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Y C Chang

Publications and source records attributed to Y C Chang.

At least 55 records · Page 3Linked to original sources
PubMed2001

Seizure frequency affects event-related potentials (P300) in epilepsy.

To analyse the effect of epilepsy an P300 event-related potentials we studied 27 patients with idiopathic generalized epilepsy (IGE), 13 patients with temporal lobe epilepsy (TLE) and 60 normal controls. The prolongation of P300 latencies was highly cor related with increasing age in controls but not epileptic patients. The age-corrected P300 latency used in this study was actual P300 latency-predicted P300 latency (predicted P300 (msec)=306.20+0.79 age, P=0.001, R2=0.32). By using ANOVA analysis, the age-corrected latencies of P300 were significantly longer in TLE patients (19.72+/-47.82 msec, mean+/-SD) than in IGE patients (10.97+/-36.97 msec) and controls (0.23+/-20.28 msec). Likewise, significantly prolonged P300 latencies were seen in the epileptic patients with a seizure frequency more than 400 times (37.21+/-47.50 msec). The multivariate-adjusted odds ratio for those who had TLE was 10.97 (95% CI=3.99 - 30.14 ) in the prolonged latencies of P300 compared with that of IGE patients. The odds ratio of longer latencies of P300 was 7.43 (95% CI=2.75 - 20.08) among those who had a high seizure frequency (> or =400 times) compared with those who had a low seizure frequency. No interaction between TLE and high frequency of attacks was found. The age at onset of seizure and duration of illness was not associated with P300 latency prolongation. From the above results, we might infer that the seizure type of TLE and a high frequency of seizure are two major independent precipitate factors for abnormal latencies of P300 in the epileptic patients.

Adult↗
PubMed2001

Cytotoxicity of fluoride on human pulp cell cultures in vitro.

OBJECTIVES: Numerous studies have revealed that conventional glass-ionomer cements might release fluoride into an aqueous environment. The objective of this study was to examine the effects of fluoride on human pulp cells in vitro. STUDY DESIGN: H33258 fluorescence, cell proliferation, protein synthesis, and mitochondrial activity assay were used to investigate the pathobiological effects of fluoride on cultured human pulp cells. RESULTS: Fluoride was found to be a cytotoxic agent to cultured human pulp cells by inhibiting cell growth, proliferation, mitochondrial activity, and protein synthesis. CONCLUSIONS: Fluoride release has significant potential for pulpal toxicity.

Analysis of Variance↗
PubMed2001

The effect of sodium hypochlorite and chlorhexidine on cultured human periodontal ligament cells.

OBJECTIVE: The objective of this study was to examine the effects of sodium hypochlorite (NaOCl) and chlorhexidine (CHx) on cultured human periodontal ligament (PDL) cells in vitro. STUDY DESIGN: The effects of irrigation solutions on human PDL cells were evaluated by propidium iodide fluorescence cytotoxicity assay, protein synthesis assay, and mitochondrial activity. RESULTS: Both NaOCl and CHx were cytotoxic to human PDL cells in a concentration- and contact time-dependent manner. In addition, CHx inhibited protein synthesis in human PDL cells. Although NaOCl displayed cellular cytotoxicity, it showed no protein inhibition in the PDL cells. Furthermore, both NaOCl and CHx exhibited an inhibitory effect on mitochondrial activity on human PDL cells. CONCLUSIONS: This study suggests that these irrigation fluids may cause detrimental effects on vital tissues. Its clinical significance, however, needs to be evaluated further because concentration used, exposure time to the agent, and exposure surface area are important factors affecting the resulting effect.

Anti-Infective Agents, Local↗
PubMed2001

An analysis of excitatory amino acids, nitric oxide, and prostaglandin E2 in the cerebrospinal fluid of pregnant women: the effect on labor pain.

