H4picoopa─Robust Chelate for 225Ac/111In Theranostics.

The nuclear decay characteristics of 225Ac (Eα = 5-8 MeV, linear energy transfer (LET) = ∼100 keV/µm, t1/2 = 9.92 days) are well recognized as advantageous for the treatment of primary and metastatic tumors; however, suitable chelation systems are required, which can accommodate this radiometal. Since 225Ac does not possess any suitable low-energy, high abundance γ-ray emissions for nuclear imaging, there is a clear need for the development of other companion radionuclides with similar coordination characteristics and comparable half-lives, which can be applied in diagnostics. H4picoopa was designed and executed as a high-denticity ligand for chelation of [225Ac]Ac3+, and the complexation characteristics have been explored through nuclear magnetic resonance (NMR) spectroscopy, solution thermodynamic stability studies, and radiolabeling. The ligand shows highly favorable complexation with La3+ (pM = 17.6), Lu3+ (pM = 21.3), and In3+ (pM = 31.2) and demonstrates effective radiolabeling of both [225Ac]Ac3+ and [111In]In3+ ions achieving quantitative radiochemical conversions (RCCs) under mild conditions (RT, 10 min), accompanied by high serum stability (>97% radiochemical purity (RCP) over 6 days). A bifunctional analogue of H4picoopa was synthesized and conjugated to the Pip-Nle-CycMSHhex peptide for targeting of MC1R positive melanoma tumors. In vivo single-photon emission computed tomography (SPECT) and biodistribution studies of the 111In-radiolabeled bioconjugate in mice bearing B16-F10 tumors showed good radiotracer stability, although improved tumor targeting could not be achieved for imaging purposes. This work highlights H4picoopa as a very promising platform for application of [225Ac]Ac3+ and [111In]In3+ as a theranostic pair and allows great versatility for the incorporation of other directing vectors. The logical synthetic approach reported here for bifunctional H4picoopa, involving an azide-functionalized covalent linker and CuI-catalyzed alkyne-azide cycloaddition, allows for ease of optimization of bioconjugate pharmacokinetics and will be valuable for further radiopharmaceutical applications moving forward.

H3TPAN-Triazole-Bn-NH2: Tripicolinate Clicked-Bifunctional Chelate for [225Ac]/[111In] Theranostics.

A new, high-denticity, bifunctional ligand─H3TPAN-triazole-Bn-NH2─has been synthesized and studied in complexation with [225Ac]Ac3+ and [111In]In3+ for radiopharmaceutical applications. The bifunctional chelator is readily synthesized, using a high-yielding four-step prep, which is highly adaptable and allows for straightforward incorporation of different covalent linkers using CuI-catalyzed alkyne-azide cycloaddition (click) chemistry. Nuclear magnetic resonance (NMR) studies of H3TPAN-triazole-Bn-NH2 with La3+ and In3+ metal ions show the formation of a single, asymmetric complex with each ion in solution, corroborated by density functional theory (DFT) calculations. Radiolabeling studies with [225Ac]Ac3+ and [111In]In3+ showed highly effective complexation, achieving quantitative radiochemical conversions at low ligand concentrations (<10-6 M) under mild conditions (RT, 10 min), which is further accompanied by high stability in human serum. The bioconjugate─H3TPAN-triazole-Bn-Aoc-Pip-Nle-CycMSHhex─was prepared for targeting of MC1R-positive tumors, and the corresponding 111In-radiolabeled tracer was studied in vivo. SPECT/CT and biodistribution studies in C57BL/6J mice bearing B16-F10 tumors were performed, with the radiotracer showing good in vivo stability; tumor uptake was achieved. This work highlights a new promising and versatile bifunctional chelator, easily prepared and encouraging for 225Ac/111In theranostics.

Head and neck cancers, Version 2.2014. Clinical practice guidelines in oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers focuses on glottic laryngeal cancer, which is the most common type of laryngeal cancer and has an excellent cure rate. The lymphatic drainage of the glottis is sparse, and early stage primaries rarely spread to regional nodes. Because hoarseness is an early symptom, most glottic laryngeal cancer is early stage at diagnosis. Updates to these guidelines for 2014 include revisions to "Principles of Radiation Therapy" for each site and "Principles of Surgery," and the addition of a new section on "Principles of Dental Evaluation and Management."

