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Balaji A, Jennifer W, Mohanasatheesh S, Hema D, Dheeraj S, Menon N. The Unilateral Enigma: An Oral-contraceptive Related Gingival Enlargement. JOURNAL OF PHARMACY AND BIOALLIED SCIENCES 2024; 16:S1490-S1493. [PMID: 38882847 PMCID: PMC11174280 DOI: 10.4103/jpbs.jpbs_1107_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 10/31/2023] [Accepted: 11/02/2023] [Indexed: 06/18/2024] Open
Abstract
This article's goal is to describe a case of oral contraceptives-related drug-induced gingival hypertrophy that was treated with nonsurgical and surgical periodontal therapy. The most prevalent negative side effect of systemic medicine on the periodontal tissues continues to be drug-induced gingival overgrowth. Specific regulatory molecules known as hormones control a variety of bodily processes. Gingival hypertrophies are sometimes linked to oral contraceptives that contain oestrogen and/or progesterone. A 32-year-old female presented with a complaint of swelling of the gingiva with spontaneous bleeding in the maxillary right quadrant region for a period of two months. The medical history documented the use of contraceptives for three months, and a clinical examination revealed the existence of poor oral hygiene and enlarged painful gingival tissues that bled when touched. Intraoral examination revealed that there was unilateral, generalized, diffuse gingival enlargement with pseudo pockets. Patient was diagnosed with gingival fibromatosis a based on the clinical, histological, and radiographic findings. The gingival enlargement was treated by conventional gingivectomy under local anaesthesia. The postoperative result was uneventful. Women who use oral contraceptives are a "risk group" for periodontal infections. On oral contraceptives, not every female reacts the same way. In periodontal therapy, plaque management is the most crucial step. Patient compliance is another element that affects a therapy's response. The patient demonstrated appropriate oral hygiene practices and adhered to home care guidelines adequately.
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Affiliation(s)
- Anitha Balaji
- Department of Periodontology and Implantology, Sree Balaji Dental College and Hospital, Chennai, Tamil Nadu, India
| | - W Jennifer
- Department of Periodontology and Implantology, Sree Balaji Dental College and Hospital, Chennai, Tamil Nadu, India
| | - S Mohanasatheesh
- Department of Periodontology and Implantology, Sree Balaji Dental College and Hospital, Chennai, Tamil Nadu, India
| | - D Hema
- Department of Periodontology and Implantology, Sree Balaji Dental College and Hospital, Chennai, Tamil Nadu, India
| | - S Dheeraj
- Department of Periodontology and Implantology, Sree Balaji Dental College and Hospital, Chennai, Tamil Nadu, India
| | - Nivedha Menon
- Department of Periodontology and Implantology, Sree Balaji Dental College and Hospital, Chennai, Tamil Nadu, India
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Frankenhaeuser F, Söder B, Källmén H, Korpi ER, Meurman JH. Periodontitis may predict the use of prescription medicines later in life, a database study. Front Pharmacol 2023; 14:1146475. [PMID: 36992840 PMCID: PMC10040546 DOI: 10.3389/fphar.2023.1146475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/02/2023] [Indexed: 03/15/2023] Open
Abstract
Medications used for the treatment of diseases also affect oral health. We investigated how having/not having periodontitis at baseline in 1985 was associated with purchases of medicines in the long term. The study paradigm is in the oral health-systemic health connections. We hypothesized that periodontitis links to purchases of medicines later in life. The study cohort consisted of 3,276 individuals from the greater Stockholm area, Sweden. Of them, 1,655 were clinically examined at baseline. Patients were followed-up for >35 years, using the national population and patient registers. The burden of systemic diseases and purchases of medicines were statistically analyzed comparing patients with (n = 285) and without (n = 1,370) periodontitis. The results showed that patients with periodontitis had purchased more of certain medications than non-periodontitis patients. Periodontitis patients purchased significantly more drugs used in diabetes (p = 0.035), calcium channel blockers (p = 0.016), drugs acting on the renin-angiotensin system (p = 0.024), and nervous system drugs (p = 0.001). Hence, patients with periodontitis indeed had purchased specific medications statistically significantly more than the periodontally healthy ones. This indicates that periodontitis, over time, might increase the risk for systemic diseases with the subsequent need for medication.