UNLABELLED: It is still unclear which neurotransmitters are involved in labor pain. We measured the concentrations of excitatory amino acids, nitric oxide, and prostaglandin E2 in the cerebrospinal fluid (CSF) of pregnant women, particularly in those with labor pain. The patients included in the study consisted of women who underwent cesarean delivery either with labor pain (Labor Pain group, n = 40) or without labor pain (Nonlabor Pain group, n = 58). All patients received spinal anesthesia (intrathecal injection of 10-12 mg of bupivacaine) for the operation, and 2 mL of CSF was collected before bupivacaine injection. Concentrations of aspartate and glutamate (0.50 +/- 0.06 microM and 0.79 +/- 0.10 microM, respectively) were significantly larger in the Labor Pain group than in the Nonlabor Pain group (0.35 +/- 0.03 microM and 0.54 +/- 0.04 microM, P < 0.05). There were no significant differences in the concentrations of nitric oxide and prostaglandin E2 between the groups. A positive correlation was found between CSF concentrations of excitatory amino acids and labor pain. IMPLICATIONS: The excitatory amino acids, aspartate and glutamate, play a role in labor pain. N-methyl-D-aspartate receptor antagonists may be useful for labor pain and postlabor uterine contraction pain relief.

Adult↗
PubMed2001

Effects of inverse ratio ventilation versus positive end-expiratory pressure on gas exchange and gastric intramucosal PCO(2) and pH under constant mean airway pressure in acute respiratory distress syndrome.

BACKGROUND: In patients with acute respiratory distress syndrome, whether inverse ratio ventilation differs from high positive end-expiratory pressure (PEEP) for gas exchange under a similar mean airway pressure has not been adequately examined. The authors used arterial oxygenation, gastric intramucosal partial pressure of carbon dioxide (PiCO(2)), and pH (pHi) to assess whether pressure-controlled inverse ratio ventilation (PC-IRV) offers more benefits than pressure-controlled ventilation (PCV) with PEEP. METHODS: Seventeen acute respiratory distress syndrome patients were enrolled and underwent mechanical ventilation with a PCV inspiratory-to-expiratory ratio of 1:2, followed by PC-IRV 1:1 initially. Then, they were randomly assigned to receive PC-IRV 2:1, then 4:1 or 4:1, and then 2:1, alternately. The baseline setting of PCV 1:2 was repeated between the settings of PC-IRV 2:1 and 4:1. Mean airway pressure and tidal volume were kept constant by adjusting the levels of peak inspiratory pressure and applied PEEP. In each ventilatory mode, hemodynamics, pulmonary mechanics, arterial and mixed venous blood gas analysis, PiCO(2), and pHi were measured after a 1-h period of stabilization. RESULTS: With a constant mean airway pressure, PC-IRV 2:1 and 4:1 decreased arterial and mixed venous oxygenation as compared with baseline PCV 1:2. Neither the global oxygenation indices with oxygen delivery and uptake nor PiCO(2) and pHi were improved by PC-IRV. During PC-IRV, applied PEEP was lower, and auto-PEEP was higher. CONCLUSION: When substituting inverse ratio ventilation for applied PEEP to keep mean airway pressure constant, PC-IRV does not contribute more to better gas exchange and gastric intramucosal PiCO(2) and pHi than does PCV 1:2 for acute respiratory distress syndrome patients, regardless of the inspiratory-to-expiratory ratios.

APACHE↗
PubMed2001

Cytotoxicity of halothane on human gingival fibroblast cultures in vitro.

Recently halothane has been reported to be the most suitable alternative to chloroform in dissolving gutta-percha. Periapical tissue toxicity of halothane is not completely known. In this study gutta-percha dissolved by halothane was evaluated with the almar blue dye assay using human gingival fibroblast cultures. The cytotoxic effects of halothane on human gingival fibroblasts depended on the exposure dose, frequency, and duration. A reduced concentration and smaller amount of gutta-percha solvents may minimize the cytotoxic effects on host tissues.

Cell Adhesion↗
PubMed2001

Cytotoxic evaluation of root canal filling materials on primary human oral fibroblast cultures and a permanent hamster cell line.

To date there has been very little data on the cytotoxic response of different cell lines to root canal sealers. The objective of this study was to determine the cytocompatibility of three different extracts of root canal sealers and to compare the cytotoxic response of these materials on two different primary human oral fibroblasts (derived from gingiva and buccal mucosa) and one permanent hamster cell line (V79 cells). Cytotoxicity was judged using an assay of tetrazolium bromide reduction. The results showed that root canal sealers (AH plus, Canals, and N2) were cytotoxic to primary human oral fibroblast cultures and V79 cells. It was found that N2 was the most toxic root canal sealer among those tested in all cultures. The toxicity decreased in an order of N2 > AH plus approximately = Canals. The sensitivity of toxicity depended on the materials tested and the cell culture system used.

