Validity of all the instruments

measuring QoL was confirmed.

Study findings suggest that QUALIDEM is the preferred instrument to evaluate QoL of residents in SHA, especially due to the high acceptability. Further research is needed to develop and improve these existing measurements.”
“Study Design. Retrospective cross-sectional study.

Objective. To evaluate the degree of postoperative pain and patients’ satisfaction after lumbar fusion from a nationwide survey in Korea.

Summary of Background Data. There have been few studies that investigated the factors related to patients’ satisfaction after spinal fusion in lumbar degenerative disease (LDD).

Methods. This study included 629 patients who underwent spinal fusion for LDD at clinics of designated members of the Korean Society of Spine Surgery. This survey was done in 123 hospitals with 171 spine surgeons. Questionnaires for patients included severity of present back pain and radicular pain GSK1904529A cost ( visual analog scale score), Oswestry Disability

Index (ODI), and subjective outcomes. Questionnaire buy AZD7762 for surgeons included preoperative diagnosis, level of fusion, operative method, and presumed patient’s pain.

Results. The patients were 199 men and 430 women, with mean age of 62.3 years. The mean visual analog scale score of back pain and radicular pain was 5.0 +/- 2.6 and 4.4 +/- 3.0, respectively. The mean ODI was 44.3 +/- 19.4. ODI was significantly increased with older age, workers’ compensation, and increased fusion extent. Correlated factors of dissatisfaction Staurosporine manufacturer were severe back pain, higher ODI, multiple operation, and insufficient explanation about postoperative pain. There was a significant correlation between preoperative explanation about postoperative pain and degree of patient’s

pain.

Conclusion. Patients’ satisfaction was not as high as expected after fusion for LDD. Therefore, the decision for performing a lumbar fusion in those patients must be done more carefully, and it should be explained more precisely that chronic pain may persist after spinal surgery.”
“This 24-week, multicenter, open-label trial was designed to evaluate the dosing, effectiveness, and safety of topiramate monotherapy for epilepsy and to identify patient and clinical characteristics predictive of optimally effective stabilized monotherapy doses. Of 406 randomized patients, 244 comprised the evaluable-for-efficacy Population (>= 12 weeks of treatment and stabilized topiramate dose during final 28 days): 2 13 were on topiramate monotherapy at the end of the trial. The mean stabilized daily dose of topiramate over the last 28 days of treatment (primary endpoint) was significantly lower for patients reporting one to three seizures (low seizure frequency, n = 147) than for those reporting more than three seizures (high seizure frequency, it = 66) during a 3-month retrospective baseline period (191 mg vs 239 mg, P = 0.003).

In conclusion, HBsAg detection levels varied among HBV genotypes. However, unique amino acid substitutions not linked to genotypes, such as T125M and T143M described here, should have more implications in HBV immunological diagnostics than the set of variations characteristic of each HBV genotype.”
“OBJECTIVE: The aim of this study was to determine the effects of occupational noise on sound localization in different spatial planes and frequencies among normal hearing firefighters.

METHOD: A total of 29 adults with pure-tone buy AP24534 hearing thresholds below 25 dB

took part in the study. The participants were divided into a group of 19 firefighters exposed to occupational noise and a control group of 10 adults who were not exposed to such noise. All subjects were assigned a sound localization task involving 117 stimuli from 13 sound sources that were spatially distributed in horizontal, vertical, midsagittal and transverse planes. The three stimuli, which were square waves with fundamental frequencies of 500, 2,000 and 4,000 Hz, were presented at a sound level of 70 dB and were randomly repeated three times from each sound source. The angle between the speaker’s axis in the same plane was 45, and the distance to the subject was 1 m.

RESULT: The results demonstrate that the sound localization ability of the firefighters was significantly

lower (p < 0.01) than that of the control group.

CONCLUSION: Exposure to occupational RG-7112 clinical trial noise, even when not resulting in hearing loss, may lead to a diminished ability to locate a sound source.”
“Laparoscopic mini-gastric bypass (MGBP) represents a simpler alternative to Roux-en-Y gastric bypass. The placement of a silastic ring (SR) may enhance excess weight loss and minimize weight regain. This study reports on the results of a consecutive cohort of patients undergoing SR-MGBP in a single centre.

Short- and medium-term outcomes 4EGI-1 chemical structure of 156 consecutive patients undergoing surgery between August 2005 and January 2008 were analysed. Weight loss, comorbidity resolution and morbidity/mortality

were assessed.

