A population-based study identifies an association of THBS2 with intervertebral disc degeneration.

OBJECTIVE: To clarify the genetic mechanisms underlying intervertebral disc degeneration (IDD), we examined the associations between single-nucleotide polymorphisms (SNPs) and indicated as coefficient of interaction term (IDD) in a general population in Japan. METHODS: This was a cross-sectional study. In 1,605 participants, C2-3 to L5/S1 in the total spine magnetic resonance imaging (MRI) were evaluated using the Pfirrmann's scoring system. Disc scores of 4 and 5 were defined as IDD. Eight SNPs in eight genes associated with IDD were examined at each disc level, considering the non-genetic risk factors of age, sex, and body mass index (BMI). RESULTS: The highest odds ratio was found for rs9406328 in the THBS2 gene at disc level T12-L1 (OR 1.27, 95%CI 1.05 to 1.53), and this association was strengthened after adjustment for age using logistic regression (OR 1.37, 95%CI 1.12 to 1.67). Among participants aged <50 years and 50-59, the average IDD score in those with 2 risk alleles of rs9406328 was markedly higher than in those with 0 or 1 risk allele, and the difference is much wider than the elderly participants. It indicates the genetic effect of rs9406328 is stronger in the younger age groups. Finally, multiple linear regression analyses of the association between rs9406328 and IDD, adjusted for age, sex, and BMI at each disc level, showed a statistical interaction between age and the number of risk alleles at C7-T1, T3-4 and T4-T5 as well as T12-L1. CONCLUSION: CONCLUSION: The association between rs9406328 in THBS2 and IDD was replicated. The contributions of genetic and environmental factors to IDD differed by disc level.

Association Between Tacrolimus Pharmacokinetics and Cytochrome P450 3A5 and Multidrug Resistance Protein 1 Exon 21 Polymorphisms.

BACKGROUND: Individual differences in the pharmacokinetics (PK) of tacrolimus (TAC), an immunosuppressive drug, are reportedly associated with single-nucleotide polymorphisms (SNPs) of cytochrome P450 (CYP) 3A5 and multidrug resistance protein 1 (MDR1). We determined the effect of SNPs in CYP3A5 and MDR1 exons 21 and 26 on TAC PK parameters. METHODS: Thirty-eight Japanese patients who underwent renal transplantation were genotyped for CYP3A5 and exons 21 and 26 of MDR1 with the use of polymerase chain reaction-restriction fragment length polymorphism analysis. TAC concentrations were determined 3 weeks after renal transplantation and PK parameters calculated. RESULTS: The area under the blood concentration-time curve (AUC) in CYP3A5 expressers was significantly higher than that in CYP3A5 nonexpressers (CYP3A5*3/*3). Patients with the MDR1 exon 21 A allele (G2677A) showed higher dose-adjusted AUC (AUC/D) and lower doses of TAC than those who did not possess that allele. Furthermore, patients with both CYP3A5*3/*3 and MDR1 G2677A showed significantly lower TAC doses and higher dose-adjusted trough levels (C/D) and AUC/D than those without those genotypes. There was no significant association between MDR1 exon 26 polymorphism and the PK of TAC. CONCLUSIONS: Patients with both CYP3A5*3/*3 and MDR1 G2677A had higher blood TAC concentrations than those without those genotypes. Japanese patients should be carefully monitored for consideration of lower TAC doses, because 24% of Japanese patients have double mutations.

Removal of anti-Stokes emission background in STED microscopy by FPGA-based synchronous detection.

In stimulated emission depletion (STED) microscopy, the role of the STED beam is to de-excite, via stimulated emission, the fluorophores that have been previously excited by the excitation beam. This condition, together with specific beam intensity distributions, allows obtaining true sub-diffraction spatial resolution images. However, if the STED beam has a non-negligible probability to excite the fluorophores, a strong fluorescent background signal (anti-Stokes emission) reduces the effective resolution. For STED scanning microscopy, different synchronous detection methods have been proposed to remove this anti-Stokes emission background and recover the resolution. However, every method works only for a specific STED microscopy implementation. Here we present a user-friendly synchronous detection method compatible with any STED scanning microscope. It exploits a data acquisition (DAQ) card based on a field-programmable gate array (FPGA), which is progressively used in STED microscopy. In essence, the FPGA-based DAQ card synchronizes the fluorescent signal registration, the beam deflection, and the excitation beam interruption, providing a fully automatic pixel-by-pixel synchronous detection method. We validate the proposed method in both continuous wave and pulsed STED microscope systems.

