scholarly journals Phenytoin and gingival mucosa: A molecular investigation

2019 ◽  
Vol 33 ◽  
pp. 205873841982825 ◽  
Author(s):  
Valentina Candotto ◽  
Furio Pezzetti ◽  
Alessandro Baj ◽  
Giada Beltramini ◽  
Dorina Lauritano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Healthy People ◽  
The Other ◽  
Channel Blockers ◽  
Gingival Fibroblasts ◽  
Gingival Overgrowth ◽  
Molecular Investigation ◽  
Matrix Metabolism ◽  
Gingival Mucosa ◽  
Inflammatory Molecules

Several distinct classes of drugs, such as anticonvulsants, immunosuppressants, and calcium channel blockers, caused gingival overgrowth. One of the main drugs associated with the gingival overgrowth is the anti-epileptic such as phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. In our study, we evaluate the effect of phenytoin, a drug whose active substance is phenytoin, on gingival fibroblasts of healthy volunteers. Gene expression of 29 genes was investigated in gingival fibroblasts’ cell culture treated with phenytoin compared with untreated cells. Among the studied genes, only 13 genes (CXCL5, CXCL10, CCR1, CCR3, CCR5, CCR6, IL-1A, IL-1B, IL-5, IL-7, IL-6R, BMP-2, and TNFSF-10) were statistically significant. All but one gene resulted downregulated after 24 h of treatment with phenytoin. BPM2 was the only, although weakly, up-expressed gene. Probably, we have not highlighted overexpression of the other inflammatory molecules because the study was performed on healthy people. Many studies show that phenytoin induces the overexpression of these cytokines but, probably, in our study, the drug does not have the same effect because we used gingival fibroblasts of healthy people.

Drug-Induced Gingival Overgrowth - A Review

1970 ◽  
pp. 26-29
Author(s):  
Mst Fatema Akhter ◽  
Shaheen Lipika Quayum ◽  
Afrin Bintal Ali ◽  
Zia Mamoon
Keyword(s):  
Extracellular Matrix ◽  
Collagen Synthesis ◽  
Immunosuppressive Agents ◽  
Channel Blockers ◽  
Gingival Fibroblasts ◽  
Connective Tissues ◽  
Drug Induced ◽  
Gingival Overgrowth ◽  
Collagen Phagocytosis ◽  
Synthesis And Degradation

Drug-induced gingival overgrowth is a side effect associated with 3 types of drugs: anticonvulsants (phenytoin), immunosuppressive agents (cyclosporine A), and various calcium channel blockers for cardiovascular diseases. Gingival overgrowth is characterized by the accumulation of extracellular matrix in gingival connective tissues, particularly collagenous components with various degrees of inflammation. Although the mechanisms of these disorders have not been elucidated, recent studies suggest that these disorders seem to be induced by the disruption of homeostasis of collagen synthesis and degradation in gingival connective tissue, predominantly through the inhibition of collagen phagocytosis of gingival fibroblasts. In this review, we focus on collagen metabolism in drug-induced gingival overgrowth, focusing on the regulation of collagen phagocytosis in fibroblasts. DOI: 10.3329/bjpp.v25i1.5743Bangladesh J Physiol Pharmacol 2009; 25(1&2) : 26-29

scholarly journals Diphenylhydantoin Induced Severe Gingival Hyperplasia

JMS SKIMS ◽  
2017 ◽  
Vol 20 (1) ◽  
pp. 44-46 ◽  
Author(s):  
Sheikh Saleem ◽  
Sawan Verma ◽  
Irfan Yousuf ◽  
Mushtaq Ahmad Wani ◽  
Ravouf Asmi
Keyword(s):  
Extracellular Matrix ◽  
Unsolved Problem ◽  
Age Groups ◽  
Chronic Administration ◽  
Channel Blockers ◽  
Gingival Hyperplasia ◽  
Gingival Overgrowth ◽  
Younger Age ◽  
Matrix Metabolism

