Predictors for clinical outcomes of tubular surgery for endoscopic decompression in selected patients with lumbar spinal stenosis.

INTRODUCTION: The success rate of decompression surgery for lumbar spinal stenosis (LSS) has been reported to vary from 60 to 80%. The purpose of this study was to analyze the predictors for clinical outcomes after tubular surgery for endoscopic decompression (microendoscopic decompression) for LSS. MATERIALS AND METHODS: A total of 100 patients with degenerative LSS (M/F: 61/39, Age: mean 69.7 years), who underwent microendoscopic decompression and had a minimum 2-year follow-up (FU) after surgery, were reviewed. All patients suffered from leg-related symptoms predominantly without severe mechanical back pain, preoperatively. The presence of chronic arterial occlusion of the lower limbs was ruled out. The primary outcome measure was clinical evaluation at 2-year FU using the Oswestry Disability Index (ODI). Furthermore, numeric rating scales, Japanese Orthopedic Association (JOA) lumbar score and JOA Back Pain Evaluation Questionnaire were used for secondary outcome measures. Based on findings of univariable analyses, multivariable logistic regression analysis was applied to identify preoperative predictors for the clinical outcomes. RESULTS: Sixty-eight patients (68%) were assessed as good outcomes, on the basis of minimum clinically important difference of the ODI (13 points ≤) and final ODI score (< 30 points). The secondary outcomes were further support for the primary outcome. In multivariable logistic regression analysis, co-existence of intradiscal vacuum phenomenon with LSS (odds ratio [OR] 8.26; 95% confidence interval [95% CI] 2.32-29.34; p = 0.001) and ischemic cardiovascular comorbidities (OR, 13.3; 95% CI, 1.9-92.57; p = 0.009) were significantly associated with poor clinical outcomes. CONCLUSIONS: We found co-existence of intradiscal vacuum phenomenon with LSS and ischemic cardiovascular comorbidity to be preoperative predictors of less favorable clinical outcomes after microendoscopic decompression in selected patients of LSS. Although the conclusion obtained from restricted state, the information would be able to help in patient selection of the tubular surgery for endoscopic decompression for LSS.

Contribution of Severe Dental Caries Induced by Streptococcus mutans to the Pathogenicity of Infective Endocarditis.

Streptococcus mutans, a major pathogen of dental caries, is regarded as a causative agent of infective endocarditis (IE), which mainly occurs in patients with underlying heart disease. However, it remains unknown whether severe dental caries that extend to pulp space represent a possible route of infection. In the present study, we evaluated the virulence of S. mutans for IE development using rats with concurrent severe dental caries and heart valve injury. Dental caries was induced in rats through the combination of a caries-inducing diet and the administration of S. mutans into the oral cavity. Then, the heart valves of a subset of rats were injured using a sterile catheter and wire under general anesthesia. The rats were euthanized at various times with various stages of dental caries. The number of teeth affected by dental caries with pulp exposure was increased in the rats in a time-dependent manner. S. mutans was recovered from injured heart tissue, which was mainly observed in rats with higher number of S. mutans bacteria in mandibular bone and a larger number of teeth in which caries extended to pulp. Dental caries was more severe in rats with heart injury than in rats without heart injury. Sequencing analysis targeting 16S rRNA revealed that specific oral bacteria appeared only in rats with heart injury, which may be related to the development of dental caries. Our findings suggest that dental caries caused by the combination of S. mutans infection and sucrose intake may contribute to S. mutans colonization in injured heart tissue.

Discovery of Novel 7-[(1R,5S)-1-Amino-5-fluoro-3-azabicyclo[3.3.0]octan-3-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropane]-8-(methoxy or methyl)quinolones.

A series of 8-methoxy or 8-methylquinolones bearing novel 3-aminooctahydrocyclopenta[c]pyrrole derivatives at the C-7 position was synthesized, and the pharmacological, physicochemical, and toxicological properties of the individual compounds were evaluated. Novel 8-methylquinolone 7, which includes a 3-amino-7-fluorooctahydrocyclopenta[c]pyrrole moiety at the C-7 position, showed potent antibacterial activity against both Gram-positive and negative pathogens. Compound 7 also demonstrated favorable pharmacokinetic and pharmacodynamic properties and an acceptably safe toxicological profile. Consequently, compound 7 was selected as a clinical candidate.

