Comparación biomecánica entre los sistemas convencionales y uni-lock en osteosíntesis del ángulo mandibular. Estudio fotoelástico / Biomechanical comparison of the conventional and uni-lock systems for mandibular osteosynthesis. A photoelastic study

Introducción. Las implicaciones biomecánicas de la interacción de las placas y tornillos de titanio con la mandíbula fracturada no son del todo conocidas. Los modelos matemáticos desarrollados hasta hoy en día muestran ciertas limitaciones, y los estudios experimentales han fracasado en reproducir las fuerzas musculares y la distribución de las tensiones internas en la interfaz entre mandíbula e implante. Material y métodos. En el presente estudio, empleamos un simulador estático del sistema musculo-esquelético masticatorio para demostrar en réplicas mandibulares de resina epoxi, por medio de la fotoelasticidad tridimensional, la distribución de tensiones que se produce en fracturas del cuerpo mandibular tras la aplicación de diferentes métodos de osteosíntesis. Resultados. Los resultados muestran que el simulador y la fotoelasticidad 3D son útiles para estudiar las interacciones entre el hueso y el material de osteosíntesis. Los sistemas «lock» o bloqueados reflejaron la distribución de tensiones más favorable en la mandíbula de resina epoxi fracturada. Conclusiones. La fotoelasticidad tridimensional en modelos de resina epoxi es un método útil para evaluar la distribución de tensiones en una estructura para estudios biomecánicos. En lo que se refiere a la osteosíntesis mandibular, las placas tipo «lock» mostraron ser las menos agresivas para el hueso(AU)

Introduction. The biomechanical effects of the interaction between titanium plates and screws and the fractured mandible are not well known. The mathematical models that have been developed to date show limitations and the experimental studies fail in reproducing muscle forces and internal stress distributions in the bone-implant interface with the mandibular structure. Material and methods. In the present study we use a static simulator of the masticatory system to show, in epoxy resin mandibular models, by means of 3D (three-dimensional) photoelasticity, the stress distribution using different osteosynthesis methods in mandibular body fractures. Results. The results showed that the simulator and 3D photoelasticity were useful for studying interactions between bone and osteosynthesis materials. The "Lock" system displayed the most favourable stress distribution in the epoxy resin mandible. Conclusions. 3D photoelasticity in epoxy resin models is a useful method to evaluate stress distribution for biomechanical studies. In terms of mandibular osteosynthesis, "lock" plates show the most favourable stress distribution due to being less aggressive to the bone(AU)

Efectos de ciprofloxacina y norfloxacina sobre la apoptosis de neutrófilos humanos in vitro / Effects of ciprofloxacin and norfloxacin on apoptosis of human neutrophils in vitro experiments.

La apoptosis de los neutrófilos (PMNs) es un evento crítico para controlar la fase de resolución de las inflamaciones. En tal sentido, la inducción farmacológica de la apoptosis mediante el empleo de antibióticos podría ser una opción terapéutica para tratar diversas enfermedades. Sin embargo, existe poca información acerca de las capacidades de los antibióticos de amplio espectro tales como las fluoroquinolonas, para acelerar la apoptosis en esas células. Entonces, en este estudio se propuso evaluar los efectos de las fluoroquinolonas ciprofloxacina (CPX) y norfloxacina (NFX) sobre la apoptosis de PMNs humanos in vitro. Métodos: Los PMNs aislados fueron incubados con ambas drogas para determinar sus efectos sobre la inducción de la apoptosis, la generación de especies reactivas de oxígeno (ERO) y el potencial de membrana mitocondrial (Δψm) mediante técnicas de microscopía (óptica o de fluorescencia), luminometría y citometría de flujo, respectivamente. Resultados: A las concentraciones de 300 y 600 μmol/L, ambas drogas indujeron tanto el colapso del Δψm como la muerte por apoptosis de modos estadísticamente significativos. Además, esos efectos probablemente dependieron de la generación de una situación de estrés oxidativo debido a que ambas drogas incrementaron la generación de ERO intracelulares y sus efectos proapoptóticos fueron parcialmente bloqueados por la catalasa y por el lipopolisacárido (LPS). Conclusión: Estos hallazgos sugirieron que, debido a sus bajas toxicidades y a sus capacidades para inducir efectos apoptóticos en PMNs, tanto la CPX como la NFX pueden ser útiles para tratar enfermedades inflamatorias no necesariamente relacionadas con infecciones bacterianas.