Structure-delivery relationships of lysine-based gemini surfactants and their lipoplexes.

The synthesis and properties of gemini surfactants of the type (R(1)(CO)-Lys(H)-NH)2(CH2)n are reported. For a spacer length of n = 6, the hydrophobic acyl tail was varied in length (R(1) = C8, C10, C12, C14, C16, and C18) and, for R(1) = C18, the degree of unsaturation. For R(1)(CO) = oleoyl (C18:1 Z) the spacer length (n = 2-8) and the stereochemistry of the lysine building block were varied; a 'half-gemini' derivative with a single oleoyl tail and head group was also prepared. The potential of the gemini surfactants to transfer polynucleotides across a cell membrane was investigated by transfection of HeLa cells with beta-galactosidase, both in the presence and absence of the helper lipid DOPE. Oleoyl was found to be by far the best hydrophobic tail for this biological activity, whereas the effect of the lysine stereochemistry was less pronounced. The effect of an optimum spacer length (n = 6) was observed only in the absence of helper lipid. The most active surfactant, i.e. the one with oleoyl chains and n = 6, formed liposomes with sizes in the range of 60-350 nm, and its lipoplex underwent a transition from a lamellar to a hexagonal morphology upon lowering the pH from 7 to 3.

A systematic review and meta-analysis on the efficacy of topical povidone iodine in adenoviral conjunctivitis.

PURPOSE: To evaluate if topical povidone iodine (alone (PI) or combined with dexamethasone (PI-DXM)) is superior to placebo for treating adenoviral conjunctivitis (AC). METHODS: A systematic review was performed according to Preferred Reporting Items for the Systematic Review and Meta-Analyses (PRISMA) Statement. An electronic search was made on PubMed, Embase and Cochrane Library. Randomized control studies that compared PI or PI-DXM with placebo were included. At least three researchers were involved in all phases. Primary outcomes were AC duration and the number of clinical resolutions during the first week. Secondary outcomes were conjunctival redness and serous discharge one week after starting treatment and the rate of AC complications. RESULTS: Only five studies met the inclusion criteria. PI-DXM reduced the duration of the disease by 2.4 days (IC95% 4.09-0.71), however this result was based only in one study. PI and PI-DXM did not modify the probability of clinical resolution during the first week; relative risk (RR) = 1.77 (IC95% 0.63-4.96) and 1.70 (IC95% 0.67-4.36). The impact of PI on the probability of pseudomembranes could not be estimated. PI-DXM did not influence the risk of developing subepithelial infiltrates RR = 0.73 (IC95% 0.02-33.38). CONCLUSIONS: At this time there is great uncertainty about the usefulness of PI on the course of adenoviral conjunctivitis. PI-DXM may have a small effect on AC duration. To make future reviews possible, it is important to standardize the way in which these results are reported. Futures studies should include etiological confirmation, unit of study (eyes vs patients) and report on those aspects that are more relevant for patient quality of life (duration of the disease, development of complications: pseudomembranes and subepithelial infiltrates).

Poly(lactide-co-glycolide) Nanoparticles Mediate Sustained Gene Silencing and Improved Biocompatibility of siRNA Delivery Systems in Mouse Lungs after Pulmonary Administration.