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Affiliation(s)
- Freja Frankenhaeuser
- Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- *Correspondence: Freja Frankenhaeuser,
| | - Birgitta Söder
- Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
| | | | - Esa R. Korpi
- Department of Pharmacology, University of Helsinki, Helsinki, Finland
| | - Jukka H. Meurman
- Department of Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Kamei H, Furui M, Matsubara T, Inagaki K. Gingival enlargement improvement following medication change from amlodipine to benidipine and periodontal therapy. BMJ Case Rep 2022; 15:e249879. [PMID: 35589267 PMCID: PMC9121430 DOI: 10.1136/bcr-2022-249879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/04/2022] [Indexed: 12/03/2022] Open
Abstract
The use of calcium channel blockers (CCBs) is associated with gingival enlargement, which adversely affects oral function, hygiene and aesthetics. Although CCB-induced gingival enlargement is a known adverse effect, it is rarely or never caused by some CCBs. In this paper, we report the case of a late 80's female patient with hypertension who experienced amlodipine-induced gingival enlargement. The patient's antihypertensive medication was changed from amlodipine to another CCB of the same class, benidipine, which has not been reported to cause gingival enlargement. The patient also received periodontal therapy. A significant improvement in gingival enlargement was noted, and blood pressure control was maintained. This case indicates that it might be beneficial for patients with hypertension presenting CCB-induced gingival enlargement to switch from the CCB that caused gingival enlargement to another CCB with little to no risk.
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Affiliation(s)
- Hidehiko Kamei
- Kamei Dental Clinic and Orthodontics, Private Practice, Utsunomiya, Japan
| | - Maria Furui
- Kamei Dental Clinic and Orthodontics, Private Practice, Utsunomiya, Japan
| | - Tatsuaki Matsubara
- Faculty of Human Sciences, Aichi Mizuho College, Nagoya, Japan
- Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan
| | - Koji Inagaki
- Department of Dental Hygiene, Aichi Gakuin University Junior College, Nagoya, Japan
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Bajkovec L, Mrzljak A, Likic R, Alajbeg I. Drug-induced gingival overgrowth in cardiovascular patients. World J Cardiol 2021; 13:68-75. [PMID: 33968305 PMCID: PMC8069521 DOI: 10.4330/wjc.v13.i4.68] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 03/01/2021] [Accepted: 03/29/2021] [Indexed: 02/06/2023] Open
Abstract
Drug-induced gingival overgrowth (DIGO) is a pathological growth of gingival tissue, primarily associated with calcium channel blockers and immunosuppressants. Consequently, it is mainly seen in cardiovascular and transplanted patients. Nifedipine remains the main calcium channel blocker related to the development of this unpleasant side-effect. As for immunosuppressants, cyclosporin is the leading causative agent, whereas other drugs from this drug-group, including tacrolimus, have better safety profiles. Accumulated collagen with inflammatory infiltrates is the histological hallmark of this condition. Several factors are involved in the pathogenesis and can increase the risk, such as male gender, younger age, pre-existing periodontal inflammation, and concomitant use of other DIGO-inducing medications. Patients with DIGO may experience severe discomfort, trouble with speech and mastication, pain, and teeth loss, aside from cosmetic implications. Furthermore, these patients also have an increased risk for cardiovascular diseases. The interdisciplinary approach and cooperation with dental care experts are necessary for patient management. Treatment includes discontinuing the drug and switching to one with a better profile, improving oral hygiene, and surgical removal of enlarged tissue. Recognizing the potential of commonly used medications to cause DIGO and its effect on patients' health is necessary for early detection and adequate management of this complication.
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Affiliation(s)
- Lucija Bajkovec
- Institute of Emergency Medicine of Medimurje County, Institute of Emergency Medicine of Međimurje County, Cakovec 40000, Croatia
| | - Anna Mrzljak
- Department of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia.
