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Article ; Online: A review of the influence of periodontal treatment in systemic diseases.

Falcao, Artur / Bullón, Pedro

Periodontology 2000

2019 Volume 79, Issue 1, Page(s) 117–128

Abstract: The effects and consequences of periodontal diseases might not be confined to the oral cavity. A great body of evidence has arisen supporting the claim demonstrating an association with several systemic conditions and diseases. With different levels of ... ...

Abstract	The effects and consequences of periodontal diseases might not be confined to the oral cavity. A great body of evidence has arisen supporting the claim demonstrating an association with several systemic conditions and diseases. With different levels of evidence, an association between periodontal disease and cardiovascular disease, diabetes, psoriasis, rheumatoid arthritis, pregnancy outcomes and respiratory diseases has been established. However, the true nature of this association, if it is causal, still remains elusive. For a better understanding of the complex relationships linking different conditions, interventional studies now begin to focus on the possible outcomes of periodontal treatment in relation to the events, symptoms and biomarkers of several systemic disorders, assessing if periodontal treatment has any impact on them, hopefully reducing their severity or prevalence. Therefore, we proceeded to review the recent literature on the subject, attempting to present a brief explanation of the systemic condition or disease, what proposed mechanisms might give biological plausibility to its association with periodontal disease, and finally and more importantly, what data are currently available pertaining to the effects periodontal treatment may have. Raising awareness and discussing the possible benefits of periodontal treatment on overall systemic health is important, in order to change the perception that periodontal diseases are only limited to the oral cavity, and ultimately providing better and comprehensive care to patients.
MeSH term(s)	Arthritis, Rheumatoid ; Cardiovascular Diseases ; Diabetes Mellitus ; Female ; Humans ; Periodontal Diseases ; Pregnancy ; Pregnancy Outcome
Language	English
Publishing date	2019-04-10
Publishing country	Denmark
Document type	Journal Article ; Review
ZDB-ID	1200504-6
ISSN	1600-0757 ; 0906-6713
ISSN (online)	1600-0757
ISSN	0906-6713
DOI	10.1111/prd.12249
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Article ; Online: Influence of the Periodontal Disease, the Most Prevalent Inflammatory Event, in Peroxisome Proliferator-Activated Receptors Linking Nutrition and Energy Metabolism.

Román-Malo, Lourdes / Bullon, Pedro

International journal of molecular sciences

2017 Volume 18, Issue 7

Abstract: Periodontal disease is considered one of the main pathologic diseases occurring in humans. Its pathologic process involves inflammatory reactions producing periodontal bone resorption and the tooth loss. But some patients do not present an evident ... ...

Abstract	Periodontal disease is considered one of the main pathologic diseases occurring in humans. Its pathologic process involves inflammatory reactions producing periodontal bone resorption and the tooth loss. But some patients do not present an evident clinical inflammation with bone resorption, and in others, the inflammation is prominent without bone resorption. A key question could be to investigate a different way of responding to aggression. Inflammation requires a complex intracellular metabolic process, starting with the harmful recognition and activation of the inflammasome, continues the energy supply with the alteration of oxidative stress conditions, and finishes with the elimination of the aggression with autophagy/apoptosis mechanisms, then concludes with recovery. Peroxisome proliferator-activated receptors (PPARs) are essential molecules produced in inflammation, and its genes and its activation have been related to periodontal disease. Also, an important aspect is the influence of PPARs in bone metabolism; the main periodontitis symptom is bone loss and PPARγ activation that can downregulate the bone resorption in experimental periodontitis, PPARγ-coated titanium dental implant surfaces could carry the antiinflammatory gene and restrain inflammation. PPARs could be one of the meeting background points with atherosclerosis/cardiovascular disease, diabetes and metabolic syndrome showing a modified proinflammatory statement such as it is described in periodontitis.
Language	English
Publishing date	2017-07-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms18071438
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Article ; Online: Inflammasome as a Key Pathogenic Mechanism in Endometriosis.

