CCI Group Research Articles

Therapeutic Effect of Tetrapanax papyriferus and Hederagenin on Chronic Neuropathic Pain of Chronic Constriction Injury of Sciatic Nerve Rats Based on KEGG Pathway Prediction and Experimental Verification.

Background Hederagenin is one of the main components of Tetrapanax papyriferus, and Tetrapanax papyriferus is one of the ingredients of Danggui Sini decoction. To explore whether Tetrapanax papyriferus and hederagenin can alleviate mechanical pain, thermal hyperalgesia, and cold pain at the same time, we comprehensively investigated the effects of two drugs on the levels of p38 MAPK phosphorylation, TRP proteins, and IL1β, IL6, and TNF-α in serum. Methods Firstly, we obtained pain-related targets and performed KEGG pathway enrichment on these targets. Then, 42 SD rats were separated randomly into six groups: sham operation group, CCI group, pregabalin group, mecobalamin group, Tetrapanax papyriferus group, and hederagenin group. All drugs were given orally. Rats in the sham operation group and CCI group were gavaged with saline. Rats in the pregabalin group were given pregabalin, while rats in the mecobalamin group were given mecobalamin. Rats in the Tetrapanax papyriferus group were given Tetrapanax papyriferus, while rats in the hederagenin group were given hederagenin. Besides, we conducted behavioral tests including acetone test, hot plate experiment, and von Frey filaments, and then dorsal root ganglion neurons were taken out on the 21st day after operation. Then, western blot, ELISA, and hematoxylin-eosin staining were conducted. Results Rats in the CCI group were more sensitive to hyperalgesia and allodynia to mechanical and thermal stimuli, as well as cold pain. All four drugs could relieve these pains. Pregabalin, mecobalamin, and Tetrapanax papyriferus can reduce the levels of IL1β, IL6, and TNF-α in serum compared to those of the CCI group. The expression of TRPM8, TRPA1, TRPV1, TRPV4, and phosphorylated p38 MAPK in DRG increased evidently on the 21st day after the operation in the CCI group. All four drugs could reduce the expressions of TRPM8, TRPA1, TRPV1, TRPV4, and phosphorylated p38 MAPK in dorsal root ganglion compared to those of the CCI group. Conclusion Tetrapanax papyriferus and hederagenin relieved sciatica by reducing inflammation levels, inhibiting p38 MAPK phosphorylation, and decreasing the levels of dorsal root ganglion proteins.

The role of phosphorylated c-Jun N-terminal kinase in Ginkgo biloba extract in ameliorating neuropathic pain

Objective To investigate the role of phosphorylated c-Jun N-terminal kinase (p-JNK) in Ginkgo biloba extract (EGb761) to alleviate neuropathic pain. Methods A total of 90 male SD rats were randomly divided into 5 groups (n=18): a sham operation group (group Sham), chronic constriction injury group (group CCI), EGb 50 mg/kg+CCI group (group EGb50), EGb 100 mg/kg+CCI group (group EGb100) and a solvent control+CCI group (group SC). Rats in group CCI were subjected to ligation of the left sciatic nerve, while those in group Sham underwent nerve separation without ligation. Other groups were intraperitoneally injected with EGb761 or solvent from day 3 after successful modeling to 14 d after surgery. Paw withdraw thermal latency (PTWL) and paw mechanical withdrawal threshold (PMWT) were measured 2 d before and 1, 3, 5, 7, 10 d and 14 d after surgery. Then, the ipsilateral dorsal root ganglion were collected on 14 d after surgery. The levels of p-JNK in the dorsal root ganglion and spinal dorsal horn were determined by immunochemistry and Western blot. Results Compared with group Sham, groups CCI and SC showed remarkable decreases in PMWT and PTWL at each time points (P<0.05), and marked increases in the positive rate and levels of p-JNK in the dorsal root ganglion 14 d after surgery (P<0.05). Compared with group CCI, groups EGb50 and EGb100 showed remarkable increases in PMWT and PTWL 7, 10 d and 14 d after surgery (P<0.05), and marked decreases in the positive rate and levels of p-JNK (P<0.05). Compared with group EGb50, group EGb100 showed remarkable increases in PMWT and PTWL 10 d and 14 d after surgery (P<0.05), and presented substantial decreases in the positive rate and levels of p-JNK in the dorsal root ganglion 14 d after surgery (P<0.05). Conclusions EGb761 may ameliorate neuropathic pain of rats with CCI through inhibiting the expression of p-JNK in the dorsal root ganglia. Key words: Neuropathic pain; Ginkgo biloba extract; Phosphorylated c-Jun N-terminal kinase

An inflammatory pulmonary insult post-traumatic brain injury worsens subsequent spatial learning and neurological outcomes.

