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Sample records for inhibits postsurgical adhesiogenesis

  1. Persistent postsurgical pain

    Werner, Mads Utke; Bischoff, Joakim Mutahi

    2014-01-01

    The prevalences of severe persistent postsurgical pain (PPP) following breast cancer surgery (BCS), groin hernia repair (GHR), and lung cancer surgery (LCS) are 13, 2, and 4-12 %, respectively. Estimates indicate that 80,000 patients each year in the U.S.A. are affected by severe pain...... duration of surgery, repeat surgery, more invasive surgical techniques, and intraoperative nerve lesion have been associated with PPP. One of the most consistent predictive factors for PPP is high intensity acute postsurgical pain, but also psychological factors including anxiety, catastrophizing trait...

  2. Epidemic of Postsurgical Infections Caused by Mycobacterium massiliense▿

    Duarte, Rafael Silva; Lourenço, Maria Cristina Silva; Fonseca, Leila de Souza; Leão, Sylvia Cardoso; Amorim, Efigenia de Lourdes T.; Rocha, Ingrid L. L.; Coelho, Fabrice Santana; Viana-Niero, Cristina; Gomes, Karen Machado; da Silva, Marlei Gomes; de Oliveira Lorena, Nádia Suely; Pitombo, Marcos Bettini; Ferreira, Rosa M. C.; de Oliveira Garcia, Márcio Henrique; de Oliveira, Gisele Pinto; Lupi, Otilia; Vilaça, Bruno Rios; Serradas, Lúcia Rodrigues; Chebabo, Alberto; Marques, Elizabeth Andrade; Teixeira, Lúcia Martins; Dalcolmo, Margareth; Senna, Simone Gonçalves; Sampaio, Jorge Luiz Mello

    2009-01-01

    An epidemic of infections after video-assisted surgery (1,051 possible cases) caused by rapidly growing mycobacteria (RGM) and involving 63 hospitals in the state of Rio de Janeiro, Brazil, occurred between August 2006 and July 2007. One hundred ninety-seven cases were confirmed by positive acid-fast staining and/or culture techniques. Thirty-eight hospitals had cases confirmed by mycobacterial culture, with a total of 148 available isolates recovered from 146 patients. Most (n = 144; 97.2%) isolates presented a PRA-hsp65 restriction pattern suggestive of Mycobacterium bolletii or Mycobacterium massiliense. Seventy-four of these isolates were further identified by hsp65 or rpoB partial sequencing, confirming the species identification as M. massiliense. Epidemic isolates showed susceptibility to amikacin (MIC at which 90% of the tested isolates are inhibited [MIC90], 8 μg/ml) and clarithromycin (MIC90, 0.25 μg/ml) but resistance to ciprofloxacin (MIC90, ≥32 μg/ml), cefoxitin (MIC90, 128 μg/ml), and doxycycline (MIC90, ≥64 μg/ml). Representative epidemic M. massiliense isolates that were randomly selected, including at least one isolate from each hospital where confirmed cases were detected, belonged to a single clone, as indicated by the analysis of pulsed-field gel electrophoresis (PFGE) patterns. They also had the same PFGE pattern as that previously observed in two outbreaks that occurred in other Brazilian cities; we designated this clone BRA100. All five BRA100 M. massiliense isolates tested presented consistent tolerance to 2% glutaraldehyde. This is the largest epidemic of postsurgical infections caused by RGM reported in the literature to date in Brazil. PMID:19403765

  3. Drug-interaction-induced hemodynamically mediated acute renal failure in postsurgical patient

    Arup K Misra

    2014-01-01

    Full Text Available Acute renal failure is a life threatening condition. Nonsteroidal antiinflammatory drugs (NSAIDs and cephalosporins are widely used postoperative drugs. NSAID-induced acute renal failure has been reported in the past. In this case, drug interaction and decompensated state of the patient precipitate the condition. NSAIDs inhibit prostaglandins synthesis and thus aggravate ischemia to the kidney that is already facing volume crisis due to surgery. Due to renal dysfunction, plasma ceftriaxone level increases due to decrease clearance and it also acts as nephrotoxic by unknown mechanism. On the other hand, ceftriaxone on its interaction with diclofenac for renal tubular clearance also increases the level of diclofenac and thus further aggravate the ischemia. It is a reversible condition with excluding diclofenac from the treatment regimen and giving adequate hydration to the patient. This highlights the importance of hydration and knowledge of drugs interactions in a postsurgical patient.

  4. The effect of postsurgical pain on attentional processing in horses.

    Dodds, Louise; Knight, Laura; Allen, Kate; Murrell, Joanna

    2017-07-01

    To investigate the effect of postsurgical pain on the performance of horses in a novel object and auditory startle task. Prospective clinical study. Twenty horses undergoing different types of surgery and 16 control horses that did not undergo surgery. The interaction of 36 horses with novel objects and a response to an auditory stimulus were measured at two time points; the day before surgery (T1) and the day after surgery (T2) for surgical horses (G1), and at a similar time interval for control horses (G2). Pain and sedation were measured using simple descriptive scales at the time the tests were carried out. Total time or score attributed to each of the behavioural categories was compared between groups (G1 and G2) for each test and between tests (T1 and T2) for each group. The median (range) time spent interacting with novel objects was reduced in G1 from 58 (6-367) seconds in T1 to 12 (0-495) seconds in T2 (p=0.0005). In G2 the change in interaction time between T1 and T2 was not statistically significant. Median (range) total auditory score was 7 (3-12) and 10 (1-12) in G1 and G2, respectively, at T1, decreasing to 6 (0-10) in G1 after surgery and 9.5 (1-12) in G2 (p=0.0003 and p=0.94, respectively). There was a difference in total auditory score between G1 and G2 at T2 (p=0.0169), with the score being lower in G1 than G2. Postsurgical pain negatively impacts attention towards novel objects and causes a decreased responsiveness to an auditory startle test. In horses, tasks demanding attention may be useful as a biomarker of pain. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. All rights reserved.

  5. Delayed diagnosis of post-surgical pyoderma gangrenosum: A multicenter case series and review of literature

    Rawaa Almukhtar

    Full Text Available Introduction: Pyoderma gangrenosum is a chronic neutrophilic dermatosis which can occur following trauma or surgery and can mimic infection. Surgical intervention can lead to progression of disease. Presentation of cases: This case series describes 3 cases of post-surgical pyoderma gangrenosum with delayed diagnosis from two large medical centers. Discussion: Epidemiology, pathogenesis, clinical and histopathologic presentation, and management of post-surgical pyoderma gangrenosum are discussed with a review of the literature. Conclusion: Post-surgical pyoderma gangrenosum (PSPG can mimic ulcerative disorders including bacterial infection. The diagnosis should be suspected in post-operative wounds with negative bacterial cultures which progress despite broad-spectrum antibiotics and surgical debridement. Recognizing the clinical features of PSPG is fundamental to prevent severe destruction and deformity. Keywords: Post-surgical, Pyoderma gangrenosum, Necrotizing fasciitis, Case report

  6. Postsurgical Acute Phase Reaction is Associated with Decreased Levels of Circulating Myostatin.

    Åkerfeldt, Torbjörn; Helmersson-Karlqvist, Johanna; Gunningberg, Lena; Swenne, Christine Leo; Larsson, Anders

    2015-08-01

    Muscle strength is of importance for postsurgical rehabilitation. Myostatin is a growth factor that regulates the size of muscles and could thus influence muscle mass and function in the postsurgical period. The aim of the present study was to study the changes in myostatin levels during the postsurgical inflammatory period. Myostatin was analysed in serum samples from two elective surgery groups, orthopaedic surgery (n = 24) and coronary bypass patients (n = 21). The samples were collected prior to surgery and 4 and 30 days after surgery. In the orthopaedic group, the median myostatin levels decreased from 3582 ng/L prior to surgery to 774 ng/L at day 4 (p myostatin from 4212 ng/L to 2574 ng/L at day 4 (p myostatin concentrations both in the early and late postsurgical period. The lowest myostatin concentration time point coincided with the highest CRP concentration time point.

  7. Low-power laser effects in equine traumatology and postsurgically

    Antikas, Theo G.

    1991-05-01

    The present field study on 800 cases of LPL treatments in situ using a preset `blind code' was designed to verify previously published field results; and to check whether a practicing equine vet, trainer, horse owner or rider may obtain beneficial therapeutic effects in traumatology and/or post-surgery, two of the most prevailing modalities in equine sportsmedicine. With the exception of chronic infected traumas, the positive/beneficial response to LPL treatment was verified in a range of 33.3% (infected) to 100% (non-infected, surgical) of the traumas under investigation. The administration of antibiotics, a modality compatible with LPL treatment in infected injuries, increased the beneficial effects of LPL irradiation to 66.7%. This fact indicates that laser irradiation should not be considered a replacement of common therapeutic routine but simply an efficient follow up or parallel treatment that may act synergistically to the benefit of an injured equine athlete. In the case of non-infected surgical trauma, LPL-treatment was additionally found to shorten the post-surgical `inactive' time period or `comeback time' (CBT), thus bringing the horse back into its sportive capacity considerably faster than without LPL irradiation, and at a statistically significant level (p < 0.001).

