Prognostic factors and impact of bone invasion in T1/2 size (<4 cm) gingival squamous cell carcinoma.

The aim of this study was to characterize the clinicopathological features and prognostic factors of T1/2 size (<4 cm) gingival squamous cell carcinoma (SCC) and to verify the impact of bone invasion. This was a single-centre, retrospective cohort study involving 206 patients with gingival SCC (maxilla or mandible), treated between 2000 and 2020. The patients were divided into three subgroups based on tumour size and bone invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were 80.6% and 67.6%, respectively. Histological differentiation, advanced T stage, positive resection margin, bone invasion, and postoperative adjuvant therapy were associated with a poor prognosis (P < 0.05). Multivariate Cox analysis indicated that only histological differentiation (hazard ratio (HR) 2.68, P = 0.007) and bone invasion (HR 2.08, P = 0.036) were significantly associated with DFS. Bone invasion was observed in 145 (70.4%) patients, of whom 43 (20.9%) had a T1/2 size tumour. The subgroup with bone invasion and T1/2 size showed significantly worse OS and DFS when compared to the subgroup without bone invasion and similar or worse survival when compared to the subgroup with bone invasion and T3/T4 size. Histological differentiation and bone invasion were poor prognostic factors for gingival SCC, even in cases with small-sized tumours. For suspected bone invasion in small-sized tumours, an adequate bone margin is necessary and postoperative adjunctive therapy needs to be considered.

Prognostic value of lymph node count from selective neck dissection in oral squamous cell carcinoma.

Unlike the levels of anatomical exploration, there is no consensus on the extent of lymph node dissection, or lymph node count (LNC), during selective neck dissection (SND). The aim of this study was to validate the prognostic impact of LNC on survival and to determine an optimal LNC cut-off value for SND. A retrospective investigation identified 78 patients with a diagnosis of oral squamous cell carcinoma (OSCC) who underwent SND (levels I-III or levels I-IV). LNC and clinicopathological variables were analyzed for any association with survival in Cox proportional hazards models. Based on the receiver operating characteristic curve, a cut-off value of 19 lymph nodes was found to predict overall survival (OS) (area under the curve 0.732, sensitivity 67.8%, specificity 75.0%; P=0.026) and disease-specific survival (DSS) (area under the curve 0.762, sensitivity 68.1%, specificity 77.8%; P=0.011). On Cox regression, LNC (≥19 vs. <19) was the only independent predictor of OS (hazard ratio 5.29, 95% confidence interval 1.39-20.05; P=0.014) and DSS (hazard ratio 6.76, 95% confidence interval 1.40-32.77; P=0.018). Similar results were obtained in the pathologically lymph node-negative subgroup (n=66). Based on the study findings, SND should include 19 or more lymph nodes for a survival benefit.

Effects of locally administered rhBMP-2 and bisphosphonate on bone regeneration in the rat fibula.

OBJECTIVE: To evaluate the ability of xenogenic bone and absorbable collagen sponge to function as an rhBMP-2 carrier and the osteoinductivity of bisphosphonate by comparison with recombinant human bone morphogenetic protein-2 (rhBMP-2). MATERIALS AND METHODS: Thirty-two Sprague-Dawley male rats were divided into four groups. Segmental ostectomy of both fibulae was performed, and the defect area was then treated with Rapiderm Pad (absorbable collagen sponge; COL_BMP) or CollaOss (xenogenic bone; XENO_BMP) with application of rhBMP-2. Alternatively, both fibulae were grafted with xenogenic bone with different bisphosphonate concentrations (XENO_Low BP, XENO_High BP). After 4 or 8 weeks, animals were sacrificed, and radiographic, histological, histomorphometric, and immunohistochemical analyses were performed. RESULTS: Recombinant human bone morphogenetic protein-2 promoted bone formation, regardless of the carrier, and exhibited continuity between the graft material and defect area. Moreover, the results showed that higher concentrations of bisphosphonate were associated with greater bone formation than lower concentrations of bisphosphonate. CONCLUSION: Absorbable collagen sponges with rhBMP-2 were advantageous in that there was no remaining graft material and that the bone was remodeled to resemble the existing fibula. The local application of bisphosphonate promoted new bone formation, particularly when used at high concentrations. High-concentration bisphosphonate induced new bone formation comparable to rhBMP-2 with lesser remaining bone material.

Teriparatide therapy for severe, refractory osteoradionecrosis of the jaw.