Severe traumatic brain injury (TBI) patients are at high risk for early aspiration and pneumonia. How pneumonia impacts neurological recovery after TBI is not well characterized. We hypothesized that, independent of the cerebral injury, pneumonia after TBI delays and worsens neurological recovery and cognitive outcomes. Fifteen CD1 male mice were randomized to sham craniotomy or severe TBI (controlled cortical impact [CCI] - velocity 6 m/s, depth 1.0 mm) ± intratracheal lipopolysaccharide (LPS-2 mg/kg in 0.1 mL saline) as a pneumonia bioeffector. Neurological functional recovery by Garcia Neurologic Testing (GNT) and body weight loss were recorded daily for 14 days. On Days 6-14, animals underwent Morris Water Maze learning and memory testing with cued trials (platform visible), spatial learning trials (platform invisible, spatial cues present), and probe (memory) trials (platform removed, spatial clues present). Intergroup differences were assessed by the Kruskal-Wallis test with Bonferroni correction (p < 0.05). Weight loss was greatest in the CCI + LPS group (maximum 24% on Day 3 vs. 8% [Sham], 7% [CCI], both on Day 1). GNT was lowest in CCI + LPS during the first week. Morris Water Maze testing demonstrated greater spatial learning impairment in the CCI + LPS group vs. Sham or CCI counterparts. Cued learning and long-term memory were worse in CCI + LPS and CCI as compared to Sham. A pneumonia bioeffector insult after TBI worsens weight loss and mortality in a rodent model. Not only is spatial learning impaired, but animals are more debilitated and have worse neurologic performance. Understanding the adverse effects of pneumonia on TBI recovery is the first step d patients.

Hyperbaric oxygen promotes mitophagy by activating CaMKKβ/AMPK signal pathway in rats of neuropathic pain.

Neuropathic pain is a kind of chronic intractable disease. HBO explored the involvement of mitophagy which is associated with energy metabolism by AMPK. CaMKKβ/AMPK signaling pathway may involve in mitophagy process. We randomly divided mice into four groups: C, S, CCI, and CCI + HBO group. Pain-related behaviors were evaluated using mechanical withdrawal threshold and thermal withdrawal latency analysis. Western blot was employed to assess expression of CaMKKβ, pAMPK, AMPK, NIX, BNIP3, and Drp1. Spinal cord was observed under the electron microscope. Immunofluorescence changes in NeuN and CaMKKβ or AMPK were examined. AMPK inhibitor compound C (CC) and CaMKKβ inhibitor STO609 were administrated prior to CCI, respectively. The changes in behaviors and Western blot are examined. HBO upregulated CaMKKβ and pAMPKα expression. NeuN and CaMKKβ were colocalizated in immunofluorescence. HBO can elevate the pain-related behaviors significantly, while it was downregulated by CC or STO609. HBO upregulated NIX, BNIP3, and Drp1 expressive level more significantly than those in CCI group. However, expression was reduced when CC or STO609 were administered. Electron microscopic examination showed that mitophagy was upregulated after HBO treatment. This phenomenon was not observed when CC or STO609 were administered. Our findings suggest that CaMKKβ/AMPK pathway maybe a potential signal pathway on analgesic mechanism of hyperbaric oxygen via mitophagy.

The epidemiology and antibiotic resistance in A. baumannii isolates from military health care facilities