Pulmonary delivery of small interfering RNA (siRNA)-based drugs is promising in treating severe lung disorders characterized by the upregulated expression of disease-causing genes. Previous studies have shown that the sustained siRNA release in vitro can be achieved from polymeric matrix nanoparticles based on poly(lactide-co-glycolide) (PLGA) loaded with lipoplexes (LPXs) composed of cationic lipid and anionic siRNA (lipid-polymer hybrid nanoparticles, LPNs). Yet, the in vivo efficacy, potential for prolonging the pharmacological effect, disposition, and safety of LPNs after pulmonary administration have not been investigated. In this study, siRNA against enhanced green fluorescent protein (EGFP-siRNA) was either assembled with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) to form LPX or co-entrapped with DOTAP in PLGA nanoparticles to form LPNs. The disposition and clearance of LPXs and LPNs in mouse lungs were studied after intratracheal administration by using single-photon emission computed tomography/computed tomography (SPECT/CT) and gamma counting. Fluorescence spectroscopy, Western blot, and confocal laser scanning microscopy were used to evaluate the silencing of the EGFP expression mediated by the LPXs and LPNs after intratracheal administration to transgenic mice expressing the EGFP gene. The in vivo biocompatibility of LPXs and LPNs was investigated by measuring the cytokine level, total cell counts in bronchoalveolar lavage fluid, and observing the lung tissue histology section. The results showed that the silencing of the EGFP expression mediated by LPNs after pulmonary administration was both prolonged and enhanced as compared to LPXs. This may be attributed to the sustained release characteristics of PLGA, and the prolonged retention in the lung tissue of the colloidally more stable LPNs in comparison to LPXs, as indicated by SPECT/CT. The presence of PLGA effectively alleviated the acute inflammatory effect of cationic lipids to the lungs. This study suggests that PLGA-based LPNs may present an effective formulation strategy to mediate sustained gene silencing effects in the lung via pulmonary administration.

Investigating Neolithic caprine husbandry in the Central Pyrenees: Insights from a multi-proxy study at Els Trocs cave (Bisaurri, Spain).

Sheep remains constitute the main archaeozoological evidence for the presence of Early Neolithic human groups in the highlands of the Southern Pyrenees but understanding the role of herding activities in the Neolithisation process of this mountain ecosystem calls for the analysis of large and well-dated faunal assemblages. Cova de Els Trocs (Bisaurri, Huesca, Spain), a cave located at 1564 m a.s.l on the southern slopes of the Central Pyrenees, is an excellent case study since it was seasonally occupied throughout the Neolithic (ca. 5312-2913 cal. BC) and more than 4000 caprine remains were recovered inside. The multi-proxy analytical approach here presented has allowed us to offer new data elaborating on vertical mobility practices and herd management dynamics as has not been attempted up until now within Neolithic high-mountain sites in the Iberian Peninsula. For the first time, δ18O and δ13C stable isotope analyses offer direct evidence on both the regular practice of altitudinal movements of sheep flocks and the extended breeding season of sheep. Autumn births are recorded from the second half of the fifth millennium cal. BC onwards. Age-at-death distributions illustrate the progressive decline in caprine perinatal mortality together with the rising survival rate of individuals older than six months of age and the larger frequency of adults. This trend alongside the 'off-season' lambing signal at the implementation of husbandry techniques over time, probably aiming to increase the size of the flocks and their productivity. Palaeoparasitological analyses of sediment samples document also the growing reliance on herding activities of the human groups visiting the Els Trocs cave throughout the Neolithic sequence. In sum, our work provides substantial arguments to conclude that the advanced herding management skills of the Early Neolithic communities arriving in Iberia facilitated the anthropisation process of the subalpine areas of the Central Pyrenees.

Quantitative comparison of three widely-used pulmonary administration methods in vivo with radiolabeled inhalable nanoparticles.

Pulmonary formulations have been attracting much attention because of their direct effects on respiratory diseases, but also their non-invasive administration for the treatment of systemic diseases. When developing such formulations, they are typically first investigated in mice. As there are various pulmonary administration methods, the researcher has to decide on the best quantitative method for their preclinical investigations among candidate methods, both for total delivery and distribution within the lung lobes. In this study, we investigated the deposition and distribution of siRNA loaded PLGA nanoparticles (NPs) in the different lung lobes via three widely used pulmonary administration methods: intratracheal instillation, intratracheal spraying and intranasal instillation. The NPs were radiolabeled with 111In, administered and a single photon emission computed tomography (SPECT/CT) whole body scan performed. Quantitative image volume of interest (VOI) analysis of all inhalation related organs was performed, plus sub-organ examinations using dissection and gamma counting. Intratracheal instillation and intratracheal spraying deposited >95% and >85% of radiolabeled NPs in the lung, respectively. However, the lung lobe distribution of the NPs was inhomogeneous. Intranasal instillation deposited only ~28% of the dose in the lungs, with even larger inhomogeneity and individual variation between animals. Furthermore, there was a high deposition of the NPs in the stomach. Intratracheal instillation and intratracheal spraying deposit a large number of NPs in the lungs, and are thus useful to test therapeutic effects in preclinical animal studies. However, the inhomogeneous distribution of formulation between lung lobes needs to be considered in the experimental design. Intranasal instillation should not be used as a means of pulmonary administration.