  8. Postsurgical Orthodontic Treatment Planning: a Case Report with 20 Years Follow-up.

    Farronato, Giampietro; Garagiola, Umberto; Carletti, Vera; Cressoni, Paolo; Mortellaro, Carmen

    2011-01-01

    Traditionally, maxillofacial deformities are corrected surgically after an initial orthodontic treatment phase. However in, this article, the authors emphasize the postsurgical therapeutic protocol which is extremely important for determining the final and permanent retention of the corrected occlusion. A 55 year old female with severe skeletal Class II malocclusion is presented. Combined surgical and orthodontic correction of the malocclusion was used. : The step-by-step procedure the authors followed for the postsurgical therapy is described. The goals of the postoperative therapy were to restore and rehabilitate neuromuscular function, obtain occlusal stabilization, grind teeth selectively, and final occlusion retention. The importance of a surgical occlusal splint for rehabilitating stomatognathic neuromuscular function postoperatively was demonstrated. Furthermore, the orthodontic-prosthodontic treatment ensured occlusion stability after the surgical correction. The long-term results confirmed the efficacy of the treatment protocol presented here from both functional and aesthetical perspectives. Postsurgical orthodontic treatment is an important step in the surgical and orthodontic therapy of maxillofacial deformities.

  9. Multi-centric clinical study of the effect of intervention time on efficacy of gastroparesis external application prescription treatment of gastrointestinal tumor postsurgical gastroparesis

    Qin Zhou

    2016-10-01

    Conclusions: Gastroparesis external application prescription can effectively treat gastrointestinal tumor postsurgical gastroparesis and may be more efficacious in progressive disease compared placebo. Patients with gastrointestinal tumor postsurgical gastroparesis should therefore undergo intervention at an earlier stage.

  10. Predicting Postsurgical Satisfaction in Adolescents With Idiopathic Scoliosis: The Role of Presurgical Functioning and Expectations.

    Sieberg, Christine B; Manganella, Juliana; Manalo, Gem; Simons, Laura E; Hresko, M Timothy

    2017-12-01

    There is a need to better assess patient satisfaction and surgical outcomes. The purpose of the current study is to identify how preoperative expectations can impact postsurgical satisfaction among youth with adolescent idiopathic scoliosis undergoing spinal fusion surgery. The present study includes patients with adolescent idiopathic scoliosis undergoing spinal fusion surgery enrolled in a prospective, multicentered registry examining postsurgical outcomes. The Scoliosis Research Society Questionnaire-Version 30, which assesses pain, self-image, mental health, and satisfaction with management, along with the Spinal Appearance Questionnaire, which measures surgical expectations was administered to 190 patients before surgery and 1 and 2 years postoperatively. Regression analyses with bootstrapping (with n=5000 bootstrap samples) were conducted with 99% bias-corrected confidence intervals to examine the extent to which preoperative expectations for spinal appearance mediated the relationship between presurgical mental health and pain and 2-year postsurgical satisfaction. Results indicate that preoperative mental health, pain, and expectations are predictive of postsurgical satisfaction. With the shifting health care system, physicians may want to consider patient mental health, pain, and expectations before surgery to optimize satisfaction and ultimately improve clinical care and patient outcomes. Level I-prognostic study.

  11. Use of iowa spaces for the orthodontic management of mandibular postsurgical skeletal relapse

    Roberto Justus

    2016-01-01

    Full Text Available It has been documented that there is a tendency for skeletal relapse after orthognathic surgery. This relapse occurs more often following mandibular bilateral sagittal split osteotomy setbacks. The possible causes for lack of postsurgical stability as well as the clinical recommendations to manage the relapse are presented. Among these recommendations is the creation of Iowa Spaces.

  12. [Pre- and post-surgical orthodontic treatment for skeletal open bite].

    Zhou, Y; Hu, W; Sun, Y

    2001-05-01

    To Study the principles and rules of pre- and post-surgical orthodontic treatment for skeletal open bite patients. Thirty-two surgically treated open bite cases were analyzed, of which 9 were males, and 23 were females, aged from 16 to 38. Open bite was from 1 to 8.5 mm, average was 4 mm. 31 patients were Class III malocclusion, while 1 patient was Class II malocclusion. 1. Totally 21 patients were treated with orthodontics before and after orthognathic surgery, while 8 patients had pre-surgical orthodontics only, and other 3 had post-surgical orthodontics only. The duration for pre-surgical orthodontics was from 4 to 33 months, average was 12 months. The duration for post-surgical orthodontics was from 3 to 17 months, average was 8.5 months. 2. Presurgical orthodontic treatment included: Alignment of arches, decompensation of incisors, avoiding extrusion of incisors, and slight expansion of arches for coordination of arches. 3. Post-surgical orthodontic treatment included: Closure of residual spaces in the arches, realignment of arches, vertical elastics and Class II or III intermaxillary elastics. Skeletal open bites require combined orthodontic-orthognathic surgery for optimal and esthetical pleasing results.

  13. Correction of sampling bias in a cross-sectional study of post-surgical complications.

    Fluss, Ronen; Mandel, Micha; Freedman, Laurence S; Weiss, Inbal Salz; Zohar, Anat Ekka; Haklai, Ziona; Gordon, Ethel-Sherry; Simchen, Elisheva

    2013-06-30

    Cross-sectional designs are often used to monitor the proportion of infections and other post-surgical complications acquired in hospitals. However, conventional methods for estimating incidence proportions when applied to cross-sectional data may provide estimators that are highly biased, as cross-sectional designs tend to include a high proportion of patients with prolonged hospitalization. One common solution is to use sampling weights in the analysis, which adjust for the sampling bias inherent in a cross-sectional design. The current paper describes in detail a method to build weights for a national survey of post-surgical complications conducted in Israel. We use the weights to estimate the probability of surgical site infections following colon resection, and validate the results of the weighted analysis by comparing them with those obtained from a parallel study with a historically prospective design. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Combined use of radioiodine therapy and radiofrequency ablation in treating postsurgical thyroid remnant of differentiated thyroid carcinoma

    Bin Long

    2015-01-01

    Conclusion: Combined use of RAI therapy and radiofrequency ablation in treating excessive postsurgical thyroid remnant of DTC can be an effective approach and avoids re-operation. Long-term efficacy monitoring would further determine its feasibility.

  15. Comparison of post-surgical MRI presentation of the pituitary gland and its hormonal function

    Bladowska, Joanna; Sokolska, Violetta; Sozański, Tomasz; Bednarek-Tupikowska, Grażyna; Sąsiadek, Marek

    2010-01-01

    Summary Background: Post-surgical evaluation of the pituitary gland in MRI is difficult because of a change of anatomical conditions. It depends also on numerous other factors, including: size and expansion of a tumour before surgery, type of surgical access, quality and volume of filling material used and time of its resorption.The aim of the study was to compare MR image of the pituitary gland after surgery with clinical findings and to establish a correlation between MRI presentation of sp...

  16. Post-surgical enterococcal meningitis: clinical and epidemiological study of 20 cases.

    Guardado, Rodríguez; Asensi, V; Torres, J M; Pérez, F; Blanco, A; Maradona, J A; Cartón, J A

    2006-01-01

    Enterococcal post-surgical meningitis is an uncommon disease. 20 episodes of nosocomial post-surgical enterococcal meningitis diagnosed between 1994 and 2003 were retrospectively studied. During the period of study 20 cases of post-surgical enterococcal meningitis (60% female, mean age 55+/-18 y, range 16-78 y) were reviewed. The mean time between admission at the hospital and surgery was 26 (SD = 15) d (range 7-61 d). The most frequent underlying diseases were: intracerebral haemorrhage (55%), brain neoplasms (25%), head trauma (15%) and hydrocephalus (5%). 11 patients had previously received antibiotic treatment. The isolates identified were Enterococcus faecalis (n = 18) (90%), E. faecium (1) and E. durans (1). 11 patients had polymicrobial infections. The treatment most frequently used was vancomycin alone or with other antibiotics (11). In 5 patients intrathecal vancomycin (20 mg/d) was also added. The mortality rate was not different in intrathecally treated patients. Cerebrospinal fluid (CSF) devices were removed in 8 patients. Four patients died due to the infection. Mortality was significantly associated with lack of removal of the CSF devices (p = 0.04). Enterococcal spp. are a cause of nosocomial meningitis associated with neurosurgical procedures and the presence of neurological devices.

  17. Postsurgical Orthodontic Treatment Planning: a Case Report with 20 Years Follow-up

    Giampietro Farronato

    2011-04-01

    Full Text Available Background: Traditionally, maxillofacial deformities are corrected surgically after an initial orthodontic treatment phase. However in, this article, the authors emphasize the postsurgical therapeutic protocol which is extremely important for determining the final and permanent retention of the corrected occlusion.Methods: A 55 year old female with severe skeletal Class II malocclusion is presented. Combined surgical and orthodontic correction of the malocclusion was used.Results: The step-by-step procedure the authors followed for the postsurgical therapy is described. The goals of the postoperative therapy were to restore and rehabilitate neuromuscular function, obtain occlusal stabilization, grind teeth selectively, and final occlusion retention. The importance of a surgical occlusal splint for rehabilitating stomatognathic neuromuscular function postoperatively was demonstrated. Furthermore, the orthodontic-prosthodontic treatment ensured occlusion stability after the surgical correction. The long-term results confirmed the efficacy of the treatment protocol presented here from both functional and aesthetical perspectives.Conclusions: Postsurgical orthodontic treatment is an important step in the surgical and orthodontic therapy of maxillofacial deformities.