| | - Robert Likic
- Unit for Clinical Pharmacology and TherapeuticsDepartment of Internal Medicine, University Hospital Centre Zagreb, Zagreb 10000, Croatia
| | - Ivan Alajbeg
- Department of Oral Medicine, University of Zagreb School of Dental Medicine and University Hospital Centre Zagreb, Zagreb 10000, Croatia
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Rapone B, Ferrara E, Santacroce L, Cesarano F, Arazzi M, Liberato LD, Scacco S, Grassi R, Grassi FR, Gnoni A, Nardi GM. Periodontal Microbiological Status Influences the Occurrence of Cyclosporine-A and Tacrolimus-Induced Gingival Overgrowth. Antibiotics (Basel) 2019; 8:antibiotics8030124. [PMID: 31438651 PMCID: PMC6784123 DOI: 10.3390/antibiotics8030124] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/13/2019] [Accepted: 08/17/2019] [Indexed: 12/14/2022] Open
Abstract
Immune suppressed renal transplant patients are more prone to developing oral tissue alterations due to medications associated with a pleiotropic set of side effects involving the oral cavity. Drug-induced gingival overgrowth (DIGO) is the most commonly encountered side effect resulting from administration of calcineurin inhibitors such as cyclosporine-A (CsA), the standard first-line treatment for graft rejection prevention in transplant patients. Pathogenesis of gingival overgrowth (GO) is determined by the interrelation between medications and a pre-existing inflammatory periodontal condition, the main modifiable risk factor. Severity of gingival hyperplasia clinical manifestation is also related to calcium channel blocker association, frequently provided in addition to pharmacological therapy of transplant recipients. Specifically, nifedipine-induced enlargements have a higher prevalence rate compared to amlodipine-induced enlargements; 47.8% and 3.3% respectively. Available epidemiological data show a gender difference in prevalence, whereby males are generally more frequently affected than females. The impact of GO on the well-being of an individual is significant, often leading to complications related to masticatory function and phonation, a side effect that may necessitate switching to the tacrolimus drug that, under a similar regimen, is associated with a low incidence of gingival lesion. Early detection and management of GO is imperative to allow patients to continue life-prolonging therapy with minimal morbidity. The purpose of this study was threefold: firstly, to determine the prevalence and incidence of GO under the administration of CsA and Tacrolimus; secondly, to assess the correlation between periodontal status before and after periodontal therapy and medications on progression or recurrence of DIGO; and finally, to analyse the effect of immunosuppressant in association to the channel blocker agents on the onset and progression of gingival enlargement. We compared seventy-two renal transplant patients, including 33 patients who were receiving CsA, of which 25% were also receiving nifedipine and 9.72% also receiving amlodipine, and 39 patients who were receiving tacrolimus, of which 37.5% were also receiving nifedipine and 5.55% also receiving amlodipine, aged between 35 and 60 years. Medical and pharmacological data were recorded for all patients. Clinical periodontal examination, in order to establish the inflammatory status and degree of gingival enlargement, was performed at baseline (T0), 3 months (T1), 6 months (T2), and 9 months (T3). All patients were subjected to periodontal treatment. Statistically significant correlation between the reduction of the mean value of periodontal indices and degree of gingival hyperplasia at the three times was revealed. The prevalence of GO in patients taking cyclosporine was higher (33.3%) in comparison with those taking tacrolimus (14.7%). In accordance with previous studies, this trial highlighted the clinical significance of the pathological substrate on stimulating drug-induced gingival lesion, confirming the key role of periodontal inflammation in pathogenesis of gingival enlargement, but did not confirm the additional effect of calcium-channel blocker drugs in inducing gingival enlargement.
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Affiliation(s)
- Biagio Rapone
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, "Aldo Moro" University of Bari, 70122 Bari, Italy.
| | - Elisabetta Ferrara
- Complex Operative Unit of Nephrology and Dialysis, Hospital S.S. Annunziata, 66100 Chieti, Italy
| | - Luigi Santacroce
- Ionian Department (DJSGEM), "Aldo Moro" University of Bari, 70122 Bari, Italy.
