Pedro Bullón

Metabolic Syndrome and Periodontitis: Is Oxidative Stress a Common Link?

A review of pathological mechanisms that can explain the relationship between periodontitis and cardiovascular disease (CVD) is necessary to improve the management of both conditions. Metabolic syndrome is a combination of obesity, hypertension, impaired glucose tolerance or diabetes, hyperinsulinemia, and dyslipidemia. All these have been examined in recent years in terms of their relationship to periodontitis. Reviewed data indicate an association between some of them (body mass index, high-density lipoprotein-cholesterol [HDL-C], triglycerides, high blood pressure, among others) and periodontitis. Oxidative stress may act as a potential common link to explain relationships between each component of metabolic syndrome and periodontitis. Both conditions show increased serum levels of products derived from oxidative damage, with a pro-inflammatory state likely influencing each other bidirectionally. Adipocytokines might modulate the oxidant/anti-oxidant balance in this relationship.

Obesity, diabetes mellitus, atherosclerosis and chronic periodontitis: a shared pathology via oxidative stress and mitochondrial dysfunction?

As many diseases have been shown to have several or indirect causes (i.e. are multifactorial) the question is what is the relative importance of each factor in a given disease? Also, what happens when some diseases, although apparently disparate, share causative factors and/or tissue pathologies? Host inflammation response mechanisms are largely shared by the bodys different tissues and systems and only recently has special attention been paid to the possible linkages among chronic periodontitis and other chronic systemic diseases. The aim of this review was to consider and discuss the mounting evidence that the basis for the inter-relationships between chronic periodontitis and atheromatous disease and diabetes lie at a fundamental intracellular level, namely oxidative stress and mitochondrial dysfunction, as a meeting background among such chronic diseases and periodontitis.

Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease

IntroductionFibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. However, it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in fibromyalgia. Furthermore, the role of mitochondria in the redox imbalance reported in fibromyalgia also is controversial. We undertook this study to investigate the role of mitochondrial dysfunction, oxidative stress, and mitophagy in fibromyalgia.MethodsWe studied 20 patients (2 male, 18 female patients) from the database of the Sevillian Fibromyalgia Association and 10 healthy controls. We evaluated mitochondrial function in blood mononuclear cells from fibromyalgia patients measuring, coenzyme Q10 levels with high-performance liquid chromatography (HPLC), and mitochondrial membrane potential with flow cytometry. Oxidative stress was determined by measuring mitochondrial superoxide production with MitoSOX™ and lipid peroxidation in blood mononuclear cells and plasma from fibromyalgia patients. Autophagy activation was evaluated by quantifying the fluorescence intensity of LysoTracker™ Red staining of blood mononuclear cells. Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells.ResultsWe found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy.ConclusionsThese findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.

Periodontitis is associated with altered plasma fatty acids and cardiovascular risk markers.

BACKGROUND AND AIMS In periodontitis it has been found that some perturbation exists in lipid biomarkers, such as increased serum total cholesterol and low-density lipoprotein cholesterol. Nevertheless, the relationship between fatty acids and periodontitis has been demonstrated only in a few studies and remains controversial. The aim of this investigation was to explore the effects of periodontitis on a cluster of traditional and novel cardiovascular risk factors such as plasma-lipids profile, types of plasma fatty acids, adhesion molecules and systemic inflammatory markers. METHODS AND RESULTS At a university dental school, 56 patients all over 35 years old were enrolled and invited to participate in the study. Total plasma fatty acids, saturated, n-6 polyunsaturated and monounsaturated fatty acids, peroxidability index, soluble VCAM, TNF-alpha, cholesterol, triacylglycerols, and VLDL-c were significantly higher in the periodontitis group compared to the non-periodontitis group. CONCLUSIONS This close association found between plasma triacylglycerols, LDL-c, saturated fatty acids, polyunsaturated fatty acids, total amount of fatty acids and coenzyme Q(10) with some periodontal data such as periodontal probing depth, recession of the gingival margin and clinical attachment level (Pearson correlation between 0.3 and 0.6), leads to the conclusion that there is an inter-relationship between periodontitis, plasma fatty acids profile and the increase in metabolic risk factors for cardiovascular diseases.