Discovery and structure-guided fragment-linking of 4-(2,3-dichlorobenzoyl)-1-methyl-pyrrole-2-carboxamide as a pyruvate kinase M2 activator.

Tumor cells switch glucose metabolism to aerobic glycolysis by expressing the pyruvate kinase M2 isoform (PKM2) in a low active form, providing glycolytic intermediates as building blocks for biosynthetic processes, and thereby supporting cell proliferation. Activation of PKM2 should invert aerobic glycolysis to an oxidative metabolism and prevent cancer growth. Thus, PKM2 has gained attention as a promising cancer therapy target. To obtain novel PKM2 activators, we conducted a high-throughput screening (HTS). Among several hit compounds, a fragment-like hit compound with low potency but high ligand efficiency was identified. Two molecules of the hit compound bound at one activator binding site, and the molecules were linked based on the crystal structure. Since this linkage succeeded in maintaining the original position of the hit compound, the obtained compound exhibited highly improved potency in an in vitro assay. The linked compound also showed PKM2 activating activity in a cell based assay, and cellular growth inhibition of the A549 cancer cell line. Discovery of this novel scaffold and binding mode of the linked compound provides a valuable platform for the structure-guided design of PKM2 activators.

[A case of laryngeal necrosis following concurrent chemoradiotherapy for advanced hypopharyngeal cancer after insertion of a nasogastric tube].

A 62-year-old male with cT4bN2cM0 hypopharyngeal carcinoma with ipsilateral vocal cord fixation was initially treated with concurrent chemoradiotherapy. Since the patient complained of dysphagia caused by mucositis, a nasogastric tube was placed on the day of irradiation with a dose of 20 Gy. Bilateral vocal cord fixation and laryngeal necrosis became evident 3 weeks after the concurrent chemoradiotherapy. He underwent a total pharyngolaryngectomy (neck dissection, and reconstruction with a free jejunal graft) followed by adjuvant chemotherapy. It is highly suspected that the nasogastric tube compressed the mucosa of the post cricoid region, resulting in laryngeal necrosis.

Knee extensor strength is associated with Mini-Mental State Examination scores in elderly men.

The present study examined whether the strength capability of knee extensor muscles is associated with global cognitive function, assessed by Mini-Mental State Examination (MMSE), in non-disabled elderly men. Isometric torques during maximal voluntary knee extension, plantar flexion, and elbow flexion and MMSE scores were determined in 39 non-disabled men aged 61-79 years and used for the cross-sectional analysis examining the associations among the measured variables. Moreover, 27 of the subjects participated in a training program consisted of body mass-based exercises (sitting down onto and standing up from a chair, hip joint extension and flexion, calf raises, side leg raises, and trunk flexion and extension) 6 days a week for 3 months. Isometric torques and MMSE scores were determined after the intervention. Among the data before intervention, only knee extension torque (KET) and KET relative to body mass (KET/BM) significantly correlated to the MMSE scores: r = 0.579 (P < 0.0001) for KET and r = 0.520 (P < 0.001) for KET/BM. After the intervention, KET and KET/BM increased significantly, but MMSE score did not. However, the absolute change in MMSE scores was significantly associated with that in KET (r = 0.381, P < 0.05) and KET/BM (r = 0.422, P < 0.05). These findings indicate that the strength capability of knee extensors is associated with global cognitive function in non-disabled elderly men, and provide a new perspective to a general concept that exercises strengthening knee extensor muscles should be included in resistance training programs for elderly individuals.

Clinical characteristics of children and guardians possessing CBP-positive Streptococcus mutans strains: a cross-sectional study.

Streptococcus mutans is a major etiological agent for dental caries. We previously demonstrated that S. mutans strains expressing collagen-binding proteins (CBPs) were related to the pathogenesis of systemic diseases. However, their acquisition and colonization remain unknown. Here, we investigated the detection rates of CBP-positive S. mutans strains in children and their guardians to clarify the background for the acquisition and colonization in children. Saliva samples were collected from children and their mothers, and detection of S. mutans and collagen-binding genes (cnm, cbm) was performed by PCR after DNA extraction. The oral status of each child was examined, and their mothers were asked to complete a questionnaire. The isolation rate of Cnm-positive S. mutans was significantly higher in mothers than in children. Notably, the possession rates of CBP-positive strains in children were significantly higher in children whose mothers had CBP-positive strains than in children whose mothers did not have these strains. Furthermore, children with CBP-positive strains had a significantly shorter breastfeeding period than children without these strains. The present results suggest that nutritional feeding habits in infancy are one of the factors involved in the acquisition and colonization of CBP-positive S. mutans strains.