Gingival overgrowth (GO) is a side effect, associated with some distinct classes of drugs, such as anticonvulsants, immunosuppressant, and calcium channel blockers. One of the main drugs associated with GO is the antiepileptic, diphenylhydantoin (DPH)/ phenytoin (1), which affects gingival tissues by altering extracellular matrix metabolism. Phenytoin (DPH)-induced gingival overgrowth (PIGO) due to chronic administration remains an unsolved problem especially in cases where this drug is taken without any supervision due usually to poor follow-up. Younger age groups experience more lesions than adults and in the mentally handicapped the prevalence appears to be highest. The most satisfactory treatment is the replacement of the drug by a safer antiepileptic. Patients who are to be maintained on DPH respond well to a program of meticulous oral hygiene at home along with frequent professional prophylaxes. We present a case of seizure disorder with mental retardation who developed severe gingival overgrowth wherein teeth are almost buried, caused by unsupervised intake of phenytoin. JMS 2017; 20(1):44-46

scholarly journals Influence of nifedipine on gingiva of Wistar rats

2004 ◽  
Vol 61 (1) ◽  
pp. 5-8 ◽  
Author(s):  
Zlata Brkic
Keyword(s):  
Wistar Rats ◽  
Water Solution ◽  
Channel Blockers ◽  
Gingival Hyperplasia ◽  
Dental Practice ◽  
Gingival Fibroblasts ◽  
Gingival Overgrowth ◽  
Time Period ◽  
Time Periods ◽  
Higher Doses

Noninflammatory hyperplastic growth of gingiva induced by calcium channel blockers, mostly nifedipine, is often seen in everyday dental practice. In order to establish an association of nifedipine and gingival hyperplasia, experimental model was used. Wistar rats were given water solution of nifedipine in different daily doses, using specially designed cannula. At the beginning of the experiment, before the application of nifedipine and in the determined time periods, gingival volume was measured. The volume of lower incisors interdental central papillas, represented multiplied values of vertical hight, mesio-distal width, and bucco-lingual depth, expressed in millimeters. The results indicated that gingival hyperplasia was more excessive in the experimental animals, which were given higher doses of the drug for longer time period. Nifedipine is a drug which induces gingival fibroblasts to produce higher quantity of collagen that causes gingival overgrowth.

scholarly journals Drug-induced gingival hyperplasia: An in vitro study using amlodipine and human gingival fibroblasts

2019 ◽  
Vol 33 ◽  
pp. 205873841982774 ◽  
Author(s):  
Dorina Lauritano ◽  
Marcella Martinelli ◽  
Alessandro Baj ◽  
Giada Beltramini ◽  
Valentina Candotto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Responses ◽  
Human Gingival Fibroblasts ◽  
Gingival Tissue ◽  
Gingival Fibroblast ◽  
Gingival Hyperplasia ◽  
Gingival Fibroblasts ◽  
Drug Induced ◽  
Gingival Overgrowth

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the inflammatory responses, we investigated its effects on gingival fibroblast gene expression as compared with untreated cells. Fragments of gingival tissue of healthy volunteers (11 years old boy, 68 years old woman, and 20 years old men) were collected during operation. Gene expression of 29 genes was investigated in gingival fibroblast cell culture treated with amlodipine, compared with untreated cells. Among the studied genes, only 15 ( CCL1, CCL2D, CCL5, CCL8, CXCL5, CXCL10, CCR1, CCR10, IL1A, IL1B, IL5, IL7, IL8, SPP1, and TNFSF10) were significantly deregulated. In particular, the most evident overexpressed genes in treated cells were CCR10 and IL1A. These results seem to indicate a possible role of amlodipine in the inflammatory response of treated human gingival fibroblasts.

scholarly journals Role of Cyclosporine in Gingival Hyperplasia: An In Vitro Study on Gingival Fibroblasts

2020 ◽  
Vol 21 (2) ◽  
pp. 595 ◽  
Author(s):  
Dorina Lauritano ◽  
Annalisa Palmieri ◽  
Alberta Lucchese ◽  
Dario Di Stasio ◽  
Giulia Moreo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Cyclosporine A ◽  
Matrix Metalloproteases ◽  
Gingival Hyperplasia ◽  
Gingival Fibroblasts ◽  
Down Regulation ◽  
Gingival Overgrowth ◽  
Expression Levels

Background: Gingival hyperplasia could occur after the administration of cyclosporine A. Up to 90% of the patients submitted to immunosuppressant drugs have been reported to suffer from this side effect. The role of fibroblasts in gingival hyperplasia has been widely discussed by literature, showing contrasting results. In order to demonstrate the effect of cyclosporine A on the extracellular matrix component of fibroblasts, we investigated the gene expression profile of human fibroblasts after cyclosporine A administration. Materials and methods: Primary gingival fibroblasts were stimulated with 1000 ng/mL cyclosporine A solution for 16 h. Gene expression levels of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway were analyzed using real-time PCR in treated cells, compared to untreated cells used as control. Results: Expression levels of different genes were significantly de-regulated. The gene CDH1, which codes for the cell adhesion protein E-cadherin, showed up-regulation. Almost all the extracellular matrix metalloproteases showed down-regulation (MMP8, MMP11, MMP15, MMP16, MMP24, MMP26). The administration of cyclosporine A was followed by down-regulation of other genes: COL7A1, the transmembrane receptors ITGB2 and ITGB4, and the basement membrane constituents LAMA2 and LAMB1. Conclusion: Data collected demonstrate that cyclosporine inhibits the secretion of matrix proteases, contributing to the accumulation of extracellular matrix components in the gingival connective tissue, causing gingival overgrowth. Patients affected by gingival overgrowth caused by cyclosporine A need to be further investigated in order to determine the role of this drug on fibroblasts.