Although osteoradionecrosis (ORN) is a serious complication of craniofacial radiotherapy, the current management methods remain suboptimal. Teriparatide (TPTD), a recombinant human parathyroid hormone (1-34), has shown beneficial effects on osseous regeneration in medication-related osteonecrosis of the jaw or periodontitis. However, TPTD therapy in irradiated bones has not been indicated yet because of the theoretical risk of osteosarcoma seen in rat models. Hence, we first report here two patients with tongue cancer with late-emerging ORN who were successfully treated with TPTD for 4-6 months with serum calcium and vitamin D supplementation. In contrast to the usual progress of ORN, the bone defect regenerated well and bone turnover markers including serum C-terminal telopeptide of type 1 collagen and osteocalcin were restored with TPTD therapy. Our experience might suggest that TPTD therapy with careful monitoring can provide an effective treatment option for patients with ORN in select refractory cases, with the benefits outweighing the potential risks.

A combined prognostic factor for improved risk stratification of patients with oral cancer.

PURPOSE: We aimed to identify a combined prognostic factor for predicting better performance in risk stratification. MATERIALS AND METHODS: We reviewed the clinical and pathological variables of 316 patients with oral squamous cell carcinoma (OSCC) who underwent surgery. To identify a combined predictor, principal component analysis (PCA) was performed. RESULTS: Univariate analysis showed that the independent prognostic variables for overall survival (OS) were pathologic T stage (T1 vs T4, HR = 1.99, 95% CI: = 1.083-3.675, P = 0.026) and pathologic N stage (N0 vs N2, HR=1.90, 95% CI: = 1.17-3.08, P = 0.008). In the multivariate analysis, only pathologic T stage was significant (P = 0.006 and P = 0.007); however, the multivariate model was not significant (P = 0.191). The multivariate model became significant by including lymph node ratio (LNR) instead of pathologic N stage (P = 0.0025 in numeric LNR, P = 0.0007 in categorized LNR). Also, the performance of prediction model was improved by a combined prognostic factor (P = 0.0002). CONCLUSIONS: The newly identified combined prognostic factor included resection margin, differentiation, and LNR, and they were insignificant factors independently except for LNR. This combined prognostic factor showed a good performance although it did not include molecular markers; therefore, it may be used conveniently for risk stratification of patients with OSCC by combining only clinical information.

High-Level Ciprofloxacin-Resistant Campylobacter jejuni Isolates Circulating in Humans and Animals in Incheon, Republic of Korea.

Campylobacter jejuni is one of the major causative pathogens of outbreaks or sporadic cases of diarrhoeal diseases worldwide. In this study, we compared the phenotypic and genetic characteristics of C. jejuni isolates of human and food-producing animal origins in Korea and examined the genetic relatedness between these two groups of isolates. Regardless of isolation source, all C. jejuni isolates harboured four virulence genes, cadF, cdtB, ciaB and racR, whereas the wlaN and virB11 genes were more frequently observed in human isolates. Antimicrobial susceptibility testing showed that the majority of C. jejuni isolates displayed high-level resistance to fluoroquinolone (95.2%) or tetracycline (76.2%) antibiotics, and 12.4% of isolates exhibited multidrug resistance (more than three classes of antibiotics tested). Pulsed-field gel electrophoresis (PFGE) of all Campylobacter isolates revealed 51 different SmaI-PFGE patterns and six major clusters containing both human and animal isolates. These results indicate that genetically diverse strains of C. jejuni with antimicrobial drug-resistance and virulence properties have prevailed in Incheon. Nevertheless, some particular populations continue to circulate within the community, providing the evidence for an epidemiological link of C. jejuni infections between humans and food-producing animals. Therefore, the continued monitoring and surveillance of C. jejuni isolates of human and food-producing animal origins are required for public health and food safety.

The fine line between 'brave' and 'reckless': amygdala reactivity and regulation predict recognition of risk.