| | - Francesca Cesarano
- Department of Dental and Maxillofacial Sciences, "Sapienza" University of Rome, 00100 Rome, Italy
| | - Marta Arazzi
- Complex Operative Unit of Nephrology and Dialysis, Hospital S.S. Annunziata, 66100 Chieti, Italy
| | - Lorenzo Di Liberato
- Complex Operative Unit of Nephrology and Dialysis, Hospital S.S. Annunziata, 66100 Chieti, Italy
| | - Salvatore Scacco
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, "Aldo Moro" University of Bari, 70122 Bari, Italy
| | - Roberta Grassi
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
| | - Felice Roberto Grassi
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, "Aldo Moro" University of Bari, 70122 Bari, Italy
| | - Antonio Gnoni
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, "Aldo Moro" University of Bari, 70122 Bari, Italy
| | - Gianna Maria Nardi
- Department of Dental and Maxillofacial Sciences, "Sapienza" University of Rome, 00100 Rome, Italy
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Han X, Yang H, Cao Y, Ge L, Han N, Zhang C, Fan Z, Yao R. The miR-3940-5p inhibits cell proliferation of gingival mesenchymal stem cells. Oral Dis 2019; 25:1363-1373. [PMID: 30908814 DOI: 10.1111/odi.13092] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 03/15/2019] [Accepted: 03/20/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Drug-induced gingival overgrowth (DIGO) is a well-recognized side effect of nifedipine (NIF). However, the molecular mechanisms of DIGO are still unknown. Here, we explored the possible role of miR-3940-5p in DIGO using NIF-treated gingival mesenchymal stem cells (GMSCs). MATERIAL AND METHODS CFSE and cell cycle assays were used to examine cell proliferation. The alkaline phosphatase (ALP) activity assay, Alizarin Red staining, quantitative calcium analysis, and osteogenesis-related gene expression were used to examine osteo/dentinogenic differentiation. RESULTS The CFSE assay showed that NIF enhanced cell proliferation, and the over-expression of miR-3940-5p inhibited the proliferation of GMSCs with or without NIF stimulation. Cell cycle assays revealed that the cell cycle was arrested at the G0/G1 phase. Furthermore, it was found that the over-expression of miR-3940-5p upregulated p15INK4b , p18INK4c , p19INK4d , and Cyclin A and downregulated Cyclin E in GMSCs with or without NIF treatment. In addition, the over-expression of miR-3940-5p enhanced ALP activity and mineralization in vitro and increased the expression of the osteo/dentinogenic differentiation markers DSPP and DMP1 and the key transcription factor DLX5 in GMSCs. CONCLUSIONS miR-3940-5p inhibited cell proliferation, enhanced the osteo/dentinogenic differentiation of GMSCs, and might play a role in DIGO as a potent agent in the treatment of nifedipine-induced gingival overgrowth.
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Affiliation(s)
- Xiao Han
- Department of Pediatric Dentistry, Tianjin Stomatology Hospital, Tianjin Medical University, Tianjin, China
| | - Haoqing Yang
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Beijing Stomatology Hospital, Capital Medical University, Beijing, China
| | - Yangyang Cao
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Beijing Stomatology Hospital, Capital Medical University, Beijing, China
| | - Lihua Ge
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Beijing Stomatology Hospital, Capital Medical University, Beijing, China
| | - Nannan Han
- Department of Periodontology, School of Stomatology, Beijing Stomatology Hospital, Capital Medical University, Beijing, China
| | - Chen Zhang
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Beijing Stomatology Hospital, Capital Medical University, Beijing, China
| | - Zhipeng Fan
- Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Beijing Stomatology Hospital, Capital Medical University, Beijing, China
| | - Rui Yao
- Department of Pediatric Dentistry, Tianjin Stomatology Hospital, Tianjin Medical University, Tianjin, China
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Desmet L, van der Meer J. Antihypertensive treatment with telmisartan in a cat with amlodipine-induced gingival hyperplasia. JFMS Open Rep 2017; 3:2055116917745236. [PMID: 29270307 PMCID: PMC5731625 DOI: 10.1177/2055116917745236] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Case summary Systemic arterial hypertension is commonly reported in middle-aged-to-older cats. Amlodipine is recommended as the initial antihypertensive drug in cats. In this case report, gingival hyperplasia secondary to the use of amlodipine in a cat is described. Benazepril as a monotherapy was unsuccessful in reducing blood pressure in this cat. After replacement of benazepril by telmisartan, gingival hyperplasia disappeared and blood pressure was well controlled. Relevance and novel information This case report describes the first reported case of reversible gingival hyperplasia as a result of the treatment with amlodipine. It also contains the first published data on the effect of telmisartan in a hypertensive cat.
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Ikeda K. Drug-Induced Oral Complications. Atlas Oral Maxillofac Surg Clin North Am 2017; 25:127-132. [PMID: 28778302 DOI: 10.1016/j.cxom.2017.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Kentaro Ikeda
- Department of Diagnostics and Biological Sciences, University of Colorado School of Dental Medicine, 13065 East 17th Avenue, Mail Stop F844, Aurora, CO 80045, USA; Department of Family Medicine, University of Colorado School of Medicine, 12631 East 17th Avenue, Aurora, CO 80045, USA.