  18. After aesthetic rhinoplasty: new looks and psychological outlooks on post-surgical satisfaction.

    Moses, S; Last, U; Mahler, D

    1984-01-01

    Thirty-four female patients who underwent rhinoplasty were followed through assessment of post-surgical satisfaction (pss), perception of subjective improvement, objective improvement (surgeon's ratings), and objective post-surgical nasal deformity. Assessments of pss and subjective improvement were obtained on 3 occasions: T1, 1 week after surgery, on cast removal; T2, 1 month after cast removal; and T3, 3 months after cast removal. The investigation was aimed at examination of the relationship of patients' subjective post-surgical appraisals of the operation with objective indices of outcome of rhinoplasty. Results indicated that at T1, pss is totally dissociated from objective outcome or its appraisal by the patient. At T2 an association between objective outcome and pss and subjective appraisal of outcome is evident, but seems to reflect the total reliance of the patients' judgment on surgeons' appraisals. At T3 a paradoxical trend is indicated: slim objective favorable outcomes correlate with high pss, while a considerable share of patients with whom a highly favorable outcome has been attained express relatively low pss. This paradoxical trend may be well understood when applying Cognitive Dissonance Theory. The whole pattern of results point again at highly complex and powerful psychological processes, some of them seemingly irrational, operating within patients when relating to rhinoplasty, a simple superficial surgical procedure.

  19. Time perspective as a predictor of acute postsurgical pain and coping with pain following abdominal surgery.

    Sobol-Kwapinska, M; Plotek, W; Bąbel, P; Cybulski, M; Kluzik, A; Krystianc, J; Mandecki, M

    2017-04-01

    The aim of this study was to predict acute postsurgical pain and coping with pain following surgery based on preoperative time perspectives. Time perspective is a basic dimension of psychological time. It is a tendency to focus on a particular time area: the past, the present and the future. Seventy-six patients completed measures of time perspective and pain 24 h before abdominal surgery. During the 3 days after surgery, measures of pain and coping with pain were completed. We performed hierarchical regression analyses to identify predictors of acute postsurgical pain and how patients cope with it. These analyses suggested that a preoperative past-negative time perspective can be a predictor of postoperative pain level and catastrophizing after surgery. The findings of our study indicate the importance of time perspective, especially the past perspective, in dealing with postoperative pain. Our research indicates that a preoperative past-negative time perspective is a significant predictor of acute postsurgical pain intensity and the strongest predictor of pain catastrophizing. © 2016 European Pain Federation - EFIC®.

  20. Reducing post-surgical adhesions utilizing a drug-enhanced device: sodium carboxymethylcellulose aqueous gel/poly(p-dioxanone) and Tranilast

    Cui, Helen; Gensini, Michel; Kataria, Ram; Twaddle, Tricia; Zhang, John; Wadsworth, Scott; Cooper, Kevin; Petrilli, Janel; Rodgers, Kathleen; DiZerega, Gere

    2009-01-01

    Post-surgical adhesion formation has numerous deleterious side effects in a wide variety of surgical settings. Physical barriers used together with laparoscopy were developed to reduce tissue trauma seen with open procedures. However, despite surgeons' meticulous techniques and the use of such barriers, adhesion formation remains a serious clinical problem, creating complications that cost the health care system over $1 billion annually. Our laboratories have combined a previously marketed drug, Tranilast, with a sodium carboxymethylcellulose (NaCMC) gel in a sustained release formulation using poly(p-dioxanone) (PDO) to provide a locally delivered medicated device that significantly reduces adhesions. This paper describes the preparation of the gel and the sustained release formulation, its key physical properties, and its sustained release kinetics. Pre-clinical data on inhibition of adhesion formation by the sustained release poly(p-dioxanone)/sodium carboxymethylcellulose/Tranilast drug enhanced device are also presented.

  1. Dexmedetomidine attenuates persistent postsurgical pain by upregulating K+–Cl− cotransporter-2 in the spinal dorsal horn in rats

    Dai S

    2018-05-01

    Full Text Available Shuhong Dai,1 Yu Qi,1 Jie Fu,1 Na Li,1 Xu Zhang,1 Juan Zhang,2 Wei Zhang,2 Haijun Xu,1 Hai Zhou,1 Zhengliang Ma2 1Department of Anesthesiology, XuZhou Central Hospital, Xuzhou, China; 2The Affiliated Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China Background: Dexmedetomidine (DEX could have an analgesic effect on pain transmission through the modulation of brain-derived neurotrophic factor (BDNF. In addition, KCC2-induced shift in neuronal Cl- homeostasis is crucial for postsynaptic inhibition mediated by GABAA receptors. Accumulating evidence shows that nerve injury, peripheral inflammation and stress activate the spinal BDNF/TrkB signal, which results in the downregulation of KCC2 transport and expression, eventually leads to GAGAergic disinhibition and hyperalgesia. The aim of this experiment was to explore the interaction between DEX and KCC2 at a molecular level in rats in the persistent postsurgical pain (PPSP. Methods: PPSP in rats was evoked by the skin/muscle incision and retraction (SMIR. Mechanical hypersensitivity was assessed with the Dynamic Plantar Aesthesiometer. Western blot and immunofluorescence assay were used to assess the expressions of related proteins. Results: In the first part of our experiment, the results revealed that the BDNF/TrkB-KCC2 signal plays a critical role in the development of SMIR-evoked PPSP; the second part showed that intraperitoneal administrations of 40 µg/kg DEX at 15 min presurgery and 1 to 3 days post-surgery significantly attenuated SMIR-evoked PPSP. Simultaneously, SMIR-induced KCC2 downregulation was partly reversed, which coincided with the inhibition of the BDNF/TrkB signal in the spinal dorsal horn. Moreover, intrathecal administrations of KCC2 inhibitor VU0240551 significantly reduced the analgesic effect of DEX on SMIR-evoked PPSP. Conclusion: The results of our study indicated that DEX attenuated PPSP by restoring KCC2 function through reducing BDNF

  2. Pain-related psychological correlates of pediatric acute post-surgical pain

    Pagé MG

    2012-11-01

    Full Text Available M Gabrielle Pagé,1 Jennifer Stinson,2,3 Fiona Campbell,2,4 Lisa Isaac,2,4 Joel Katz1,4,51Department of Psychology, Faculty of Health, York University, 2Department of Anesthesia and Pain Medicine, Hospital for Sick Children, 3Lawrence S Bloomberg Faculty of Nursing, University of Toronto, 4Department of Anesthesia, Faculty of Medicine, University of Toronto, 5Department of Psychology, Hospital for Sick Children, Toronto, ON, CanadaBackground: Post-surgical pain is prevalent in children, yet is significantly understudied. The goals of this study were to examine gender differences in pain outcomes and pain-related psychological constructs postoperatively and to identify pain-related psychological correlates of acute post-surgical pain (APSP and predictors of functional disability 2 weeks after hospital discharge.Methods: Eighty-three children aged 8–18 (mean 13.8 ± 2.4 years who underwent major orthopedic or general surgery completed pain and pain-related psychological measures 48–72 hours and 2 weeks after surgery.Results: Girls reported higher levels of acute postoperative anxiety and pain unpleasantness compared with boys. In addition, pain anxiety was significantly associated with APSP intensity and functional disability 2 weeks after discharge, whereas pain catastrophizing was associated with APSP unpleasantness.Conclusion: These results highlight the important role played by pain-related psychological factors in the experience of pediatric APSP by children and adolescents.Keywords: acute post-surgical pain, children, adolescents, pain anxiety, pain catastrophizing

  3. ALLOTRANSPLANTATION OF MACROENCAPSULATED PARATHYROID CELLS IN SEVERE POSTSURGICAL HYPOPARATHYROIDISM: A CASE REPORT

    V. Ja. Khryshchanovich

    2011-01-01

    Full Text Available The last therapeutic alternative in severe postsurgical hypoparathyroidism is allotransplantation of macroen- capsulated parathyroid cells. With this technique, it is possible to implant cells or tissue of parathyroid origin to replace them in such patients, without immusupression. We report an allotransplant of parathyroid cells in a patient with continous endovenous requirement of calcium to survive. The macroencapsulation was carried out with a polyvinylidine difluoride (PVDF. We implant ~100 000 parathyroid cells in the deep femoral artery. In this article, we show functionality of the graft for at least 3 months without requirement of endovenous calcium. We report this procedure as a therapeutical alternative in severe hypoparathyroidism. 

  4. Imaging of posterior cruciate ligament (PCL) reconstruction: normal postsurgical appearance and complications

    Alcala-Galiano, Andrea; Baeva, Maria; Jose Argueeso, Maria [Hospital ASEPEYO Coslada, Department of Radiology, Madrid (Spain); Ismael, Maryem [Hospital ASEPEYO Coslada, Department of Traumatology and Orthopaedic Surgery, Madrid (Spain)

    2014-12-15

    This article reviews the normal postsurgical anatomy and appearance of PCL reconstructions on MDCT and MRI with the different operative techniques considering the type of tibial fixation, use of a single or double bundle, type of tendon graft and the fixation material. Tunnel positioning, appearance of the ligament graft and findings at the donor site are considered. Imaging signs of PCL graft failure and its possible causes are discussed. Imaging manifestations of other potential complications of both the PCL graft and donor sites are described, such as laxity, impingement, arthrofibrosis, ganglion cyst formation or complications related to the fixation material. (orig.)

  5. Virtual simulation of the postsurgical cosmetic outcome in patients with Pectus Excavatum

    Vilaça, João L.; Moreira, António H. J.; L-Rodrigues, Pedro; Rodrigues, Nuno; Fonseca, Jaime C.; Pinho, A. C. M.; Correia-Pinto, Jorge

    2011-03-01

    Pectus excavatum is the most common congenital deformity of the anterior chest wall, in which several ribs and the sternum grow abnormally. Nowadays, the surgical correction is carried out in children and adults through Nuss technic. This technic has been shown to be safe with major drivers as cosmesis and the prevention of psychological problems and social stress. Nowadays, no application is known to predict the cosmetic outcome of the pectus excavatum surgical correction. Such tool could be used to help the surgeon and the patient in the moment of deciding the need for surgery correction. This work is a first step to predict postsurgical outcome in pectus excavatum surgery correction. Facing this goal, it was firstly determined a point cloud of the skin surface along the thoracic wall using Computed Tomography (before surgical correction) and the Polhemus FastSCAN (after the surgical correction). Then, a surface mesh was reconstructed from the two point clouds using a Radial Basis Function algorithm for further affine registration between the meshes. After registration, one studied the surgical correction influence area (SCIA) of the thoracic wall. This SCIA was used to train, test and validate artificial neural networks in order to predict the surgical outcome of pectus excavatum correction and to determine the degree of convergence of SCIA in different patients. Often, ANN did not converge to a satisfactory solution (each patient had its own deformity characteristics), thus invalidating the creation of a mathematical model capable of estimating, with satisfactory results, the postsurgical outcome.