BACKGROUND: High sensation-seekers (HSS) pursue novelty even at the cost of self-harm. When challenged, HSS are less anxious, show blunted physiological (cortisol, startle) and neurobiological (prefrontal-limbic) responses, and devalue aversive outcomes. Here, we investigate how these features interact under conditions of physical danger, in distinguishing between adaptive and maladaptive approaches to risk. METHODS: We recruited a cohort of individuals who voluntarily sought out recreational exposure to physical risk, and obtained serial cortisol values over two time-locked days. On the 'baseline' day, we scanned subjects' brains with functional and structural MRI; on the 'skydiving day,' subjects completed a first-time tandem skydive. During neuroimaging, subjects viewed cues that predicted aversive noise; neural data were analyzed for prefrontal-limbic reactivity (activation) and regulation (non-linear complexity), as well as cortical thickness. To probe threat perception, subjects identified aggression for ambiguous faces morphed between neutral and angry poles. RESULTS: Individuals with prefrontal-limbic meso-circuits with less balanced regulation between excitatory and inhibitory components showed both diminished cortisol/anxiety responses to their skydives, as well as less accurate perceptual recognition of threat. This impaired control was localized to the inferior frontal gyrus, with associated cortical thinning. Structural equation modeling suggests that sensation-seeking is primarily mediated via threat-perception, which itself is primarily mediated via neural reactivity and regulation. CONCLUSIONS: Our results refine the sensation-seeking construct to provide important distinctions (brain-based, but with endocrine and cognitive consequences) between the brave, who feel fear but nonetheless overcome it, and the reckless, who fail to recognize danger. This distinction has important real-world implications, as those who fail to recognize risk are less likely to mitigate it.

Distinctive role of 6-month teriparatide treatment on intractable bisphosphonate-related osteonecrosis of the jaw.

UNLABELLED: The administration of teriparatide (TPTD) in conjunction with periodontal care could provide faster and more favorable clinical outcomes in previously refractory bisphosphonate-related osteonecrosis of the jaws (BRONJ) cases compared to conventional dental care, combination of surgery and antimicrobial treatment. We also found that underlying vitamin D levels might influence the response to TPTD treatment. INTRODUCTION: Treatment of BRONJ is quite challenging and there are no standard treatment modalities. In this retrospective, longitudinal study, we examined whether additional TPTD administration could be beneficial for the resolution of BRONJ lesions compared to conservative management, such as antimicrobial treatment with or without surgery, and also studied the factors influencing the response to TPTD. METHODS: Twenty-four cases of intractable BRONJ were included: 15 subjects were assigned to the TPTD group and the other 9 subjects, who refused TPTD administration, were assigned to the non-TPTD group. All subjects in both groups continued calcium and vitamin D supplementation and the TPTD group additionally received a daily subcutaneous injection of 20 µg TPTD for 6 months. RESULTS: While 60.0% of the non-TPTD group showed one stage of improvement in BRONJ, 40.0% of the group did not show any improvement in disease status. In the TPTD group, 62.5% of the treated subjects showed one stage of improvement and the other 37.5% demonstrated a marked improvement, including two stages of improvement or complete healing, and there was not a single case that did not improve. The clinical improvement of BRONJ was statistically better in the TPTD group after the 6-month treatment (p < 0.05). Moreover, patients with higher baseline serum 25(OH)D levels showed better clinical therapeutic outcomes with TPTD. CONCLUSIONS: We observed the beneficial effects of TPTD on BRONJ, and subjects with optimal serum vitamin D concentrations seemed to reap the maximum therapeutic effects of TPTD. A prospective, randomized, controlled trial should be needed to further evaluate the therapeutic efficacy of TPTD in the resolution of BRONJ.

Socioeconomic disparities of periodontitis in Koreans based on the KNHANES IV.

OBJECTIVES: The aim of this study was to identify the socioeconomic factors associated with the prevalence of periodontitis in Koreans. METHODS: Cross-sectional data from 12 763 subjects, 15 years old and above, who underwent periodontal examinations were obtained from the Korean National Health and Nutrition Examination Survey IV (2007-209). Multivariate linear and logistic regression analyses were applied to estimate the association between socioeconomic indicators and prevalence of periodontitis. RESULTS: A significant association was found between increasing age and periodontitis. Participants with higher income were less likely to have periodontitis (aOR = 0.9 and 95% CI = 0.78-0.98, and aOR = 0.7 and 95% CI = 0.60-0.80 in the middle and highest quintiles of monthly household income, respectively). In addition, participants living in rural areas were less likely to have periodontitis (aOR = 0.9 and 95% CI = 0.81-0.99), and current smokers were more likely to have periodontitis (aOR = 1.7 and 95% CI = 1.49-1.89). The analysis of comorbidities revealed that individuals with diabetes mellitus (DM) were significantly more likely to have periodontitis (aOR = 1.4 and 95% CI = 1.18-1.68). CONCLUSIONS: In a rapidly increasing Korean population, the lower socioeconomic groups as well as individuals with DM were significantly more likely to present with periodontitis.