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Umeizudike KA, Olawuyi AB, Umeizudike TI, Olusegun-Joseph AD, Bello BT. Effect of Calcium Channel Blockers on Gingival Tissues in Hypertensive Patients in Lagos, Nigeria: A Pilot Study. Contemp Clin Dent 2017; 8:565-570. [PMID: 29326507 PMCID: PMC5754977 DOI: 10.4103/ccd.ccd_536_17] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Background: Long-term treatment of common chronic cardiac conditions such as hypertension with calcium channel blockers (CCBs) has long been associated with gingival hyperplasia. This oral side effect may affect esthetics and function, yet often overlooked and therefore underreported among Nigerians. Aim: This study aimed to determine the association of CCBs with gingival overgrowth (GO) in hypertensive patients. Methods: This was a hospital-based, case–control study conducted among 116 hypertensive patients (58 CCB and 58 non-CCB age-matched controls) attending the medical outpatient clinic of a tertiary health institution in Lagos, Nigeria. Data collection tools included interviewer-administered questionnaires and periodontal examination. Sociodemographic details, medical history, and periodontal indices (gingival index, plaque index, class of GO according to drug-induced GO [DIGO] Clinical Index) were recorded. Results: The mean age was 59.4 ± 12.6 years, females representing 50.9%. In the CCB group, 39 (67.2%) participants were on amlodipine and 19 (32.8%) were on nifedipine. The mean duration of CCB use was 55.6 ± 53 months. DIGO was higher in CCB (36.2%) than that in non-CCB participants (17.2%) (χ2 = 4.4, P = 0.036). The risk of GO was higher in CCB users (odds ratio [OR] 2.7, [95% confidence interval (CI)]: 1.1–6.5). Amlodipine users had higher DIGO (37.5%) than that of nifedipine users (21.1%) (OR 2.3, [95% CI]: 1.0–5.3). The predominant class of DIGO among the CCB users was Class 2 DIGO Clinical Index (90.5%). Conclusion: The study reveals that the risk of GO is nearly three times in CCB than that of non-CCB users and twice higher in amlodipine than nifedipine users in Nigeria.
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Affiliation(s)
- Kehinde Adesola Umeizudike
- Department of Preventive Dentistry, Faculty of Dental Sciences, College of Medicine University of Lagos, Lagos, Nigeria
| | - Adetokunbo B Olawuyi
- Department of Oral and Maxillofacial Pathology/Biology, Lagos University Teaching Hospital, Lagos, Nigeria
| | | | | | - Babawale T Bello
- Department of Medicine, Faculty of Clinical Sciences, College of Medicine University of Lagos, Idi-Araba, Lagos, Nigeria
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Kim SS, Michelsons S, Creber K, Rieder MJ, Hamilton DW. Nifedipine and phenytoin induce matrix synthesis, but not proliferation, in intact human gingival connective tissue ex vivo. J Cell Commun Signal 2015; 9:361-75. [PMID: 26296421 DOI: 10.1007/s12079-015-0303-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2015] [Accepted: 08/05/2015] [Indexed: 12/20/2022] Open
Abstract
Drug-induced gingival enlargement (DIGE) is a fibrotic condition that can be caused by the antihypertensive drug nifedipine and the anti-seizure drug phenytoin, but the molecular etiology of this type of fibrosis is not well understood and the role of confounding factors such as inflammation remains to be fully investigated. The aim of this study was to develop an ex vivo gingival explant system to allow investigation of the effects of nifedipine and phenytoin alone on human gingival tissue. Comparisons were made to the histology of human DIGE tissue retrieved from individuals with DIGE. Increased collagen, fibronectin, and proliferating fibroblasts were evident, but myofibroblasts were not detected in DIGE samples caused by nifedipine and phenytoin. In healthy gingiva cultured in nifedipine or phenytoin-containing media, the number of cells positive for p-SMAD2/3 increased, concomitant with increased CCN2 and periostin immunoreactivity compared to untreated explants. Collagen content assessed through hydroxyproline assays was significantly higher in tissues cultured with either drug compared to control tissues, which was confirmed histologically. Matrix fibronectin levels were also qualitatively greater in tissues treated with either drug. No significant differences in proliferating cells were observed between any of the conditions. Our study demonstrates that nifedipine and phenytoin activate canonical transforming growth factor-beta signaling, CCN2 and periostin expression, as well as increase collagen density, but do not influence cell proliferation or induce myofibroblast differentiation. We conclude that in the absence of confounding variables, nifedipine and phenytoin alter matrix homeostasis in gingival tissue explants ex vivo, and drug administration is a significant factor influencing ECM accumulation in gingival enlargement.
