Estudio experimental de la estabilidad de micro implantes e influencia de los metales pesados sobre los sistemas antioxidantes (SOD-1 y glutatión) en portadores de amalgamas dentales : protocolos con filtros

Este trabajo tiene como objetivo analizar la estabilidad de los Microimplantes bajo carga inmediata, a través de parámetros biomecánicos e histológicos (PIT: Torque máximo de Inserción, PRT: Torque máximo de Remoción y BIC: Superficie de contacto hueso-implante) en modelo canino. A los perros se les colocó un total de 144 Microimplantes en boca durante 16 semanas. Los perros se alimentaron con dietas de diferente consistencia física (dura/blanda), a partir de los 5 meses de edad hasta el final del experimento, de forma que aquellos perros alimentados con dieta dura (HD) mostraban un incremento en el porcentaje del PIT, frente a los que recibían dieta blanda (SD). Por el contrario, los porcentajes de BIC y PRT aumentaban en la dieta blanda (SD). El análisis histomorfométrico reflejó diferencias estadísticamente significativas entre ambos grupos experimentales. Nuestros resultados sugieren que los impactos masticatorios no solo influyen en el hueso per se, sino también en la estabilidad de los Microimplantes. Las ventajas que derivan de los Microimplantes han incrementado los tratamientos de ortodoncia y multidisciplinares en pacientes adultos. A parte de las aleaciones que conlleva la ortodoncia, éstas, podrían estar combinadas con prótesis, implantes y o amalgamas dentales. En la combinación de estas aleaciones, destaca por su toxicidad la amalgama dental, en comparación con las demás, que pudieran inducir corrosión galvánica, donde ha de asumirse que el paciente puede sufrir algún grado de exposición a los productos de corrosión. Por ello hemos evaluado si los niveles de una plétora de metales pesados medidos en pelo por espectrometría de masas (ICP-MS en μg/g Ba, Sb, As, Be, Bi, Cd, Pb, Pt, Ti, Th, U, Ni; especialmente en aquellos que conforman la amalgama dental: Al, Hg, Ag, Zn, Cu, Sn, Ti) pudieran incrementar significativamente en aquellas portadoras de amalgamas durante al menos diez años (media: 15 años, n=55) frente a controles sanos (sin amalgamas y sin implantes) (n=13). Dado que el mercurio puede aumentar los niveles de radicales libres, hemos evaluado si existe una relación entre liberación de metales pesados y un posible aumento del Glutatión reducido (GSH) o de la actividad Superóxido Dismutasa-1 (SOD-1), que elimina el radical libre denominado anión superóxido. En nuestro estudio, las portadoras de amalgamas dentales (edad media: 44 años) se clasificaron en portadoras de cuatro o menos amalgamas dentales (4, n=15), todas ellas con amalgamas en boca durante al menos 10 años (media: 15 años). La principal conclusión de nuestro estudio indica que los niveles de mercurio (Hg), aluminio (Al), plata (Ag) y bario (Ba) estaban significativamente incrementados en las portadoras de amalgamas dentales. Dado que el Glutatión reducido (GSH) correlacionó con los niveles de aluminio y la actividad (SOD-1) correlacionó con los niveles de mercurio total, el presente estudio sugiere que existen mecanismos compensatorios endógenos protectores en portadoras durante largo tiempo de amalgamas dentales. De acuerdo a nuestros resultados y ante la alta prevalencia de cambios de amalgamas por razones estéticas, o como parte de tratamientos ortodóncicos multidisciplinarios, la implementación de medidas de bioseguridad minimizaría la liberación de vapor de mercurio durante su eliminación. Aplicando el Principio de Precaución, el uso de filtros nasales de carbón activo evitaría, durante el proceso de eliminación de la amalgama dental, el riesgo de exposición a metales pesados tanto para el paciente, el personal de la clínica como para el medio ambiente. The aim of this Doctoral Thesis is to study the stability of Microimplants (MIs) under an immediate load by analyzing biomechanical and histological parameters (PIT: Peak Insertion Torque; PRT: Peak Removal Torque; BIC: Bone-to- Implant Contact) in female Beagle dogs. There were 144 MIs placed in dogs’ mouths for 16 weeks. The dogs were fed with diets of different consistence (hard/soft) from 5 months of age until the end of the experiment. The dogs fed with the hard diet (HD) showed an increase in the percentage PIT. Conversely, those fed with a soft diet (SD) showed an increase in the percentage of BIC and PRT in comparison to animals fed with hard diet (HD). The histomorphometric analysis reflected statistically significant differences between both experimental groups. Our results suggest that the impactsof mastication not only influence the bone per se but also the stability of the MIs. The advantages associated with the use of MIs are increasing in the orthodontic field and also allow the implementation of multidisciplinary treatments in adult patients. For that reason the alloys used in orthodontics could be combined with prosthesis, implants and/or dental amalgams. In the combination of these alloys and compared with others, dental amalgams stand out for their toxicity and, as they could induce galvanic corrosion, it must be assumed that the patient may suffer some degree of exposure to corrosion products. Therefore, we have evaluated whether levels of a plethora of heavy metals measured in hair samples by mass spectrometry (ICP-MS in µ/g Ba, Sb, As, Be, Bi, Cd, Pb, Pt, Ti, Th, U, Ni; especially those that make dental amalgam: Al, Hg, Ag, Zn, Cu, Sn, Ti) could increase significantly in those who had been carrying amalgam for at least ten years (mean: 15 years, n = 55) compared with healthy controls (without amalgams or implants n = 13). Since mercury can increase levels of free radicals, we have evaluated whether there is a link between release of heavy metals and a possible increase in Glutathione (GSH; reduced form) or upregulation of activity of Superoxide Dismutase-1 (SOD-1), which eliminates the free radical called superoxide anion. In our study, the dental amalgam carriers (average age: 44 years) were classified into those who had four or fewer dental amalgams ( 4, n = 15). All of them had dental amalgams in their mouth for at least 10 years (average: 15 years). The main finding of our study indicates that levels of mercury (Hg), aluminium (Al), silver (Ag) and barium (Ba) were significantly elevated in women who had dental amalgams. Since the glutathione (GSH) levels correlated with aluminium levels and the activity SOD-1 correlated with levels of total mercury, the present study suggests that there are protective endogenous compensatory mechanisms in women who had dental amalgams for a long period of time. According to our results, facing the high prevalence of amalgam changes for cosmetic reasons or as part of multidisciplinary orthodontic treatment, the implementation of biosecurity measures would minimize the release of mercury vapour during removal. Applying the precautionary principle, the use of nasal filters of activated carbon prevent the patient, the clinic staff and the environment from the risk of exposure to heavy metals released in the amalgam removal process