Mitochondrial dysfunction promoted by Porphyromonas gingivalis lipopolysaccharide as a possible link between cardiovascular disease and periodontitis

Oxidative stress is one of the factors that could explain the pathophysiological mechanism of inflammatory conditions that occur in cardiovascular disease (CVD) and periodontitis. Such inflammatory response is often evoked by specific bacteria, as the lipopolysaccharide (LPS) of Porphyromonas gingivalis is a key factor in this process. The aim of this research was to study the role of mitochondrial dysfunction in peripheral blood mononuclear cells (PBMCs) from periodontitis patients and to evaluate the influence of LPS on fibroblasts to better understand the pathophysiology of periodontitis and its relationship with CVD. PBMCs from patients showed lower CoQ10 levels and citrate synthase activity, together with high levels of ROS production. LPS-treated fibroblasts provoked increased oxidative stress and mitochondrial dysfunction by a decrease in mitochondrial protein expression, mitochondrial mass, and mitochondrial membrane potential. Our study supports the hypothesis that LPS-mediated mitochondrial dysfunction could be at the origin of oxidative stress in periodontal patients. Abnormal PBMC performance may promote oxidative stress and alter cytokine homeostasis. In conclusion, mitochondrial dysfunction could represent a possible link to understanding the interrelationships between two prominent inflammatory diseases: periodontitis and CVD.

Autophagy in periodontitis patients and gingival fibroblasts: unraveling the link between chronic diseases and inflammation

BackgroundPeriodontitis, the most prevalent chronic inflammatory disease, has been related to cardiovascular diseases. Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. The aim of this research was to study the role of autophagy in peripheral blood mononuclear cells from patients with periodontitis and gingival fibroblasts treated with a lipopolysaccharide of Porphyromonas gingivalis. Autophagy-dependent mechanisms have been proposed in the pathogenesis of inflammatory disorders and in other diseases related to periodontitis, such as cardiovascular disease and diabetes. Thus it is important to study the role of autophagy in the pathophysiology of periodontitis.MethodsPeripheral blood mononuclear cells from patients with periodontitis (n = 38) and without periodontitis (n = 20) were used to study autophagy. To investigate the mechanism of autophagy, we evaluated the influence of a lipopolysaccharide from P. gingivalis in human gingival fibroblasts, and autophagy was monitored morphologically and biochemically. Autophagosomes were observed by immunofluorescence and electron microscopy.ResultsWe found increased levels of autophagy gene expression and high levels of mitochondrial reactive oxygen species production in peripheral blood mononuclear cells from patients with periodontitis compared with controls. A significantly positive correlation between both was observed. In human gingival fibroblasts treated with lipopolysaccharide from P. gingivalis, there was an increase of protein and transcript of autophagy-related protein 12 (ATG12) and microtubule-associated protein 1 light chain 3 alpha LC3. A reduction of mitochondrial reactive oxygen species induced a decrease in autophagy whereas inhibition of autophagy in infected cells increased apoptosis, showing the protective role of autophagy.ConclusionResults from the present study suggest that autophagy is an important and shared mechanism in other conditions related to inflammation or alterations of the immune system, such as periodontitis.

AMPK as a new attractive therapeutic target for disease prevention: The role of dietary compounds

AMPK is a serine/threonine protein kinase that has the function of maintaining the balance between ATP production and consumption in most eukaryotic cells. It plays a relevant role in regulating cellular metabolism, preserving cellular energy homeostasis, and is involved in many other cellular processes as well as metabolic ones, including cell cycle regulation and endothelial and vascular relaxation. Recently, the effects of naturally occurring compounds able to prevent and treat diseases through AMPK activation have attracted the attention of many researchers. Among such compounds, flavonoids found in natural sources, like quercetin, genistein, epigallocatechins, resveratrol, have been proposed as AMPK activators. This review summarizes and updates the most recent findings concerning the mechanisms through which different dietary compounds, from plant foods, affect the AMPK pathway in healthy and pathological in vitro and in vivo models, paying particular attention to molecular mechanisms involved in diabetes, obesity, metabolic syndrome, cardiovascular disease and cancer.