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Affiliation(s)
- Shawna S Kim
- Department of Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
| | - Sarah Michelsons
- Department of Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
| | - Kendal Creber
- Graduate Program of Biomedical Engineering, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
| | - Michael J Rieder
- Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada
| | - Douglas W Hamilton
- Department of Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada. .,Graduate Program of Biomedical Engineering, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada. .,Division of Oral Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, Dental Sciences Building, London, ON, N6A 5C1, Canada.
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11
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Fardal Ø, Lygre H. Management of periodontal disease in patients using calcium channel blockers - gingival overgrowth, prescribed medications, treatment responses and added treatment costs. J Clin Periodontol 2015; 42:640-6. [PMID: 26076712 DOI: 10.1111/jcpe.12426] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/17/2015] [Indexed: 12/23/2022]
Abstract
OBJECTIVES Gingival overgrowth (GO) is an adverse drug reaction in patients using calcium channel blockers (CCBs). Little is known about the effects of CCBs on the management of periodontal diseases. The aim of this study was to assess how the use of CCBs affects the long-term supportive treatment and outcomes in patients undergoing periodontal therapy. METHODS All patients using CCBs during the initial treatment and/or the supportive periodontal therapy (SPT) were selected from a periodontal practice. Patients were scored using a Gingival Overgrowth Index (GOI). The effects of CCB types and dosages were assessed in terms of the frequency and the severity of GO, treatment responses, substitutions and extra treatment costs. Mean values, Standard Deviation (SD) and range were calculated. The Mann-Whitney test was used to assess statistically significant differences (p < 0.05) for GO between patients with good and poor oral hygiene, differences between before and after terminating or replacing the CCBs, possible differences between drug dosages (Dihydropyridine 5 mg and 10 mg) and differences between three drug combinations (CCB and inhibitors of the renin-angiotensin system (IRAS), CCB and non-IRAS, CCB and statins). RESULTS One hundred and twenty-four patients (58 females, 66 males, 4.6% of the patient population) were using CCBs. 103 patients were assessed. Average age was 66.53 years (SD. 9.89, range 42-88) and the observation time was 11.30 years (SD 8.06, range 1-27). Eighty-nine patients had GO, 75 of these required treatment for GO. Terminating or replacing with alternatives to CCBs resulted in significant decreases in GO (p = 0.00016, p = 0.00068) respectively. No differences were found between good and poor oral hygiene (p = 0.074), drug dosages or the various drug combinations. Surgical treatment was more effective than non-surgical treatment in controlling the GO. Long-term tooth loss was 0.11 teeth per patient per year. Forty-two patients needed re-treatments for GO, resulting in an extra life cost per patient of €13471 (discounted €4177). CONCLUSION The majority of patients (86.4%) using CCBs experienced GO. 47.2% of these experienced recurrence(s) of GO during the SPT and needed re-treatments with resulting added costs. The long-term tooth loss was considerably higher for patients using CCBs than for other patients groups from the same practice setting.
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Affiliation(s)
| | - Henning Lygre
- Department of Clinical Science, University of Bergen, Bergen, Norway
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12
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Hemmati AA, Mojiri Forushani H, Mohammad Asgari H. Wound Healing Potential of Topical Amlodipine in Full Thickness Wound of Rabbit. Jundishapur J Nat Pharm Prod 2014; 9:e15638. [PMID: 25237643 PMCID: PMC4165190 DOI: 10.17795/jjnpp-15638] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 02/08/2014] [Accepted: 03/02/2014] [Indexed: 01/17/2023] Open
Abstract
Background: Wound healing is a complicated and integrated process. Researches have indicated the wound healing effects of calcium channel blockers in animal models in recent years. Objectives: The aim of this study was to evaluate the wound-healing activity of amlodipine as a calcium channel blocker and combination of amlodipine with phenytoin on excisional cutaneous wound models in rabbit. Materials and Methods: Animals were divided into 5 groups (n = 5). The control group was treated topically with eucerin. The untreated control group received no healing agent. The reference standard group was treated with phenytoin1%. A treatment group was treated with amlodipine 1%. The last group was treated with combination of amlodipine1% and phenytoin 1%. Results: Results indicated significant difference between days needed for complete healing in both of the treatment groups. Wound closure was completed on 13th day and 9th day in amlodipine and combination groups respectively. Conclusions: In conclusion, calcium channel blockers can be used to enhance wound healing, especially if this treatment becomes with phenytoin. Further studies are needed to find out the mechanism of this healing effect.