CO2 low-level laser therapy has an early but not delayed pain effect during experimental tooth movement.

OBJECTIVES: To test the hypothesis that the use of low-level laser therapy (LLLT) reduces elevated pain by controlling the release of neurochemicals during orthodontic tooth movement. SETTING AND SAMPLE POPULATION: Department of Orthodontics and Dentofacial Orthopedics, Okayama University. Sixty-five Sprague Dawley rats were subjected to tooth movement and LLLT. MATERIALS AND METHODS: Adult Sprague Dawley rats were used in this study. Groups included day 0 controls, irradiation only controls and with or without irradiation sacrificed at 1, 3, 5, 7 and 14 days after tooth movement (n=5 each, total n=65). Tooth movement was achieved by insertion of an elastic module between molar teeth. Immunohistochemistry for CD-11b, GFAP and c-fos in the brain stem was performed. Stains were quantified by constructing a three-dimensional image using IMARIS, and counted using NEURON TRACER and WinROOF software. Two-way ANOVA followed by a Tukey's post hoc test (P<.05) was used for statistical comparison between groups. RESULTS: C-fos expression was significantly increased at one and three days after tooth movement. LLLT significantly diminished this increase in c-fos expression only at one day after tooth movement CD-b11 and GFAP expression also significantly increased after tooth movement. No significant change was observed for CD-11b and GFAP expression in the central nervous system upon LLLT. CONCLUSION: Low-level laser therapy may reduce early neurochemical markers but have no effect on delayed pain neurochemical markers after tooth movement.

Impact of surgical margins on survival of 37 dogs with massive hepatocellular carcinoma.

AIMS: To compare the survival of dogs with completely resected massive hepatocellular carcinoma (HCC) with that of dogs in which HCC were incompletely excised. METHODS: A retrospective cohort study was conducted. Dogs that underwent surgical excision of massive HCC between November 2006 and April 2015 were included. Dogs that died in the perioperative period or were lost to follow-up within 2 months after surgery were excluded. Data were collected from the medical records and a single pathologist examined all available histology slides to confirm the diagnosis of HCC. Surgical margins were defined as complete if no neoplastic cells were seen at the edge of excised tissues, based on original histopathology reports. Progression-free survival (PFS) and overall survival (OS) were compared between dogs with complete surgical margins (CM) and those with incomplete margins (IM) using a log-rank test. RESULTS: Of the 37 dogs included in the study, 25 were allocated to the CM group and 12 to the IM group. Progressive local disease developed after surgery in three dogs in the CM group and seven dogs in the IM group. Three dogs in the CM group and five dogs in the IM group died due to tumour progression. Median PFS was longer for dogs in the CM group (1,000 (95% CI=562-1,438) days) compared to dogs in the IM group (521 (95% CI=243-799) days; p=0.007). OS was also longer for dogs in the CM group (>1,836 days) compared to those in the IM group (median 765 (95% CI=474-1,056) days; p=0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Compared with complete resection, incomplete resection decreased PFS and OS in dogs with massive HCC. Dogs with incompletely excised HCC should be closely monitored for local recurrence, although median OS was >2 years following incomplete excision. Further prospective studies are warranted to confirm these findings.

Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan.

Recent studies revealed that a substantial proportion of patients with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harbor fusions involving tyrosine kinase and cytokine receptors, such as ABL1, PDGFRB, JAK2 and CRLF2, which are targeted by tyrosine kinase inhibitors (TKIs). In the present study, transcriptome analysis or multiplex reverse transcriptase-PCR analysis of 373 BCP-ALL patients without recurrent genetic abnormalities identified 29 patients with kinase fusions. Clinically, male predominance (male/female: 22/7), older age at onset (mean age at onset: 8.8 years) and a high white blood cell count at diagnosis (mean: 94 200/µl) reflected the predominance of National Cancer Institute high-risk (NCI-HR) patients (NCI-standard risk/HR: 8/21). Genetic analysis identified three patients with ABL1 rearrangements, eight with PDGFRB rearrangements, two with JAK2 rearrangements, three with IgH-EPOR and one with NCOR1-LYN. Of the 14 patients with CRLF2 rearrangements, two harbored IgH-EPOR and PDGFRB rearrangements. IKZF1 deletion was present in 16 of the 22 patients. The 5-year event-free and overall survival rates were 48.6±9.7% and 73.5±8.6%, respectively. The outcome was not satisfactory without sophisticated minimal residual disease-based stratification. Furthermore, the efficacy of TKIs combined with conventional chemotherapy without allogeneic hematopoietic stem cell transplantation in this cohort should be determined.