Analysis of Variance↗
PubMed2001

Regulation of matrix metalloproteinase-2 production by cytokines and pharmacological agents in human pulp cell cultures.

Type IV matrix metalloproteinases (MMPs) are members of the family of MMPs and are thought to play an important role in degradation of extracellular components. Human pulp cells can secrete and produce these enzymes. Recent evidence shows that MMPs may play a role in pulpal inflammation. To date little is known regarding the regulation of MMPs in human pulp cell cultures. The purpose of this study was to determine the effects of cytokines (interleukin-1 and transforming growth factor-beta (TGF-beta), protein synthesis inhibitor cycloheximide (CD), and protein kinase C inhibitors (H7 and Go6976) on the secretion and production of MMPs by human pulp cell cultures using gelatin zymography. The main gelatinase secreted by human pulp cells migrated at 72 kDa and represented MMP-2. Minor gelatinolytic bands were also observed at 92 kDa regions that correspond to MMP-9. After an 8-day culture period TGF-beta, CD, H7, and Go6976 were found to depress MMP-2 production. The inhibition decreased in an order of CD > H7 > TGF-beta > Go6976. IL-1 was found to elevate MMP-2 production. Human pulp cells, however treated with either cytokines or pharmacological agents had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. These observations suggest that the cytokines and pharmacological agents can regulate MMP-2 produced by human pulp cells. Inflammatory cytokines stimulate the production of elevated levels of MMP-2 and MMP-2 might play a role in pulpal inflammation. In addition agents that target protein synthesis or the protein kinase C pathway in human pulp cells inhibit MMP-2 production, and such inhibition may contribute to the pathogenesis of pulpal inflammation. Such inhibition might contribute to therapeutic efficacy.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Cooperation of E2F-p130 and Sp1-pRb complexes in repression of the Chinese hamster dhfr gene.

In mammalian cells reiterated binding sites for Sp1 and two overlapping and inverted E2F sites at the transcription start site regulate the dhfr promoter during the cell growth cycle. Here we have examined the contributions of the dhfr Sp1 and E2F sites in the repression of dhfr gene expression. In serum-starved cells or during serum stimulation, the Chinese hamster dhfr gene was not derepressed by trichostatin A (TSA), an inhibitor of histone deacetylases (HDAC). Immunoprecipitation experiments showed that HDAC1 and hypophosphorylated retinoblastoma protein (pRb) are associated with Sp1 in serum-starved CHOC400 cells. In transfection experiments, reporter plasmids containing the reiterated dhfr Sp1 sites were stimulated 10-fold by TSA, while a promoter containing four dhfr E2F sites and a TATA box was responsive to E2F but was completely unaffected by TSA. HDAC1 did not coprecipitate with p130-E2F DNA binding complexes, the predominant E2F binding activity in cell extracts after serum starvation, suggesting that p130 imposes a TSA-insensitive state on the dhfr promoter. In support of this notion, recruitment of GAL4-p130 to a dihydrofolate reductase-GAL4 reporter rendered the promoter insensitive to TSA, while repression by GAL4-pRb was sensitive to TSA. Upon phosphorylation of pRb and p130 after serum stimulation, the Sp1-pRb and p130-E2F interactions were lost while the Sp1-HDAC1 interaction persisted into S phase. Together these studies suggest a dynamic model for the cooperation of pRb and p130 in repression of dhfr gene expression during withdrawal from the cell cycle. We propose that, during initial phases of cell cycle withdrawal, the binding of dephosphorylated pRb to Sp1-HDAC1 complexes and complexes of E2F-1 -to -3 with DP results in transient, HDAC-dependent suppression of dhfr transcription. Upon withdrawal of cells into G(0), recruitment of p130 to E2F-4-DP-1 complexes at the transcription start site results in a TSA-insensitive complex that cooperates with Sp1-HDAC-pRb complexes to stably repress dhfr promoter activity in quiescent cells.

Animals↗
PubMed2001

Clinicopathologic correlation of serum tissue polypeptide specific antigen in hepatocellular carcinoma.