Bullon, Pedro / Navarro, Jose Manuel

Current drug targets

2017 Volume 18, Issue 9, Page(s) 997–1002

Abstract: Background: Endometriosis remains a challenging condition for clinicians to treat. To improve our results, we have to develop new treatment strategies based on pathophysiological mechanisms targeting the etiologic and pathogenic processes involved.: ... ...

Abstract	Background: Endometriosis remains a challenging condition for clinicians to treat. To improve our results, we have to develop new treatment strategies based on pathophysiological mechanisms targeting the etiologic and pathogenic processes involved. Objectives: Revise new inflammatory pathogenic mechanisms involved in endometriosis, namely inflammasome. Method: Literature review for the updating of data to give new clues for different options of treatments. Results: Inflammasome has been described as a multiprotein complex and is considered a key regulator of the innate and adaptive host response that surveys the cytosol and other compartments into the cell. It is involved in the immediate detection and responds to the presence of danger- and pathogen-associated molecular patterns named DAMPs and PAMPs respectively, and has been described in several cells, mainly on immune cells of the myeloid lineage and epithelial cells in tissues with mucosal surfaces. Four inflammasome are formed in a stimulus-dependent manner of distinct composition. They are the Noll Like Receptors (NLR) proteins Nlrp1b, Nlrp3, Nlrc4, and Nlrp6, as well as the absent in melanoma 2 (AIM2). They activate the production of IL-1β and IL-18 that induce a host response such as pyroptosis, a proinflammatory cell death and the secretion of leaderless cytokines and growth factors. Inflammasome is linked to atherosclerosis, periodic fever syndromes, vitiligo, Crohn's disease, gout, asbestosis, silicosis, Alzheimer's disease and periodontitis. Endometriosis has been related with IL-1β and Another NLR, Nlrp7, was correlated with myometrial invasion in human endometrial cancer tissue. Conclusions: These new clues regarding the pathogenic mechanisms involving the inflammasome may be crucial in the future development for endometriosis therapy.
Language	English
Publishing date	2017
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2064859-5
ISSN	1873-5592 ; 1389-4501
ISSN (online)	1873-5592
ISSN	1389-4501
DOI	10.2174/1389450117666160709013850
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Article ; Online: Prevalence of undiagnosed diabetes and prediabetes related to periodontitis and its risk factors in elderly individuals.

Portes, Juliana / Bullón, Beatriz / Gallardo, Isabel / Fernandez-Riejos, Patricia / Quiles, Jose Luis / Giampieri, Francesca / Bullón, Pedro

Journal of dentistry

2023 Volume 132, Page(s) 104480

Abstract: Objective: The prevalence of undiagnosed diabetes was estimated to increase with age and can reach 3.5%. The purpose of the study was to evaluate the prevalence of undiagnosed diabetes and prediabetes in the elderly patients who attended a dental clinic ...

Abstract	Objective: The prevalence of undiagnosed diabetes was estimated to increase with age and can reach 3.5%. The purpose of the study was to evaluate the prevalence of undiagnosed diabetes and prediabetes in the elderly patients who attended a dental clinic and to find common risk factors. Methods: Male patients, older than 50 years, attended their first dental visit to the School of Dentistry for a period of two years, and it was proposed to evaluate undiagnosed type 2 diabetes mellitus. Periodontal, biochemical, microbiological examinations, nutritional profile, and physical activity were performed. Results: A total of 106 patients were examined, 6 (5.6%) had diabetes, and 37 (34.9%) had prediabetes without prior diagnosis. The severity of periodontitis was greater in patients with diabetes. Most of the patients were overweight and had increased systolic blood pressure. Patients with prediabetes and periodontitis had a low adherence to the Mediterranean diet. Tannerella forsythia was present in more patients with periodontitis, and the prevalence of Aggregatibacter actinomycetemcomitans is practically absent in groups with periodontitis, except for the group with diabetes. Conclusions: In the population studied, the prevalence of patients without a diagnosis of diabetes and prediabetes was very high and underestimated. The increased severity of periodontitis in patients with diabetes and in conjunction with the high level of cortisol seen in patients with periodontitis, especially those with diabetes, emphasize the dysregulation of the immunoinflammatory system. Clinical significance: It is essential to add all this data to our dental practice to cover patient health with a broader landscape.
MeSH term(s)	Humans ; Male ; Aged ; Prediabetic State/diagnosis ; Prediabetic State/epidemiology ; Prediabetic State/complications ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/etiology ; Prevalence ; Periodontitis/complications ; Risk Factors
Language	English
Publishing date	2023-03-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186068-9
ISSN	1879-176X ; 0300-5712
ISSN (online)	1879-176X
ISSN	0300-5712
DOI	10.1016/j.jdent.2023.104480
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Article: Potential Role of the Mitochondria for the Dermatological Treatment of Papillon-Lefèvre.