Monosized Polymeric Microspheres Designed for Passive Lung Targeting: Biodistribution and Pharmacokinetics after Intravenous Administration.

Local as well as systemic therapy is often used to treat bacterial lung infections. Delivery of antibiotics to the vascular side of infected lung tissue using lung-targeting microspheres (MS) is a good alternative to conventional administration routes, allowing for localized high levels of antibiotics. This delivery route can also complement inhaled antibiotic therapy, especially in the case of compromised lung function. We prepared and characterized monodisperse poly(lactic-co-glycolic acid) (PLGA) MS loaded with levofloxacin using a flow-focusing glass microfluidic chip. In vitro characterization showed that the encapsulated LVX displayed a biphasic controlled release during 5 days and preserved its antibacterial activity. The MS degradation was investigated in vitro by cross-sectioning the MS using a focused ion beam scanning electron microscope and in vivo by histological examination of lung tissue from mice intravenously administered with the MS. The MS showed changes in the surface morphology and internal matrix, whereas the degradation in vivo was 3 times faster than that in vitro. No effect on the viability of endothelial and lung epithelial cells or hemolytic activity was observed. To evaluate the pharmacokinetics and biodistribution of the MS, complete quantitative imaging of the 111indium-labeled PLGA MS was performed in vivo with single-photon emission computed tomography imaging over 10 days. The PLGA MS distributed homogeneously in the lung capillaries. Overall, intravenous administration of 12 µm PLGA MS is suitable for passive lung targeting and pulmonary therapy.

Microplastics in the Bay of Biscay: An overview.

Microplastics (MPs) are an environmental problem of growing concern, and several studies have defined the Bay of Biscay (BoB) as a marine litter accumulation area. To address the abundance of MPs in this region, a critical overview is presented compiling the research performed to date on the different water bodies, sediments and biota. The comparative assessment highlights high spatial and temporal variability in MP distribution. MPs appear in at least 50% of the samples in waters and sediments. Polypropylene, polyethylene, polyester and polystyrene are the most frequent polymers, with a significant predominance of fragments and fibres. The BoB can be considered a region with medium concentration of MPs. However, monitoring programmes are needed to compile data over time and thus evaluate the historical trends of MP pollution. The difficulty of comparing studies is highlighted, due to the use of different methodologies. Hence, the harmonisation of monitoring methods is urgently required.

Wound Complications in Head and Neck Squamous Cell Carcinomas After Anti-PD-1 Therapy.

Immune checkpoint inhibitors have demonstrated activity in recurrent/metastatic head and neck squamous cell cancer, but less is known regarding their long-term sequelae. We describe four patients who, after complete responses to anti-PD-1 therapy, developed complications requiring surgical intervention. Patient 1 is a 57-year-old female whose marked tumor regression exposed some mandibular hardware. Patient 2 is a 39-year-old male who developed an ulcerated buccal lesion with exposed mandible. Patient 3 is a 66-year-old male with craniofacial osteoradionecrosis. Patient 4 is a 71-year-old male who developed an exposed and fractured mandible. All patients successfully underwent surgical intervention and remain disease free. Laryngoscope, 129:E428-E433, 2019.

Radioembolization of Hepatocellular Carcinoma with Built-In Dosimetry: First in vivo Results with Uniformly-Sized, Biodegradable Microspheres Labeled with 188Re.