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Bharti V, Bansal C. Drug-induced gingival overgrowth: The nemesis of gingiva unravelled. J Indian Soc Periodontol 2013; 17:182-7. [PMID: 23869123 PMCID: PMC3713748 DOI: 10.4103/0972-124x.113066] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2011] [Accepted: 03/27/2013] [Indexed: 12/11/2022] Open
Abstract
Drug-induced gingival overgrowth or enlargement manifests as abnormal growth of the gingiva due to an adverse drug reaction (ADR) in patients treated with anticonvulsants, immunosuppressants, and calcium channel blockers. As gingival enlargement develops, it affects the normal oral hygiene practice and may interfere with masticatory functions. It gradually becomes a source of pain and the condition often leads to disfiguration. Within the group of patients that develop this unwanted effect, there appears to be variability in the extent and severity of the gingival changes. It would seem pertinent to identify and explore possible risk factors and relating them with the treatment plan. This article throws light on respective drugs and their association with gingival overgrowth and approaches to treatment based on current knowledge and investigative observations.
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Affiliation(s)
- Vipin Bharti
- Department of Periodontology, Government Dental College and Hospital, Patiala, Punjab, India
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Di CP, Sun Y, Zhao L, Li L, Ding C, Xu Y, Fan Y. Effect of nifedipine on the expression of keratinocyte growth factor and its receptor in cocultured/monocultured fibroblasts and keratinocytes. J Periodontal Res 2013; 48:740-7. [PMID: 23528007 DOI: 10.1111/jre.12064] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/19/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND OBJECTIVE Keratinocyte growth factor (KGF) and its receptor (KGFR) are involved in hyperplastic diseases. This study explored the effect of intercellular communication on KGF and KGFR in cocultured/monocultured gingival fibroblasts and keratinocytes following treatment with nifedipine. MATERIAL AND METHODS Human gingival fibroblasts and keratinocytes were monocultured and cocultured, respectively. MTT was used to investigate the effects of nifedipine on the proliferation of gingival fibroblasts and keratinocytes. Monoculture and coculture systems were treated with different concentrations (0, 0.2 or 20 μg/mL) of nifedipine, and the expression of KGF and KGFR mRNAs was examined by RT-PCR, whilst the secretion of KGF and the expression of KGFR on the membrane were analyzed using ELISA and flow cytometry, respectively. RESULTS Nifedipine (0, 0.2 and 20 μg/mL) had no influence on cell proliferation within 3 d. KGF and KGFR mRNAs were up-regulated, but only in the cocultures. In coculture, the secretion of KGF was significantly increased by nifedipine, while it was only significantly up-regulated by 20 μg/mL of nifedipine in monoculture. Moreover, the level of KGFR protein in the membrane was significantly increased by 20 μg/mL of nifedipine in monocultures, while it was significantly down-regulated by 20 μg/mL of nifedipine in cocultures. CONCLUSION The expression of KGF and KGFR are influenced by the interplay of gingival keratinocytes and fibroblasts. Epithelial keratinocytes and mesenchymal fibroblasts may interplay to dynamically regulate gene expression, which may have an effect on the gingival condition following treatment with nifedipine.
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Affiliation(s)
- C-P Di
- Institute of Stomatology, Nanjing Medical University, Nanjing, China; Department of Periodontology, College of Stomatology, Nanjing Medical University, Nanjing, China
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Hogan J, Radhakrishnan J. The assessment and importance of hypertension in the dental setting. Dent Clin North Am 2012; 56:731-45. [PMID: 23017548 DOI: 10.1016/j.cden.2012.07.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Many patients with hypertension have uncontrolled disease. The dental visit presents a unique opportunity to screen patients for undiagnosed and undertreated hypertension, which may lead to improved monitoring and treatment. Although there are no clinical studies, it is generally recommended that nonemergent procedures be avoided in patients with a blood pressure of greater than 180/110 mm Hg. Because of the high prevalence of disease and medication use for hypertension, dentists should be aware of the oral side effects of antihypertensive medications as well as the cardiovascular effects of medications commonly used during dental visits.