Radioresistance of cancer stem-like cell derived from canine tumours.

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are a small subpopulation of cancer cells that are responsible for the initiation, recurrence and metastasis of cancer. We previously demonstrated that, using the Hoechst 33342 dye-based side population technique, CSCs/CICs in canine lung adenocarcinoma cell line exist. In this study, as CSCs/CICs are known to form spheres in anchorage-independent environment in vitro, we evaluated the stemness of spheroid cells derived from canine lung adenocarcinoma and osteosarcoma cells by expression of stemness markers, and investigated radioresistance. Spheroid cells showed greater expression of stemness markers Oct-4 and CD133 gene than those of adherent-cultured cells. In nude mouse xenograft models, spheroid cells showed higher tumourigenic ability than adherent-cultured cells. In addition, spheroid cells showed significantly resistant against radioactivity as compared with adherent-cultured cells. These results suggest that spheroid cells could possess stemness and provide a CSCs/CICs research tool to investigate CSCs/CICs of canine tumour cells.

A software tool for tomographic axial superresolution in STED microscopy.

A method for generating three-dimensional tomograms from multiple three-dimensional axial projections in STimulated Emission Depletion (STED) superresolution microscopy is introduced. Our STED< method, based on the use of a micromirror placed on top of a standard microscopic sample, is used to record a three-dimensional projection at an oblique angle in relation to the main optical axis. Combining the STED< projection with the regular STED image into a single view by tomographic reconstruction, is shown to result in a tomogram with three-to-four-fold improved apparent axial resolution. Registration of the different projections is based on the use of a mutual-information histogram similarity metric. Fusion of the projections into a single view is based on Richardson-Lucy iterative deconvolution algorithm, modified to work with multiple projections. Our tomographic reconstruction method is demonstrated to work with real biological STED superresolution images, including a data set with a limited signal-to-noise ratio (SNR); the reconstruction software (SuperTomo) and its source code will be released under BSD open-source license.

Early use of allogeneic hematopoietic stem cell transplantation for infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia.

Sixty-two infants with MLL gene-rearrangement-positive acute lymphoblastic leukemia (MLL-r ALL) were treated with the MLL03 protocol of the Japanese Pediatric Leukemia/Lymphoma Study Group: short-course intensive chemotherapy followed by early allogeneic hematopoietic stem cell transplantation (HSCT) within 4 months of the initial induction. The 4-year event-free survival and overall survival rates were 43.2% (95% confidence interval (CI)=30.7-55.1%) and 67.2% (53.8-77.4%), respectively. A univariate analysis showed younger age (<90 days at diagnosis), central nervous system disease and poor response to initial prednisolone therapy significantly associated with poor prognosis (P<0.05). In a multivariate analysis, younger age at diagnosis tended to be associated with poor outcome (hazard ratio=1.969; 95% CI=0.903-4.291; P=0.088). Although the strategy of early use of HSCT effectively prevented early relapse and was feasible for infants with MLL-r ALL, the fact that substantial number of patients still relapsed even though transplanted in their first remission indicates the limited efficacy of allogeneic HSCT for infants with MLL-r ALL. Considering the risk of severe late effects, indications for HSCT should be restricted to specific subgroups with poor risk factors. An alternative approach incorporating molecular-targeted drugs should be established.

Preoperative oral supplementation support in patients with esophageal cancer.