Is inflammation a mitochondrial dysfunction-dependent event in fibromyalgia?

Fibromyalgia (FM) is a complex disorder that affects up to 5% of the general population worldwide. Both mitochondrial dysfunction and inflammation have been implicated in the pathophysiology of FM. We have investigated the possible relationship between mitochondrial dysfunction, oxidative stress, and inflammation in FM. We studied 30 women diagnosed with FM and 20 healthy women. Blood mononuclear cells (BMCs) from FM patients showed reduced level of coenzyme Q₁₀ (CoQ₁₀) and mtDNA contents and high level of mitochondrial reactive oxygen species (ROS) and serum tumor necrosis factor (TNF)-alpha and transcript levels. A significant negative correlation between CoQ₁₀ and TNF-alpha levels (r=-0.588; p<0.01), and a positive correlation between ROS and TNF-alpha levels (r=0.791; p<0.001) were observed accompanied by a significant correlation of visual analogical scale with serum TNF-alpha and transcript levels (r=0.4507; p<0.05 and r=0.7089; p<0.001, respectively). TNF-alpha release was observed in an in vitro (BMCs) and in vivo (mice) CoQ₁₀ deficiency model. Oral CoQ₁₀ supplementation restored biochemical parameters and induced a significant improvement in clinical symptoms (p<0.001). These results lead to the hypothesis that inflammation could be a mitochondrial dysfunction-dependent event implicated in the pathophysiology of FM in several patients indicating at mitochondria as a possible new therapeutic target.

Stress-induced depressive behaviors require a functional NLRP3 inflammasome

Depression is a major public health concern in modern society, yet little is known about the molecular link between this condition and neuroinflammation. The inflammasome complex was recently shown to be implicated in depression. The present study shows the implication of NLRP3 inflammasome in animal model of stress-induced depression. Accordingly, we show here that in the absence of a NLRP3 inflammasome, prolonged stress does not provoke depressive behaviors or microglial activation in mice or dampen hippocampal neurogenesis. Indeed, NLRP3 deletion or inhibition of microglial activation impairs the stress-induced alterations associated with depression. According to these findings in animal model, the inflammasome could be a target for new therapeutic interventions to prevent depression in patients.

Accidental displacement and migration of endosseous implants into adjacent craniofacial structures: A review and update

Objectives: Accidental displacement of endosseous implants into the maxillary sinus is an unusual but potential complication in implantology procedures due to the special features of the posterior aspect of the maxillary bone; there is also a possibility of migration throughout the upper paranasal sinuses and adjacent structures. The aim of this paper is to review the published literature about accidental displacement and migration of dental implants into the maxillary sinus and other adjacent structures. Study Design: A review has been done based on a search in the main on-line medical databases looking for papers about migration of dental implants published in major oral surgery, periodontal, dental implant and ear-nose-throat journals, using the keywords “implant,” “migration,” “complication,” “foreign body” and “sinus.” Results: 24 articles showing displacement or migration to maxillary, ethmoid and sphenoid sinuses, orbit and cranial fossae, with different degrees of associated symptoms, were identified. Techniques found to solve these clinical issues include Cadwell-Luc approach, transoral endoscopy approach via canine fossae and transnasal functional endoscopy surgery. Conclusion: Before removing the foreign body, a correct diagnosis should be done in order to evaluate the functional status of the ostiomeatal complex and the degree of affectation of paranasal sinuses and other involved structures, determining the size and the exact location of the foreign body. After a complete diagnosis, an indicated procedure for every case would be decided. Key words:Implant, oral surgery, foreign body, paranasal sinuses, displacement, migration.