  6. Atlas of postsurgical neuroradiology. Imaging of the brain, spine, and neck

    Ginat, Daniel Thomas; Westesson, Per-Lennart A.

    2012-01-01

    Covers the normal appearances and complications that may be encountered on neuroradiological examinations following surgery to the head, neck, and spine. Contains numerous images and to-the-point case descriptions. Serves as an invaluable and convenient resource for both neuroradiologists and neurosurgeons. The number of surgical procedures performed on the brain, head, neck, and spine has increased markedly in recent decades. As a result, postoperative changes are being encountered more frequently on neuroradiological examinations and constitute an important part of the workflow. However, the imaging correlates of postsurgical changes can be unfamiliar to neuroradiologists and neurosurgeons and are sometimes difficult to interpret. This book is written by experts in the field and contains an abundance of high-quality images and concise descriptions, which should serve as a useful guide to postsurgical neuroradiology. It will familiarize the reader with the various types of surgical procedure, implanted hardware, and complications. Indeed, this work represents the first text dedicated to the realm of postoperative neuroimaging. Topics reviewed include imaging after facial cosmetic surgery; orbital and oculoplastic surgery; sinus surgery; scalp and cranial surgery; brain tumor treatment; psychosurgery, neurodegenerative surgery, and epilepsy surgery; skull base surgery including transsphenoidal pituitary resection; temporal bone surgery including various ossicular prostheses; orthognathic surgery; surgery of the neck including the types of dissection and flap reconstruction; CSF diversion procedures and devices; spine surgery; and vascular and endovascular neurosurgery.

  7. Effect of a baking soda-peroxide dentifrice on post-surgical wound healing.

    Dentino, A R; Ciancio, S G; Bessinger, M; Mather, M A; Cancro, L; Fischman, S

    1995-06-01

    To investigate the effect of a baking soda-hydrogen peroxide (0.75%) dentifrice on wound healing, plaque formation, gingival inflammation, patient comfort, probing depth, and clinical attachment level following gingival flap surgery. A randomized, double-blind crossover study involving 25 patients requiring bilateral maxillary gingival flap surgery was completed. The effects of twice daily brushing with a baking soda-hydrogen peroxide dentifrice (Mentadent) or a placebo dentifrice (Crest) were observed over a 28-day post-surgical period. Gingival Index (GI), plaque index (PI), probing depth (PD), clinical attachment level (CAL) and gingival bleeding index (BI) were recorded pre-surgically and at day 28 for each surgical sextant. At days 7 and 14, soft tissue appearance/wound healing (STA) was assessed based on color and edema, PIs were determined and patient comfort was ascertained by report. Post-surgical wound healing was statistically significantly improved at day 7 with the trend continuing to day 14 when Mentadent dentifrice was used as compared to Crest dentifrice. However, there was no statistical difference in the PI values between the test and control dentifrice throughout the study. Use of Mentadent may be an effective aid in the early phase of healing following gingival flap surgery.

  8. Sports-specific differences in postsurgical infections after arthroscopically assisted anterior cruciate ligament reconstruction.

    Krutsch, Werner; Zellner, Johannes; Zeman, Florian; Nerlich, Michael; Koch, Matthias; Pfeifer, Christian; Angele, Peter

    2017-12-01

    Post-operative infection after arthroscopically assisted anterior cruciate ligament (ACL) reconstruction is a rare but severe complication, particularly for young and active patients. It is unclear whether the prevalence of knee infection is correlated with the type of sports or the level of performance. From 2008 to 2012, the internal single-centre ACL registry of the FIFA Medical Centre of Excellence Regensburg was retrospectively screened for sex, age, time between isolated primary ACL rupture and surgery, surgical technique, rate of infection after ACL reconstruction and the type of sports practised. In total, 4801 ACL reconstructions had been conducted over 5 years, 4579 in amateur and 221 in professional athletes. After application of the exclusion criteria, 1809 athletes with ACL reconstruction were analysed regarding postsurgical infection and the type of sports practised. Professionals and amateurs did not significantly differ with regard to infection rates (n.s.) but in the timing of ACL repair (p sports (n.s.). Staphylococcus aureus and epidermidis were the predominant detected bacteria. All patients were hospitalised and successfully treated with arthroscopic lavage and antibiotic medication. ACL infections showed sports-related differences. Athletes practising summer outdoor sports such as football had a significantly higher risk of infection after ACL reconstruction than winter sports athletes. No difference was found between professional and amateur athletes. Relevant prevention strategies for postsurgical ACL infections should consider influencing patient factors such as the type of sports activity and attendant circumstances. III.

  9. Heterogeneous postsurgical data analytics for predictive modeling of mortality risks in intensive care units.

    Yun Chen; Hui Yang

    2014-01-01

    The rapid advancements of biomedical instrumentation and healthcare technology have resulted in data-rich environments in hospitals. However, the meaningful information extracted from rich datasets is limited. There is a dire need to go beyond current medical practices, and develop data-driven methods and tools that will enable and help (i) the handling of big data, (ii) the extraction of data-driven knowledge, (iii) the exploitation of acquired knowledge for optimizing clinical decisions. This present study focuses on the prediction of mortality rates in Intensive Care Units (ICU) using patient-specific healthcare recordings. It is worth mentioning that postsurgical monitoring in ICU leads to massive datasets with unique properties, e.g., variable heterogeneity, patient heterogeneity, and time asyncronization. To cope with the challenges in ICU datasets, we developed the postsurgical decision support system with a series of analytical tools, including data categorization, data pre-processing, feature extraction, feature selection, and predictive modeling. Experimental results show that the proposed data-driven methodology outperforms traditional approaches and yields better results based on the evaluation of real-world ICU data from 4000 subjects in the database. This research shows great potentials for the use of data-driven analytics to improve the quality of healthcare services.

  10. Evaluation of post-surgical relapse after mandibular setback surgery with minimal orthodontic preparation.

    Lee, Nam-Ki; Kim, Young-Kyun; Yun, Pil-Young; Kim, Jong-Wan

    2013-01-01

    The aim of this study was to evaluate of the patterns of post-surgical relapse after mandibular setback surgery with minimal orthodontic preparation (MS-MO). The subjects consisted of 15 patients with minimal pre-surgical orthodontic preparation (1.37 ± 1.69 months). Lateral cephalograms were taken in pre-surgical (T0), post-surgical 1 month (T1) and immediately after debonding (T2) stages. To evaluate the surgical changes (T1-T0) and the relapse (T2-T1), the linear and angular measurements were analyzed using paired t-test. Pearson's correlation coefficients of the horizontal and vertical relapses of Pog and Me to other measurements were calculated. Pog or Me in T1 were displaced rotationally on Ar-Pog or Ar-Me lines in T2 to evaluate the remaining surgical relapse except the rotational relapse from total relapse. The mandible relapsed anteriorly 3.53 mm (Pog) and 4.00 mm (Me) and superiorly 2.72 mm (Pog) and 2.44 mm (Me). FH to Ar-Pog and FH to Ar-Me decreased by about 2°. Pure surgical relapses at Pog and Me, except rotational relapses, were about 0.5 mm anteriorly and inferiorly 0.8 mm. The vertical relapse might induce mandibular rotation with the horizontal relapse. For an accurate prediction after MS-MO, the rotational relapse might be considered. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  11. Postsurgical complications in patients with renal tumours with venous thrombosis treated with surgery.

    Caño-Velasco, J; Herranz-Amo, F; Barbas-Bernardos, G; Mayor-de Castro, J; Aragón-Chamizo, J; Arnal-Chacón, G; Lledó García, E; Hernández-Fernández, C

    2018-04-06

    Surgery on renal tumours with venous thrombosis suffers a high rate of complications and non-negligible perioperative mortality. Our objective was to analyse the postoperative complications, their relationship with the level of the thrombus and its potential predisposing factors. A retrospective analysis was conducted of 101 patients with renal tumours with venous thrombosis operated on between 1988 and 2017. Two patients were excluded because of intraoperative pulmonary thromboembolism and exitus (2%). The postsurgical complications were classified according to Clavien-Dindo. To compare the qualitative variables, we employed the chi-squared test. We performed a multivariate analysis using binary logistic regression to identify the independent predictors. Some type of postsurgical complication occurred in 34 (34.3%) patients, 11 (11.1%) of which were severe (Clavien III-V). There were significant differences in the total complications (P=.003) and severe complications (Clavien≥III; P=.03) depending on the level of the tumour thrombus. Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Development of a risk index for the prediction of chronic post-surgical pain.