A common form of treatment for patients with hepatocellular carcinoma (HCC) is transarterial radioembolization (TARE) with non-degradable glass or resin microspheres (MS) labeled with 90Y (90Y-MS). To further simplify the dosimetry calculations in the clinical setting, to have more control over the particle size and to change the permanent embolization to a temporary one, we developed uniformly-sized, biodegradable 188Re-labeled MS (188Re-MS) as a new and easily imageable TARE agent. Methods: MS made of poly(L-lactic acid) were produced in a flow focusing microchip. The MS were labeled with 188Re using a customized kit. An orthotopic HCC animal model was developed in male Sprague Dawley rats by injecting N1-S1 cells directly into the liver using ultrasound guidance. A suspension of 188Re-MS was administered via hepatic intra-arterial catheterization 2 weeks post-inoculation of the N1-S1 cells. The rats were imaged by SPECT 1, 24, 48, and 72 h post-radioembolization. Results: The spherical 188Re-MS had a diameter of 41.8 ± 6.0 µm (CV = 14.5%). The site and the depth of the injection of N1-S1 cells were controlled by visualization of the liver in sonograms. Single 0.5 g tumors were grown in all rats. 188Re-MS accumulated in the liver with no deposition in the lungs. 188Re decays to stable 188Os by emission of ߯ particles with similar energy to those emitted by 90Y while simultaneously emitting γ photons, which were imaged directly by single photon computed tomography (SPECT). Using Monte Carlo methods, the dose to the tumors was calculated to be 3-6 times larger than to the healthy liver tissue. Conclusions:188Re-MS have the potential to become the next generation of ߯-emitting MS for TARE. Future work revolves around the investigation of the therapeutic potential of 188Re-MS in a large-scale, long-term preclinical study as well as the evaluation of the clinical outcomes of using 188Re-MS with different sizes, from 20 to 50 µm.

Técnicas alternativas del manejo de la conducta en odontopediatría / Técnicas alternativas para a gestão comportamental em odontologia pediátrica / Alternative behavioral management techniques in pediatric dentistry

Diversas técnicas convencionales han sido utilizadas con gran eficacia; sin embargo, la no aceptación de algunas de ellas por los padres, ciertos condicionamientos éticos y legales así como cambios en la educación actual y el avance en nuevas tecnologías, obligan al odontólogo a un replanteamiento de actitudes. Objetivo: El objetivo del presente trabajo es identificar qué técnicas alternativas son empleadas en la clínica dental por los profesionales para el manejo de la conducta de pacientes infantiles. Material y métodos: Se realizó un cuestionario en la plataforma de Google, remitido vía email a 190 odonto/estomatólogos que tratasen pacientes infantiles, obteniendo una participación de 132 encuestas adecuadas para el análisis de 6 técnicas alternativas de manejo de la conducta. El estudio estadístico se realizó en el programa SPSS aplicando el test de ANOVA para una significación de p= 0,05. Resultados: Un 35,1% de los encuestados utilizaban medios audiovisuales para el tratamiento dental, siendo la televisión el más frecuentemente empleado. La musicoterapia fue la técnica más utilizada (70,5% de los participantes) con mayor frecuencia del sexo femenino, aunque sin diferencias significativas, siendo la música moderna la de mayor aceptación. Un 32,8% utilizaron la ludoterapia como técnica de manejo seguida del empleo de técnicas de relajación con un 25%, ambas con mayor porcentaje femenino. Las dos técnicas menos utilizadas fueron la aromaterapia (6,8%) y la hipnosis (2,3%). Conclusiones: A pesar del incremento en la utilización de técnicas alternativas en el manejo de la conducta, todavía su empleo es escaso por los odonto/estomatólogos.