Nanoparticles and Mesenchymal Stem Cell (MSC) Therapy for Cancer Treatment: Focus on Nanocarriers and a si-RNA CXCR4 Chemokine Blocker as Strategies for Tumor Eradication In Vitro and In Vivo

Mesenchymal stem cells (MSCs) have a high tropism for the hypoxic microenvironment of tumors. The combination of nanoparticles in MSCs decreases tumor growth in vitro as well as in rodent models of cancers in vivo. Covalent conjugation of nanoparticles with the surface of MSCs can significantly increase the drug load delivery in tumor sites. Nanoparticle-based anti-angiogenic systems (gold, silica and silicates, diamond, silver, and copper) prevented tumor growth in vitro. For example, glycolic acid polyconjugates enhance nanoparticle drug delivery and have been reported in human MSCs. Labeling with fluorescent particles (coumarin-6 dye) identified tumor cells using fluorescence emission in tissues; the conjugation of different types of nanoparticles in MSCs ensured success and feasibility by tracking the migration and its intratumor detection using non-invasive imaging techniques. However, the biosafety and efficacy; long-term stability of nanoparticles, and the capacity for drug release must be improved for clinical implementation. In fact, MSCs are vehicles for drug delivery with nanoparticles and also show low toxicity but inefficient accumulation in tumor sites by clearance of reticuloendothelial organs. To solve these problems, the internalization or conjugation of drug-loaded nanoparticles should be improved in MSCs. Finally, CXCR4 may prove to be a promising target for immunotherapy and cancer treatment since the delivery of siRNA to knock down this alpha chemokine receptor or CXCR4 antagonism has been shown to disrupt tumor–stromal interactions

The Bluegreen Algae (AFA) Consumption over 48 h Increases the Total Number of Peripheral CD34+ Cells in Healthy Patients: Effect of Short-Term and Long-Term Nutritional Supplementation (Curcumin/AFA) on CD34+ Levels (Blood)