Neutrophil apoptosis (PMNs) is thought to be a critical event for the control of the resolution phase of inflammation. In consequence, the pharmacological induction of apoptosis by antibiotics could be a therapeutic option for the treatment of a number of diseases. However, there is scarce information about the abilities of broad-spectrum antibiotics, such as the fluoroquinolones to accelerate this metabolic event. Therefore, the purpose of this study was to evaluate the in vitro effects of the fluoroquinolones ciprofloxacin (CPX) and norfloxacin (NFX) on the human PMNs apoptosis. Methods: Isolated PMNs were incubated in the presence of both drugs to determine their effects on apoptosis induction, reactive oxygen species (ROS) generation and mitochondrial membrane potential (Δψm). These events were assessed by the use of optical or fluorescence microscopy, luminometry and flow citometry techniques, respectively. Results: Both drugs, at concentrations of 300 and 600 μmol/L, induced disruption of Δψm, as well as apoptotic cell death in a statically significant degree. In addition, these effects were probably dependent on the induction of an oxidative stress response since both drugs increased the generation of intracellular ROS, and their proapoptotic effects could be partially blocked by both catalase and the lipopolysaccharide (LPS). Conclusion: These findings suggest that due to their low toxicity and their ability to induce apoptotic effects, CPX and NFX may be useful drugs for the treatment of inflammatory diseases not necessarily related to bacterial infections.

Effect of a gold-chloroquine complex on inflammation-related leukocyte functions and cell viability. Comparison with auranofin.

This study evaluates a new gold-chloroquine complex [hexafluorophosphate triphenylphosphine chloroquine gold (I), Au(CQ)(PPh3)PF6, referred to hereinafter as CQAu] in terms of its anti-inflammatory and toxic effects on immune cells compared to auranofin (AF). CQAu and AF were compared for their effects on a) tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release by human lymphocytes and murine macrophages, b) functionality and survival of polymorphonuclear leukocytes (PMN), c) PMN function in the presence of human serum albumin as a competitive inhibitor, d) mitogen-induced proliferation of human lymphocytes and e) TNF-alpha and IL-6 response of mice to lipopolysaccharide (LPS). CQAu was found to be generally similar to AF, or somewhat less effective, in terms of its activity in different assays of human immune cell function. For several of the assays, this was related to the greater cytotoxicity of AF. However, the two drugs did show comparable inhibitory effects on TNF-alpha and IL-6 production in a mouse model in vitro and in vivo, which were independent of a cytotoxic effect. CQAu merits further investigation as a gold drug with potential applications in treating inflammatory disease.

Synthesis and characterization of new copper- and zinc-chloroquine complexes and their activities on respiratory burst of polymorphonuclear leukocytes.

The metal-chloroquine (CQ) complexes, Cu(CQ)2Cl (1), Cu(CQ)(PPh3)(NO3) (2), [Cu(OAc)2(CQ)]2 (3) ZnCl2(CQ)(H2O)2 (4), [Zn(OAc)2(CQ)(H2O)]2 (5), were synthesized and characterized by NMR, FAB-mass, elemental analysis, and UV-Vis, EPR and IR spectroscopies. The effects of these compounds on the generation of reactive oxygen species (ROS) from human neutrophils (PMNs) were tested in the concentration range 1-100 microM and compared to that of chloroquine. The data show that the copper-chloroquine complexes 1-3 inhibit neutrophil release of ROS in PMNs activated either by a phorbol ester or by phagocytosable particles. Both effects were dose-dependent, with an IC50 of approximately 10 microM. With the same stimulants, there was only modest inhibition of ROS generation by any of the zinc-chloroquine complexes 4-5 at 10-100 microM. All complexes did not show significant in vitro toxicity as assayed by the trypan blue exclusion method. Our results reinforce previous observations that many metal derivatives of anti-inflammatory drugs affect neutrophil functions with higher potency than their parent ligands.

In vitro activities of transition metal derivatives of ketoconazole and clotrimazole against a wild type strain of Saccharomyces cerevisiae in absence or presence of human neutrophils.