Osteolytic mandible presenting as an initial manifestation of an adult acute lymphoblastic leukaemia.

A case of adult acute lymphoblastic leukaemia is reported. A 35-year-old male presented with an osteolytic lesion of the mandible. There was no definitive involvement in other craniofacial bones. A panoramic radiograph taken 4 months previously showed no bony involvement. A complete blood count showed a slightly decreased red blood cell count, but normal white blood cell count, white blood cell differential count and platelet count. Routine chemistry revealed hypercalcemia with an increased level of parathyroid hormone-related protein. Histopathological examination of bone marrow biopsy confirmed the diagnosis of acute lymphoblastic leukaemia.

Detection of antigenic proteins expressed by lymphocystis virus as vaccine candidates in olive flounder, Paralichthys olivaceus (Temminck & Schlegel).

Although the major capsid proteins (MCPs) of lymphocystis disease virus (LCDV) have been characterized, little is known about the host-derived immune response to MCPs and other LCDV antigenic proteins. To identify antigenic proteins of LCDV that could be used as vaccine candidates in olive flounder, Paralichthys olivaceus, we analysed the viral proteins responsible for its virulence by applying immuno-proteomics. LCDV proteins were separated by one-dimensional gel electrophoresis, transferred to polyvinylidene difluoride membrane, and probed with homogeneous P. olivaceus antisera elicited by LCDV natural infection and vaccination with formalin-killed LCDV. Four immune-reactive proteins were obtained at 68-, 51-, 41- and 21 kDa using antisera collected from natural infection while two proteins at 51- and 21 kDa exhibited response to antisera from vaccinated fish, indicating that the latter two proteins have vaccine potential. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nanoelectrospray MS/MS, the 51 and 21 kDa proteins were identified as MCP and an unknown protein, respectively.

Spinal cord injury subsequent to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.

Transcatheter arterial chemoembolization is one of the most common treatment modalities for hepatocellular carcinoma. Transcatheter arterial chemoembolization is considered to be a relatively safe procedure, but transcatheter arterial chemoembolization is associated with a number of disastrous complications. Among the ischaemic complications caused by transcatheter arterial chemoembolization, spinal cord injury is very rare, but can occur via the intercostal or lumbar arteries. We report two cases of extremely rare spinal cord injuries after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. The patients had sensory loss below the T9 or T10 dermatomes and paraparesis or paraplegia within 6-8h after transcatheter arterial chemoembolization. One patient sustained paraplegia until death 2 months after transcatheter arterial chemoembolization and the other patient recovered almost completely 2 months after transcatheter arterial chemoembolization.

Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia.

UNLABELLED: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of bisphosphonate therapy. The incidence of BRONJ is known to be low among patients treated with oral bisphosphonates. We investigated the prevalence, demographics, clinical manifestations, and treatment outcome of 24 patients with oral BRONJ in Asian populations. INTRODUCTION: The long-term safety of oral bisphosphonates is clinically important considering the rare but potentially serious complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ) versus the effect of reducing and preventing osteoporotic fracture. The incidence of BRONJ is known to be low among patients treated with oral bisphosphonates around the world. However, the prevalence in those taking oral bisphosphonates for osteoporosis in Asian populations is unknown. Moreover, a recent article, showing that the majority of reported patients who received alendronate were Asian American, raised concern about the prevalence of oral BRONJ in Asian populations. The objective of this study was to investigate the estimated prevalence, clinical characteristics, and treatment outcome of oral BRONJ in Asian populations. METHODS: From October 2005 to December 2008, a retrospective review of medical charts identified 24 patients receiving oral bisphosphonates diagnosed as BRONJ at the Department of Oral and Maxillofacial Surgery, Yonsei University Dental Hospital, Seoul, South Korea. RESULTS: The estimated prevalence of oral BRONJ was 0.05-0.07%. The average oral bisphosphonate treatment duration was 43.1 months (range, 5-120 months). Treatment with oral antibiotics and/or surgery including sequestrectomy or alveolectomy showed relatively favorable results. CONCLUSIONS: The prevalence of oral BRONJ in Korea is similar to that reported previously in Western populations. We suggest that recognition of BRONJ and appropriate management pre- and post-dental surgery might reduce the frequency of BRONJ among patients receiving oral bisphosphonates.

