Drug-induced gingival overgrowth is a side effect associated principally with 3 types of drugs: anticonvulsant (phenytoin), immunosuppressant (cyclosporine A), and various calcium channel blockers (nifedipine, verapamil, diltiazem). In this review, we describe the features of phenytoin-, cyclosporine A- and nifedipine-induced gingival overgrowth in rats and discuss factors influencing the onset and severity of these disorders. There are several features common to the gingival overgrowth induced by these drugs: 1) gingival overgrowth is more conspicuous in the buccal than in the lingual gingiva and less severe in the maxilla than in the mandible; 2) once the blood concentration of the drug reaches a certain level as a result of increasing the dose, the incidence of gingival overgrowth is 100% and its severity is dependent on the blood level, the most severe overgrowth being induced by cyclosporine A; 3) the duration of drug administration for maximal gingival overgrowth to develop is about 40 days; 4) the gingival overgrowth regresses spontaneously after discontinuing the drug; 5) accumulation of dental plaque is not essential for the onset of overgrowth, but plays a role in its severity; and 6) more severe overgrowth is induced in young than in old rats. Furthermore, male rats are more susceptible than females to nifedipine-induced gingival overgrowth. These results suggest that drug-induced gingival overgrowth in rats is dependent on the oral drug dose, blood drug level, age, and sex and that preexisting gingival inflammation is a factor relevant to its severity. Since these factors have also been suggested to be important determinants for human drug-induced gingival overgrowth, the rat model may prove valuable in the future for elucidating the molecular pathogenesis of the disorder.

We determined the nucleotide sequence of a 1.9-kilobase fragment of Pseudomonas paucimobilis SYK6 chromosomal DNA that included genes encoding protocatechuate 4,5-dioxygenase, the enzyme responsible for the aromatic ring fission of protocatechuate. Two open reading frames of 417 and 906 base pairs were found that had no homology with previously reported sequences, including those encoding protocatechuate 3,4-dioxygenase. Since both open reading frames were indispensable for the enzyme activity, they should encode the subunits of protocatechuate 4,5-dioxygenase. We named these genes ligA and ligB. Protocatechuate 4,5-dioxygenase was efficiently expressed in Escherichia coli with the aid of the lac promoter, and the polypeptides of the ligA and ligB gene products were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino acid sequencing.

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Cleavage of the arylglycerol-fl-aryl ether linkage is the most important process in the biological degradation of lignin.We determined the activity of the enzyme cleaving the fl-aryl ether linkage in membranes of Pseudomonas paucimobilis SYK-6. This enzyme was tightly associated with the cellular membrane and catalyzed the unique and reductive cleavage of compound II but not cleavage of compound I. This enzymatic activity was stimulated by addition of NADH. On the basis of this evidence, we present a model of the specific cellular assimilation offl-aryl ether by P. paucimobilis Lignin metabolism; Arylglycerol-fl-aryl ether linkage; Aryl ether cleaving enzyme, fl-; Cell-free lysate; Membrane enzyme;( Pseudomonas paucimobilis