A total of 156 patients (78% female, 22% male) with a mean (range) age of 44 years (18-63), pre-operative weight of 129 kg (83-197) and body mass index of 46 kg/m(2) (35-64) underwent surgery. Eighty-seven percent had pre-operative comorbidities, and median (range) follow-up was 35 months (6-72). Mean (SD) % excess weight loss (EWL) at 6, 12, 24, 36 and 60 months was 74.6 (19.5), 93.4 (21.1), 98.8 (27.6), 93.5 (20.1) and 89 (16.1) respectively. Thirty-seven percent had complete resolution of comorbidities and 67.3% required vitamin/mineral supplementation. Overall, 10.3% patients suffered early complications, of which 7.7% were minor and 2.6% were major. A total of 45.5% patients suffered late complications, of which 34.6% were minor and 10.9% were major. Food intolerance/vomiting, bile reflux and stomal ulcer were seen in 18.6, 10.3 and 7.

We present the first known report of a Kawasaki disease case complicated with acute myocarditis and mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). These findings may be valuable for the diagnosis and treatment

of affected patients.”
“Diabetic macular edema (DME) is an advanced symptom of diabetic retinopathy and can lead to irreversible vision loss. In this paper, a two-stage methodology for the detection and classification of DME severity from color fundus images is proposed. DME detection is carried out via a supervised learning approach using the normal fundus images. A feature extraction mTOR inhibitor technique is introduced to capture the global characteristics of the fundus images and discriminate the normal from DME images. Disease severity

is assessed using a rotational asymmetry metric by examining the symmetry of macular region. The performance of the proposed methodology and features are evaluated against several publicly available datasets. The detection performance has a sensitivity of 100% with specificity between 74% and 90%. Cases needing immediate referral are detected with a sensitivity of 100% and specificity of 97%. The severity classification accuracy is 81% for the moderate case and 100% for severe cases. These results establish the effectiveness of the proposed solution.”
“Background and Objectives LDL apheresis is used to treat patients with familial hypercholesterolaemia, and low-volume plasmapheresis MK-2206 research buy for plasma donation may similarly click here lower cholesterol levels in some donors. This study was designed to assess the effect of plasmapheresis on total, LDL and HDL cholesterol levels in a plasma donor population.

Materials and Methods This was a prospective, unblinded longitudinal cohort study in which a blood sample was obtained for analysis before each donation. Data from 663 donors were analysed using a multivariable repeated measures regression model with a general estimating equations approach with changes in cholesterol as the primary outcome measure.

Results

The model predicted a significant decrease in total and LDL cholesterol for both genders and all baseline cholesterol levels (P < 0.01). The greatest total cholesterol decreases (women, -46.8 mg/dL; men, -32.2 mg/dL) were associated with high baseline levels and 2-4 days between donations. Small but statistically significant increases (P <= 0.01) in HDL cholesterol were predicted for donors with low baseline levels.

Conclusions These results suggest that, in donors with elevated baseline cholesterol levels, total and LDL cholesterol levels may decrease during routine voluntary plasmapheresis.”
“Methods. aEuro integral Topical ocular prophylaxis must be instituted early after birth. Recommended prophylactic regimen are: 1%% nitrate solution; 1%% tetracycline solution; 1%% erythromycin solution; 2.5%% povidone-iodine solution; and fusidic acid.

Results.

“
“OBJECTIVE: To estimate the risk of metastatic disease in microinvasive adenocarcinoma of the cervix in a large cohort.

METHODS: Thirty-six cases were identified from the Mayo Clinic

health information database, and 30 cases were identified using the University of Southern California gynecologic oncology patient database. Histopathology was reviewed by a single pathologist at each institution to confirm histologic subtype and grade of tumor, depth of invasion, linear extent of the tumor, the presence or absence of lymphovascular space invasion, margin status, parametrial involvement, and the presence of nodal metastasis.

RESULTS: Fifty-two patients had stage IA1 cancers and 14 had stage IA2 cancers. Therapy ranged from cold knife conization to radical

hysterectomy Dibutyryl-cAMP with lymphadenectomy. No parametrial involvement was noted in any selleck chemical of the patients who underwent parametrial resection. One patient with stage IA1 cancer had micrometastasis to a pelvic lymph node. No recurrences were noted with an average follow-up of 80 months.

