesion development. Results: CCR2 KO mice showed wider lesions than WT mice. CCR2 KO mice also expressed higher levels of the osteoclastogenic and osteolytic factors, receptor activator of nuclear factor kappa B ligand (RANKL) and cathepsin K, of the proinflammatory cytokine tumor necrosis factor alpha, and of the neutrophil migration related chemokine, KC. Conclusions: These results suggest that CCR2 is important in host protection to periapical osteolysis. (J Endod 2010;36:244-250)

In vitro basal cytotoxicity assay applied to estimate acute oral systemic toxicity of grandisin and its major metabolite

Preclinical investigations can start with preliminary in vitro studies before using animal models. Following this approach, the number of animals used in preclinical acute toxicity testing can be reduced. In this study, we employed an in-house validated in vitro cytotoxicity test based on the Spielmann approach for toxicity evaluation of the lignan grandisin, a candidate anticancer agent, and its major metabolite. the 4-O-demethylgrandisin, by neutral red uptake (NRU) assay, on mouse fibroblasts Balb/c 3T3 cell line. Using different concentrations of grandisin and its major metabolite (2.31; 1.16; 0.58; 0.29; 0.14; 0.07; 0.04; 0.002 mu M) in Balb/c 3T3-A31 NRU cytotoxicity assay, after incubation for 48 h, we obtained IC(50) values for grandisin and its metabolite of 0.078 and 0.043 mu M, respectively. The computed LD(50) of grandisin and 4-O-demethylgrandisin were 617.72 and 429.95 mg/kg, respectively. Both were classified under the Globally Harmonized System as category 4. Since pharmacological and toxicological data are crucial in the developmental stages of drug discovery, using an in vitro assay we demonstrated that grandisin and its metabolite exhibit distinct toxicity profiles. Furthermore, results presented in this work can contribute to reduce the number of animals required in subsequent pharmacological/toxicological studies. (C) 2010 Elsevier GmbH. All rights reserved.