Endovenous laser ablation of the incompetent small saphenous vein with a 980-nm diode laser: our experience with 3 years follow-up.

PURPOSE: To demonstrate the long-term treatment outcomes of endovenous laser ablation (EVA) of incompetent small saphenous veins (SSV) with a 980-nm diode laser. MATERIALS AND METHODS: Eighty-four patients (96 limbs), with varicose veins and reflux in the SSV on duplex ultrasound examination, were treated with a 980-nm diode laser under ultrasound- or fluoroscopy-guidance. Patients were evaluated at 1 week and 1, 3, 6 months, 1 year and yearly thereafter. RESULTS: In the 96 limbs, the technical success rate was 100%. The SSV remained closed in 89 of 93 limbs (96%) after 1 month, all of 82 limbs after 6 months, 77 limbs after 1 year, 71 limbs after 2 years and 55 limbs after 3 years. In four limbs where recanalisation was observed, repeat EVA was done resulting in successful obliteration of the SSV. No major complication occurred however bruising (27%), tightness or pain (13%) and paraesthesia (4.2%) were observed. CONCLUSION: Endovenous laser ablation with a 980-nm laser wavelength is an easy and safe procedure in incompetent SSVs. After successful treatment, there is a very low rate of recanalisation of the SSV, which suggests that the procedure will provide lasting results.

Development of the "Inje cocktail" for high-throughput evaluation of five human cytochrome P450 isoforms in vivo.

To develop and validate an in vivo cocktail method for high-throughput phenotyping of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A, 12 healthy subjects received five probe drugs alone or simultaneously. The in vivo phenotyping index of CYP2C9, the ratio of 8 h urine concentration of losartan to its metabolite after a single administration of losartan, was not significantly different from that obtained using the five-drug cocktail. Similarly, the ratios of [omeprazole]/[5-hydroxyomeprazole] (CYP2C19) and [paraxanthine]/[caffeine] (CYP1A2) in 4 h plasma samples and the log ratio of [dextromethorphan]/[dextrorphan] (CYP2D6) in 8 h urine samples and the 4 h plasma concentrations of midazolam (CYP3A) after single administration or well-established three-drug cocktail of caffeine, omeprazole, and dextromethorphan were not significantly different from those after the new five-drug cocktail. In conclusion, the new five-drug cocktail regimen, named the "Inje cocktail," can be used as a tool to phenotype in vivo enzyme activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A with only 4 h blood sampling and 8 h urine collection following simultaneous administration of the five probe drugs.

Spontaneous bone formation on the maxillary sinus floor in association with an extraction socket.

A case is reported of spontaneous bone formation on the maxillary sinus floor associated with the extraction socket of a maxillary impacted tooth. An impacted maxillary second premolar of a 20-year-old male had been pushed into the maxillary sinus during surgical extraction. The tooth was removed using the sinus elevation technique. After 5 months of healing, the space between the sinus floor and the socket was filled with new bone. Later, implant surgery was successfully carried out without any sinus augmentation. Osteogenic activity of sinus mucosa and the blood clot in the extraction socket beneath the elevated sinus would have been important factors in this spontaneous bone formation.

Enhancing insecticidal efficacy of baculovirus by early expressing an insect neurotoxin, LqhIT2, in infected Trichoplusia ni larvae.

LqhIT(2), an insect specific neurotoxin from the venom of Leiurus quinquestriatus hebraeus, has been demonstrated to improve insecticidal efficacy of Autographa californica nuclear polyhedrosis virus (AcMNPV). A polyhedrin-positive recombinant AcMNPVvAcP(hsp70)EGFP/P(pag90)IT(2) was engineered for larvae to express the enhanced green fluorescence protein (EGFP) and LqhIT(2) under the control of P(hsp70) and P(pag90) promoters, respectively. This would allow a visual observation of the viral infection and an improvement of the insecticidal efficacy. The insecticidal activity of this recombinant baculovirus, a wild type AcMNPV and four other recombinant baculoviruses, was evaluated and compared in terms of mortality, body weight, median lethal time (LT(50)), and median lethal concentration (LC(50)). Insecticidal efficacy was unaltered when treated with vAcP(hsp70)EGFP, moderately improved when infected by vAcP(10)IT(2) (a P(10)-promoted LqhIT ( 2 ) gene), and significantly elevated when treated with vAcP(pag90)IT(2) or vAcP(hsp70)EGFP/P(pag90)IT(2). No apparent difference was observed in insecticidal efficacy when additional EGFP was expressed as a visible marker. These results suggest that recombinant AcMNPV vAcP(hsp70)EGFP/P(pag90)IT(2) may be used as an effective insecticide against Trichoplusia ni and other lepidopterous insect pests.