CONCLUSION: The management of microinvasive adenocarcinoma remains controversial, and radical therapy is applied more frequently to microinvasive adenocarcinoma than microinvasive squamous cell carcinoma of the cervix. The risk of extracervical disease is low and the risk of recurrence is not affected by the radicality find more of resection. Our data suggest that microinvasive adenocarcinoma is amenable to treatment with nonradical surgery. (Obstet Gynecol 2010;116:1150-7)”
“The role of surgery for gastric linitis plastica (GLP) is questioned. This study aimed to analyze our experience in the surgical treatment of GLP with specific reference to the resectability rate, prognosis, and mode of recurrence.

Results of surgery

were analyzed in 102 patients with GLP.

Of the 102 patients, 92 underwent surgical exploration, with resection performed in 60 cases. R2 resection was carried out in 20 patients and R1 in 12 patients, while the resection was considered potentially curative (R0) in 28 (27.5%). Overall, the median (95% confidence interval [CI]) survival time was 5.7 (3.7-7.5) months, with none of the patients alive at the end date of the study. For R0 patients the median (95% CI) survival time was 15.8 (11-20.7) months. The great majority of recurrences were intra-abdominal (peritoneal and/or locoregional), with a systemic component of the relapse that was rarely observed (5 cases).

After primary surgery, GLP showed a poor prognosis without regard to the extent or type of resection. The failure of surgical treatment related mainly to the peritoneal spread of the disease. Specifically designed multimodality treatment protocols should be tested in this setting.

More studies are needed to evaluate the validity of TEG in the prediction of bleeding risk and the safety of this regional technique in a mildly coagulopathic patients.”
“Systemic

lupus erythematosus in some cases is characterized for development of thrombotic events with a significantly increased risk of mortality. The frequencies and clinical associations of Ser(413)/Cys(413) PAI-2 polymorphism in 40 systemic lupus erythematosus, 50 rheumatoid arthritis patients, and 100 healthy subjects frequency were investigated. The Ser(413)/Ser(413) genotype was 53% (lupus), 36% (rheumatoid arthritis), and 35% (healthy subjects). The Ser(413) allele was associated with systemic lupus erythematosus (P =.04, odds ratio 1.76, 95% confidence interval = 1,01-3.06). KU-57788 datasheet In all, 4 patient carriers of Ser(413)/Ser(413) genotype, developed thrombotic events. The lupus patients identified with Ser(413)/Ser(413) genotype showed an increased damage (57%), compared with Ser(413)/Cys(413) and Cys(413)/Cys(413)

genotypes, with significant difference (P =.03). These findings suggest an association selleckchem of Ser(413)/Ser(413) genotype with greater damage index score and Ser(413) allele with Systemic lupus erythematosus. Besides, PAI-2 polymorphism Could be related with thrombotic phenomena in systemic lupus erythematosus”
“Background: Cardiovascular diseases represent the major cause of mortality in hemodialysis (HD) patients. HD increases oxidative stress and oxidation of low-density lipoprotein (LDL) is a crucial step in the development of atherosclerosis. Vitamin E has been shown to reduce LDL oxidation. Our aim was to test the effect of a single HD P505-15 session and chronic vitamin E supplementation on LDL oxidizability in HD patients.

Methods: LDL susceptibility to copper-induced oxidation (lag-phase, LP) was measured in 19 HD patients, both immediately before and after hemodialysis; 18 age-matched healthy subjects served as controls. Both pre-HD and post-HD measurements were repeated after 12 weeks of vitamin E supplementation (800 IU/day)

in a placebo-controlled, randomized design.

Results: At baseline, HD patients showed hypertriglyceridemia, a significant triglyceride enrichment in LDL and HDL and an enhanced LDL resistance to oxidation (186 +/- 6 vs. 163 +/- 4 min, p<0.003). A single HD session decreased (to 172 +/- 6 min, or -8%, p<0.002), and chronic vitamin E administration increased, LDL resistance to oxidation (+19%, p = 0.002 vs. placebo) without changing the serum lipid profile or lipoprotein lipid composition.

Conclusions: We conclude that in patients on chronic hemodialysis, hypertriglyceridemia and triglyceride enrichment of LDL and HDL particles are associated with increased resistance of LDL to in vitro oxidation despite the fact that each dialysis session acutely increases LDL oxidizability. Vitamin E supplementation improves LDL resistance to oxidation without modifying circulating lipid levels and partitioning.