A.baumannii is one of the main causers of health care associated infections. The epidemiological situation has worsened in the past years, with a higher number of countries reporting interregional spread or endemicity of carbapenem-resistant A.baumannii. For these reasons to investigate epidemiology and susceptibility to antibiotics of A.baumannii in modern war wounds is crucial for correct treatment choice. The patients enrolled in study had combat wounds of upper or lower extremities which were treated in the Military Medical Clinical Center of Central Region (MMCC CR) Ukraine in 2014-2016 years. The recovered A.baumannii after primary identification in Department of Microbiology of National Pirogov Memorial Medical University were forwarded to the Multi-drug resistant repository and surveillance network (MRSN) in Walter Reed Army Institute of Research where they underwent additional antibiotic susceptibility testing (AST) and analysis by whole genome sequencing (WGS). There were analyzed 10 isolates. Testing revealed that all isolates were resistant to ampicillin, cefazolin, ciprofloxacin, and levofloxacin and all were sensitive to tigecycline. Susceptibility to other antibiotics varied considerably, with just two isolates displaying resistance to the carbapenems (imipenem and meropenem). An analysis of the antibiotic resistance genes carried by the isolates was in broad agreement with the AST data. Carbapenem resistance in VNMU001 was correlated with the presence of blaOXA-23, while carbapenem resistance in VNMU133 was correlated with the blaOXA-24 variant, blaOXA-72. Overall, 28 different antibiotic resistance genes were identified among the 10 isolates, with the majority encoding β-lactamases or aminoglycoside modifying enzymes (AMEs). The ten A. baumannii isolates represent four separate clades that include a single isolate from ST-1 and ST-2, members of the globally distributed CCI and CCII groups. Both of these clades are notorious for harboring multi-drug resistant strains, and this is reflected in this study where VNMU133 (CCI) and VNMU001 (CCII) displayed resistance to a wide variety of antibiotics and carried multiple antibiotic resistant genes. The remaining 8 isolates were assigned to ST-19, which is also a member of CCI, and all four isolates were closely related. Similarly, the four isolates from ST-400 clustered together, but only the two isolates from the same culture would be considered related. It is possible that ST-19 and ST-400 isolates are circulating within this population and additional surveillance is warranted. These data indicate that ST-19 and ST-400 isolates are still susceptible to many antibiotics but have the potential to acquire and develop more resistance mechanisms.

Application of the chronic constriction injury of the partial sciatic nerve model to assess acupuncture analgesia.

PurposeTo validate and explore the application of a rat model of chronic constriction injury to the partial sciatic nerve in investigation of acupuncture analgesia.MethodsChronic constriction injury of the sciatic nerve (CCI) and chronic constriction injury of the partial sciatic nerve (CCIp) models were generated by ligating either the sciatic nerve trunk or its branches in rats. Both models were evaluated via paw mechanical withdrawal latency (PMWL), paw mechanical withdrawal threshold (PMWT), nociceptive reflex-induced electromyogram (C-fiber reflex EMG), and dorsal root ganglion immunohistochemistry. Electroacupuncture (EA) was performed at GB30 to study the analgesic effects on neuropathic pain and the underlying mechanisms.ResultsFollowing ligation of the common peroneal and tibial nerves, CCIp rats exhibited hindlimb dysfunction, hind paw shrinkage and lameness, mirroring those of CCI rats (generated by ligating the sciatic nerve trunk). Compared to presurgery measurements, CCIp and CCI modeling significantly decreased the PMWL and PMWT. EA at GB30 increased the PMWL and PMWT in both CCI and CCIp rats. Calcitonin gene-related polypeptide and substance P expressions were apparently increased in both CCI and CCIp groups, but were not different from each other. The C-fiber reflex EMG of the biceps femoris was preserved in CCIp rats, but it could not be recorded in CCI rats on the 5th day after nerve ligation. The C-fiber reflex EMG was reduced at 0, 1, and 2 minutes after EA in CCIp rats, but only at 0 and 1 minute after EA in normal rats.ConclusionThe CCIp model is better than the CCI model for studying acupuncture analgesia on chronic neuropathic pain and the underlying mechanisms.

Investigation of flurbiprofen axetil on analgesic efficacy in nerve-injured rats

Objective To investigate the influence of different doses of flurbiprofen axetil on neurological behavior in CCI rats. Methods All SD rats were randomly assigned to 3 groups: control group(C group), operation but without CCI, n=5; CCI group, without injection, n=5; flurbiprofen axetil (FA) group, different doses of flurbiprofen axetil were intraperitoneally administered every 12 hours for 7 days beginning on postoperative 6 hours in CCI rats (FA1 group: 2mg/kg, FA2 group: 4mg/kg, FA3 group: 8mg/kg, FA4 group: 16mg/kg ), 5 rats in each subgroup.The thermal withdrawal latency(TWL) and mechanical withdrawal threshold(MWT) were tested on preoperative 1, 3, 5 and 7 days and postoperative 1, 3, 5 and 7 days. Results Firstly, compared with C group[TWL: (12.396±1.144)s; MWT: (12.801±0.494)g], the TWL and MWT of CCI and FA groups[TWL: (5.645±1.144)s, (5.901±0.914)s, (6.300±0.835)s, (7.631±0.597)s, (7.894±0.526)s; MWT: (5.14±0.71)g, (5.28±0.60)g, (6.74±0.50)g, (6.74±0.25)g, (6.70±0.42)g]were significantly declined after surgery (tTWL=26.973, 31.047, 31.176, 30.373, 30.772; tMWT=44.192, 48.132, 51.136, 54.326, 46.937, all P 0.05). However, the TWL and MWT of FA2 group, FA3 group and FA4 group[TWL: (6.300±0.835)s, (7.631±0.597)s, (7.894±0.526)s; MWT: (6.74±0.50)g, (6.74±0.25)g, (6.70±0.42)g] increased significantly compared with CCI group(tTWL=-3.768, -11.569, -13.867, tMWT=-3.898, -15.233, -14.801, all P 0.05). Conclusion Over 4mg/kg of flurbiprofen axetil can significantly reduce the thermal hyperalgesia and mechanical allodynia in CCI rats, however, there is a ceiling effect of flurbiprofen axetil, and the dosage of 8mg/kg can provide a maximum analgesic effect. Key words: Neuralgia; Flurbiprofen axetil