Several active principles from plants could trigger the release of stem cells from the bone marrow. Stem cell mobilizers have shown side effects in patients. Thus, the purpose of this paper is to find the natural products from plants (curcuminoids, glycosinolate of sulforaphane, AFA bluegreen algae), which could be potential stem mobilizes without adverse side effects. The antioxidant curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-2,5-dione], glycosinolate of sulforaphane (broccoli) or AFA (Aphanizomenon flos) extract promote beneficial effects in patients. The number of circulating stem cells were monitored by HSC marker-CD34 by flow cytometry in peripheral blood from healthy subjects. CD34 is a hematological stem cells (HSC) marker. A double-blind study was conducted in 22 healthy subjects. We have evaluated whether short-term AFA—Aphanizomenon flos aquae—algae or curcuminoids consumption (powder or liquid formulation) over 48 consecutive hours could increase the total number of peripheral CD34+ blood cells (n = 22, n = 5 subjects/group). The total number of circulating CD34+ cells were quantified after short-term and long-term nutritional supplementation; their levels were compared with their own basal levels (n = 5/group, controls: before taking any supplement) or placebo-treated patients (n = 7); their average age was 54 years old. We also evaluated whether long-term nutritional supplementation with several nutraceuticals could enhance HSC mobilization by increasing the total number of peripheral CD-34+ cell after seven or 38 consecutive days of administration (n = 5, with seven placebo-treated patients). The long-term administration take place with these doses/day [curcuminoids: 2000 mg/day, equivalent to 120 mg of curcuminoids/day), glycosinolate of sulforaphane (66 mg/day), plus AFA Algae bluegreen extract (400 mg/day)]. On the last day (10 a.m.) of treatment, blood samples were collected six hours after taking these supplements; the average age was 54 years old. Notably, the blue green AFA algae extract consumption over 48 h enhances HSC mobilization by increasing the total number of peripheral CD34+ cells. The long-term administration with curcuminoids, glycosinolate of sulforaphane, and AFA bluegreen algae extract also increased the total number of CD34-HSC cells after seven or 38 days of consecutive of administration in healthy subjects

Adult Mesenchymal Stem Cells from Oral Cavity and Surrounding Areas: Types and Biomedical Applications

Adult mesenchymal stem cells are those obtained from the conformation of dental structures (DMSC), such as deciduous and permanent teeth and other surrounding tissues. Background: The self-renewal and differentiation capacities of these adult stem cells allow for great clinical potential. Because DMSC are cells of ectomesenchymal origin, they reveal a high capacity for complete regeneration of dental pulp, periodontal tissue, and other biomedical applications; their differentiation into other types of cells promotes repair in muscle tissue, cardiac, pancreatic, nervous, bone, cartilage, skin, and corneal tissues, among others, with a high predictability of success. Therefore, stem and progenitor cells, with their exosomes of dental origin and surrounding areas in the oral cavity due to their plasticity, are considered a fundamental pillar in medicine and regenerative dentistry. Tissue engineering (MSCs, scaffolds, and bioactive molecules) sustains and induces its multipotent and immunomodulatory effects. It is of vital importance to guarantee the safety and efficacy of the procedures designed for patients, and for this purpose, more clinical trials are needed to increase the efficacy of several pathologies. Conclusion: From a bioethical and transcendental anthropological point of view, the human person as a unique being facilitates better clinical and personalized therapy, given the higher prevalence of dental and chronic systemic diseases

The Long-Term Algae Extract (Chlorella and Fucus sp) and Aminosulphurate Supplementation Modulate SOD-1 Activity and Decrease Heavy Metals (Hg++, Sn) Levels in Patients with Long-Term Dental Titanium Implants and Amalgam Fillings Restorations