OBJECTIVE: Recently, tissue polypeptide specific antigen (TPS) has been introduced as a cell proliferation marker. Little is known about its clinical significance in hepatocellular carcinoma (HCC). This study aimed to clarify serum TPS levels and tumor invasiveness of HCC. METHODS: Serum TPS levels were determined with a monoclonal TPS IRMA assay in 69 patients with HCC. A correlation between serum TPS levels and clinical, biochemical, and pathological features was sought and compared with that of alpha-fetoprotein (AFP). In 57 healthy subjects, 56 patients with biopsy-proven chronic hepatitis and in 49 patients with liver cirrhosis, serum TPS levels were assayed and compared. RESULTS: Serum TPS levels were significantly correlated with glutamic oxalacetic transaminase (p < 0.0001), glutamic pyruvic transaminase (p < 0.001), and lactate dehydrogenase (p = 0.027). There tended to be a positive relationship between serum TPS levels and tumor size, histological differentiation, capsular invasion, portal invasion, and clinical staging, although it did not reach statistical significance. A significant correlation, however, was observed between AFP and tumor size (p = 0.01), number (p = 0.042), histological grading (p = 0.028), portal invasion (p = 0.009), and clinical staging (p = 0.03). Patients with HCC had significantly higher TPS than healthy subjects (p < 0.001). However, there was substantial overlap between patients with HCC, chronic hepatitis, and liver cirrhosis. CONCLUSIONS: Our data suggest that serum TPS is not significantly related to tumor invasiveness in patients with HCC. Serum TPS levels are affected by the proliferative activity of the underlying chronic liver disease, which is frequently associated with HCC in Chinese patients. As a cell proliferation marker, serum TPS should be interpreted cautiously in the presence of chronic liver disease.

Adult↗
PubMed2001

Repeated ingestion of grapefruit juice does not alter clozapine's steady-state plasma levels, effectiveness, and tolerability.

BACKGROUND: Grapefruit juice can inhibit the gastrointestinal activity of cytochrome P450 (CYP) 3A4, while its effect on CYP1A2 remains controversial. Several grapefruit juice bioflavonoids also modulate the activity of the drug transporter P-glycoprotein in the gut and in the blood-brain barrier. Both CYP1A2 and CYP3A4 are involved in clozapine metabolism. This study investigated the effects of repeated ingestion of grapefruit juice on multiple-dose pharmacokinetics and pharmacodynamics of clozapine in schizophrenic patients. METHOD: Clozapine therapy was initiated for fifteen treatment-resistant schizophrenic inpatients (DSM-IV criteria). The doses were individually titrated from day -35 to day -15 and then kept unchanged from day -14 to day 49. Regular-strength grapefruit juice (250 mL) was coadministered b.i.d. with each clozapine dose from day 15 to day 28. Plasma levels of clozapine and its main metabolites (norclozapine and clozapine N-oxide) were obtained, and clinical efficacy and safety assessments were completed prior to juice administration (days 0, 7, and 14), during the coadministration (days 17, 21, and 28), and after cessation of the juice (days 35, 42, and 49). RESULTS: After reaching steady states, plasma concentrations of clozapine and its metabolites and Positive and Negative Syndrome Scale scores were not significantly altered by the effect of grapefruit juice ingestion. The Clinical Global Impressions scale scores, Calgary Depression Scale scores, and side effect profiles (by the Extrapyramidal Symptom Rating Scale, the UKU Side Effect Rating Scale, and thorough examinations including electrocardiography and electroencephalography) also remained constant during the study. CONCLUSION: Consumption of regular-strength grapefruit juice, 250 mL b.i.d., for 14 days did not significantly impact clozapine metabolism, clinical efficacy, or tolerability. One reason is that enzymes other than CYP3A4 also mediate clozapine disposition. Also, grapefruit juice inhibits CYP3A4 in the gut, but not in the liver. The preliminary results also suggest that clozapine is unlikely to be a P-glycoprotein substrate. Further rigorous studies are necessary to reconfirm these findings.

Adult↗
PubMed2001

Acute flaccid paralysis in infants and young children with enterovirus 71 infection: MR imaging findings and clinical correlates.