MP72-12 SURVEILLANCE AFTER SURGERY FOR RENAL CELL CARCINOMA: A RISK-ADAPTED APPROACH

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy V1 Apr 2017MP72-12 SURVEILLANCE AFTER SURGERY FOR RENAL CELL CARCINOMA: A RISK-ADAPTED APPROACH William Parker, Suzanne Merrill, Phillip Schulte, Ross Mason, R. Houston Thompson, Christine Lohse, and Igor Frank William ParkerWilliam Parker More articles by this author , Suzanne MerrillSuzanne Merrill More articles by this author , Phillip SchultePhillip Schulte More articles by this author , Ross MasonRoss Mason More articles by this author , R. Houston ThompsonR. Houston Thompson More articles by this author , Christine LohseChristine Lohse More articles by this author , and Igor FrankIgor Frank More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2248AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The risk of recurrence following surgical excision of clear cell renal cell carcinoma (ccRCC) varies based on clinical and pathologic features, while risk of non-cancer death evolves as a function of age and comorbidities. Despite these differences in how these competing risks mature over time, current guidelines recommend surveillance based on stage alone. We therefore sought to develop risk adapted postoperative surveillance recommendations. METHODS Patients with ccRCC managed surgically between 1990 and 2008 (n=2,511) were identified from the Mayo Clinic Nephrectomy registry and risks of abdominal and chest recurrence estimated using accelerated failure-time (AFT) models by pathology stage (pT1a, pT1b, pT2, pT3/4, or pTanyN+). Similarly, risk of non-cancer death was estimated by age (<50, 51-59, 60-69, 70-79, and ≥80) and comorbidity index (CCI: ≤1 versus >1). Recommended surveillance schedules balance estimated risk of non-cancer death with recurrence risk where allowable recurrence is up to the risk of non-cancer death. Surveillance intervals were calculated based on each 1%, 3%, and 5% recurrence risk increase to a maximum 10 years. Intervals shorter than 3 months were not allowed, with the next risk increase calculated from the date of the adjusted interval. RESULTS AFT models for recurrence and death for stage, age, and comorbidity risk groups were generated (tables). Recommended interval schedules (e.g. 1%, 3%, or 5%) are based on the predicted risk of non-cancer death for a given age and CCI group. For example, patients <70 years with a CCI score ≤1 would be followed on a 1% risk of recurrence schedule for the duration of 10 years of follow-up regardless of stage. Conversely, patients 60-69 years old with a CCI >1, would follow a 1% interval for the first year only, then switch to 3% interval until year 6, at which point they would follow a 5% schedule. CONCLUSIONS Using an AFT model for estimating risk of recurrence and risk of death we were able to generate risk-adapted screening intervals for surgical managed patients with RCC. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e958-e959 Advertisement Copyright & Permissions© 2017MetricsAuthor Information William Parker More articles by this author Suzanne Merrill More articles by this author Phillip Schulte More articles by this author Ross Mason More articles by this author R. Houston Thompson More articles by this author Christine Lohse More articles by this author Igor Frank More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effects of Neto1-siRNA on conditioned avoidance behavior and expression of NMDA receptor subunits in anterior cingulate cortex in rats with pain