OBJECTIVE: Surgeries for cancer of the esophagus are still associated with a high rate of postoperative morbidity. There are few reports of perioperative nutritional support for patients undergoing esophageal cancer surgery, and there is insufficient evidence to recommend routine use of immunonutrition in these patients. The aim of this study was to determine whether preoperative immunonutrition positively influences key clinical outcomes such as postoperative infectious complications, mortality, length of hospital stay, and short-term survival in this population. DESIGN AND SETTING: We undertook a retrospective investigation of the effects of preoperative nutritional support on the postoperative course of esophageal cancer surgery at the Department of Gastroenterological Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan. PARTICIPANTS: Fifty-five patients who underwent esophagectomy for esophageal cancer were included in this study. Of the 55 patients, 26 patients consumed a liquid dietary supplement (IMPACT group) before surgery and 29 patients did not (STANDARD group). INTERVENTION: Before surgery, the IMPACT group consumed 750 ml (3 packs)/day of Impact for 5 consecutive days. MEASUREMENTS: The analysis was based on postoperative complications, hospital mortality, length of hospital stay, and short-term survival. RESULTS: Significantly fewer patients developed postoperative infections in the IMPACT group compared with the STANDARD group (p=.007): 4 of 21 patients in the IMPACT group and 10 of 29 patients in the STANDARD group. Either an infectious complication or another complication developed in 8 patients in the IMPACT group and 13 patients in the STANDARD group, with the result that 6 patients in the STANDARD group died of postoperative complications (p=.001). The duration of hospitalization was 34 days in the IMPACT group and 48 days in the STANDARD group; hence, hospitalization was significantly shorter in patients treated with Impact (p=.008). The mean 6-month survival rates for the IMPACT group and the STANDARD group were 92% (24/26) and 72% (21/29), respectively (p=.028). CONCLUSION: Simple preoperative supplementation significantly improved outcome. Administration of the supplemental diet before esophageal surgery appeared to be an effective strategy in reducing infectious complications, mortality, and hospitalization, and improving short-term survival.

Bacterial loads of Ureaplasma urealyticum contribute to development of urethritis in men.

Ureaplasma urealyticum could be a pathogen of non-gonococcal urethritis (NGU) in men. However, ureaplasma is often detected in men without NGU, and the proportion of cases possibly attributable to this pathogen is still undefined. We attempted to determine the bacterial loads of U. urealyticum significantly associated with NGU. The 16S rRNA genes of U. urealyticum were quantified by a real-time polymerase chain reaction-based assay in first-void urine (FVU) from 26 asymptomatic and 25 symptomatic men positive for U. urealyticum. The leucocyte counts in first-void urine (FVU) were determined as an objective measure of inflammatory response to ureaplasma in the hosts by automated quantitative urine particle analysis. Positive correlations were observed between copies of the 16S rRNA genes of U. urealyticum per ml and the leucocyte counts per µl in FVU (r = 0.49, p = 0.0003). Loads of ≥10(4) copies of the 16S rRNA gene of U. urealyticum/ml, corresponding to ≥5 × 10(3) cells of U. urealyticum/ml in FVU, were significantly associated with the presence of urethritis symptoms (p < 0.0001) and with higher leukocyte counts in FVU (p < 0.0001). The bacterial load of U. urealyticum, possibly of ≥5 × 10(3) cells of U. urealyticum/ml in FVU, could be significantly associated with the development of symptomatic NGU.

Orthodontic miniscrew failure rate and root proximity, insertion angle, bone contact length, and bone density.

OBJECTIVES: To test the hypothesis that there is no significant correlation between miniscrew failure rate and root proximity, insertion angle, bone contact length, and bone density. SETTING AND SAMPLE POPULATION: This study included 107 patients in whom 190 miniscrews had been placed from April 2008 to October 2009 in Tohoku University Hospital (Sendai, Japan). MATERIALS AND METHODS: Cone beam computed tomography scans (CBCT) and periapical radiographs were taken before and after miniscrew placement. Differences in root proximity, screw insertion angle, bone contact length, and bone density were statistically compared; comparisons were also made between the CBCT images and periapical radiographs. RESULTS: A significantly higher success rate was observed in the maxilla than in the mandible. The distance between the miniscrew and the root surface was significantly smaller in the failure group. There were no significant differences in the insertion angle, bone contact length, or bone density between the success group and the failure group. The concordance rate between the periapical dental radiographs and CBCT images was 46.5%. CONCLUSION: While bone contact length, miniscrew angle, and bone density did not exert major effects on miniscrew failure, root proximity was the factor that most affected miniscrew failure, especially for miniscrews placed in the mandible. CBCT was superior to periapical dental X-rays for evaluating the proximity of miniscrews to the root. Correction of the X-ray attenuation coefficient value was necessary for measuring bone density using CBCT.