Várias técnicas convencionais têm sido usadas com grande eficácia; contudo, a não aceitação de algumas delas pelos pais, certas condições éticas e legais, assim como as mudanças na educação atual e o avanço das novas tecnologias, forçam o dentista a repensar as atitudes. Objetivo: O objetivo do presente estudo é identificar quais técnicas alternativas são utilizadas na clínica odontológica por profissionais para gerenciar o comportamento de pacientes infantis. Material e métodos: Foi realizado um questionário na plataforma Google, enviado por e-mail a 190 dentistas/stomatologistas que trataram crianças, obtendo 132 pesquisas adequadas para a análise de 6 técnicas alternativas de gestão comportamental. O estudo estatístico foi realizado no programa SPSS aplicando o teste ANOVA para uma significância de p= 0,05. Resultados: 35,1% dos inquiridos utilizaram meios audiovisuais para tratamento dentário, sendo a televisão a mais frequentemente utilizada. A musicoterapia foi a técnica mais utilizada (70,5% dos participantes) pelo sexo feminino, embora sem diferenças significativas, sendo a música moderna a mais amplamente aceita. 32,8% utilizaram a terapia lúdica como técnica de gestão seguida do uso de técnicas de relaxamento com 25%, ambas com uma percentagem maior de mulheres. As duas técnicas menos utilizadas foram a aromaterapia (6,8%) e a hipnose (2,3%). Conclusões: Apesar do aumento do uso de técnicas alternativas na gestão do comportamento, o seu uso ainda é escasso pelos odontologistas/estomatologistas.

Various conventional techniques have been used with great efficiency; nevertheless, the non-acceptance of some of them by the parents, certain ethical and legal conditions as well as changes in the current education and the advance in new technologies, force the dentist to a rethinking of attitudes. Aim: The aim of this paper is to identify what alternative techniques are used by professionals for the behavior's management of pediatric patients in the dental clinic. Material and methods: A questionnaire was carried out on the Google platform, sent via email to 190 odonto / stomatologists who treated pediatric patients, obtaining a participation of 132 appropriate surveys for the analysis of 6 alternative behavior management techniques. The statistical study was carried out in the SPSS program, applying the ANOVA test for a significance of p = 0.05. Results: 35.1% of respondents used audiovisual media for dental treatment, being television the most frequently used. Music therapy was the most applied technique (70.5% of the participants) with the highest frequency of female sex, without significant differences though, being modern music the most widely accepted. 32.8% used play therapy as a management technique followed by the use of relaxation techniques with 25%, both with a higher female percentage. The two least used techniques were aromatherapy (6.8%) and hypnosis (2.3%). Conclusions: Despite the increase in the use of alternative techniques in behavior management, their use is still scarce by dentists / stomatologists.

Low-density lipoprotein upregulates low-density lipoprotein receptor-related protein expression in vascular smooth muscle cells: possible involvement of sterol regulatory element binding protein-2-dependent mechanism.

BACKGROUND: Low-density lipoprotein (LDL) receptor-related protein (LRP) is highly expressed in vascular smooth muscle cells (VSMCs) of both normal and atherosclerotic lesions. However, little is known about LRP regulation in the vascular wall. METHODS AND RESULTS: We analyzed the regulation of LRP expression in vitro in human VSMCs cultured with native LDL (nLDL) or aggregated LDL (agLDL) by semiquantitative reverse transcriptase-polymerase chain reaction, real-time polymerase chain reaction, and Western blot and in vivo during diet-induced hypercholesterolemia by in situ hybridization. LRP expression in human VSMCs is increased by nLDL and agLDL in a time- and dose-dependent manner. Maximal induction of LRP mRNA expression was observed after 24 hours of exposure to LDL. However, agLDL induced higher LRP mRNA expression (3.0-fold) than nLDL (1.76-fold). LRP mRNA upregulation was associated with an increase on LRP protein expression with the greatest induction by agLDL. VSMC-LRP upregulation induced by nLDL or agLDL was reduced by an inhibitor of sterol regulatory element binding protein (SREBP) catabolism (N-acetyl-leucyl-leucyl-norleucinal). In situ hybridization analysis indicates that there is a higher VSMC-LRP expression in hypercholesterolemic than in normocholesterolemic pig aortas. CONCLUSIONS: These results indicate that LRP expression in VSMCs is upregulated by intravascular and systemic LDL.

Subgingivally applied minocycline microgranules in subjects with chronic periodontitis: A randomized clinical and microbiological trial.