Objective To evaluate the effects of Neto1-siRNA on pain-related negative affection and expression of Neto1 (Neuropilin and tolloid-like 1) and NMDA (N-methyl-D-aspartate) receptor NR2A and NR2B subunits in anterior cingulate cortex (ACC) in neuropathic pain (NP) model rats. Methods 40 healthy male Wistar rats were randomly divided into sham operated group (SO group, n=10) and chronic constriction injury of the sciatic nerve group(CCI group, n=10). Twenty-four days after injury LV-Neto1-RNAi (30160-1) was injected in ACC in rats of SO group and CCI group by stereotaxic apparatus to prepare siRNA SO group(n=10) and siRNA CCI group(n=10). The CCI model was established by the chronic constriction injury of the sciatic nerve. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of each groups were measured on 7th, 14th, 21th and 28th day after operation. The expression of Neto1, NR2A and NR2B subunit mRNA and protein in ACC by RT-PCR and Western Blotting respectively. Results Compared with SO group, TWL and MWT in CCI group were both decreased (P 0.05). In RT-PCR, expression of Neto1, NR2A and NR2B in CCI group was increased compared with SO group (P<0.05), and expression of Neto1 and NR2A was both decreased by Neto1-siRNA (P<0.05), while there was no difference of NR2B. In Western Blotting, expression of Neto1, NR2A and NR2B in CCI group was increased compared with SO group (P<0.05), and expression of Neto1 and NR2A was both decreased by Neto1-siRNA (P<0.05), while there was no difference of NR2B. Conclusion Decreased-expression of Neto1 in ACC may down-regulate NMDA receptor NR2A subunit in NP rats and does not affect pain-related negative affection. Key words: Pain; Anterior cingulate cortex; Conditioned avoidance behavior; Neuropilin and tolloid-like1 Protein; N-methyl-D-aspartate receptor

Effect of Candida albicans on Intestinal Ischemia-reperfusion Injury in Rats.

Background:Inflammation is supposed to play a key role in the pathophysiological processes of intestinal ischemia-reperfusion injury (IIRI), and Candida albicans in human gut commonly elevates inflammatory cytokines in intestinal mucosa. This study aimed to explore the effect of C. albicans on IIRI.Methods:Fifty female Wistar rats were divided into five groups according to the status of C. albicans infection and IIRI operation: group blank and sham; group blank and IIRI; group cefoperazone plus IIRI; group C. albicans plus cefoperazone and IIRI (CCI); and group C. albicans plus cefoperazone and sham. The levels of inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and diamine oxidase (DAO) measured by enzyme-linked immunosorbent assay were used to evaluate the inflammation reactivity as well as the integrity of small intestine. Histological scores were used to assess the mucosal damage, and the C. albicans blood translocation was detected to judge the permeability of intestinal mucosal barrier.Results:The levels of inflammatory factors TNF-α, IL-6, and IL-1β in serum and intestine were higher in rats undergone both C. albicans infection and IIRI operation compared with rats in other groups. The levels of DAO (serum: 44.13 ± 4.30 pg/ml, intestine: 346.21 ± 37.03 pg/g) and Chiu scores (3.41 ± 1.09) which reflected intestinal mucosal disruption were highest in group CCI after the operation. The number of C. albicans translocated into blood was most in group CCI ([33.80 ± 6.60] ×102 colony forming unit (CFU)/ml).Conclusion:Intestinal C. albicans infection worsened the IIRI-induced disruption of intestinal mucosal barrier and facilitated the subsequent C. albicans translocation and dissemination.

PD27-03 ONCOLOGIC SURVEILLANCE FOLLOWING RADICAL CYSTECTOMY: AN INDIVIDUALIZED RISK-BASED APPROACH.