The toxicity of heavy metals such as Hg++ is a serious risk for human health. We evaluated whether 90 days of nutritional supplementation (d90, n = 16) with Chlorella vulgaris (CV) and Fucus sp extracts in conjunction with aminosulphurate (nutraceuticals) supplementation could detox heavy metal levels in patients with long-term titanium dental implants (average: three, average: 12 years in mouth) and/or amalgam fillings (average: four, average: 15 years) compared to baseline levels (d0: before any supplementation, n = 16) and untreated controls (without dental materials) of similar age (control, n = 21). In this study, we compared levels of several heavy metals/oligoelements in these patients after 90 days (n = 16) of nutritional supplementation with CV and aminozuphrates extract with their own baseline levels (d0, n = 16) and untreated controls (n = 21); 16 patients averaging 44 age years old with long-term dental amalgams and titanium implants for at least 10 years (average: 12 years) were recruited, as well as 21 non-supplemented controls (without dental materials) of similar age. The following heavy metals were quantified in hair samples as index of chronic heavy metal exposure before and after 90 days supplementation using inductively coupled plasma-mass spectrometry (ICP-MS) and expressed as μg/g of hair (Al, Hg++, Ba, Ag, Sb, As, Be, Bi, Cd, Pb, Pt, Tl, Th, U, Ni, Sn, and Ti). We also measured several oligoelements (Ca++, Mg++, Na+, K+, Cu++, Zn++, Mn++, Cr, V, Mo, B, I, P, Se, Sr, P, Co, Fe++, Ge, Rb, and Zr). The algae and nutraceutical supplementation during 90 consecutive days decreased Hg++, Ag, Sn, and Pb at 90 days as compared to baseline levels. The mercury levels at 90 days decreased as compared with the untreated controls. The supplementation contributed to reducing heavy metal levels. There were increased lithium (Li) and germanium (Ge) levels after supplementation in patients with long-term dental titanium implants and amalgams. They also (d90) increased manganesum (Mn++), phosphorum (P), and iron (Fe++) levels as compared with their own basal levels (d0) and the untreated controls. Finally, decreased SuperOxide Dismutase-1 (SOD-1) activity (saliva) was observed after 90 days of supplementation as compared with basal levels (before any supplementation, d0), suggesting antioxidant effects. Conversely, we detected increased SOD-1 activity after 90 days as compared with untreated controls. This SOD-1 regulation could induce antioxidant effects in these patients. The long-term treatment with algae extract and aminosulphurates for 90 consecutive days decreased certain heavy metal levels (Hg++, Ag, Sn, Pb, and U) as compared with basal levels. However, Hg++ and Sn reductions were observed after 90 days as compared with untreated controls (without dental materials). The dental amalgam restoration using activated nasal filters in conjunction with long-term nutritional supplementation enhanced heavy metals removal. Finally, the long-term supplementation with these algae and aminoazuphrates was safe and non-toxic in patients. These supplements prevented certain deficits in oligoelements without affecting their Na+/K+ ratios after long-term nutraceutical supplementation.Funds # 20151602 from CIROM (Murcia, Spain), Article processing charge (APC) supported by Nutergia Laboratories (San Sebastian)We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI

Zirconia implants and peek restorations for the replacement of upper molars

Abstract Background One of the disadvantages of the zirconia implants is the lack of elasticity, which is increased with the use of ceramic or zirconia crowns. The consequences that could result from this lack of elasticity have led to the search for new materials with improved mechanical properties. Case presentation A patient who is a 45-year-old woman, non-smoker and has no medical record of interest with a longitudinal fracture in the palatal root of molar tooth 1.7 and absence of tooth 1.6 was selected in order to receive a zirconia implant with a PEEK-based restoration and a composite coating. The following case report describes and analyses treatment with zirconia implants in molars following a flapless surgical technique. Zirconia implants are an alternative to titanium implants in patients with allergies or who are sensitive to metal alloys. However, one of the disadvantages that they have is their lack of elasticity, which increases with the use of ceramic or zirconia crowns. The consequences that can arise from this lack of elasticity have led to the search for new materials with better mechanical properties to cushion occlusal loads. PEEK-based restoration in implant prosthetics can compensate these occlusal forces, facilitating cushioning while chewing. Conclusion This procedure provides excellent elasticity and resembles natural tooth structure. This clinical case suggests that PEEK restorations can be used in zirconia implants in dentistry

<i>Origanum majorana</i> Essential Oil Inhalation during Neurofeedback Training Reduces Saliva Myeloperoxidase Activity at Session-1 in Bruxistic Patients

Introduction: Bruxism affects teeth and provokes sleep alterations. We evaluated whether saliva Myeloperoxidase (MPO) activity could be reduced after 21 neurofeedback training (NO) sessions in Origanum majorana (AE) bruxistic-treated patients (n = 12 patients, 120 saliva samples). The term divergence evaluates cerebral activity, which was compared between bruxistic patients with/without this essential oil exposure during 21 NO training sessions (n = 12, n = 120 saliva samples). The nasal filter used allow us to vehiculizate this Origanum majorana essential oil in patients. MPO activity was measured in six training NO sessions (Session S1, 6, 12, 18, 21). We included a total of 104 patients and 500 saliva samples. Results: there was a fast reduction in MPO activity after NO session-1 in bruxistic patients; divergence (an index of NO training brain efficacy) is the difference in cerebral activity found between pre-training and post-training levels. Thus, Divergence can fluctuate during NO training before reaching a final calm state after many sessions (21). Repeated NO training lead to habituation in so far as cerebral activity as well as MPO activity after 21 training sessions. Origanum majorana essential oil modulates cerebral activity at certain training sessions in bruxistic patients. Stress levels were reduced on the perceived stress scores (PSS: Cohen Scale) after 21 NO sessions than for those bruxistic without NO training sessions. Conclusions: MPO activity could predict stress level in bruxistic patients and repeated NO reduced their stress level; Origanum majorana essential oil enhanced these anxiolytic effects

Increased Zn/Glutathione Levels and Higher Superoxide Dismutase-1 Activity as Biomarkers of Oxidative Stress in Women with Long-Term Dental Amalgam Fillings: Correlation between Mercury/Aluminium Levels (in Hair) and Antioxidant Systems in Plasma.