The aim of this study was to evaluate clinical and microbiological effects of subgingival minocycline microgranules when used as an adjunct to scaling and root planing in subjects with Chronic periodontitis. Twenty-six non-smoker volunteers participated in the study. Four opposite sites, clinically standardized, with bleeding on probing (BOP) and pocket depth (PD) ≥ 6 mm were selected. Baseline BOP, PD and Clinical attachment level (CAL) were measured and microbiological samples were collected from the study sites and analyzed using PCR. Porphyromonas gingivalis (Pg) Tannerella forsythia (Tf), Treponema denticola (Td) and Aggregatibacter actinomycetemcomitans (Aa) were detected. One side of the mouth was randomly allocated to the experimental treatment: scaling and root planing plus minocycline microgranules (Test group=T) and the other side of the mouth to scaling and root planing alone (Control group=C). At days 30 and 90, clinical and microbiological examination was repeated. After 30 days BOP was reduced to 81% in C and to 12% in T and at day 90 to 58% in C and to 8% in T (p<0.05). PD was significantly reduced in both groups (C: 4.8mm, T: 4.2mm) favoring T at days 30 and 90 (p<0.05). CAL reduction at day 30 showed no difference between groups. At day 90, CAL reduction was higher in T (p<0.05). At days 30 and 90 Pg, Tf, Td and Aa was reduced in both groups. Pg reduction was significantly greater in group T. At day 90 frequency of sites with Td decreased in T and increased in C (p<0.05). No adverse effect was observed. This study showed that minocycline microgranules adjunct to scaling and root planing resulted in grater reduction of BOP and PD, higher CAL gain, increased probability of Pg suppression and retarded recolonization of Td than root instrumentation alone.

Gemini surfactants: new synthetic vectors for gene transfection.

The superior surfactant properties of cationic gemini surfactants are applied to the complex problem of introducing genes into cells. Of almost 250 new compounds tested, of some 20 different structural types, a majority showed very good transfection activity in vitro. The surfactant is shown to bind and compact DNA efficiently, and structural studies and calculations provide a working picture of the "lipoplex" formed. The lipoplex can penetrate the outer membranes of many cell types, to appear in the cytoplasm encapsulated within endosomes. Escape from the endosome--a key step for transfection--may be controlled by changes in the aggregation behavior of the lipoplex as the pH falls. The evidence suggests that DNA may be released from the lipoplex before entry into the nucleus, where the new gene can be expressed with high efficiency.

Subgingivally applied minocycline microgranules in subjects with chronic periodontitis: a randomized clinical and microbiological trial / Microgránulos de minociclina subgingival en sujetos con periodontitis crónica. Estudio clínico y microbiológico aleatorizado

El objetivo de este estudio fue evaluar el efecto clínico y microbiológico de microgránulos de Minociclina, colocados subgingivalmente como coadyuvante del raspaje y alisado radicular en pacientes con Periodontitis crónica severa. Participaron 26 sujetos voluntarios con Periodontitis crónica, no fumadores. Se seleccionaron 4 sitios contralaterales con Sangrado al Sondaje (SS) y Profundidad al Sondaje (PS) > 6 mm. Condición Basal (CB): se registró, PS y Nivel de Inserción (NI). Se determinó mdiante PCR la presencia de Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td) y Aggregatibacter actinomycetemcomitans (Aa). Un lado de la boca fue aleatoriamente asignado al tratamiento experimental: grupo T, el otro al tratamiento control: grupo C. Al día 30 y 90 se repitieron los exámenes clínicos y microbiológicos. Día 30: el SS se redujo al 81 por ciento en el grupo C y al 12 por ciento en el grupo T (p<0,05). Estas diferencias se mantuvieron al día 90 (C: 58 por ciento, T: 8 por ciento) (p<0.05). Día 30 y 90: hubo disminución de la PS en ambos grupos, siendo significativamente mayor en el grupo T (p<0,05). En ambos grupos hubo disminución significativa del NI (p<0,05), no hubo diferencias entre los grupos al día 30 y sí al día 90. A los 30 y 90 días en ambos grupos se redujo la prevalencia para Pg, Tf ,Td y Aa. A los 30 y 90 días la reducción de sitios con Pg fue mayor en el grupo T (p=0,002). A los 90 días Td disminuyó en el grupo T y aumentó en el grupo C (p=0,023). No se observaron efectos adversos. Los resultados mostraron que la aplicación subgingival de microgránulos de minociclina adjunta al raspaje y alisado radicular produjo una reducción mayor del SS, la PS y el NI que el raspaje y alisado solo, aumentó la probabilidad de suprimir Pg y retardó la recolonización con Td.