You have accessJournal of UrologyBladder Cancer: Invasive II1 Apr 2016PD27-03 ONCOLOGIC SURVEILLANCE FOLLOWING RADICAL CYSTECTOMY: AN INDIVIDUALIZED RISK-BASED APPROACH. Suzanne Stewart-Merrill, Stephen Boorjian, R. Houston Thompson, Sarah Psutka, John Cheville, Prabin Thapa, Matthew Tollefson, and Igor Frank Suzanne Stewart-MerrillSuzanne Stewart-Merrill More articles by this author , Stephen BoorjianStephen Boorjian More articles by this author , R. Houston ThompsonR. Houston Thompson More articles by this author , Sarah PsutkaSarah Psutka More articles by this author , John ChevilleJohn Cheville More articles by this author , Prabin ThapaPrabin Thapa More articles by this author , Matthew TollefsonMatthew Tollefson More articles by this author , and Igor FrankIgor Frank More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.377AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The appropriate duration of surveillance for bladder cancer (BC) following radical cystectomy (RC) remains unknown. Uniform adherence to current guidelines has the potential for over utilization of resources in some patients and deficiency of testing in others. Herein, we provide an approach to surveillance which balances the risk of recurrence versus the risk of non-BC death. METHODS We identified 2438 patients who underwent RC for M0 BC between 1980 and 2007. Patients were stratified for analysis by pathologic stage (pT0Nx-0, pTa/CIS/1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN+), relapse location (urethra, upper urinary tract, abdomen, thorax, and other), age (<= 60, 61-70, 71-80, >80yrs) and Charlson Co-morbidity Index (CCI <= 2 and CCI >= 3). Risks of disease recurrence and non-BC death were estimated using parametric models for time-to-failure using Weibull distributions. Surveillance duration was estimated at the point when the risk of non-BC death exceeded the risk of recurrence. RESULTS At a median follow-up of 6.0 yrs (IQR 2.0,11.1), a total of 713 patients developed recurrence. As shown in the Table, vastly different surveillance durations were appreciated for various stage, age, and CCI groups before the risk of non-BC death exceeded the risk of recurrence. Specifically, among patient's age <= 60yrs with pT2Nx-0 disease, the risk of non-BC death exceeded the risk of recurrence to the abdomen at 7.5yrs if the patients CCI was >= 3, but failed to do so until 10 years if the patient's CCI was <= 2. On the other hand, for patient's age > 80yrs with pT2Nx-0 disease, the risk of non-BC death exceeded the risk of abdominal recurrence at 1yr following surgery regardless of the patient's CCI. CONCLUSIONS We present an individualized approach to post-RC surveillance that bases duration of follow-up on the interplay between competing risk factors of recurrence and non-BC death. This strategy may improve the balance between the derived benefit from surveillance and medical resource allocation. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e650 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Suzanne Stewart-Merrill More articles by this author Stephen Boorjian More articles by this author R. Houston Thompson More articles by this author Sarah Psutka More articles by this author John Cheville More articles by this author Prabin Thapa More articles by this author Matthew Tollefson More articles by this author Igor Frank More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The Upper Limit of Cerebral Blood Flow Autoregulation Is Decreased with Elevations in Intracranial Pressure.

The upper limit of cerebrovascular pressure autoregulation (ULA) is inadequately characterized. We sought to delineate the ULA in a neonatal swine model. Neonatal piglets with sham surgery (n = 9), interventricular fluid infusion (INF; n = 10), controlled cortical impact (CCI; n = 10), or impact + infusion (CCI + INF; n = 11) had intracranial pressure monitoring and bilateral cortical laser-Doppler flux recordings during arterial hypertension until lethality. An increase in red cell flux as a function of cerebral perfusion pressure was determined by piecewise linear regression and static rates of autoregulation (SRoRs) were determined above and below this inflection. When identified, the ULA (median [interquartile range]) was as follows: sham group: 102 mmHg (97-109), INF group: 75 mmHg (52-84), CCI group: 81 mmHg (69-101), and CCI + INF group: 61 mmHg (52-57; p = 0.01). Both groups with interventricular infusion had significantly lower ULA compared with the sham group. Neonatal piglets without intracranial pathological conditions tolerated acute hypertension, with minimal perturbation of cerebral blood flow. Piglets with acutely elevated intracranial pressure, with or without trauma, demonstrated loss of autoregulation when subjected to arterial hypertension.

Effects of Light-Curing on the Immediate and Delayed Micro-Shear Bond Strength between Yttria-Tetragonal Zirconia Polycrystal Ceramics and Universal Adhesive