scholarly journals Phenytoin-Induced Gingival Overgrowth: A Review of the Molecular, Immune, and Inflammatory Features

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jôice Dias Corrêa ◽  
Celso Martins Queiroz-Junior ◽  
José Eustáquio Costa ◽  
Antônio Lúcio Teixeira ◽  
Tarcilia Aparecida Silva
Keyword(s):  
Extracellular Matrix ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Side Effect ◽  
Channel Blockers ◽  
Connective Tissues ◽  
Drug Induced ◽  
Gingival Overgrowth ◽  
Matrix Metabolism

Gingival overgrowth (GO) is a side effect associated with some distinct classes of drugs, such as anticonvulsants, immunosuppressant, and calcium channel blockers. GO is characterized by the accumulation of extracellular matrix in gingival connective tissues, particularly collagenous components, with varying degrees of inflammation. One of the main drugs associated with GO is the antiepileptic phenytoin, which affects gingival tissues by altering extracellular matrix metabolism. Nevertheless, the pathogenesis of such drug-induced GO remains fulfilled by some contradictory findings. This paper aims to present the most relevant studies regarding the molecular, immune, and inflammatory aspects of phenytoin-induced gingival overgrowth.

Reparação óssea no implante dental

2020 ◽  
Vol 12 (45) ◽  
pp. 63-66
Author(s):  
Halim Nagem Filho ◽  
Reinaldo Francisco Maia ◽  
Reinaldo Missaka ◽  
Nasser Hussein Fares
Keyword(s):  
Gene Expression ◽  
Titanium Surface ◽  
Close Contact ◽  
The Other ◽  
Main Function ◽  
Indirect Interaction ◽  
M2 Macrophages ◽  
Activated Macrophages ◽  
M1 Macrophages ◽  
High Production

The osseointegration is the stable and functional union between the bone and a titanium surface. A new bone can be found on the surface of the implant about 1 week after its installation; the bone remodeling begins between 6 and 12 weeks and continues throughout life. After the implant insertion, depending on the energy of the surface, the plasma fluid immediately adheres, in close contact with the surface, promoting the adsorption of proteins and inducing the indirect interaction of the cells with the material. Macrophages are cells found in the tissues and originated from bone marrow monocytes. The M1 macrophages orchestrate the phagocytic phase in the inflammatory region and also produce inflammatory cytokines involved with the chronic inflammation and the cleaning of the wound and damaged tissues from bacteria. On the other hand, alternative-activated macrophages (M2) are activated by IL-10, the immune complex. Its main function consists on regulating negatively the inflammation through the secretion of the immunosuppressant IL-10. The M2 macrophages present involvement with the immunosuppression, besides having a low capacity for presenting antigens and high production of cytokines; these can be further divided into M2a, M2b, and M2c, based on the gene expression profile.

scholarly journals Analysis of the Mechanism by Which Glucose Inhibits Maltose Induction of MAL Gene Expression in Saccharomyces

Genetics ◽  
2000 ◽  
Vol 154 (1) ◽  
pp. 121-132
Author(s):  
Zhen Hu ◽  
Yingzi Yue ◽  
Hua Jiang ◽  
Bin Zhang ◽  
Peter W Sherwood ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Repression ◽  
Protein A ◽  
The Other ◽  
Maltose Permease ◽  
Inducer Exclusion ◽  
Glucose Inhibition ◽  
Independent Mechanism ◽  
Mal Genes

Abstract Expression of the MAL genes required for maltose fermentation in Saccharomyces cerevisiae is induced by maltose and repressed by glucose. Maltose-inducible regulation requires maltose permease and the MAL-activator protein, a DNA-binding transcription factor encoded by MAL63 and its homologues at the other MAL loci. Previously, we showed that the Mig1 repressor mediates glucose repression of MAL gene expression. Glucose also blocks MAL-activator-mediated maltose induction through a Mig1p-independent mechanism that we refer to as glucose inhibition. Here we report the characterization of this process. Our results indicate that glucose inhibition is also Mig2p independent. Moreover, we show that neither overexpression of the MAL-activator nor elimination of inducer exclusion is sufficient to relieve glucose inhibition, suggesting that glucose acts to inhibit induction by affecting maltose sensing and/or signaling. The glucose inhibition pathway requires HXK2, REG1, and GSF1 and appears to overlap upstream with the glucose repression pathway. The likely target of glucose inhibition is Snf1 protein kinase. Evidence is presented indicating that, in addition to its role in the inactivation of Mig1p, Snf1p is required post-transcriptionally for the synthesis of maltose permease whose function is essential for maltose induction.