Castejón-Vega, Beatriz / Battino, Maurizio / Quiles, José L / Bullon, Beatriz / Cordero, Mario D / Bullón, Pedro

Antioxidants (Basel, Switzerland)

2021 Volume 10, Issue 1

Abstract: The Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder caused by mutations in the Cathepsin C (CTSC) gene, characterized by periodontitis and palmoplantar hyperkeratosis. The main inflammatory deficiencies include oxidative stress and ...

Abstract	The Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder caused by mutations in the Cathepsin C (CTSC) gene, characterized by periodontitis and palmoplantar hyperkeratosis. The main inflammatory deficiencies include oxidative stress and autophagic dysfunction. Mitochondria are the main source of reactive oxygen species; their impaired function is related to skin diseases and periodontitis. The mitochondrial function has been evaluated in PLS and mitochondria have been targeted as a possible treatment for PLS. We show for the first time an important mitochondrial dysfunction associated with increased oxidative damage of mtDNA, reduced CoQ10 and mitochondrial mass and aberrant morphologies of the mitochondria in PLS patients. Mitochondrial dysfunction, determined by oxygen consumption rate (OCR) in PLS fibroblasts, was treated with CoQ10 supplementation, which determined an improvement in OCR and a remission of skin damage in a patient receiving a topical administration of a cream enriched with CoQ10 0.1%. We provide the first evidence of the role of mitochondrial dysfunction and CoQ10 deficiency in the pathophysiology of PLS and a future therapeutic option for PLS.
Language	English
Publishing date	2021-01-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10010095
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Article ; Online: Diabetes Mellitus and Periodontitis Share Intracellular Disorders as the Main Meeting Point.

Portes, Juliana / Bullón, Beatriz / Quiles, José Luis / Battino, Maurizio / Bullón, Pedro

Cells

2021 Volume 10, Issue 9

Abstract: Diabetes and periodontitis are two of the most prevalent diseases worldwide that negatively impact the quality of life of the individual suffering from them. They are part of the chronic inflammatory disease group or, as recently mentioned, non- ... ...

Abstract	Diabetes and periodontitis are two of the most prevalent diseases worldwide that negatively impact the quality of life of the individual suffering from them. They are part of the chronic inflammatory disease group or, as recently mentioned, non-communicable diseases, with inflammation being the meeting point among them. Inflammation hitherto includes vascular and tissue changes, but new technologies provide data at the intracellular level that could explain how the cells respond to the aggression more clearly. This review aims to emphasize the molecular pathophysiological mechanisms in patients with type 2 diabetes mellitus and periodontitis, which are marked by different impaired central regulators including mitochondrial dysfunction, impaired immune system and autophagy pathways, oxidative stress, and the crosstalk between adenosine monophosphate-activated protein kinase (AMPK) and the renin-angiotensin system (RAS). All of them are the shared background behind both diseases that could explain its relationship. These should be taken in consideration if we would like to improve the treatment outcomes. Currently, the main treatment strategies in diabetes try to reduce glycemia index as the most important aspect, and in periodontitis try to reduce the presence of oral bacteria. We propose to add to the therapeutic guidelines the handling of all the intracellular disorders to try to obtain better treatment success.
MeSH term(s)	Animals ; Diabetes Mellitus/physiopathology ; Humans ; Inflammation/physiopathology ; Oxidative Stress ; Periodontitis/physiopathology
Language	English
Publishing date	2021-09-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10092411
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Article ; Online: Incidence of Peri-Implantitis and Relationship with Different Conditions: A Retrospective Study.