    Althaus, A; Hinrichs-Rocker, A; Chapman, R; Arránz Becker, O; Lefering, R; Simanski, C; Weber, F; Moser, K-H; Joppich, R; Trojan, S; Gutzeit, N; Neugebauer, E

    2012-07-01

    The incidence of chronic post-surgical pain (CPSP) after various common operations is 10% to 50%. Identification of patients at risk of developing chronic pain, and the management and prevention of CPSP remains inadequate. The aim of this study was to develop an easily applicable risk index for the detection of high-risk patients that takes into account the multifactorial aetiology of CPSP. A comprehensive item pool was derived from a systematic literature search. Items that turned out significant in bivariate analyses were then analysed multivariately, using logistic regression analyses. The items that yielded significant predictors in the multivariate analyses were compiled into an index. The cut-off score for a high risk of developing CPSP with an optimal trade-off between sensitivity and specificity was identified. The data of 150 patients who underwent different types of surgery were included in the analyses. Six months after surgery, 43.3% of the patients reported CPSP. Five predictors multivariately contributed to the prediction of CPSP: capacity overload, preoperative pain in the operating field, other chronic preoperative pain, post-surgical acute pain and co-morbid stress symptoms. These results suggest that several easily assessable preoperative and perioperative patient characteristics can predict a patient's risk of developing CPSP. The risk index may help caregivers to tailor individual pain management and to assist high-risk patients with pain coping. © 2011 European Federation of International Association for the Study of Pain Chapters.

  13. Atlas of postsurgical neuroradiology. Imaging of the brain, spine, and neck

    Ginat, Daniel Thomas [Massachusetts General Hospital, Boston, MA (United States). Harvard Medical School; Westesson, Per-Lennart A. [Univ. of Rochester Medical Center, Rochester, NY (United States). Div. of Neuroradiology

    2012-11-01

    Covers the normal appearances and complications that may be encountered on neuroradiological examinations following surgery to the head, neck, and spine. Contains numerous images and to-the-point case descriptions. Serves as an invaluable and convenient resource for both neuroradiologists and neurosurgeons. The number of surgical procedures performed on the brain, head, neck, and spine has increased markedly in recent decades. As a result, postoperative changes are being encountered more frequently on neuroradiological examinations and constitute an important part of the workflow. However, the imaging correlates of postsurgical changes can be unfamiliar to neuroradiologists and neurosurgeons and are sometimes difficult to interpret. This book is written by experts in the field and contains an abundance of high-quality images and concise descriptions, which should serve as a useful guide to postsurgical neuroradiology. It will familiarize the reader with the various types of surgical procedure, implanted hardware, and complications. Indeed, this work represents the first text dedicated to the realm of postoperative neuroimaging. Topics reviewed include imaging after facial cosmetic surgery; orbital and oculoplastic surgery; sinus surgery; scalp and cranial surgery; brain tumor treatment; psychosurgery, neurodegenerative surgery, and epilepsy surgery; skull base surgery including transsphenoidal pituitary resection; temporal bone surgery including various ossicular prostheses; orthognathic surgery; surgery of the neck including the types of dissection and flap reconstruction; CSF diversion procedures and devices; spine surgery; and vascular and endovascular neurosurgery.

  14. The correlation of matrix metalloproteinase 9-to-albumin ratio in wound fluid with postsurgical complications after body contouring.

    Sexton, Kevin W; Spear, Marcia; Pollins, Alonda C; Nettey, Chenai; Greco, Joseph A; Shack, R Bruce; Hagan, Kevin F; Nanney, Lillian B

    2014-10-01

    The authors' earlier retrospective report of surgical complications after abdominal contouring surgery provided evidence that post-bariatric surgery patients are at increased risk of developing wound complications compared with a normal population. This prospective pilot study was designed as a comparative analysis of both surgical and wound healing characteristics between massive weight loss and normal patients who present for abdominal contouring surgery. Excisional wounds were created and polytetrafluoroethylene tubing was inserted during the preoperative period for later harvesting in patients undergoing abdominal contouring following Roux-en-Y gastric bypass for weight loss (n = 16) or abdominoplasty (n = 17). Wound fluids were sequentially collected from drains and subjected to matrix metalloproteinase (MMP) analysis. Standard postsurgical complications were documented. Surgical complications were more common in weight loss patients (47 percent) than in control patients (25 percent). MMP analyses showed that MMP-9 levels remained significantly elevated at postoperative day 4 in patients who subsequently experienced complications in either the weight loss group (p = 0.02) or the control group (p = 0.03). Other parameters showed no significant differences between massive weight loss patients and controls. Although many markers were examined, the ratio of MMP-9 to albumin was the only predictor of postsurgical complications in any group. This lends further support to growing evidence that MMP-9 may be a useful biomarker of postsurgical complications. This pilot work showed no causal factors that explain the higher rates of postsurgical complications in the post-bariatric surgery patient population. Risk, II.

  15. Psychogenic nonepileptic seizures in patients with surgically treated temporal lobe epilepsy: Presurgical and de novo postsurgical occurrence.

    González Otárula, Karina A; Tan, Yee-Leng; Dubeau, François; Correa, José A; Chang, Edward; Hall, Jeffery A; Knowlton, Robert C; Kobayashi, Eliane

    2017-10-01

    Whether occurring before or after an epilepsy surgery, psychogenic nonepileptic seizures (PNES) impact treatment options and quality of life of patients with epilepsy. We investigated the frequency of pre- and postsurgical PNES, and the postsurgical Engel and psychiatric outcomes in patients with drug-resistant temporal lobe epilepsy (TLE). We reviewed 278 patients with mean age at surgery of 37.1±12.4years. Postsurgical follow-up information was available in 220 patients, with average follow-up of 4years. Nine patients (9/278 or 3.2%) had presurgical documented PNES. Eight patients (8/220 or 3.6%) developed de novo PNES after surgery. Pre- and postsurgery psychiatric comorbidities were similar to the patients without PNES. After surgery, in the group with presurgical PNES, five patients were seizure-free, and three presented persistent PNES. In the group with de novo postsurgery PNES, 62.5% had Engel II-IV, and 37.5% had Engel I. All presented PNES at last follow-up. Presurgical video-EEG monitoring is crucial in the diagnosis of coexisting PNES. Patients presenting presurgical PNES and drug-resistant TLE should not be denied surgery based on this comorbidity, as they can have good postsurgical epilepsy and psychiatric outcomes. Psychogenic nonepileptic seizures may appear after TLE surgery in a low but noteworthy proportion of patients regardless of the Engel outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Options for investigative postsurgical therapy for gastric cancer, and case report of using the option for combined immunotherapy and chemotherapy.

    Gerhardt, P

    2001-02-01

    The investigative therapy for a senior patient after radical subtotal gastroesophagectomy for regional lymph node and proximal esophagus metastasized adenocarcinoma (stage IIIA, T3, N 1 M0) of the cardioesophageal junction is reported. The case has several unusual features: (1) the patient is the author and is not a physician; (2) in the absence of codified postsurgical treatment, he used his academic biomedical background, commercial associations, and international contacts to find and prioritize six clinically tested options for investigative postsurgical therapy; (3) after unsuccessful efforts to append ongoing clinical trials of new immunotherapies for breast adenocarcinoma (the first two therapy options), an innovative protocol was designed and gained allowance by the U.S. Food and Drug Administration for his use of combined nonspecific immunotherapy and chemotherapy based on extensive trials in South Korea that showed the synergistic effect of the two postsurgical therapies used together. A potent, new, nonspecific immunostimulant (DetoxPC) was injected subcutaneously in 10 diminishing doses during 105 weeks. Two standard chemotherapeutic drugs (5-fluorouracil and mitomycin-C) were injected intravenously in six equal doses during three weeks. Five years after the surgery, the patient enjoys good health without signs or symptoms of recurrence or metastasis. He discusses his perspectives on future clinical trials and on a patient actively pursuing investigative postsurgical therapy for a malignancy when otherwise poor survival is indicated.

  17. [Post-surgical Achilles tendon and correlation with functional outcome: a review of 40 cases].

    Wagnon, R; Akayi, M

    2005-12-01

    To assess the value of MRI in the post operative evaluation of Achilles tendon rupture. 40 patients treated for acute Achilles tendon rupture at the Pasteur Hospital of Cherbourg between 1994 and 2002 underwent postoperative MRI. The objective was to look for correlations between functional outcome and reproducible measurements from imaging data previously described in the literature. We obtained only two positive correlations among all the combinations of comparisons: the first one between the perimeter of the calf and the surface area of the posterior muscle compartment, the second between the surface area of the operated tendon and its elongation estimated by the recalculated ratio of ankle dorsiflexion amplitude. MRI plays no role in the routine follow-up of post-surgical Achilles tendons. It should consequently only be used as a specific tool in problem cases, such as evaluation of possible re-tear.

  18. [Prevention of the post-surgical insatisfactions and possible medico-legal complications].

    Flageul, G; Pessis, R

    2017-10-01

    The purpose of this work is to better understand the reasons for post-surgical instability and what makes up the bed of medico-legal complications. Beyond technical competence, it is essential to observe a very high degree of rigor in listening to the real motivations in order to give the most accurate possible surgical indications and in particular to know to detect and never to operate certain patients who, whatever we do, will always be dissatisfied. The quality of information is one of the essential elements of prevention: information is part of the care and there is no therapeutic success without a successful relationship between a caregiver and a carereceiver. Before the surgery, it is essential to pre-establish written proof of the proper delivery of the information by signing a receipt and an informed consent document. However, the information does not stop at the time of the operative gesture and it is necessary to be able to provide complete and timely information about any post-surgical complications. Furthermore, aesthetic medicine is well understood and rigorously implemented, contributes to the prevention of surgical and medico-legal complications, reducing the heaviness of certain surgical gestures. The question of e-reputation should in no way be neglected. From this point of view, prevention consists in controlling as much as possible the Internet environment. Indeed, where, in the past, in the presence of a dissatisfied patient awaited us, the fear of word-of-mouth or trial is added to the risk of harm E-reputation whose implications can be very damaging. At a time when the intensive use of the Internet allows anyone to get out of anonymity, we must also control these tools at the risk of sacrificing our expertise at the coronation of amateurs. Copyright © 2017. Published by Elsevier Masson SAS.