Sphingomonas paucimobilis SYK-6 is able to grow on a wide variety of dimeric lignin compounds. These compounds are degraded via vanillate and syringate by a unique enzymatic system, composed of etherases, O demethylases, ring cleavage oxygenases and side chain cleaving enzymes. These unique and specific lignin modification enzymes are thought to be powerful tools for utilization of the most abundant aromatic biomass, lignin. Here, we focus on the genes and enzymes involved in beta-aryl ether cleavage and biphenyl degradation. Two unique etherases are involved in the reductive cleavage of beta-aryl ether. These two etherases have amino acid sequence similarity with the glutathione S-transferases, and use glutathione as a hydrogen donor. It was found that 5,5'-dehydrodivanillate, which is a typical lignin-related biphenyl structure, was transformed into 5-carboxyvanillate by the reaction sequence of O-demethylation, meta-ring cleavage, and hydrolysis, and the genes involved in the latter two reactions have been characterized. Vanillate and syringate are the most common intermediate metabolites in lignin catabolism. These compounds are initially O-demethylated and the resulting diol compounds, protocatechuate (PCA) and 3-O-methylgallate, respectively, are subjected to ring cleavage catalyzed by PCA 4,5-dioxygenase. The ring cleavage products generated are further degraded through the PCA 4,5-cleavage pathway. We have isolated and characterized genes for enzymes involved in this pathway. Disruption of a gene for 2-pyrone-4,6-dicarboxylate hydrolase (ligI) in this pathway suggested that an alternative route for 3-O-methylgallate degradation, in which ligI is not involved, would play a role in syringate catabolism. In this article, we describe the genetic and biochemical features of the S. paucimobilis SYK-6 genes involved in degradation of lignin-related compounds. A possible application of the SYK-6 lignin degradation system to produce a valuable chemical material is also described.

In the soil bacterium (Pseudomonas paucimobilis , the metabolism of DDVA (biphenyl structure of lignin) and syringic acid (characteristic aromatic ring in hardwood lignin) proceeds via a common intermediate, 3-methylgallic acid. Protocatechuate is also an intermediate in the metabolism of vanillate and p-hydroxybenzoic acid. 3-Methylgallic acid and protocatechuate are the final aromatic intermediates in lignin microbial degradation and these compounds are substrates of protocatechuate-4,5-dioxygenase, which is a key enzyme in obtaining metabolic energy from various structures of lignin in this bacterium.Lignin metabolism; Biphenyl structure; Syringic acid; Aromatic ring fission; Protocatechuate-4,5-dioxygenase;( Pseudomonas paucimobilis

The effectiveness of a 5% potassium nitrate dentifrice as a daily home treatment for dentinal hypersensitivity was evaluated in a double-blind study in 36 Japanese subjects who complained of cold and/or tactile hypersensitivity. The subjects were divided into 2 groups, with 18 being given a 5% potassium nitrate dentifrice (treated group) and the other 18 a vehicle paste (control group). Both groups were instructed to brush their teeth 2 x a day. The hypersensitivity levels of the affected teeth were assessed by 2 stimuli, one tactile and the other cold air, and by the perception of pain. The results of all 3 assessment methods indicated that the potassium nitrate dentifrice significantly decreased the level of hypersensitivity at weeks 4, 8, and 12. In the treated group, a rapid decrease of positive scores for both the cold air stimulus and the subjective symptoms appeared from week 2. Although a significant decrease of the assessment score was also observed in the control group, the reduction rate of the score was much greater in the treated group by all 3 assessment methods at weeks 4, 8, and 12. Complete relief of subjective symptoms throughout the 12 weeks' examination was noted in 67% of the subjects in the treated group, but in only 6% in the control group. These results suggest the usefulness of a 5% potassium nitrate dentifrice in Japanese patients with dentinal hypersensitivity.

Two cases of gingival hyperplasia associated with long-term administration of nifedipine, a drug that dilates coronary arteries, are reported. The clinical and histopathological features of the gingival hyperplasia induced by nifedipine were similar to those induced by phenytoin, an anticonvulsant drug. In the present cases, gingival inflammation had developed before drug administration. In one case, extensive dental plaque control in addition to surgical removal of the overgrown gingival tissues resulted in satisfactory progress without the need to discontinue drug administration, suggesting that the preexisting gingival inflammation was involved in the development of this periodontal disease. In the other case, change from nifedipine to another drug resulted in spontaneous recovery, strongly suggesting that the drug had induced the gingival hyperplasia. Nifedipine had no direct effects in vitro on proliferation or collagen synthesis of gingival fibroblastic cells from one of the patients. Study of these two cases suggests that both local inflammatory factors and long-term administration of nifedipine were responsible for the gingival hyperplastic changes observed.