In vitro activities of a series of gold, copper and ruthenium clotrimazole (CTZ, CAS 23593-75-1) and ketoconazole (KTZ, CAS 65277-42-1) derivatives were investigated individually and in combination with human neutrophils (PMNs) against a wild type strain of Saccharomyces cerevisiae. For 11 out of 12 tested metal complexes, the minimal inhibitory concentrations (MICs) at which 100 % of yeast growth was inhibited ranged from 0.75 to 3.0 micromol/L. The complex RuCl3(CTZ)3 x 2CH3OH (1f) (MIC = 0.75 micromol/L) was, although modestly, the only one able to increase the fungistatic activity of the parental drug (MIC = 1 micromol/L). On the other hand, at a sub-MIC concentration (0.5 micromol/L), the complexes [Cu(KTZ)Cl2]2 x 2H2O (2c) and RuCl2(KTZ)2 (2e) displayed synergistic fungicidal effects with PMNs whereas phagocytic capacity was enhanced by complexes [Cu(KTZ)3Cl2] (2b) and RuCl2(KTZ)2 (2e). The findings suggest that the metal-based agents may give rise to drugs with improved antifungal properties.

Effects of gold-chloroquine complexes on respiratory burst of polymorphonuclear leukocytes.

The effects of gold-chloroquine derivatives with the formula [Au(PR3)(CQ)]PF6 (where R = Ph (1), Et or Me) on the superoxide anion production by human neutrophils (PMNs, polymorphonuclear cells) were investigated. When these complexes (0.1-3 mumol/l) were added to PMNs prior to the activators formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), they inhibited isoluminol-horseradish peroxidase-dependent chemiluminescence (CLisol). The inhibition was a direct result of effects on PMNs since chemiluminescence in the cell-free system (horseradish peroxidase-hydrogen peroxidase-isoluminol) was not affected. The above mentioned concentrations of the complexes did not show in vitro toxicity on the cells. On the other hand, when 1 mumol/l of complex 1 was added to cells after stimulation, the chemiluminescence of PMNs stimulated by PMA was inhibited, but not the chemiluminescence stimulated by fMLP. The gold-chloroquine binding was essential for the referred activity as chemiluminescence was not influenced by the precursors chloroquine (CAS 54-05-7) and AuCl(PPh3). Furthermore, the extent of inhibition of chemiluminescence in PMNs activated by PMA did not increase with the duration of preincubation in presence of 1 mumol/l of 1. Extensive washing of cells after preincubation with 1 mumol/l of 1 reversed the aforementioned inhibition. All these results show that the gold-chloroquine binding can lead to compounds with specific properties that could make them useful in the treatment of some inflammatory diseases.

Efectos tóxicos en rheina y naftazarina en neutrofilos humanos in vitro / Toxic effects of rhein and naphthazarin in human neutrophilus in vitro

Recientemente se demostró en el BIOMED que la fracción de bajo peso molecular de Aloe barbadensis, rica en antraquinonas, es citotóxica en neutrófilos humanos (PMNs). Sin embargo, algunas antraquinonas como rheína (RH) han mostrado propiedades antiinflamatorias. Debido a que los PMNs son células proinflamatorias cuando se activan, se estudiaron los efectos relacionados con la activación de su NADPH-oxidasa en presencia de rheína. Paralelamente, se estudiaron afectos similares de la naftoquinona naftazarina (NZ), ya que ésta ha mostrado ser una de las quinonas de mayor toxicidad, a través de mecanismos relacionados con estrés oxidativo y adición nucleofílica de compuestos sulfhidrílicos. Así, la incubación de los PMNs con las quinonas a altas concentraciones no produjo pérdidas de viabilidad importantes; NZ ocasionó una pérdida cercana al 40 por ciento y RH mostró poca toxicidad con respecto al control. Además, no se observaron indicios de peroxidación lipídica en los PMNs incubados con ambas drogas. La exposición de las células con NZ ocasionó disminución del glutatión intracelular. Sin embargo, RH no mostró efecto alguno sobre el mismo. Cuando los PMNs se incubaron con las quinonas a bajas concentraciones y se realizaron ensayos sobre la NADPH oxidasa, se mostró que NZ es un potente inhibidor del estallido respiratorio en presencia de los activadores fMLP y PMA. La antraquinona RH mostró un comportamiento diferente ya que se produjo inhibición del estallido respiratorio sólo en presencia de fMLP. Esta conducta se asemeja a conocidos inhibidores de tirosina quinasas y puede estar relacionada con sus efectos antiflamatorios