BACKGROUND AND PURPOSE: Enterovirus 71 (EV71) infection is now considered an important cause of childhood acute flaccid paralysis. The purpose of our study was to determine whether EV71-infection-related acute flaccid paralysis in infants and young children has characteristic MR imaging patterns. METHODS: Seven infants and young children with acute paralysis of the upper or lower extremities and positive EV71 cultures underwent spinal MR studies during an outbreak of hand-foot-and-mouth disease in Taiwan in 1998. RESULTS: Acute paralysis was observed in one upper extremity in two patients, in one lower extremity in three patients, and in both lower extremities in two patients. None of the patients had sensory impairment or bulbar palsy. MR studies showed unilateral or bilateral hyperintense lesions in the anterior horn regions of the cord on T2-weighted images in six patients. No abnormal signal was present in one patient. Two of three patients who received intravenous injections of contrast material had ventral root enhancement on T1-weighted images. One of them also had enhancement of the unilateral anterior horn cells. At clinical follow-up, both patients with bilateral anterior horn abnormalities had residual motor weakness, whereas only one of the five patients with unilateral involvement had residual weakness. CONCLUSION: EV71 radiculomyelitis tends to be unilateral and to specifically involve both the anterior horn cells of the cord and the ventral roots. MR imaging allows early detection of spinal cord and root lesions.

Acute Disease↗
PubMed2001

Video-assisted thoracoscopic surgery for the diagnosis of patients with hilar and mediastinal lymphadenopathy.

In areas where tuberculosis (TB) is rare, cases of hilar and mediastinal lymphadenopathy are often attributed to the diagnosis of sarcoidosis or a malignant process. However, these manifestations have been only sparsely reported in countries with high rates of TB. The role of simultaneous lung biopsy in the differential diagnosis of these patients using a thoracoscopic approach is also undetermined. In this prospective study, 15 adult patients with hilar and mediastinal lymphadenopathy were evaluated using video-assisted thoracoscopy during the period from May 1995 through September 1999. Biopsy of the hilar and mediastinal lymph nodes was undertaken in all 15 patients, and a wedge biopsy of the lungs was performed whenever frozen section of the nodes disclosed granulomatous inflammation. The final diagnoses included sarcoidosis (10 patients), TB (2), metastatic small cell carcinoma (2), and reactive lymphoid hyperplasia (1). No morbidity or mortality was associated with the operation. In patients with sarcoidosis and TB, most of the lymph node biopsy specimens disclosed extensive hyaline fibrosis. Lung biopsy specimens presented small non-necrotizing granulomas with multinucleated giant cells even in the absence of demonstrable parenchymal lesions. In the two patients with TB, identification of acid-fast bacilli and growth of Mycobacterium tuberculosis occurred only in lung specimens and not in specimens from lymph nodes. Video-assisted thoracoscopic surgery is a safe, simple, and effective procedure for the diagnosis of patients with hilar and mediastinal lymphadenopathy. Our results suggest that for a better differentiation between TB and sarcoidosis, an additional lung biopsy could be undertaken to provide specimens for microscopic examination and culture.

Adult↗
PubMed2001

Purification, cloning, and sequencing of an enzyme mediating the reductive dechlorination of tetrachloroethylene (PCE) from Clostridium bifermentans DPH-1.

An enzyme mediating the reductive dechlorination of tetrachloroethylene (PCE) from cell-free extracts of Clostridium bifermentans DPH-1 was purified, cloned, and sequenced. The enzyme catalyzed the reductive dechlorination of PCE to cis-1,2-dichloroethylene via trichloroethylene, at a Vmax and Km of 73 nmol/mg protein and 12 microM, respectively. Maximal activity was recorded at 35 degrees C and pH 7.5. Enzymatic activity was independent of metal ions but was oxygen sensitive. A mixture of propyl iodide and titanium citrate caused a light-reversible inhibition of enzymatic activity suggesting the involvement of a corrinoid cofactor. The molecular mass of the native enzyme was estimated to be approximately 70 kDa. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption ionization-time of flight/mass spectrometry (MALDI-TOF/MS) revealed molecular masses of approximately 35 kDa and 35.7 kDa, respectively. A broad spectrum of chlorinated aliphatic compounds (PCE, trichloroethylene, cis-1,2-dichloroethylene, trans-1,2-dichloroethylene, 1,1-dichloroethylene, 1,2-dichloropropane, and 1,1,2-trichloroethane) was degraded. With degenerate primers designed from the N-terminal sequence (27 amino acid residues), a partial sequence (81 bp) of the encoding gene was amplified by polymerase chain reaction (PCR) and sequenced. Southern analysis of C. bifermentans genomic DNA using the PCR product as a probe revealed restriction fragment bands. A 5.0 kb ClaI fragment, harboring the relevant gene (designated pceC) was cloned (pDEHAL5) and the complete nucleotide sequence of pceC was determined. The gene showed homology mainly with microbial membrane proteins and no homology with any known dehalogenase, suggesting a distinct PCE dehalogenase.