Purpose: To evaluate the effect of light-curing on the immediate and delayed micro-shear bond strength (<TEX>${\mu}SBS$</TEX>) between yttria-tetragonal zirconia polycrystal (Y-TZP) ceramics and RelyX Ultimate when using Single Bond Universal (SBU). Materials and Methods: Y-TZP ceramic specimens were ground with #600-grit SiC paper. SBU was applied and RelyX Ultimate was mixed and placed on the Y-TZP surface. The specimens were divided into three groups depending on whether light curing was done after adhesive (SBU) and resin cement application: uncured after adhesive and uncured after resin cement application (UU); uncured after adhesive, but light cured after resin cement (UC); and light cured after adhesive and light cured resin cement (CC). The three groups were further divided depending on the timing of <TEX>${\mu}SBS$</TEX> testing: immediate at 24 hours (UUI, UCI, CCI) and delayed at 4 weeks (UUD, UCD, CCD). <TEX>${\mu}SBS$</TEX> was statistically analyzed using one-way ANOVA and Student-Newman-Keuls multiple comparison test (P<0.05). The surface of the fractured Y-TZP specimens was analyzed under a scanning electron microscope (SEM). Result: At 24 hours, <TEX>${\mu}SBS$</TEX> of UUI group (<TEX>$8.60{\pm}2.06MPa$</TEX>) was significantly lower than UCI group (<TEX>$25.71{\pm}4.48MPa$</TEX>) and CCI group (<TEX>$29.54{\pm}3.62MPa$</TEX>) (P<0.05). There was not any significant difference between UCI and CCI group (P>0.05). At 4 weeks, <TEX>${\mu}SBS$</TEX> of UUD group (<TEX>$24.43{\pm}2.88MPa$</TEX>) had significantly increased over time compared to UUI group (P<0.05). The SEM results showed mixed failure in UCI and CCI group, while UUI group showed adhesive failure. Conclusion: Light-curing of universal adhesive before or after application of RelyX Ultimate resin cement significantly improved the immediate <TEX>${\mu}SBS$</TEX> of resin cement to air-abrasion treated Y-TZP surface. After 4 weeks, the delayed <TEX>${\mu}SBS$</TEX> of the non-light curing group significantly improved to the level of light-cured groups.

Covering a finite group by the conjugates of a coset

We study pairs (G,A) where G is a finite group and A<G is maximal, satisfying ⋃g∈G(Ax)g=G−{1G} for all x∈G−A. We prove that this condition defines a class of permutation groups, denoted CCI, which is a subclass of the class of primitive permutation groups. We prove that CCI contains the class of 2-transitive groups. We also prove that groups in CCI are either affine or almost simple. In the affine case each CCI group must be 2-transitive, while an almost simple CCI group needs not be 2-transitive. We give various results on the almost simple case and compare between the CCI class and other recently studied classes of groups which lie between the 2-transitive and the primitive permutation groups.

Analysis of Early Mortality of Chronic Lymphocytic Leukemia (CLL) Patients Treated in US Practices in the Connect CLL® Registry

Analysis of Early Mortality of Chronic Lymphocytic Leukemia (CLL) Patients Treated in US Practices in the Connect CLL® Registry

Research in length of stay, early complications and treatment cost in radical cystectomy patients with different Charlson Comorbidity Index score

Objective To assess the length of stay, early complication and cost of treatment in radical cystectomy (RC) patients with different Charlson Comorbidity Index Score (CCI). Methods A prospective study of a total of 102 patients who underwent RC between March 2012 and August 2014 in Center for Research of Urology in Yunnan Province, China. They were divided into three groups: 69 cases in CCI=0 or 1 group, 19 cases in CCI=2 group, 14 cases in CCI≥3 group. Comorbidities were graded according to CCI, and each patient was followed-up for 3 months after RC. Length of stay, early complications and treatment cost were analyzed by statistics. Results A total of 102 patients were analyzed. There were obvious differences with respect to length of stay, early complication and cost of treatment comparing patients in each CCI group,H=20.722, 6.025, and 7.047,P 0.05. Conclusions Patients with different CCI showed difference in the length of stay, early complication and cost of treatment in RC patients with different CCI. CCI≥3 might help to identify patients at risk for early complications after RC, especially in the orthotopic urinary diversion operation. Patients' complication should be evaluated standardized before operation and these should be included in patients' consideration. Key words: Cystectomy; Length of stay; Comorbidity; Early complication; Cost of treatment

Regulation of Neurotrophin-3 and Interleukin-1β and Inhibition of Spinal Glial Activation Contribute to the Analgesic Effect of Electroacupuncture in Chronic Neuropathic Pain States of Rats.

Growing evidence indicates that neurotrophin-3, interleukin-1β, and spinal glia are involved in neuropathic pain derived from dorsal root ganglia to spinal cord. Electroacupuncture is widely accepted to treat chronic pain, but the precise mechanism underlying the analgesic effect of EA has not been fully demonstrated. In this study, the mechanical withdrawal threshold and thermal withdrawal latency were recorded. We used immunofluorescence and western blots methods to investigate the effect of EA on the expression of NT-3 and IL-1β in DRG and spinal cord of CCI rats; we also examined the expression of spinal GFAP and OX-42 in spinal cord. In present study, the MWT and TWL of CCI group rats were lower than those in the Sham CCI group rats, but EA treatment increased the pain thresholds. Furtherly, we found that EA upregulates the expression of NT-3 in DRG and spinal cord of CCI rats, while EA downregulates the expression of IL-1β. Additionally, immunofluorescence exhibited that CCI-induced activation of microglia and astrocytes was inhibited significantly by EA treatment. These results demonstrated that the analgesic effect of EA may be achieved through promoting the neural protection of NT-3 as well as the inhibition of IL-1β production and spinal glial activity.