  19. Safety and Efficacy of a Pharmacist-Managed Patient-Controlled Analgesia Service in Postsurgical Patients.

    McGonigal, Katrina H; Giuliano, Christopher A; Hurren, Jeff

    2017-09-01

    To compare the safety and efficacy of a pharmacist-managed patient-controlled analgesia (PCA) service with physician/midlevel provider-managed (standard) PCA services in postsurgical patients. This was a multicenter, retrospective cohort study performed at 3 major hospitals in the Detroit, Michigan, metropolitan area. Postsurgical patients from October 2012 to December 2013 were included. The primary outcome compared the pain area under the curve adjusted for time on PCA (AUC/T) of patients receiving pharmacist-managed PCA services vs. standard care, up to 72 hours after initiation of PCA. Secondary outcomes included initial opioid selection, programmed PCA settings, duration of PCA use, frequency of adjunct analgesia utilization, and frequency of breakthrough analgesia utilization. Safety outcomes were assessed as a composite safety endpoint and individually. Total pain AUC/T scores did not differ between the pharmacist-managed and standard-managed groups (3.25 vs. 3.25, respectively; P = 0.98). Adjunct pain medications were given with similar frequency in the 2 groups; however, significantly fewer patients required breakthrough pain medication in the pharmacist-managed group (11% vs. 36%, respectively; P patients requiring antiemetic use (46% vs. 32%; P = 0.04). A pharmacist-managed PCA service provided no difference in pain control compared to standard management. The requirement for breakthrough analgesia was decreased in the pharmacist group, while the need for antiemetic use was increased. Further research should be conducted to evaluate different PCA management strategies. © 2016 World Institute of Pain.

  20. Howling at the moon? The effect of lunar phases on post-surgical pain outcome.

    Komann, Marcus; Weinmann, Claudia; Meissner, Winfried

    2014-05-01

    Many people are convinced that lunar phases influence their lives - despite the fact that a lot of studies have shown that this belief is wrong. In this article, we investigate the effect of lunar phases on acute post-surgical pain and on treatment-related side effects. We hypothesize that there is no influence. The data for the study were collected in 2010 and 2011 in 10 international hospitals participating in the research project PAIN OUT. Hospitalized patients were asked for their pain after surgery and pain treatment side effects using numerical ratings scales from 0 to 10. We applied Kurskal-Wallis H-tests to find out if the four moon phases show significant differences in 14 outcome variables. Afterwards, we adjusted for age, gender and three tracer surgeries. A total of 12,224 patient data sets were assessed. For most variables and sub-groups, there is no lunar effect on the observed outcome variables. The only items that show statistically significant differences are pain interference with sleep (p = 0.01) and drowsiness (p = 0.01). The only sub-groups that show statistically significant connections to lunar phases in some variables are men (7 out of 14 variables significant) and elderly people (4 out of 14 variables significant). Even in the statistically significant sub-groups, the differences are small and only show up in some variables. We conclude that lunar phases have no effect on post-surgical pain or its side effects. The hypothesis holds. Thus, there is no reason for patients to postpone surgeries or to fear surgeries on any given date.

  1. POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL.

    Carroll, Ty B; Javorsky, Bradley R; Findling, James W

    2016-10-01

    To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC). The design was a single-center, retrospective chart review. Patients treated by the authors from 2008-2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST). We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had ≥1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements. LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker. ACTH = adrenocorticotropic hormone CD = Cushing disease CS = Cushing syndrome CV = coefficient of variation DST = dexamethasone suppression test IPSS = inferior petrosal sinus sampling LNSC = late-night salivary cortisol QoL = quality of life TSS = transsphenoidal

  2. The voice of postsurgical lung cancer patients regarding supportive care needs

    Hoffman AJ

    2014-04-01

    Full Text Available Amy J Hoffman,1 Ruth Ann Brintnall,2 Alexander von Eye,3 Julie Cooper,2 Jean K Brown41College of Nursing, Michigan State University, East Lansing, MI, USA; 2Kirkhof College of Nursing, Grand Valley State University, Grand Rapids, MI, USA; 3Psychology Department, Michigan State University, East Lansing, MI, USA; 4School of Nursing, State University of New York at Buffalo, Buffalo, NY, USAObjective: Individuals with lung cancer present with multiple comorbid conditions and complex treatment plans. They are frequently vulnerable during critical transitions in the cancer survivorship trajectory. Limited research exists on the postsurgical non-small-cell lung cancer (NSCLC population, relative to unmet supportive care needs. However, what is known is that the lung cancer population reports significantly more unmet supportive care needs than other cancer populations. The purpose of this study was to identify the postsurgical NSCLC patients’ unmet supportive care needs during transition from hospital to home and through recovery after participating in a 16-week exercise intervention.Materials and methods: Participants were 53–73 years of age with NSCLC (stage Ib-IIIa and participated in a 16-week light-intensity exercise program after hospital discharge. For this study, participants were interviewed 12-18 months post-thoracotomy. A qualitative design was used, incorporating a semistructured guide with open-ended questions to support discussion regarding recovery experiences through 16 weeks after transitioning from hospital to home. The interview was transcribed verbatim, and data were analyzed using content analysis. Content themes were independently coded by investigators and later combined into a single report verified through participant verification of the report.Results: Participants reviewed and agreed with the focus group report. Dominant themes included: 1 unpreparedness for post-thoracotomy recovery; 2 significant unmet needs upon

  3. Post-surgical infections and perioperative antibiotics usage in pediatric genitourinary procedures.

    Ellett, Justin; Prasad, Michaella M; Purves, J Todd; Stec, Andrew A

    2015-12-01

    Post-surgical infections (PSIs) are a source of preventable perioperative morbidity. No guidelines exist for the use of perioperative antibiotics in pediatric urologic procedures. This study reports the rate of PSIs in non-endoscopic pediatric genitourinary procedures at our institution. Secondary aims evaluate the association of PSI with other perioperative variables, including wound class (WC) and perioperative antibiotic administration. Data from consecutive non-endoscopic pediatric urologic procedures performed between August 2011 and April 2014 were examined retrospectively. The primary outcome was the rate of PSIs. PSIs were classified as superficial skin (SS) and deep/organ site (D/OS) according to Centers for Disease Control and Prevention guidelines, and urinary tract infection (UTI). PSIs were further stratified by WC1 and WC2 and perioperative antibiotic usage. A relative risk and chi-square analysis compared PSI rates between WC1 and WC2 procedures. A total of 1185 unique patients with 1384 surgical sites were reviewed; 1192 surgical sites had follow-up for inclusion into the study. Ten total PSIs were identified, for an overall infection rate of 0.83%. Of these, six were SS, one was D/OS, and three were UTIs. The PSI rate for WC1 (885 sites) and WC2 (307 sites) procedures was 0.34% and 2.28%, respectively, p antibiotics (0.35% vs. 0.33%). All WC2 procedures received antibiotics. Post-surgical infections are associated with significant perioperative morbidity. In some studies, PSI can double hospital costs, and contribute to hospital length of stay, admission to intensive care units, and impact patient mortality. Our study demonstrates that the rate of PSI in WC1 operations is low, irrespective of whether the patient received perioperative antibiotics (0.35%) or no antibiotics (0.33%). WC2 operations were the larger source of morbidity with an infection rate of 2.28% and a 6.7 fold higher increase in relative risk. WC1 procedures have a rate of

  4. Parental risk factors for the development of pediatric acute and chronic postsurgical pain: a longitudinal study

    Pagé MG

    2013-09-01

    main risk factor for the development of postsurgical pain chronicity. Keywords: pain anxiety, pain catastrophizing, children, parental risk factors, postsurgical pain

  5. Effectiveness of Surgical and Postsurgical Interventions for Carpal Tunnel Syndrome-A Systematic Review.

    Huisstede, Bionka M; van den Brink, Janneke; Randsdorp, Manon S; Geelen, Sven J; Koes, Bart W

    2017-05-31

    To present an evidence-based overview of the effectiveness of surgical and postsurgical interventions for carpal tunnel syndrome (CTS). The Cochrane Library, PubMed, EMBASE, CINAHL, and PEDro were searched for relevant systematic reviews and randomized controlled trials (RCTs) up to April 8, 2016. Two reviewers independently applied the inclusion criteria to select potential studies. Two reviewers independently extracted the data and assessed the methodologic quality. A best-evidence synthesis was performed to summarize the results. Four systematic reviews and 33 RCTs were included. Surgery versus nonsurgical interventions, timing of surgery, and various surgical techniques and postoperative interventions were studied. Corticosteroid injection was more effective than surgery (strong evidence, short-term). Surgery was more effective than splinting or anti-inflammatory drugs plus hand therapy (moderate evidence, midterm and long-term). Manual therapy was more effective than surgical treatment (moderate evidence, short-term and midterm). Within surgery, corticosteroid irrigation of the median nerve before skin closure as additive to CTS release or the direct vision plus tunneling technique was more effective than standard open CTS release (moderate evidence, short-term). Furthermore, short was more effective than long bulky dressings, and a sensory retraining program was more effective than no program after surgery (moderate evidence, short-term). For all other interventions only conflicting, limited, or no evidence was found. Surgical treatment seems to be more effective than splinting or anti-inflammatory drugs plus hand therapy in the short-term, midterm, and/or long-term to treat CTS. However there is strong evidence that a local corticosteroid injection is more effective than surgery in the short-term, and moderate evidence that manual therapy is more effective than surgery in the short-term and midterm. There is no unequivocal evidence that suggests one