Amino Acid Sequence↗
PubMed2001

The effect of combined 5-fluorouracil and dexamethasone on cultured human retinal pigment epithelial cells.

This study was designed to investigate the inhibitory effect of 5-fluorouracil (5-FU) and dexamethasone (DEX) on the proliferation of human retinal pigment epithelial (RPE) cells in vitro. The human RPE cells (R-50 cell line) were cultured and exposed to various concentrations of combined 5-FU (0, 250, 500, 1000, 2000 ng/ml) and DEX (0, 1, 10, 100, 200 micrograms/ml). The cells were incubated for 96 hr and the medium was changed every 48 hr to replenish the drug action. Cell viability was assessed using cell counting and trypan blue exclusion method. Tetrazolium salt, which can be metabolized by mitochondrial dehydrogenase to form a formazan dye, was used to assay cell proliferation. Treatment with 5-FU alone inhibited cell proliferation in a dose-dependent manner. The concentration of 5-FU that inhibited growth by 50% (IC50) was found to be 704.12 ng/ml. There was a bimodal effect of DEX on RPE cells--stimulation at low concentrations (1, 10 micrograms/ml) and inhibition at high concentrations (100, 200 micrograms/ml). When the two drugs were combined, there was additive inhibition in the concentration of 200 micrograms/ml of DEX. These results indicate that a combination of 5-FU and DEX is no more effective in the inhibition of human RPE cells, except in combination with high concentrations of DEX (> or = 200 micrograms/ml).

Cell Division↗
PubMed2001

[Cloning and characterization of syap1, a down regulated gene in human hepatocellular carcinoma].

Using a different fragment DE6 obtained from DD-PCR as probe, a full-length cDNA has been cloned from human liver cDNA library and named as syap1 (Synapse-associated protein 1) because its deduced amino acid sequence is homologous to SAP47 of D. melanogaster. Northern blot analysis reveals that two transcripts of syap1 mRNA are expressed in cultured human liver L-02 cells. Moreover, the syap1 mRNA was also detected in most of adult human tissues by RT-PCR analysis. Down-regulated expression of syap1 mRNA was confirmed by semi-quantitative RT-PCR assay in 5 of 10 (50%) cases of human hepatocellular carcinoma (HCC).

Adult↗
PubMed2000

Synergistic effects of peroxynitrite on arecoline-induced cytotoxicity in human buccal mucosal fibroblasts.

Epidemiological studies have demonstrated a clear association between betel nut chewing and an increased risk for oral mucosal lesions. Arecoline, the most abundant betel alkaloid, is considered the most important etiologic factor in betel nuts. In addition, most betel nut chewers are also smokers. In order to elucidate the potential toxicological implications of interactions of arecoline and peroxynitrite (a reaction product of cigarette smoking), cell viability, and cellular levels of glutathione (GSH) were investigated, using cultured human buccal mucosal fibroblasts. At a concentration higher than 0.8 mM, arecoline was cytotoxic to buccal mucosal fibroblasts in a concentration- and time-dependent manner. Arecoline also depleted intracellular GSH in a dose-dependent manner (P<0.05). The addition of extracellular peroxynitrite acted as a synergistic effect on the arecoline-induced cytotoxicity (P<0.05). Furthermore, at a concentration of 0.8 mM, arecoline depleted intracellular GSH by about 42%, while 2 mM peroxynitrite enhanced the arecoline-depleted GSH level further to 86% as compared with the control. During GSH depletion, arecoline may render the human buccal mucosal fibroblasts more vulnerable to other reactive agents within cigarette smoking. Taken together, we suggest that people who combine the habits of betel nut chewing with cigarette smoking could be more susceptible to oral mucosal damage than betel quid chewing alone.

Arecoline↗