Aloperine attenuated neuropathic pain induced by chronic constriction injury via anti-oxidation activity and suppression of the nuclear factor kappa B pathway

ObjectiveTo investigate whether aloperine (ALO) has antinociceptive effects on neuropathic pain induced by chronic constriction injury, whether ALO reduces ROS against neuropathic pain, and what are the mechanisms involved in ALO attenuated neuropathic pain. MethodsMechanical and cold allodynia, thermal and mechanical hyperalgesia and spinal thermal hyperalgesia were estimated by behavior methods such as Von Frey filaments, cold-plate, radiant heat, paw pressure and tail immersion on one day before surgery and days 7, 8, 10, 12 and 14 after surgery, respectively. In addition, T-AOC, GSH-PX, T-AOC and MDA in the spinal cord (L4/5) were measured to evaluate anti-oxidation activity of ALO on neuropathic pain. Expressions of NF-κB and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in the spinal cord (L4/5) were analyzed by using Western blot. ResultsAdministration of ALO (80mg/kg and 40mg/kg, i.p.) significantly increased paw withdrawal threshold, paw pressure, paw withdrawal latencies, tail-curling latencies, T-AOC, GSH-PX and T-SOD concentration, reduced the numbers of paw lifts and MDA concentration compared to CCI group. ALO attenuated CCI induced up-regulation of expressions of NF-κB, TNF-α, IL-6, IL-1β at the dose of 80mg/kg (i.p.). Pregabalin produced similar effects serving as positive control at the dose of 10mg/kg (i.p.). ConclusionALO has antinociceptive effects on neuropathic pain induced by CCI. The antinociceptive effects of ALO against neuropathic pain is related to reduction of ROS, via suppression of NF-κB pathway.

Abstracts fromThe 32nd AnnualNational Neurotrauma SymposiumJune 29–July 2, 2014San Francisco, California

Abstracts fromThe 32^nd AnnualNational Neurotrauma SymposiumJune 29–July 2, 2014San Francisco, California

Effect of intrathecal injection of neuropeptide S and gabapentin on pain and anxiety behavior in rats with neuropathic pain

Objective To investigate the effects of intrathecal injection of Neuropeptide S and Gabapentin on pain behavior and anxiety behavior in rats with neuropathic pain,and to explore the possible mechanisms of of N-methyl-D-aspartic acid(NMDA) receptor 1.Methods Seventy-two male Sprague-Dawley (SD) rats,which were successfully deployed intrathecal catheter,were randomly divided into six groups (n=12),including sham group,CCI group,neuropeptide S low-dose group (NPSl group),neuropeptide S high-dose group (NPSh group),gabapentin low dose group (Gbl group) and gabapentin high dose group(Gbh group).Pain-related behaviors,depression-related behaviors,and expression of NMDA receptor1 in the dorsal horn of the spinal cord were measured at 14 d after 7 d via intrathecal injection.Results Compared with the sham group,the rats suffering CCI demonstrated significant pain and anxiety behavior (P＜0.01).High dose NPS and each dose gabapentin (but not low dose NPS) can significantly reduce mechanical withdrawal threshold (MWT) [(2.7±1.3) g vs (4.5±1.7),(5.4±1.0),(8.1±3.6) g]and thermal hyperalgesia foot withdrawal lantency(FWL) [(3.9±0.6) s vs (5.8± 1.5),(6.3± 1.2),(7.6± 1.6) s] compared with CCI group(P＜0.05).In the EPM test,compared with CCI group,only high dose NPS significantly extended numbers entries into the open arms (6.3±1.6 vs 2.9±1.5)(P＜0.05) and time spent in the open arms(22.4±4.3)％ vs (10.9±2.7)％(P＜0.05).In the open field test,each dose NPS and gabapentin added the proportion of central Zone cross (P＜0.05) and time spent (P＜0.05).Immunofluorescence and western blot experiments showed that,regardless of the level measurement group,both drugs can suppress the increase NR1 receptor expression in the dorsal horn of the spinal cord,and has a statistical significance.Conclusions Neuropeptide S and gabapentin dosedependent pain and anxiety behavior reversal CCI rats,which may be related NMDA receptor pathway. Key words: Neuropeptide S; Gabapentin; Neuropathic Pain; Anxiety; Intrathecal injection