Carlos Arana

Melatonin stimulates osteointegration of dental implants.

Abstract:  The aim of this study was to evaluate the effect of the topical application of melatonin on osteointegration of dental implants in Beagle dogs 14 days after their insertion. In preparation for subsequent insertion of dental implants, upper and lower premolars and molars were extracted from 12 Beagle dogs. Each mandible received cylindrical screw implants of 3.25 mm in diameter and 10 mm in length. The implants were randomly assigned to the mesial and distal sites on each side of the mandible. Prior to implanting, 1.2 mg lyophylized powdered melatonin was applied to one bone hole at each side of the mandible. None was applied at the control sites. Eight histological sections per implant were obtained for histomorphometric studies. After a 2‐wk treatment period, melatonin significantly increased the perimeter of bone that was in direct contact with the treated implants (P < 0.0001), bone density (P < 0.0001), new bone formation (P < 0.0001) and inter‐thread bone (P < 0.05) in comparison with control implants. Topical application of melatonin may act as a biomimetic agent in the placement of endo‐osseous dental implants.

Hereditary Blood Coagulation Disorders: Management and Dental Treatment

Patients with hereditary hemostatic disorders, characterized by a tendency to bleeding or thrombosis, constitute a serious challenge in the dental practice. Advances in the medical diagnosis of hemostatic disorders have exposed dental professionals to new patients not amenable to the application of the management protocols associated with other, more well-known, disorders. It is the aim of this paper to review the evidence, to highlight the areas of major concern, and to suggest management regimens for patients with hereditary hemostatic disorders. An extensive review has been made (PubMed, Science Direct, Web of Knowledge, etc.) of literature pertaining to hereditary disorders affecting blood coagulation factors and how they affect the practice of dentistry. Several aspects relating to the care of such patients must be recognized and taken into consideration when dental treatment is planned. Replacement of deficient coagulation factors ensures that safe dental treatment will be carried out. However, the half-life of such coagulation factors requires that dental treatment be specifically planned and adapted to the type of pathology involved.

Melatonin reduces oxidative stress because of tooth removal

Previous studies have reported that oral inflammatory processes, such as periodontitis, can trigger signals to increase not only plasma melatonin levels, but also melatonin levels in the oral cavity, where indoleamine may have an antioxidant effects. The direct action of melatonin as a free radical scavenger of both reactive oxygen (ROS) and reactive nitrogen species (RNS) [1] is complemented by an indirect stimulatory effect on antioxidant enzymes, including glutathione peroxidase (GPx) and reductase (GRd), superoxide dismutase, and catalase [2]. Because of GRd stimulation, melatonin favors the recycling of glutathione (GSH) from glutathione disulfide (GSSG), maintaining a high GSH/GSSG ratio. Melatonin also promotes the de novo synthesis of GSH by stimulating the activity of c-glutamyl-cysteine synthetase. But melatonin is also capable of reducing nitric oxide (NO) and the peroxynitrite anion (ONOO ) generation because of its ability to inhibit iNOS activity and expression which increase as a consequence of inflammation [3]. Melatonin may also play an immunoenhancing role in the mouth, as patients with poorer periodontal status, exhibiting bone damage and gingival involvement, show concomitant high IL-2 and melatonin levels, which may stimulate CD-4 lymphocytes in response to periodontal disease [4]. It is now well established that the acute inflammatory response of gingival tissue during the first 24–48 postextraction hours causes an intense polymorphonuclear neutrophil infiltration, which is responsible for the increase in ROS and RNS production [5]. Thus, the aim of this study was to ascertain whether plasma reflects the acute inflammatory response as a result of tooth extractions in Beagle dogs, and whether melatonin treatment can prevent it. Maxillary and mandibular premolars and molars of eight Beagle dogs were removed under general anesthesia. After the tooth extractions and before suturing, four dogs received local melatonin (2 mg) applied in extraction wounds and gingival tissue surrounding the premolar and molar area. Measurements were made 24 hr later [6]. The findings are summarized in Table 1. Research into inflammatory processes in the oral cavity, such as periodontitis, has demonstrated the involvement of oxidative stress. One day after oral surgery, the group of dogs that did not receivemelatonin presented a significant increase in oxidative stress in plasma as a consequence of the subsequent inflammatory process. Besides the inflammatory processes, other mechanisms, such as severing of gingival fibers, damage to periodontal vessels, and mechanical aggression to oral tissues, also contribute to oral damage after tooth removal [7]. Together, these events may provoke increased oxidative stress. In turn, increased ROS stimulate the production of pro-inflammatory cytokines, transcription factors and vascular cell adhesion molecules, increasing the severity of the inflammatory process and the synthesis of RNS, such as NO and ONOO – [5]. Both ROS andRNS locally generated in the oral cavity after tooth removal may pass to the blood stream. In this study, plasma levels of LPO and of NOx, which indicate increased ROS and RNS production, respectively, were significantly higher 24 hr after oral surgery. Overproduction of lipid hydroperoxides and aldehyde compounds can cause depletion of GSH, disrupting mucosal turnover [8]. Our results further confirmed these observations, as GSSG levels and the GSSG/GSH ratio were significantly higher in the untreated group. The increased GPx activity observed after tooth extraction probably reflects the activation of antioxidant processes. However, the increased GSSG produced in these circumstances could not efficiently be reduced to GSH because of the barely perceptible increase in GRd activity. The application of melatonin into the alveolar sockets resulting from tooth removal caused a statistically significant reduction in oxidative stress in blood. Increased levels of LPO following tooth removal were counteracted by melatonin 24 hr after surgery. Our findings support those of other studies that have demonstrated that in vivo melatonin efficiently limits the peroxidation of lipids [1, 3, 9]. It may be that melatonin achieves this high degree of lipid protection by interfering with the radicals that initiate the peroxidation process, mainly the hydroxyl radical (HO) and ONOO , and by positioning itself among the membrane lipids in such a way as to impede the oxidation of the polyunsaturated fatty acids [10]. Treatment with melatonin also counteracted NOx levels increased after oral surgery, reducing their concentrations below those of the control group. The inhibition of iNOS by melatonin application might be responsible for the reduction in NOx, by diminishing gingival damage and postextraction oxidative stress in the oral cavity. Additionally, melatonin might also decrease nitrosative stress in gingival cells by directly neutralizing ONOO . In addition to reducing plasma markers of oxidative (LPO) and nitrosative (NOx) damage, melatonin also significantly lowered the GSSG/GSH ratio, the best index of intracellular oxidative damage in red blood cells. Besides its direct antioxidant role, which reduces GSH consumption, melatonin treatment also promoted GRd activity, which may account for the reduction of GSSG and for the increase in GSH levels, which may provide the cell with an extra amount of GSH [11]. Besides protecting GRd from oxidative damage, the effect of melatonin on GRd activity also may depend on a genomic effect of indoleamine in increasing the expression of the enzyme [12, 13]. Regulation of the GSH redox cycling system might be of great significance for oral tissue homeostasis, as GSH J. Pineal Res. 2007; 42:419–420