Inhibitory effect of toothbrush monofilament containing surface pre-reacted glass-ionomer (S-PRG) filler on Streptococcus mutans.

The oral environment affects not only oral health, but also general health, and the importance of oral self-care has recently been recognised. Although toothbrushes are the most important self-care product, there are few toothbrushes that have an inhibitory effect on oral bacteria. In the present study, monofilaments used for toothbrushes containing surface pre-reacted glass-ionomer (S-PRG) filler (a component recently applied to various dental materials) were developed. Among nylon and polyester monofilaments commonly used for toothbrushes, nylon monofilaments can accommodate more S-PRG filler than polyester monofilaments, resulting in greater release of ions from the S-PRG filler. These monofilaments containing S-PRG filler formed less biofilm containing Streptococcus mutans, a major pathogen of dental caries, than monofilaments without S-PRG filler. Moreover, S. mutans adhering to monofilaments containing S-PRG filler were more easily exfoliated and eliminated than those adhering to monofilaments without S-PRG filler. Such inhibitory effects on S. mutans were more marked in nylon monofilaments than in polyester monofilaments. These findings that monofilaments containing S-PRG filler can release ions and have an inhibitory effect on S. mutans suggest that they may be an effective material for toothbrushes.

Occipital bone erosion induced by C1 pedicle screw as a late complication of atlantoaxial fixation: a case report and literature review.

PURPOSE: The objective of this case report is to highlight occipital bone erosion as an unusual late complication of C1-C2 instrumented fixation. CASE PRESENTATION: A 60-year-old man of a displaced Anderson type II odontoid fracture was surgically treated by C1-C2 pedicle screw fixation. Occipital bone erosions, caused by a repeat irritation of the end of rod to the occipital bone, were detected on multiplane reconstructed computed tomography at 3 months after surgery. The lesion progressed over time with increasing the C2 anteversion on radiological evaluations. Eventually, the bony shell had been reactively formed around the protruded screw-rod construct and the Oc-C1 segment had been spontaneously stabilized. Fortunately, he had experienced no symptoms caused by the lesion at 5-year follow-up. CONCLUSION: The occipital bone erosion is an unusual late complication in C1-C2 posterior fixation using C1 pedicle screw. The increasing occipital-C1 lordosis compensating for the great C2 anteversion (high C2 slope) was related to the progression of the lesion. In C1-C2 pedicle screw fixation, surgeons should recognize a possibility of this complication and realize a relation between the occurrence of the lesion and the sagittal alignment of the cervical spine to take measures to avoid the complication.

Inhibitory effect of a gel paste containing surface pre-reacted glass-ionomer (S-PRG) filler on the cariogenicity of Streptococcus mutans.

Surface pre-reacted glass-ionomer (S-PRG) filler is a bioactive functional glass that releases six different ions. Although several dental materials containing S-PRG filler have been developed, few self-care products containing S-PRG filler have been reported. We investigated the inhibitory effects of PRG gel paste containing S-PRG filler on Streptococcus mutans, a major pathogen of dental caries. PRG gel paste inhibited bacterial growth of S. mutans in a concentration-dependent manner, and all S. mutans were killed in the presence of ≥ 1% PRG gel paste. Additionally, it was difficult for S. mutans to synthesize insoluble glucan from sucrose in the presence of 0.1% PRG gel paste. A biofilm formation model was prepared in which slices of bovine enamel were infected with S. mutans after treatment with or without PRG gel paste. Biofilm formation was inhibited significantly more on the enamel treated with PRG gel paste than on enamel without PRG gel paste (P < 0.001). The inhibitory effects on bacterial growth and biofilm formation were more prominent with PRG gel paste than with S-PRG-free gel paste, suggesting that PRG gel paste may be effective as a self-care product to prevent dental caries induced by S. mutans.

Isolated sphenoid sinus opacification is often asymptomatic and is not referred for otolaryngology consultation.