  6. The New MIRUS System for Short-Term Sedation in Postsurgical ICU Patients.

    Romagnoli, Stefano; Chelazzi, Cosimo; Villa, Gianluca; Zagli, Giovanni; Benvenuti, Francesco; Mancinelli, Paola; Arcangeli, Giulio; Dugheri, Stefano; Bonari, Alessandro; Tofani, Lorenzo; Belardinelli, Andrea; De Gaudio, A Raffaele

    2017-09-01

    To evaluate the feasibility and safety of the MIRUS system (Pall International, Sarl, Fribourg, Switzerland) for sedation with sevoflurane for postsurgical ICU patients and to evaluate atmospheric pollution during sedation. Prospective interventional study. Surgical ICU. February 2016 to December 2016. Postsurgical patients requiring ICU admission, mechanical ventilation, and sedation. Sevoflurane was administered with the MIRUS system targeted to a Richmond Agitation Sedation Scale from -3 to -5 by adaptation of minimum alveolar concentration. Data collected included Richmond Agitation Sedation Scale, minimum alveolar concentration, inspired and expired sevoflurane fraction, wake-up times, duration of sedation, sevoflurane consumption, respiratory and hemodynamic data, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment, and laboratory data and biomarkers of organ injury. Atmospheric pollution was monitored at different sites: before sevoflurane delivery (baseline) and during sedation with the probe 15 cm up to the MIRUS system (S1) and 15 cm from the filter-Reflector group (S2). Sixty-two patients were enrolled in the study. No technical failure occurred. Median Richmond Agitation Sedation Scale was -4.5 (interquartile range, -5 to -3.6) with sevoflurane delivered at a median minimum alveolar concentration of 0.45% (interquartile range, 0.4-0.53) yielding a mean inspiratory and expiratory concentrations of 0.79% (SD, 0.24) and 0.76% (SD, 0.18), respectively. Median awakening time was 4 minutes (2.2-5 min). Median duration of sevoflurane administration was 3.33 hours (2.33-5.75 hr), range 1-19 hours with a mean consumption of 7.89 mL/hr (SD, 2.99). Hemodynamics remained stable over the study period, and no laboratory data indicated liver or kidney injury or dysfunction. Median sevoflurane room air concentration was 0.10 parts per million (interquartile range, 0.07-0.15), 0.17 parts per million (interquartile range, 0

  7. Short-term sleep disturbance-induced stress does not affect basal pain perception, but does delay postsurgical pain recovery

    Wang, Po-Kai; Cao, Jing; Wang, Hongzhen; Liang, Lingli; Zhang, Jun; Lutz, Brianna Marie; Shieh, Kun-Ruey; Bekker, Alex; Tao, Yuan-Xiang

    2015-01-01

    Chronic sleep disturbance-induced stress is known to increase basal pain sensitivity. However, most surgical patients frequently report short-term sleep disturbance/deprivation during pre- and post-operation periods and have normal pain perception pre-surgery. Whether this short-term sleep disturbance affects postsurgical pain is elusive. We here reported that pre- or post-exposure to rapid eye movement sleep disturbance (REMSD) 6 h daily for 3 consecutive days did not alter basal responses t...

  8. Fetus dose estimation in thyroid cancer post-surgical radioiodine therapy

    Mianji, Fereidoun A.; Karimi Diba, Jila; Babakhani, Asad

    2015-01-01

    Unrecognised pregnancy during radioisotope therapy of thyroid cancer results in hardly definable embryo/fetus exposures, particularly when the thyroid gland is already removed. Sources of such difficulty include uncertainty in data like pregnancy commencing time, amount and distribution of metastasized thyroid cells in body, effect of the thyroidectomy on the fetus dose coefficient etc. Despite all these uncertainties, estimation of the order of the fetus dose in most cases is enough for medical and legal decision-making purposes. A model for adapting the dose coefficients recommended by the well-known methods to the problem of fetus dose assessment in athyrotic patients is proposed. The model defines a correction factor for the problem and ensures that the fetus dose in athyrotic pregnant patients is less than the normal patients. A case of pregnant patient undergone post-surgical therapy by I-131 is then studied for quantitative comparison of the methods. The results draw a range for the fetus dose in athyrotic patients using the derived factor. This reduces the concerns on under- or over-estimation of the embryo/fetus dose and is helpful for personal and/or legal decision-making on abortion. (authors)

  9. [Intramuscular depot steroids : Possible treatment of postsurgical cystoid macula edema with steroid response?

    Seuthe, A-M; Szurman, P; Boden, K T

    2017-11-01

    We report on a patient with postsurgical cystoid macular edema (CME) after phacoemulsification and multifocal intraocular lens (MIOL) implantation. At first, there was a very good reaction to intravitreal triamcinolone, inducing complete regression of the edema without increasing intraocular pressure (IOP). One year later the patient suffered from retinal detachment and was treated with vitrectomy, laser, and gas tamponade. Afterward, he developed macular pucker with edema. After surgical treatment with pucker peeling and intravitreal triamcinolone, the patient showed a steroid response and an increase IOP. Postoperatively, there was a recurrence of CME. A coincidental administration of a steroid injection intramuscularly by the general practitioner achieved a prompt reduction of the CME without increasing IOP. This case shows that an initially good reaction to triamcinolone without increasing IOP does not rule out a future steroid response, and that a potential treatment option for CME in patients with a known steroid response could consist of intramuscularly injected steroids.

  10. Difference in Postsurgical Prognostic Factors between Lung Adenocarcinoma and Squamous Cell Carcinoma

    Sakai, Hiroki; Kimura, Hiroyuki; Miyazawa, Tomoyuki; Marushima, Hideki; Saji, Hisashi

    2017-01-01

    Purpose: The aim of this study was to compare the clinicopathologic prognostic factors between patients who underwent lung resection for adenocarcinoma (AD) and those with squamous cell carcinoma (SQ). Methods: A database of patients with lung AD or SQ who underwent surgery with curative intent in our department from January 2008 to December 2014 was reviewed. Associations between various clinicopathologic factors, postsurgical recurrence-free survival (RFS), and overall survival (OS) were analyzed to find significant prognostic factors. Results: A total of 537 lung cancer patients (AD, 434; SQ, 103) were included in this study. Although RFS was similar in patients with AD and SQ, OS was significantly poorer in those with SQ. Multivariate analysis in patients with AD revealed that age (≥69 vs. <69), lymphatic invasion, and histologic pleural invasion (p0 vs. p1–3) were associated with RFS, while gender and pleural invasion were associated with OS. In SQ, however, smoking, clinical stage, and pulmonary metastasis were associated with RFS in the multivariate analysis. Conclusion: Since significant postoperative prognostic factors are quite different between lung AD and SQ, these two histologic types should be differently analyzed in a clinical study. PMID:28966230

  11. [Pre- and post-surgical orthodontic treatment of mandibular asymmetry and prognathism].

    Chen, Song; Chen, Yang-xi; Hu, Jing

    2005-01-01

    The purpose of this study was to analyze the pre- and post surgical orthodontic treatment of mandibular asymmetry and prognathism in our hospital, and to summarize some helpful experiences for future clinical work. The data were derived from 21 adults aged from 19 - 28 years who had severe mandibular asymmetry and prognathism. The ANB angle of all patients is from -3 degrees to -8 degrees. The value of wits of all patients is from -7 mm to -14 mm. The deviation of chin point of all patients is from 3 mm to 7 mm. The duration of pre- and post-surgical orthodontic treatment was 10-20 months (mean 18 months) and 5-10 months (mean 7.5 months), respectively. The keys in pre-surgical orthodontic treatment include (1) three dimensional dental decompensation; (2) arch form and transverse discrepancy correction; (3) model surgery and the splint making. The main objective of post surgical orthodontic treatment is to detail the occlusion. Pre- and post surgical orthodontic treatment is essential for the orthognathic treatment of patients with mandibular asymmetry and prognathism.

  12. Comparison of post-surgical MRI presentation of the pituitary gland and its hormonal function.

    Bladowska, Joanna; Sokolska, Violetta; Sozański, Tomasz; Bednarek-Tupikowska, Grażyna; Sąsiadek, Marek

    2010-01-01

    Post-surgical evaluation of the pituitary gland in MRI is difficult because of a change of anatomical conditions. It depends also on numerous other factors, including: size and expansion of a tumour before surgery, type of surgical access, quality and volume of filling material used and time of its resorption.The aim of the study was to compare MR image of the pituitary gland after surgery with clinical findings and to establish a correlation between MRI presentation of spared pituitary and its hormonal function. 124 patients after resection of pituitary adenomas - 409 MRI results in total - were studied. With a 1.5-T unit, T1-weighted sagittal and coronal, enhanced and unenhanced images were obtained. The pituitary gland seemed to be normal in MRI in 11 patients, 8 of them had completely regular pituitary function but in 3 of them we noticed a partial hypopituitarism. In 99 patients only a part of the pituitary gland was recognised, 53 of them had hypopituitarism but 46 of them were endocrinologically healthy. 14 patients seemed to have no persistent pituitary gland in MRI, in comparison to hormonal studies: there was panhypopituitarism in 6 and hypopituitarism in 8 cases. MRI presentation of post - surgical pituitary gland doesn't necessarily correlate with its hormonal function - there was a significant statistical difference. Some patients with partial pituitary seems normal hormonal function. In some cases the pituitary seem normal in MRI but these patients have hormonal disorders and need substitution therapy.

  13. Distinction of infected and non-infected post-surgical incisions with In-111-WBC scintigraphy

    Abdel-Nabi, H.; Hinkle, G.H.; Olsen, J.O.