Their thermosensitive behaviors in a buffer solution comprising sodium chloride, sodium citrate, and sodium dodecyl sulfate, which are generally used in biochips, were investigated. At low temperatures, the gel in the buffer solution was absolutely transparent. However,

when the gel was heated, it became milky white or opaque without changes in the gel size. It is well known that the network or cross-link distribution of the high throughput screening assay transparent gel is homogeneous macroscopically, whereas that of the opaque gel is inhomogeneous; in other words, the network of the opaque gel consists of coarse and dense parts. The structural changes in the gel network were confirmed by the temperature dependence of the permeability of the buffer solution through the semi-IPN gel membrane. The permeability increased stepwise when the gel became

opaque due to selleck kinase inhibitor heating. The structural changes in the semi-IPN gel network depended on the compositions of the buffer solution and gel, i.e., the copolymerization ratio of NIPAM in the gel and the content of the poly(NIPAM) molecules in the gel. These results suggest that the thermosensitive behaviors of the semi-IPN gel strongly depend on the interactions between the copolymerized NIPAM in the gel network and the poly(NIPAM) molecules. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 122: 15301537, 2011″
“Photodynamic therapy (PDT) is a minimally invasive treatment for cervical intraepithelial neoplasia. The purpose of this study was to assess the feasibility and effectiveness of PDT in patients with CIN and high-risk HPV infection.

Five patients diagnosed CIN 2 or CIN 3 with human papillomavirus (HPV) infection were included. Each patient had gynecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy. Two grams of 5-aminolevulinic acid (ALA) gel (118 mg/g) was topically applied to the cervix and covered with a special plastic cap for 3-4 h, followed

by 20 min illumination of both ecto- and endo-cervical canal with red coherent light (wavelength 633 nm) using a PDT laser and a special light catheter. The PDT therapy was repeated with an interval of 1 week. Follow-up examination including biopsy and histology, colposcopy, HPV DNA testing were carried CT99021 price out after 3, 6 and 9 months.

Treatment could be accomplished in all cases and no severe side effect was encountered. All the CIN2 patients had a complete response for 9 months and one CIN3 HPV remained positive for 6 months after three or four treatments.

PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects and can be easily performed on outpatient basis.”
“Using molecular dynamics simulations, we study axial compressive behavior of single-walled carbon nanotubes (SWCNTs) with a wide range of aspect ratios (length to diameter ratio). It is shown that the difference in aspect ratio leads to distinct buckling modes in SWCNTs.

A total of 231 patients affected by mCRC (55% males; mean age 63.7 +/- 10.31 yrs) were studied. Total direct costs per patient per month in capecitabine and 5-FU groups were (sic)1,001.66 +/- (sic)434.93 GS-9973 mouse and (sic)3,172.81

+/- (sic)1,232.37 respectively (p<0.0001). Oral capecitabine therapy cost the health service less than intravenous therapies.”
“The aim of this study was to conduct a randomized, double-blind and placebo-controlled study to investigate the effects of D-004, a lipid extract of the Roystonea regia fruit that prevents testosterone-and phenylepinephrine-induced prostate hyperplasia in rodents, on plasma oxidative markers in healthy men. We enrolled male volunteers (20-55 years) in good health and without lower urinary tract symptoms. Thirty-four eligible participants were randomized to placebo or D-004 (320 mg) capsules administered daily for 6 weeks. An interim check-up and a final visit were conducted after 3 and 6 weeks of therapy, respectively. Physical examinations were performed at each visit, and laboratory tests were performed at baseline and at treatment completion. Oxidative variables

included plasma malondialdehyde (MDA), total hydroxyperoxides (TOH), sulphydryl (SH) groups and total antioxidant status (TAS). We assessed treatment compliance and addressed adverse experiences (AEs) at weeks 3 and 6. At week 6, with D-004, the mean reductions of plasma MDA (26.7%), TOH (18.8%) Y-27632 in vivo and SH groups (31.6%), and the mean

increase of TAS (35.3%) were significantly different from those of placebo (P < 0.001 for plasma TAS, P < 0.0001 for all other comparisons). D-004 did not differ from the placebo in safety indicators. There were two withdrawals (both in the D-004 group), with one due to dyspepsia (the only AE during the trial). In conclusion, D-004 displayed antioxidant effects on plasma oxidative markers in healthy men, which was consistent with findings from laboratory experimental studies.”
“We have studied electric field induced (Stark) shifts in mid-infrared (IR) transitions that occur in type II AlSb/InAs/GaSb quantum wells. Because of the spatial separation of the electron AZD8055 in vitro and hole wave functions in the type II system, the potential drop between the layers dominates the shift in the real-space-indirect transition energies when an external electric field is applied. This can result in either a redshift or a blueshift, depending on the ordering of the quantum well layers within the intrinsic region of a p-i-n diode. The case in which a reverse bias on the diode yields a blueshift in the transition energy is of particular interest for IR electro-optic device applications. The modulator section of an integrated source/waveguide modulator would strongly absorb at zero bias and could be biased into transparency, and bistable optical switches could be made more efficient than with redshifting devices.