Isolated sphenoid sinus opacifications (ISSOs) are clinically important because they can lead to serious complications. However, some patients with ISSOs are asymptomatic, and not all patients are properly referred to the otolaryngology department. Because past studies of ISSOs focused only on patients who received treatment, in this study we selected ISSO cases based on radiology reports, then determined whether these patients had symptoms and were appropriately referred for specialty care. We conducted a retrospective analysis of data collected from patients who underwent computed tomography or magnetic resonance imaging from January 2007 to March 2017 at Osaka General Medical Center. We searched for the terms "sphenoid" or "sphenoidal" using F-REPORT to identify patients who had a sphenoid disease. We checked all selected images and diagnosed ISSOs. Examination of 1115 cases revealed 223 cases of ISSOs, of whom 167 (74.9%) were asymptomatic. We categorized patients with ISSOs into four groups: inflammation, mucocele, fungal diseases, and unclassifiable; the final category was used when edges were irregular or complete opacity was encountered. In the unclassifiable group, the majority of cases required otolaryngology consultation, but 37 of 47 unclassifiable patients did not have an otolaryngology visit. ISSOs are often identified by chance on imaging tests performed by non-otolaryngologists. However, our study revealed that many patients with ISSOs who should be treated by otolaryngologists were not referred to the otolaryngology department. Accordingly, it is important to promote awareness of the disease among other types of clinicians.

Xanthine oxidase-derived reactive oxygen species mediate 4-oxo-2-nonenal-induced hepatocyte cell death.

Among the aldehydes derived from lipid peroxidation, there have been several reports concerning the toxicity of 4-hydroxy-2-nonenal (4-HNE), whereas little information is available about 4-oxo-2-nonenal (4-ONE). In the present study, we examined the effects of 4-HNE and 4-ONE on the cell viability of primary rat hepatocyte cultures. At concentrations of 5, 10, and 20 µM, 4-HNE had no significant effect on the cell viability of primary rat hepatocytes cultures, whereas 4-ONE potently decreased the cell viability in a dose-dependent manner (5-20 µM, 23-69% inhibition). The TUNEL assay showed that 4-ONE causes apoptosis in the cells. 4-ONE also increased 2',7'-dichlorofluorescein-fluorescence intensity from 2',7'-dichlorodihydrofluorescein, an indicator of reactive oxygen species (ROS) generation. Allopurinol, a xanthine oxidase (XO) inhibitor, diminished the 4-ONE-induced increase in the 2',7'-dichlorofluorescein-fluorescence intensity and the decrease in viability, indicating the role of XO in mediating 4-ONE-induced cell death. These observations suggest that 4-ONE has the potential to induce liver cell death via XO-derived ROS generation.

[A case of advanced adenocarcinoma of the ethmoid sinus treated by chemoradiation with S-1].

We report a case of advanced adenocarcinoma in the left ethmoid sinus invading the frontal sinus, the frontal skull base and the orbits(T4bN0M0 and Stage IVB). With the goal of functional preservation, we carried out radiation therapy with total 60 Gy irradiation and chemotherapy with S-1 80 mg/body/day before a radical operation. The tumor clinically disappeared without surgical treatment, and there was no sign of recurrence for 2.5 years. When we decide the treatment policy for advanced adenocarcinoma of the ethmoid sinus, chemoradiotherapy wit S-1 might be one of the effective treatments before radical operation to control the disease with preservation of functions.

Automatic Segmentation of the Paranasal Sinus from Computer Tomography Images Using a Probabilistic Atlas and a Fully Convolutional Network.

In this paper, we present an automatic approach to paranasal sinus segmentation in computed tomography (CT) images. The proposed method combines a probabilistic atlas and a fully convolutional network (FCN). The probabilistic atlas was used to automatically localize the paranasal sinus and determine its bounding box. The FCN was then used to automatically segment the paranasal sinus in the bounding box. Comparing our proposed method with the conventional FCN (without probabilistic atlas) and the state-of-the-art method using active contour with group similarity, the proposed method demonstrated an improvement in the paranasal sinus segmentation. The segmentation accuracy (Dice coefficient) was about 0.83 even for the case with unclear boundary.

Sphenopalatine artery surgery for refractory idiopathic epistaxis: Systematic review and meta-analysis.