Effect of conversion from twice-daily to once-daily tacrolimus on glucose intolerance in stable kidney transplant recipients.

BACKGROUND: Tacrolimus is an established immunosuppressant for the prevention and treatment of allograft rejection in organ transplantation. However, tacrolimus therapy also has several adverse effects. The main aim of this study was to evaluate the effect of conversion from twice-daily tacrolimus (tacrolimus-BID) to once-daily tacrolimus (tacrolimus-OD) on glucose intolerance in stable kidney transplant patients. METHODS: The study comprised 43 kidney transplant recipients with stable renal function. The same 1 mg:1 mg dose conversion was used for all patients. Follow-up, which included clinical evaluation and laboratory testing, was performed at 30, 60, and 120 days after conversion. The parameters for which the baseline and end-point values were determined included homeostasis model assessment of beta-cell function (HOMA-B) scores, hemoglobin A(1c) (HbA(1c)) levels, serum insulin levels, and fasting glucose levels. RESULTS: The tacrolimus trough levels did not differ significantly at 120 days after conversion. There was a significant increase in serum insulin level at 120 days after conversion (baseline, 5.6 ± 2.7 µU/mL; end point, 6.6 ± 3.4 µU/mL; P < .009). The HOMA-B score slightly increased (baseline, 58.7 ± 33.1; end point, 65.6 ± 32.8; P = .091) at 120 days after conversion, indicating beta-cell function. Serum creatinine concentration, blood glucose level, and HbA(1c) level did not change significantly during follow-up examinations. Episodes of acute rejection or graft loss did not occur. CONCLUSION: The results of this study suggests that conversion from tacrolimus-BID to tacrolimus-OD may benefit kidney transplant patients with glucose intolerance because of improved insulin secretion. Further studies involving a larger sample population and longer follow-up time are required to verify the results of this study.

Rapamycin causes upregulation of autophagy and impairs islets function both in vitro and in vivo.

Autophagy is a lysosomal degradation process of redundant or faulty cell components in normal cells. However, certain diseases are associated with dysfunctional autophagy. Rapamycin, a major immunosuppressant used in islet transplantation, is an inhibitor of mammalian target of rapamycin and is known to cause induction of autophagy. The objective of this study was to evaluate the in vitro and in vivo effects of rapamycin on pancreatic ß cells. Rapamycin induced upregulation of autophagy in both cultured isolated islets and pancreatic ß cells of green fluorescent protein-microtubule-associated protein 1 light chain 3 transgenic mice. Rapamycin reduced the viability of isolated ß cells and down-regulated their insulin function, both in vitro and in vivo. In addition, rapamycin increased the percentages of apoptotic ß cells and dead cells in both isolated and in vivo intact islets. Treatment with 3-methyladenine, an inhibitor of autophagy, abrogated the effects of rapamycin and restored ß-cell function in both in vitro experiments and animal experiments. We conclude that rapamycin-induced islet dysfunction is mediated through upregulation of autophagy, with associated downregulation of insulin production and apoptosis of ß cells. The results also showed that the use of an autophagy inhibitor abrogated these effects and promoted islet function and survival. The study findings suggest that targeting the autophagy pathway could be beneficial in promoting islet graft survival after transplantation.

Relationship between bone fragility of the mandibular inferior cortex and tooth loss related to periodontal disease in older people.

OBJECTIVE: The purpose of this study was to evaluate the relationship between bone fragility of the mandibular inferior cortex and tooth loss in older adults by accounting for periodontal disease and bone metabolism markers. RESEARCH DESIGN: A total of 177 subjects aged 77 years participated in this study. We counted the number of remaining teeth. The mandibular cortex condition was examined using the mandibular inferior cortex classification (MICC) on dental panoramic radiographs. The mandibular inferior cortex was detected on both sides of the mandible, distally from the mental foramen (C1, normal; C2, mild/moderate erosion; C3, severe erosion). Multiple linear regression analysis was performed to assess the relationship between the mandibular cortex condition with the MICC and the number of remaining teeth after controlling for confounding factors such as gender, the percentage of sites with > or = 4 mm clinical attachment levels, and serum osteocalcin levels. RESULTS: The mean +/- SD number of remaining teeth of MICC C1, C2 and C3 were 20.7 +/- 7.5, 14.6 +/- 8.1 and 4.0 +/- 0.0 for males, and MICC C1, C2, and C3 were 21.7 +/- 7.6, 17.2 +/- 8.0, and 16.2 +/- 10.4 for females. The MICC was significantly associated with the number of remaining teeth using multiple linear regression analysis (beta = -0.21, p = 0.031). CONCLUSION: This study suggests that there is a relationship between bone fragility of the mandibular inferior cortex and tooth loss related to periodontal disease.