OBJECTIVE: A reverse blot hybridisation assay, REBA Myco-ID, was applied to formalin-fixed

paraffin-embedded (FFPE) tissue showing granulomatous lymphadenitis to define the causative agents.

DESIGN: A total of 119 granulomatous lymphadenitis cases observed between 2000 and 2010 were studied. All tissue samples were treated by haematoxylin and eosin and Ziehl-Neelsen stain. Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) were identified using the REBA Myco-ID assay, and resistance to rifampicin (RMP) and isoniazid (INH) was determined using REBA MTB-MDR (R).

RESULTS: Of the 119 cases, 113 (95%) were positive see more with the REBA Myco-ID assay, while 20 (16.8%) were positive on acid-fast bacilli smear. Of the 113 positive REBA Myco-ID cases, 110 (92.43%) were identified as M. tuberculosis, 2 (1.7%) as NTM, and 1 (0.8%)

as coinfection with M. tuberculosis and M. chelonae. Only 1 (0.9%) of the 110 M. tuberculosis cases was identified as RMP-resistant.

CONCLUSION: REBA Myco-ID is a highly sensitive and specific assay for detecting M. tuberculosis and NTM. M. tuberculosis is the main cause of granulomatous lymphadenitis.”
“Introduction and FK228 objectives. To determine the prevalence of acute myocardial infarction (AMI) without classical risk factors, and to ascertain whether affected patients exhibit a higher prevalence of emergent risk factors and whether the presence of specific emergent risk factors influence prognosis at 6 months.

Methods. The FORTIAM (Factores Ocultos de Riesgo Tras un Infarto Agudo de Miocardio) study is a multicenter cohort study that includes 1371 AMI patients who were admitted within 24 hours of symptom onset. Strict definitions were used for classical risk factors and the concentrations of the following markers were determined: lipoprotein (a) [Lp(a)], oxidized low-density lipoprotein (oxLDL), high-sensitivity C-reactive protein, Fosbretabulin mw fibrinogen, homocysteine and antibody to Chlamydia. The end-points observed during the

6-month follow-up were death, angina and re-infarction.

Results. The prevalence of AMI without classical risk factors was 8.0%. The absence of classical risk factors did not affect the 6-month prognosis. The only emergent risk factors independently associated with a poorer prognosis were the Lp(a) and oxLDL concentrations. Cut-points were determined using smoothing splines: 60 mg/dL for Lp(a) and 74 U/L for oxLDL. The associated hazard ratios, adjusted for age, sex and classical risk factors, were 1.40 (95% confidence interval, 1.06-1.84) and 1.48 (95% confidence interval, 1.06-2.06), respectively.

Conclusions. The proportion of AMI patients without classical risk factors was low and their prognosis was similar to that in other AMI patients. Both oxLDL and Lp(a) concentrations were independently associated with a poorer 6-month prognosis, irrespective of the presence of classical risk factors.”
“SETTING: Villa Marelli Institute (VMI), Niguarda Ca’Granda Hospital, Milan, Italy.

To analyse the mutants further, zyp1, the maize orthologue of the Arabidopsis central element component ZYP1 was cloned and an antibody was made against it. Cytoskeletal Signaling inhibitor Using antibodies against ZYP1 and the lateral element components AFD1 and ASY1, it was found that most mutants form normal SCs but are defective in pairing. The large number of non-homologous synapsis mutants defective in pairing illustrates that synapsis and pairing can be uncoupled. Of the ten mutants studied, only dsy2 undergoes normal homologous chromosome recognition needed for homologous

pairing. The dsy2 mutation fails to maintain the SC. ZYP1 elongation is blocked at zygotene, and only dots of ZYP1 are seen at prophase I. Another mutant, mei*N2415 showed incomplete but homologous synapsis and ASY1 and AFD1 have a normal distribution. Although installation of ZYP1 is initiated at zygotene, its progression is slowed down and not completed by pachytene in some cells and ZYP1 is not retained on pachytene chromosomes. The mutants described here are now available through the Maize Genetics Cooperation Stock Center (http://maizecoop.cropsci.uiuc.edu/).”
“Herein, we report the study of singlet energy transfer dynamics in 3-MA molecular weight two host-guest systems: CNPPP (poly [2-(6'-cyano-6'-methylheptyloxy)-1,4-phenylene]) as host in both and as guests btpIr (iridium (III) bis[2-(2'-benzothienyl) pyridinato-N,C(3)']