OBJECTIVES: Epistaxis, especially posterior epistaxis, is occasionally refractory to treatment. In these cases, sphenopalatine artery surgeries, including cauterization and ligation, are required. Previous reports have demonstrated treatment results for these procedures but failed to provide high-level evidence. The aim of this study was to quantify the rates of failure and perioperative complications of these procedures by using a meta-analysis technique. METHODS: We systematically searched electronic databases and identified articles regarding epistaxis, sphenopalatine artery ligation, or cauterization. Pooled rebleeding and complication rates were calculated by using a random effects model. RESULTS: A total of 896 cases of sphenopalatine ligation or cauterization for epistaxis were analyzed. Pooled rebleeding rates for the entire cohort, cauterization group, and ligation group were 13.4% (95% confidence interval [CI] 10.0-17.8, P < 0.001), 7.2% (95% CI 4.6-11.0, P < 0.001), and 15.1% (95% CI 9.8-22.5, P < 0.001), respectively. Pooled perioperative complication rates for the entire cohort, cauterization group, and ligation group were 8.7% (95% CI 4.9-15.1, P < 0.001), 10.2% (95% CI 3.8-24.5, P < 0.001), and 6.4% (95% CI 1.8-20.9, P < 0.001), respectively. CONCLUSION: Overall, sphenopalatine surgery for refractory epistaxis is an effective method because of its low rates of failure and complications. Cauterization is more effective than ligation, whereas complications are comparable between the two procedures. Laryngoscope, 129:1731-1736, 2019.

Design, Synthesis, and Biological Evaluation of Novel 7-[(3 aS,7 aS)-3 a-Aminohexahydropyrano[3,4- c]pyrrol-2(3 H)-yl]-8-methoxyquinolines with Potent Antibacterial Activity against Respiratory Pathogens.

Novel 7-[(3 aS,7 aS)-3 a-aminohexahydropyrano[3,4- c]pyrrol-2(3 H)-yl]-6-fluoro-1-[(1 R,2 S)-2- fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 5 (DS21412020) was designed and synthesized to obtain potent antibacterial drugs for the treatment of respiratory tract infections. Compound 5 possessing a trans-fused pyranose ring on the pyrrolidine moiety at the C-7 position of the quinolone scaffold exhibited potent in vitro antibacterial activity against respiratory pathogens, including quinolone-resistant and methicillin-resistant Staphylococcus aureus (QR- MRSA) and quinolone-resistant Escherichia coli (QR- E. coli). Furthermore, compound 5 showed in vivo activity against the experimental murine pneumonia model due to penicillin-resistant Streptococcus pneumoniae ( PRSP) and favorable profiles in preliminary toxicological and nonclinical pharmacokinetic studies. In particular, the reduced lipophilicity and basicity of compound 5 as compared to those of the previously synthesized carba-type compound 4 resulted in a significant reduction in the human ether-a-go-go (hERG) related gene channel inhibition, which have the potential to prolong the QT interval.

Surgical Outcomes of Minimally Invasive Stabilization for Spinal Fractures in Patients with Ankylosing Spinal Disorders.

STUDY DESIGN: A retrospective study. PURPOSE: To evaluate the clinical and radiological outcomes of ankylosing spinal disorder (ASD) patients with spinal fractures treated by minimally invasive stabilization (MISt) using percutaneous pedicle screws (PPSs). OVERVIEW OF LITERATURE: ASDs, such as ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH), increase susceptibility to spinal fractures because of extremely decreased spinal flexibility. Such fractures tend to be unstable and, consequently, should be treated with multiple-segmental internal fixation. However, conventional internal fixation procedures can severely damage the soft tissue, resulting in severe hemorrhage. Therefore, MISt is the preferred approach to treat spinal fractures in ASD patients. METHODS: Nine ASD patients (four males and five females; three AS and six DISH patients) with spinal fractures who were treated by MISt using PPSs, were reviewed from April 2009 to August 2016. One patient died of aspiration pneumonia during follow-up (FU), and the remaining eight patients underwent clinical and radiological evaluation. RESULTS: The mean age at surgery was 79.6 years (range, 68-95 years). The mean duration of postoperative FU was 14.2 months (range, 3-30 months). All treated fractures were anterior and posterior element injuries with distraction. Three patients presented delayed onset preoperative neurological deficit following trauma. The mean operation time was 179.6 minutes (range, 92-340 minutes). The mean hemorrhage was 103.6 mL (range, unquantifiable to 480 mL). Radiological evaluations at FU showed preservation of the acceptable postoperative correction of the fractured vertebra, as there were no re-collapses of the fractured vertebrae during FU. CONCLUSIONS: ASD patients must be acknowledged as highly susceptible to unstable spinal fractures, even after relatively mild trauma. MISt using PPSs may be an effective treatment for spinal fractures in such patients.