The aim of this study was to evaluate clinical and microbiological effects of subgingival minocycline microgranules when used as an adjunct to scaling and root planing in subjects with Chronic periodontitis. Twenty-six non-smoker volunteers participated in the study. Four opposite sites, clinically standardized, with bleeding on probing (BOP) and pocket depth (PD) ≥ 6 mm were selected. Baseline BOP, PD and Clinical attachment level (CAL) were measured and microbiological samples were collected from the study sites and analyzed using PCR. Porphyromonas gingivalis (Pg) Tannerella forsythia (Tf), Treponema denticola (Td) and Aggregatibacter actinomycetemcomitans (Aa) were detected. One side of the mouth was randomly allocated to the experimental treatment: scaling and root planing plus minocycline microgranules (Test group=T) and the other side of the mouth toscaling and root planing alone (Control group=C). At days 30 and 90, clinical and microbiological examination was repeated. After 30 days BOP was reduced to 81% in C and to 12% in T and at day 90 to 58% in C and to 8% in T (p<0.05). PD wassignificantly reduced in both groups (C: 4.8mm, T: 4.2mm) favoring T at days 30 and 90 (p<0.05). CAL reduction at day 30 showed no difference between groups. At day 90, CAL reduction was higher in T (p<0.05). At days 30 and 90 Pg, Tf, Td and Aa was reduced in both groups. Pg reduction wassignificantly greater in group T. At day 90 frequency of sites with Td decreased in T and increased in C (p<0.05). No adverse effect was observed. This study showed that minocycline microgranules adjunct to scaling and root planing resulted in grater reduction of BOP and PD, higher CAL gain, increased probability of Pg suppression and retarded recolonization of Td than root instrumentation alone.

Avaliação da influência de ciclagem compressiva na resistência à tração de coroas implantossuportadas retidas com cimento provisório / Influence of compressive cyclic loading on tensile forces of implant supported crowns with provisional cement

A cimentação provisória tem sido o tratamento de escolha de muitos profissionais quando da instalação de coroas implantossuportadas. Este estudo avaliou a resistência à tração de coroas metálicas cimentadas, com cimento provisório, sobre pilares protéticos implantossuportados. Trinta e dois corpos-de-prova, cada qual constituído por um pilar protético aparafusado sobre um implante, com uma estrutura fundida em NiCr cimentada sobre ele, foram confeccionados. Para cimentação utilizou-se o cimento provisório Temp Bond e pressão de 5KgF por 10 minutos. Os corpos-de-prova foram submetidos a ciclos de carga compressiva - 500.000 ciclos (2,5Hz) com uma força de 50N - durante 48 horas e levados a uma máquina universal de ensaios, para teste de tração, até completo deslocamento das estruturas cimentadas. Estas foram recimentadas para novo ensaio, desta vez sem ciclagem prévia. A ciclagem compressiva reduziu em, aproximadamente, 36% a força retentiva dos espécimes. A opção pela utilização de cimentos provisórios parece viável na prática clínica, no entanto, análise criteriosa deverá ser realizada previamente à seleção desta opção como mantenedora de coroas sobre implantes.

Temporary luting agents have been chosen for cementation of cement-retained crowns on dental implants in order to facilitate it's retrieve when a repair is required, The aim of this study was to evaluate the tensile bond strengths of metallic crowns fixed with a provisional luting agent on implant abutments, Thirty two samples composed by an abutment screwed on a implant were prepared, Over the abutment a nickel¬chromium metallic structure was cemented using a temporary luting agent (Temp Bond Kerr) under pressure of 5KgF during 10 minutes, The samples were submitted to loading cycles - 500.000 cycles (2.5Hz) 50N - during 48 hours, before tensile test until complete dislodgement of the cemented structures. These ones were re-cemented for a new tensile essay with no compressive cycling, Compressive forces reduced about 36% of the specimens' tensile forces. The option for using provisional luting agents seems to be available at clinical trails, however, criterious analysis should be performed previously to selecting this option to maintain implant supported restorations.