Inhibition of human cytochrome P450 isoforms and NADPH-CYP reductase in vitro by 15 herbal medicines, including Epimedii herba.

OBJECTIVE: We evaluated the potential of 15 herbal medicines (HMs), commonly used in Korea, to inhibit the catalytic activities of several cytochrome P450 (CYP) isoforms and microsomal NADPH-CYP reductase. METHODS: The abilities of 1-1000 microg/mL of freeze-dried aqueous extracts of 15 HMs to inhibit phenacetin O-deethylation (CYP1A2), tolbutamide 4-methylhydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), midazolam 1-hydroxylation (CYP3A4) and NADPH-CYP reductase were tested using human liver microsomes. RESULTS: The HMs Epimedii herba, Glycyrrhizae radix and Leonuri herba inhibited one or more of the CYP isoforms or NADPH-CYP reductase. Of the three HMs, Epimedii herba extracts were the most potent inhibitors of several CYP isoforms (IC(50) 67.5 microg/mL for CYP2C19, 104.8 microg/mL for CYP2E1, 110.9 microg/mL for CYP2C9, 121.9 microg/mL for CYP3A4, 157.8 microg/mL for CYP2D6 and 168.7 microg/mL for CYP1A2) and NADPH-CYP reductase (IC(50) 185.9 microg/mL ). CONCLUSION: These results suggest that some of the HMs used in Korea have the potential to inhibit CYP isoforms in vitro. Although the plasma concentrations of the active constituents of the HMs were not determined, some herbs could cause clinically significant interactions because the usual doses of those individual herbs are several grams of freeze-dried extracts. Controlled trials to test the significance of these results are necessary.

Stereoselective inhibition of cytochrome P450 forms by lansoprazole and omeprazole in vitro.

The stereoselectivity of the inhibitory interaction potential of lansoprazole and omeprazole isomers on six human cytochrome P450 forms was evaluated using human liver microsomes. Lansoprazole enantiomers showed stereoselective inhibition of CYP2C9-catalysed tolbutamide 4-methylhydroxylation, CYP2C19-catalysed S-mephenytoin 4'-hydroxylation, CYP2D6-catalysed dextromethorphan O-demethylation, CYP2E1-catalysed chlorzoxazone 6-hydroxylation and CYP3A4-catalysed midazolam 1-hydroxylation, whereas omeprazole only inhibited CYP2C19 stereoselectively. Of the P450 forms tested, CYP2C19-catalysed S-mephenytoin 4'-hydroxylation was extensively inhibited by both the lansoprazole and omeprazole enantiomers in a competitive and stereoselective manner; the S-enantiomers of both drugs inhibited the hydroxylation more than the R-enantiomers. The estimated K(i) values determined for CYP2C19-catalysed S-mephenytoin 4'-hydroxylation were 0.6, 6.1, 3.4 and 5.7 microM for S-lansoprazole, R-lansoprazole, S-omeprazole and R-omeprazole, respectively. The results indicate that although both lansoprazole and omeprazole are strong inhibitors of CYP2C19, the inhibition of CYP2C19 by lansoprazole is highly stereoselective, whereas the inhibition by omeprazole is less stereoselective. In addition, S-lansoprazole, the most potent CYP2C19 inhibitor, is not a good CYP2C19-selective inhibitor owing to its inhibition of other P450 forms.

Comparison of Current BLAST Software on Nucleotide Sequences.

The computational power needed for searching exponentially growing databases, such as GenBank, has increased dramatically. Three different implementations of the most widely used sequence alignment tool, known as BLAST (Basic Local Alignment Search Tool), are studied for their efficiency on nucleotide-nucleotide comparisons. The performance of these implementations are evaluated using target databases and query sequences of varying lengths and number of entries constructed from human genomic and EST sequences. In general, WU BLAST was found to be most efficient when the database and query composition are unknown. NCBI BLAST appears to work best when the database contains a small number of sequences, while mpiBLAST shows the power of database distribution when the number of bases per target database is large. The optimal number of compute nodes in mpiBLAST varies depending upon the database, yet in the cases studied, remains surprisingly low.