Astolfi, Víctor / Ríos-Carrasco, Blanca / Gil-Mur, Francisco Javier / Ríos-Santos, José Vicente / Bullón, Beatriz / Herrero-Climent, Mariano / Bullón, Pedro

International journal of environmental research and public health

2022 Volume 19, Issue 7

Abstract: Articles on the prevalence of peri-implant diseases showed that 90% of peri-implant tissues had some form of inflammatory response and a prevalence of peri-implantitis from 28% to 51% according to various publications. Objective: To provide an overview ... ...

Abstract	Articles on the prevalence of peri-implant diseases showed that 90% of peri-implant tissues had some form of inflammatory response and a prevalence of peri-implantitis from 28% to 51% according to various publications. Objective: To provide an overview of how risk factors can be related with peri-implantitis. Methods: A retrospective longitudinal study including 555 implants placed in 132 patients was evaluated based on the presence of peri-implantitis following the criteria of Renvert et al. 2018. Results: In total, 21 patients (15.9%) suffered peri-implantitis (PPG) and 111 patients (84.1%) did not suffer peri-implantitis (NPG). The results reveal that smokers have a high incidence of peri-implantitis (72.7%) compared to non-smokers (27.3%) (p < 0.0005). Another variable with significant results (p < 0.01) was periodontitis: 50% PPG and 23.9% NPG suffered advanced periodontitis. Systemic diseases such as arterial hypertension, diabetes mellitus, osteoporosis, and cardiovascular diseases do not show a statistically significant influence on the incidence of peri-implantitis. Patients who did not attend their maintenance therapy appointment had an incidence of peri-implantitis of 61.4%, compared to 27.3% in those who attend (p < 0.0001). From the results obtained, we can conclude that relevant factors affect peri-implantitis, such as tobacco habits, moderate and severe periodontitis, and attendance in maintenance therapy.
MeSH term(s)	Humans ; Incidence ; Longitudinal Studies ; Peri-Implantitis/epidemiology ; Peri-Implantitis/etiology ; Periodontitis/complications ; Periodontitis/epidemiology ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2022-03-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph19074147
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Article: Fibroblasts Collagen Production and Histological Alterations in Hereditary Gingival Fibromatosis.

Roman-Malo, Lourdes / Bullon, Beatriz / de Miguel, Manuel / Bullon, Pedro

Diseases (Basel, Switzerland)

2019 Volume 7, Issue 2

Abstract: Hereditary gingival fibromatosis is a disorder for which the etiology remains unknown. We aimed to evaluate the fibroblasts and histological alterations to give new clues. A father and a daughter of a family showing gingival hereditary fibromatosis were ... ...

Abstract	Hereditary gingival fibromatosis is a disorder for which the etiology remains unknown. We aimed to evaluate the fibroblasts and histological alterations to give new clues. A father and a daughter of a family showing gingival hereditary fibromatosis were treated, and gingival biopsies were obtained. A histological study revealed dense fibrous tissue, basal lamina disruption, and epithelial cell migration into the connective tissue. Fibroblasts were cultured from the father and daughter and compared with those from a healthy control patient. The results of the biochemical analysis showed increased collagen synthesis, reduced antioxidant CoQ
Language	English
Publishing date	2019-05-25
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2720869-2
ISSN	2079-9721
ISSN	2079-9721
DOI	10.3390/diseases7020039
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Article: Potential Role of the Mitochondria for the Dermatological Treatment of Papillon-Lefèvre

Castejón-Vega, Beatriz / Battino, Maurizio / Quiles, José L / Bullon, Beatriz / Cordero, Mario D / Bullón, Pedro

Antioxidants. 2021 Jan. 12, v. 10, no. 1

2021

Abstract: The Papillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder caused by mutations in the Cathepsin C (CTSC) gene, characterized by periodontitis and palmoplantar hyperkeratosis. The main inflammatory deficiencies include oxidative stress and ...