Minimally Invasive Transtubular Endoscopic Decompression for L5 Radiculopathy Induced by Lumbosacral Extraforaminal Lesions.

STUDY DESIGN: Retrospective study. PURPOSE: This study aimed to evaluate the efficacy of minimally invasive transtubular endoscopic decompression for the treatment of lumbosacral extraforaminal lesion (LSEFL). OVERVIEW OF LITERATURE: Conventional procedures for surgical decompression for the treatment of LSEFL involve certain technical challenges because the lumbosacral extraforaminal region has unique anatomical features. Moreover, the efficacy of minimally invasive procedures performed via the posterolateral approach for LSEFL has been reported. METHODS: Twenty-five patients who had undergone minimally invasive transtubular endoscopic decompression for the treatment of LSEFL and could be followed up for at least 1 year postoperatively were enrolled. Five of these patients had a history of lumbar surgery, and seven had concomitant adjacent-level spinal stenosis. The clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) lumbar score, numeric rating scale (NRS), and the JOA Back Pain Evaluation Questionnaire (JOABPEQ). The mean postoperative follow-up (FU) duration was 3.8 years. RESULTS: All procedures could be completed without any severe surgical complications, and all patients could resume their previous activity level within 1 month postoperatively. The JOA score significantly increased from 14.1±4.0 at baseline to 23.1±3.7 at the 1-year FU and 22.1±3.8 at the last FU. Similarly, there were significant improvements in the postoperative NRS and JOABPEQ scores. An additional surgery was performed in two patients (8%) during the FU period. Patients with degenerative scoliosis exhibited significantly poorer outcomes compared with those without this condition. CONCLUSIONS: Transtubular endoscopic decompression can overcome certain technical challenges involved in the conventional procedures for LSEFL treatment; therefore, it can be recommended as a useful procedure for treating LSEFL. This procedure can provide some benefits to LSEFL patients and offer a well-illuminated surgical field and high surgical safety for the surgeon. However, the procedure should be carefully adapted for LSEFL patients with concomitant degenerative scoliosis.

A case of adult congenital laryngeal cleft asymptomatic until hypopharynx cancer treatment.

Laryngeal cleft is an anomaly of failed posterior closure of the larynx. Most cases are diagnosed and need treatment early in life due to respiratory and swallowing problems. We report an unusual case of a 66-year-old man with an asymptomatic laryngeal cleft until treatment for hypopharyngeal cancer. During concurrent chemoradiotherapy (CCRT), despite reduced tumor volume, he presented severe dysphagia and dyspnea, followed by severe pneumonia twice. Because CCRT had to be discontinued, a pharyngolaryngectomy was performed for the cancer treatment. The resected specimen showed total removal of the tumor and a total longitudinal cleft of the cricoid cartilage, classified as a type III laryngeal cleft by the Benjamin and Inglis' classification. A review of computed tomography images indicated that the redundant mucosa from bilateral edges closed the separation of the posterior cricoid cartilage and narrowed the laryngeal airway during CCRT. Adult presentations of laryngeal cleft are quite rare with only ten reported cases in English literature; the present case is of the oldest patient. Undiagnosed cases with laryngeal cleft may exist asymptomatically or without severe symptoms. The awareness of this condition may increase its diagnosis as a cause of diseases such as aspiration and recurrent pneumonia even in adult patients.

Exploration of DPP-IV inhibitors with a novel scaffold by multistep in silico screening.

Dipeptidyl peptidase-IV (DPP-IV), an enzyme that degrades incretins-hormones that promote insulin secretion-is a therapeutic target for type 2 diabetes, with a number of its inhibitors having been launched as therapies for diabetes. Since adverse effects of these inhibitors have recently been reported, the development of novel DPP-IV inhibitors with higher efficacy and safety is required. We, therefore, screened for novel DPP-IV inhibitors using the combination of an in silico drug discovery technique and a DPP-IV assay system. We initially selected seven candidate compounds as DPP-IV inhibitors from a database consisting of four million compounds by a multistep in silico screening procedure combining pharmacophore-based screening, docking calculation and the analysis of three-dimensional quantitative structure-activity relationship. We then measured the inhibitory activity of the selected compounds and identified a hit compound. In addition, we discuss the structure-activity relationship between the binding mode model and inhibitory activity of the hit compound.