(acetylacetonate)) and Irppy (fac tris(2-phenylpyridine) iridium (III), two triplet emitters. In both systems, the energy transfer was evaluated using the Forster transfer model. Utilizing time-resolved and stationazry measurements, it could be concluded that the behavior of both systems was in good

agreement with the proposed model. In addition, this analysis provides a clear indication to the homogenous distribution of the dopants. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3631784]“
“Increasing amounts of plastic waste in the environment have become a problem of gigantic proportions. The case of linear low-density polyethylene (LLDPE) is especially significant as it is widely used for packaging and other applications. This synthetic polymer is normally not biodegradable until it is degraded into low molecular mass fragments that can be assimilated by microorganisms. Blends of nonbiodegradable polymers and biodegradable PF-00299804 nmr commercial polymers such as poly (vinyl alcohol) (PVA) can facilitate a reduction in the volume of plastic waste when they undergo partial degradation. Further, the remaining fragments stand a greater chance of undergoing biodegradation in a much shorter span of time. In this investigation, LLDPE was blended with different proportions of PVA (530%) in a torque rheometer. Mechanical, thermal, and biodegradation studies were carried out on the blends. The biodegradability of LLDPE/PVA blends has been studied in two environments: (1) in a culture medium containing Vibrio sp.

This prospective study evaluates the predictive value of intrahepatic, peripheral blood mononuclear cells (PBMCs) and blood TAC concentrations during the early postliver transplantation (LT) period. In a cohort of 90 adult liver recipients under TAC-based monotherapy, NU7441 price liver biopsies were performed at day 7 post-LT, and PBMCs TAC concentrations were measured at day 1, 3, 5, and 7 post-LT. Both intrahepatic and PBMCs TAC concentrations were determined. All biopsies were graded following the Banff scoring. Intrahepatic, and day 3, 5, 7 PBMCs concentrations correlated very well with day 7 liver Banff rejection scores (P < 0.05). Clinical rejection was characterized by significantly

lower mean TAC PBMCs concentrations at day 5 and 7 (P < 0.05) and tended to be associated to lower mean intrahepatic TAC concentrations at day 7 (P = 0.059). Intrahepatic TAC concentrations at day 7 significantly correlated with TAC PBMCs concentrations from day 5 post-LT (P < 0.05). TAC PBMCs concentrations might be reliable markers of immunosuppression efficacy during the early phase after LT. This finding could represent an additional tool to individualize more precisely early immunosuppressive this website schemes after liver transplantation.”
“Study Design. Controlled, interventional, animal study. Objective. To examine the involvement of high-mobility group box 1 (HMGB1)

in the neuropathic pain state induced by the CYT387 clinical trial application of nucleus pulposus onto the dorsal root ganglion (DRG) and to investigate the effect of HMGB1 neutralization antibody in the pathogenesis.

Summary of Background Data. HMGB1 is a potent proinflammatory mediator when present extracellularly, and anti-HMGB1 neutralization antibody inhibits inflammation, cytokine expression, and macrophage activation.

Methods. Thirty-nine

adult female Sprague-Dawley rats (200-300 g) were used. The left L5/6 facet joint was removed, and the L5 DRG was exposed. Nucleus pulposus harvested from the tail was applied to the left L5 DRG. Then, 400 mu g of anti-HMGB1 neutralization antibody was administered intraperitoneally after surgery. Behavioral testing using von Frey hairs was performed to investigate the mechanical withdrawal threshold. Neuronal damage was investigated by counting the number of activating transcription factor 3 (ATF3) neurons. The expressions of tumor necrosis factor-alpha (TNF-alpha) and HMGB1 were measured by double-labeled immunohistochemistry and immunoblotting.

Results. Immunoblotting of harvested nucleus pulposus revealed HMGB1 in the nucleus pulposus. Double-labeled immunohistochemistry revealed that macrophages in the applied nucleus pulposus expressed HMGB1 and TNF-alpha. Administration of anti-HMGB1 neutralization antibody significantly reduced the TNF-alpha expression in the DRG and improved the pain-related behavior from day 2 to day 14.

Conclusion.