Abstract	The Papillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder caused by mutations in the Cathepsin C (CTSC) gene, characterized by periodontitis and palmoplantar hyperkeratosis. The main inflammatory deficiencies include oxidative stress and autophagic dysfunction. Mitochondria are the main source of reactive oxygen species; their impaired function is related to skin diseases and periodontitis. The mitochondrial function has been evaluated in PLS and mitochondria have been targeted as a possible treatment for PLS. We show for the first time an important mitochondrial dysfunction associated with increased oxidative damage of mtDNA, reduced CoQ10 and mitochondrial mass and aberrant morphologies of the mitochondria in PLS patients. Mitochondrial dysfunction, determined by oxygen consumption rate (OCR) in PLS fibroblasts, was treated with CoQ10 supplementation, which determined an improvement in OCR and a remission of skin damage in a patient receiving a topical administration of a cream enriched with CoQ10 0.1%. We provide the first evidence of the role of mitochondrial dysfunction and CoQ10 deficiency in the pathophysiology of PLS and a future therapeutic option for PLS.
Keywords	antioxidants ; cream ; dipeptidyl-peptidase I ; fibroblasts ; genes ; hyperkeratosis ; mass ; mitochondria ; mutation ; oxidative stress ; oxygen consumption ; pathophysiology ; patients ; periodontitis ; remission ; topical application
Language	English
Dates of publication	2021-0112
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10010095
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Is AMP-Activated Protein Kinase Associated to the Metabolic Changes in Primary Ovarian Insufficiency?

Navarro-Pando, José M / Bullón, Pedro / Cordero, Mario D / Alcocer-Gómez, Elísabet

Antioxidants & redox signaling

2020 Volume 33, Issue 15, Page(s) 1115–1121

Abstract: Primary ovarian insufficiency (POI) is a critical fertility defect characterized by anticipated impairment of the follicular reserve, which pathophysiological mechanisms have not yet been identified. We have investigated the possible relationship between ...

Abstract	Primary ovarian insufficiency (POI) is a critical fertility defect characterized by anticipated impairment of the follicular reserve, which pathophysiological mechanisms have not yet been identified. We have investigated the possible relationship between AMP-activated protein kinase (AMPK) and the pathophysiology of POI. We studied 35 POI patients with altered levels of follicle-stimulating hormone (FSH) and estradiol and increased percentage of overweight compared with 20 healthy women. Blood mononuclear cells from POI patients showed reduced levels of phosphorylated AMPK, adenosine triphosphate, and high serum levels of leptin and tumor necrosis factor-alpha. All these alterations were also observed in granulosa cells, a more closer environment of the ovary. Significant negative correlations between AMPK and body mass index, FSH and leptin levels, and a positive correlation between AMPK and estradiol levels were observed. Oral metformin supplementation restored biochemical parameters. Interestingly, AMPK levels from patients were negatively correlated with age, suggesting an accelerated aging in POI mediated by the impairment of AMPK. These results lead to the hypothesis that an impairment of AMPK could be implicated in the metabolic pathophysiology of POI indicating at AMPK induction as a possible new therapeutic target.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Biomarkers ; Case-Control Studies ; Disease Management ; Disease Susceptibility ; Energy Metabolism/drug effects ; Female ; Follicle Stimulating Hormone/blood ; Follicle Stimulating Hormone/metabolism ; Humans ; MAP Kinase Signaling System/drug effects ; Metformin/pharmacology ; Metformin/therapeutic use ; Ovarian Follicle/metabolism ; Primary Ovarian Insufficiency/diagnosis ; Primary Ovarian Insufficiency/drug therapy ; Primary Ovarian Insufficiency/etiology ; Primary Ovarian Insufficiency/metabolism
Chemical Substances	Biomarkers ; Follicle Stimulating Hormone (9002-68-0) ; Metformin (9100L32L2N) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2020-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2020.8144
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