Identification of cancer stem cells derived from a canine lung adenocarcinoma cell line.

Accumulating evidence supporting the cancer stem cell (CSC) hypothesis is based on the finding that tumors contain a small population of self-renewing cells that generate differentiated progeny and thereby contribute to tumor heterogeneity. CSCs are reported to exist in several human cancers, yet only a few reports demonstrate the existence of CSCs in primary lung cancer in dogs. In this study, the authors established a cancer cell line derived from a canine primary lung adenocarcinoma and identified a side population (SP) of cells that displayed drug-resistant features. To confirm the characteristics of these SP cells, the authors investigated the tumorigenicity of the cells in vivo by using a nude mouse xenograft model. Only 100 SP cells were able to give rise to new tumors, giving a 10-fold enrichment over the main population (MP) of cells, suggesting that these cells have the cancer-initiating ability of CSCs. Further studies characterizing CSCs in canine lung adenocarcinoma might contribute to the elucidation of the mechanisms of tumorigenesis and to the establishment of novel therapeutic strategies.

Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian regions, 2007-2008.

Long-term surveillance of antimicrobial resistance in Neisseria gonorrhoeae has been conducted in the World Health Organization (WHO) Western Pacific Region (WPR) to optimise antibiotic treatment of gonococcal disease since 1992. In 2007 and 2008, this Gonococcal Antimicrobial Surveillance Programme (GASP) was enhanced by the inclusion of data from the South East Asian Region (SEAR) and recruitment of additional centres within the WPR. Approximately 17,450 N. gonorrhoeae were examined for their susceptibility to one or more antibiotics used for the treatment of gonorrhoea by external quality controlled methods in 24 reporting centres in 20 countries and/or jurisdictions. A high proportion of penicillin and/or quinolone resistance was again detected amongst isolates tested in North Asia and the WHO SEAR, but much lower rates of penicillin resistance and little quinolone resistance was present in most of the Pacific Island countries. The proportion of gonococci reported as 'resistant', 'less susceptible' or 'non-susceptible' gonococci to the third-generation cephalosporin antibiotic ceftriaxone lay in a wide range, but no major changes were evident in cephalosporin minimal inhibitory concentration (MIC) patterns in 2007-2008. Altered cephalosporin susceptibility was associated with treatment failures following therapy with oral third-generation cephalosporins. There is a need for revision and clarification of some of the in vitro criteria that are currently used to categorise the clinical importance of gonococci with different ceftriaxone and oral cephalosporin MIC levels. The number of instances of spectinomycin resistance remained low. A high proportion of strains tested continued to exhibit a form of plasmid mediated high level resistance to tetracyclines. The continuing emergence and spread of antibiotic resistant gonococci in and from the WHO WPR and SEAR supports the need for gonococcal antimicrobial resistance surveillance programs such as GASP to be maintained and potentially expanded.

Effects of CO2 laser irradiation of the gingiva during tooth movement.

Patients often feel pain or discomfort in response to orthodontic force. It was hypothesized that CO(2) laser irradiation may reduce the early responses to nociceptive stimuli during tooth movement. The distribution of Fos-immunoreactive (Fos-IR) neurons in the medullary dorsal horn of rats was evaluated. Two hrs after tooth movement, Fos-IR neurons in the ipsilateral part of the medullary dorsal horn increased significantly. CO(2) laser irradiation to the gingiva just after tooth movement caused a significant decrease of Fos-IR neurons. PGP 9.5- and CGRP-positive nerve fibers were observed in the PDL of all study groups. The maximum temperature below the mucosa during CO(2) laser irradiation was less than 40 degrees C. It was suggested that CO(2) laser irradiation reduced the early responses to nociceptive stimuli during tooth movement and might not have adverse effects on periodontal tissue.