The induction of oxidative stress by Hg can affect antioxidant enzymes. However, epidemiological studies have failed to establish clear association between dental fillings presence and health problems.To determine whether heavy metals (in hair), antioxidant enzymes (SOD-1) and glutathione levels could be affected by the chronic presence of heavy metals in women who had dental amalgam fillings.55 hair samples (42 females with amalgam fillings and 13 female control subjects) were obtained. All subjects (mean age 44 years) who had dental amalgam filling for more than 10 years (average 15 years). Certain metals were quantified by ICP-MS (Mass Spectrophotometry) in hair (μg/g: Al, Hg, Ba, Ag, Sb, As, Be, Bi, Cd, Pb, Pt, Tl, Th, U, Ni, Sn, Ti) and SOD-1 and Glutathione (reduced form) levels in plasma. Data were compared with controls without amalgams, and analyzed to identify any significant relation between metals and the total number of amalgam fillings, comparing those with four or less (n = 27) with those with more than four (n = 15). As no significant differences were detected, the two groups were pooled (Amlgam; n = 42).Hg, Ag, Al and Ba were higher in the amalgam group but without significant differences for most of the heavy metals analyzed. Increased SOD-1 activity and glutathione levels (reduced form) were observed in the amalgam group. Aluminum (Al) correlated with glutathione levels while Hg levels correlated with SOD-1. The observed Al/glutathione and Hg/SOD-1 correlation could be adaptive responses against the chronic presence of mercury.Hg, Ag, Al and Ba levels increased in women who had dental amalgam fillings for long periods. Al correlated with glutathione, and Hg with SOD-1. SOD-1 may be a possible biomarker for assessing chronic Hg toxicity

Elevated Systemic L-Kynurenine/L-Tryptophan Ratio and Increased IL-1 Beta and Chemokine (CX3CL1, MCP-1) Proinflammatory Mediators in Patients with Long-Term Titanium Dental Implants

Titanium is the mean biocompatible metal found in dental titanium alloys (Ti-6Al-4V). The safety of certain dental biomaterial amalgams has been questioned in patients. The levels of several systemic cytokines (interleukin (IL)-1 beta, IL-4: pg/mL) and chemokines (monocyte chemoattractant protein-1 (MCP-1), soluble fractalkine (CX3CL1: pg/mL) were determined using ELISA and compared between these study groups. The study included 30 controls without dental materials (cont), 57 patients with long-term titanium dental implants plus amalgams (A + I group) as well as 55 patients with long-term dental amalgam alone (A group). All patients (except controls) have had dental titanium implants (Ti-6Al-4V) and/or amalgams for at least 10 years (average: 15 years). We evaluated whether systemic levels of cytokines/chemokines, kyn/L-trp ratio and aromatic amino acid levels (HPLC: mM/L, Phe, L-Trp, His, Treo) could be altered in patients with long-term dental titanium and/or amalgams. These systemic markers were evaluated in 142 patients. The A + I group had higher L-Kynurenine/L-Tryptophan ratios than patients with long-term dental amalgam fillings alone (A). In addition, levels of IL-1 Beta cytokine, CX3CL1 and MCP-1 chemokines were higher in the A + I group than in the A group (A). The increased L-kyn/L-trp ratio and MCP-1 and fractalkine receptor (CX3CR1) elevations could suggest enhanced chemotactic responses by these chemokines in the A + I group

The analysis of the dental filling number and levels of other heavy metal levels in hair did not shown significant differences between both amalgam groups (total number of amalgams; Pooled; n = 42); >4 (n = 15) or <4 (n = 27), as compared to controls (n = 13).

<p>There were no differences for Sn, Ni, Bi, Ti. Pb, Cd or either (data not shown: Sb, Be, Bi, Tl, Th, U; μg/g).p>0.05: n.s (<b>Sb, Be, Bi, TI, Th, U</b>); (p>0.05; n.s; data not shown</p><p>The analysis of the dental filling number and levels of other heavy metal levels in hair did not shown significant differences between both amalgam groups (total number of amalgams; Pooled; n = 42); >4 (n = 15) or <4 (n = 27), as compared to controls (n = 13).</p