POEMS Syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy and Skin Changes) Treated with Autologous Hematopoietic Stem Cell Transplantation: A Case Report and Literature Review

Patient: Male, 62 Final Diagnosis: POEMS syndrome Symptoms: General malaise • pretibial edemas • weight loss Medication: — Clinical Procedure: Autologous hematopoietic stem cell transplantation Specialty: Hematology Objective: Rare disease Background: POEMS syndrome is a rare systemic pathology of paraneoplastic origin that is associated with plasma cell dyscrasia. It is characterized by the presence of sensorimotor polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes, and other systemic manifestations. The pathogenesis of the syndrome is unknown but over-production of vascular endothelial growth factor is probably responsible for most of the more characteristic symptoms. There is no standard treatment for POEMS syndrome and no randomized controlled clinical trials of treatment exist in the available literature. High-dose melphalan with autologous hematopoietic stem cell transplantation should be considered for younger patients with widespread osteosclerotic lesions, and for patients with rapidly progressive neuropathy. Case Report: This is the case of a 62-year-old Caucasian man who was admitted to our center presenting pretibial edema accompanied by significant weight loss and difficulty walking. POEMS criteria were present and an immunofixation test confirmed the presence of a monoclonal plasmaproliferative disorder. After autologous hematopoietic stem cell transplantation, the monoclonal component disappeared and the patient’s clinical status improved markedly. Conclusions: Autologous hematopoietic stem cell transplantation following high-dose melphalan is an effective therapy for younger patients with widespread osteosclerotic lesions in POEMS syndrome.

Incremento de los parámetros de estrés oxidativo salival en pacientes con diabetes tipo 2: relación con la enfermedad periodontal

OBJECTIVE The aim of this study was to determine whether there are differences in salivary oxidative stress between patients with diabetes mellitus type 2 (DM2) and healthy non-diabetic patients, and whether this oxidative stress is associated with the presence of periodontal disease in diabetic patients. MATERIAL AND METHODS This observational study included 70 patients divided into three groups according to metabolic control levels: 19 non-diabetic patients (control group); 24 patients with good metabolic control (HbA1c<7%), and 27 patients DM2 with poor metabolic control (HbA1c>7%). The following oxidative stress parameters were measured in all subjects: glutathione peroxidase (GPx), glutathione reductase (GRd), reduced glutathione (GSH) and oxidized glutathione (GSSG). Periodontal health was determined by means of the community periodontal index (CPI) recommended by the WHO. RESULTS The diabetic group with good metabolic control showed a significant increase in GPx and GRd activity in comparison with the control group (P<.001). The activity of the enzymes measured was significantly less in patients with poor metabolic control in comparison with the control group and well-controlled diabetic groups (P<.001). Both diabetic groups showed higher GSSG/GSH quotients and CPI in comparison with the control group, and both parameters were significantly higher in diabetic patients with poor metabolic control in comparison with well-controlled diabetic patients. CONCLUSIONS Poor metabolic control in DM2 patients is associated with higher levels of salivary oxidative stress and worse periodontal health.

Superficies bioactivas en implantología: una nueva perspectiva

Actualmente, tras anos de investigacion en implantologia, en los cuales se han realizado muchos trabajos, en donde se han estudiado diferentes tipos de superficies de implantes, lisas y rugosas, en un intento de mejorar, tanto en el tiempo como en la calidad , la osteointegracion, se ha concluido que los implantes de superficie rugosa con un intervalo de rugosidad entre 1,0-2,0 nm, son los que parecen dar una mejor respuesta osea y mejores resultados clinicos, pero desde un punto de vista exclusivamente mecanico. Hoy en dia las investigaciones se centran en el desarrollo de superficies denominadas bioactivas, las cuales son capaces de interaccionar con el hueso que rodea al implante, como ocurre cuando el implante es revestido con carbonato calcico o bien con fluor. Pero sabemos que dentro del metabolismo oseo, juegan importantes papeles, moleculas, como son la melatonina y la hormona del crecimiento entre otras, las cuales deben de ser tenidas en cuenta a la hora de hablar de osteointegracion. Se realiza una breve descripcion de la fisiologia de ambas moleculas y se valora su aplicacion al concepto de superficie bioactiva en implantologia.