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Affiliation(s)
- Jonathan Hogan
- Division of Nephrology, Department of Medicine, Columbia University College of Physician and Surgeons, New York, NY 10032, USA
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Abstract
Nonneoplastic mucocutaneous lesions are frequent in organ transplant recipients. Many of them are caused by a direct toxicity of immunosuppressive drugs, in particular glucocorticoids and cyclosporine. The effects of these agents are dose- and time-dependent. Glucocorticoids can cause acne, Cushingoid appearance, irregular purpuric areas, friable skin, and wide and violaceous stripes. Cyclosporine can cause hypertrichosis, pilosebaceous lesions, and gum hypertrophy. Patients with esthetic changes may show poor adherence to treatment with these immunosuppressive agents that may lead to progressive graft dysfunction. Apart from this direct toxicity, vigorous immunosuppression may render the transplant recipients more susceptible to mucocutaneous infections. Fungal infection, viral warts, and bacterial folliculitis are the most frequent types of mucocutaneous infection. Some fungal infections, such as oral candidiasis and pityriasis versicolor, are relatively trivial, but other mycotic infections can cause severe or disfigurating lesions. Among viral infections, warts and condylomata caused by human papilloma virus are frequent and may favor the development of nonmelanoma skin cancer. Bacterial infections are usually trivial in the early period after transplantation, being represented almost exclusively by folliculitis. However, subcutaneous infections may cause a necrotizing fasciculitis which is a life-threatening disorder, usually sustained by polymicrobial pathogens.
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Affiliation(s)
- Claudio Ponticelli
- Division of Nephrology, Istituto Scientifico Humanitas, Rozzano, Milan, Italy.
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Ahmad N, Mullakary J, El-Chaar GM. Amlodipine-Induced Gingival Hyperplasia in a Child: Case Report and a Review of the Literature. J Pharm Technol 2011. [DOI: 10.1177/875512251102700403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Objective: To increase awareness of amlodipine-induced gingival hyperplasia in children, as well as review whether a dose-related relationship exists. Case Summary: A 9-year-old girl with a past medical history of membranous nephropathy and hypertension presented with failure to thrive and inability to gain weight. She had a history of allergy to enalapril. On admission, she was found to have gingival hyperplasia. A review of her medication profile found amlodipine and azathioprine to be possible agents for this adverse reaction. The child's mother noticed this adverse effect after an increase in amlodipine dosage. We recommended substituting the angiotensin receptor blocker losartan for amlodipine; however, the nephrologist feared a cross-reactivity with enalapril and decided to continue amlodipine therapy. A follow-up call after hospital discharge revealed that the patient could no longer eat by mouth and that her gums bled upon brushing. Discussion: We reviewed the possible role of azathioprine in causing our patient's gingival hyperplasia. Due to the timeliness of this occurrence and the possibility of a dose-related response, we selectively reviewed the literature associated with amlodipine in children. A PubMed search and subsequent review of the literature revealed 1 study in rats that showed a relationship between amlodipine dose/plasma concentration and gingival hyperplasia. In humans, this relationship was reported with other calcium channel blockers, but not with amlodipine and not in a child. The Naranjo probability scale revealed a possible adverse reaction of gingival hyperplasia associated with amlodipine. Conclusions: To our knowledge, this is the first report of a possible dose-related occurrence of gingival hyperplasia in a child receiving amlodipine.
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Affiliation(s)
- Nazia Ahmad
- NAZIA AHMAD PharmD, Pharmacist, Department of Pharmacy, Mercy Medical Center, Rockville Center, NY
| | - Jacquline Mullakary
- JACQULINE MULLAKARY, PharmD Student 2011, College of Pharmacy and Allied Health Professions, St. John's University, New York, NY
| | - Gladys M El-Chaar
- GLADYS M EL-CHAAR PharmD, Associate Clinical Professor, Department of Clinical Pharmacy Practice, College of Pharmacy and Allied Health Professions, St. John's University; Clinical Coordinator, Pediatric Pharmacy, Department of Pharmacy Services, Steven & Alexandra Cohen Children's Medical Center of New York
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