scholarly journals Connective Tissue Metabolism and Gingival Overgrowth

2004 ◽  
Vol 15 (3) ◽  
pp. 165-175 ◽  
Author(s):  
P. C. Trackman ◽  
A. Kantarci
Keyword(s):  
Extracellular Matrix ◽  
Connective Tissue ◽  
Oral Hygiene ◽  
Tissue Specificity ◽  
Gingival Fibroblast ◽  
Drug Induced ◽  
Gingival Overgrowth ◽  
Connective Tissue Metabolism ◽  
Matrix Metabolism ◽  
Systemic Health

Gingival overgrowth occurs mainly as a result of certain anti-seizure, immunosuppressive, or antihypertensive drug therapies. Excess gingival tissues impede oral function and are disfiguring. Effective oral hygiene is compromised in the presence of gingival overgrowth, and it is now recognized that this may have negative implications for the systemic health of affected patients. Recent studies indicate that cytokine balances are abnormal in drug-induced forms of gingival overgrowth. Data supporting molecular and cellular characteristics that distinguish different forms of gingival overgrowth are summarized, and aspects of gingival fibroblast extracellular matrix metabolism that are unique to gingival tissues and cells are reviewed. Abnormal cytokine balances derived principally from lymphocytes and macrophages, and unique aspects of gingival extracellular matrix metabolism, are elements of a working model presented to facilitate our gaining a better understanding of mechanisms and of the tissue specificity of gingival overgrowth.

scholarly journals Potassium channel contributions to afferent arteriolar tone in normal and diabetic rat kidney

2008 ◽  
Vol 295 (1) ◽  
pp. F171-F178 ◽  
Author(s):  
Carmen M. Troncoso Brindeiro ◽  
Rachel W. Fallet ◽  
Pascale H. Lane ◽  
Pamela K. Carmines
Keyword(s):  
Potassium Channel ◽  
Rat Kidney ◽  
The Other ◽  
Diabetic Rat ◽  
Channel Blockers ◽  
Juxtamedullary Nephron ◽  
Afferent Arterioles ◽  
Arteriolar Tone ◽  
Constrictor Response

We previously reported an enhanced tonic dilator impact of ATP-sensitive K+ channels in afferent arterioles of rats with streptozotocin (STZ)-induced diabetes. The present study explored the hypothesis that other types of K+ channel also contribute to afferent arteriolar dilation in STZ rats. The in vitro blood-perfused juxtamedullary nephron technique was utilized to quantify afferent arteriolar lumen diameter responses to K+ channel blockers: 0.1–3.0 mM 4-aminopyridine (4-AP; KV channels), 10–100 μM barium (KIR channels), 1–100 nM tertiapin-Q (TPQ; Kir1.1 and Kir3.x subfamilies of KIR channels), 100 nM apamin (SKCa channels), and 1 mM tetraethylammonium (TEA; BKCa channels). In kidneys from normal rats, 4-AP, TEA, and Ba2+ reduced afferent diameter by 23 ± 3, 8 ± 4, and 18 ± 2%, respectively, at the highest concentrations employed. Neither TPQ nor apamin significantly altered afferent diameter. In arterioles from STZ rats, a constrictor response to TPQ (22 ± 4% decrease in diameter) emerged, and the response to Ba2+ was exaggerated (28 ± 5% decrease in diameter). Responses to the other K+ channel blockers were similar to those observed in normal rats. Moreover, exposure to either TPQ or Ba2+ reversed the afferent arteriolar dilation characteristic of STZ rats. Acute surgical papillectomy did not alter the response to TPQ in arterioles from normal or STZ rats. We conclude that 1) KV, KIR, and BKCa channels tonically influence normal afferent arteriolar tone, 2) KIR channels (including Kir1.1 and/or Kir3.x) contribute to the afferent arteriolar dilation during diabetes, and 3) the dilator impact of Kir1.1/Kir3.x channels during diabetes is independent of solute delivery to the macula densa.

Sign in / Sign up

Export Citation Format

Share Document