    1985-01-01

    To determine if In-111-WBCs scintigraphy can distinguish between healing and infection in post-surgical wounds, a prospective study was performed in patients with 3-14 day old surgical incisions. Eighteen patients (11 males and 7 females) were scanned 24 hrs after injection of 0.5 mCi of In-111 labeled autologous leukocytes. The scan findings were correlated with blood and/wound cultures results and diagnosis at time of discharge. Incisional uptake of In-111-WBCs was noted in 9 patients with infected surgical wounds and was absent in those 9 patients with non-infected surgical wounds. The results of the authors' study show that In-111-WBCs do not accumulate in non-infected surgical incisions. This confirms their previous findings in rats. The high specificity of In-111 leukocytes imaging makes it a valuable study in the evaluation of post-operative patients with suspected surgical wound infections. In-111 WBCs scintigraphy can distinguish between normal healing and infection at the site of recent (3-14 days) surgical incisions

  14. Psychosocial predictors and correlates for chronic post-surgical pain (CPSP) - a systematic review.

    Hinrichs-Rocker, Anke; Schulz, Kerstin; Järvinen, Imke; Lefering, Rolf; Simanski, Christian; Neugebauer, Edmund A M

    2009-08-01

    Chronic post-surgical pain (CPSP) is a serious problem. Incidence as high as 50% has been reported, depending on type of surgery undergone. Because the etiology of chronic pain is grounded in the bio-psychosocial model, physical, psychological, and social factors are implicated in the development of CPSP. Biomedical factors such as pre-operative pain, severe acute post-operative pain, modes of anesthesia, and surgical approaches have been extensively examined, therefore this systematic review focuses on psychosocial elements. A systematic search was performed using the PubMed, PsychINFO, Embase, and Cochrane Databases. Fifty relevant publications were selected from this search, in which psychosocial predictors for and correlates to CPSP were identified. The level of evidence was assessed for each study, and corresponding score points were awarded for ease of comparison. The grade of association with CPSP for each predictor/correlate was then determined. Depression, psychological vulnerability, stress, and late return to work showed likely correlation with CPSP (grade of association=1). Other factors were determined to have either unlikely (grade of association=3) or inconclusive (grade of association=2) correlations. In addition, results were examined in light of the type of surgery undergone. This review is intended as a first step to develop an instrument for identifying patients at high risk for CPSP, to optimize clinical pain management.

  15. Constructing post-surgical discharge instructions through a Delphi consensus methodology.

    Scott, Aaron R; Sanderson, Cody J; Rush, Augustus J; Alore, Elizabeth A; Naik, Aanand D; Berger, David H; Suliburk, James W

    2018-05-01

    Patient education materials are a crucial part of physician-patient communication. We hypothesize that available discharge instructions are difficult to read and fail to address necessary topics. Our objective is to evaluate readability and content of surgical discharge instructions using thyroidectomy to develop standardized discharge materials. Thyroidectomy discharge materials were analyzed for readability and assessed for content. Fifteen endocrine surgeons participated in a modified Delphi consensus panel to select necessary topics. Using readability best practices, we created standardized discharge instructions which included all selected topics. The panel evaluated 40 topics, selected 23, deemed 4 inappropriate, consolidated 5, and did not reach consensus on 8 topics after 4 rounds. The evaluated instructions' reading levels ranged from grade 6.5 to 13.2; none contained all consensus topics. Current post surgical thyroidectomy discharge instructions are more difficult to read than recommended by literacy standards and omit consensus warning signs of major complications. Our easy-to-read discharge instructions cover pertinent topics and may enhance patient education. Delphi methodology is useful for developing post-surgical instructions. Patient education materials need appropriate readability levels and content. We recommend the Delphi method to select content using consensus expert opinion whenever higher level data is lacking. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Comparison of post-surgical MRI presentation of the pituitary gland and its hormonal function

    Bladowska, J.; Sokolska, V.; Sasiadek, M.; Sozanski, T.; Bednarek-Tupikowska, G.

    2010-01-01

    Background: Post-surgical evaluation of the pituitary gland in MRI is difficult because of a change of anatomical conditions. It depends also on numerous other factors, including: size and expansion of a tumour before surgery, type of surgical access, quality and volume of filling material used and time of its resorption.The aim of the study was to compare MR image of the pituitary gland after surgery with clinical findings and to establish a correlation between MRI presentation of spared pituitary and its hormonal function. Material/Methods: 124 patients after resection of pituitary adenomas - 409 MRI results in total - were studied. With a 1.5-T unit, T1-weighted sagittal and coronal, enhanced and unenhanced images were obtained. Results: The pituitary gland seemed to be normal in MRI in 11 patients, 8 of them had completely regular pituitary function but in 3 of them we noticed a partial hypopituitarism. In 99 patients only a part of the pituitary gland was recognised, 53 of them had hypopituitarism but 46 of them were endocrinologically healthy. 14 patients seemed to have no persistent pituitary gland in MRI, in comparison to hormonal studies: there was panhypopituitarism in 6 and hypopituitarism in 8 cases. Conclusions: MRI presentation of post - surgical pituitary gland doesn't necessarily correlate with its hormonal function - there was a significant statistical difference. Some patients with partial pituitary seems normal hormonal function. In some cases the pituitary seem normal in MRI but these patients have hormonal disorders and need substitution therapy. (authors)

  17. Trans-sphenoidal treatment of postsurgical cerebrospinal fluid fistula: CT-guided closure

    Floris, R.; Salvatore, C.; Simonetti, G.

    1998-01-01

    Cerebrospinal fluid (CSF) leakage after trans-sphenoidal surgery is a troublesome complication with a risk of meningitis and pneumocephalus. We suggest CT-guided intrasphenoidal injection of fibrin sealant through a 12-gauge needle as a simple alternative to surgical management of CSF fistulae. We treated eight patients, operated via the trans-sphenoidal route (five pituitary adenomas, three craniopharyngiomas), for a postoperative CSF leak by CT-guided intrasphenoidal injection of fibrin sealant alone in three cases and fibrin sealant and autologous blood in 5. CT was obtained 10 days after the procedure in all cases. In four patients, the CSF leak was closed successfully at the first attempt. The procedure was repeated on the four remaining patients because only a reduction in leakage was obtained at the first attempt. This procedure preserves olfaction and avoids the risk of frontal lobe damage. It could therefore represent the treatment of choice in many cases of anterior cranial fossa postsurgical CSF leaks. (orig.) (orig.)

  18. Bilateral PLA/alginate membranes for the prevention of postsurgical adhesions.

    Kessler, Martina; Esser, Eva; Groll, Jürgen; Tessmar, Jörg

    2016-11-01

    A bilateral barrier membrane for the prevention of postsurgical adhesions was developed. Thereby, a smooth PLA side was supposed to keep the affected tissues glidingly separated, while a mucoadhesive side made of alginate was meant to keep the barrier resident on the site of injury so that suturing becomes redundant or at least the membrane stays long enough to facilitate surgical handling. Because hydrophilic alginate and lipophilic PLA films show only low cohesion, solution electrospun meshes of PLA and PLA-PEG-PLA triblock copolymers with varying poly(ethylene glycol) [PEG] content were investigated as cohesion promoter to avoid an easy separation of the functionally different layers. Using direct electrospinning onto the PLA film, a modified contact surface of the mesh was created, which allowed the tested alginate solutions (3%, 5%) to infiltrate to different extents. Thereby, an increasing content of hydrophilic PEG within the mesh copolymer and a lower alginate concentration facilitated the infiltration. As a result, the PLA film with a PLA35k-PEG10k-PLA35k (racemic PLA chains) mesh and an alginate layer cast from a 3% alginate solution appeared to be the most effective combination as examined by means of a t peel test, a mucoadhesion test, a tensile test and optical evaluations. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1563-1570, 2016. © 2015 Wiley Periodicals, Inc.

  19. Local infiltration for postsurgical analgesia following total hip arthroplasty: a comparison of liposomal bupivacaine to traditional bupivacaine.

    Asche, Carl V; Ren, Jinma; Kim, Minchul; Gordon, Kate; McWhirter, Marie; Kirkness, Carmen S; Maurer, Brian T

    2017-07-01

    To assess postsurgical clinical and economic outcomes of patients who received local infiltration containing liposomal bupivacaine versus traditional bupivacaine for pain management following total hip arthroplasty (THA). This retrospective study included two groups of consecutive patients undergoing THA. The experimental group received local infiltration with a combination of liposomal bupivacaine, bupivacaine HCl 0.25% with epinephrine 1:200,000, and ketorolac for postsurgical analgesia. The historical control group received the previous standard of care: local infiltration with a combination of bupivacaine HCl 0.25% with epinephrine 1:200,000 and ketorolac. Key outcomes included distance walked, length of stay (LOS), opioid medication use, numeric pain scores, hospital charges, hospital costs, all-cause 30 day readmission rate, and adverse events (AEs). Both unadjusted and adjusted (i.e. age, sex, insurance type, living situation, body mass index, procedure side, and comorbidity) outcomes were compared between the two groups. The experimental group (n = 64) demonstrated statistically significant improvement versus the historical control group (n = 66) in mean distance walked on discharge day (249.2 vs. 180.0 feet; unadjusted p = .025, adjusted p = .070), mean LOS (2.0 vs. 2.7 days; p bupivacaine was associated with improved postsurgical outcomes when compared with traditional bupivacaine in patients undergoing THA.

  20. Utility of Tc-99m Sestamibi scintigraphy in predicting the post-surgical recurrences in patients with osteosarcoma

    Racioppi, S.; Lastiri, J.; Pallotta, G.; Dibar, E.; Makiya, M.; Jager, V.; Montivero, M.; Muscolo, L.; Parysow, O.

    2004-01-01

    Full text: Anatomic modalities are not specific enough to evaluate local recurrences in the post-surgical follow up of patients with osteosarcoma. The purpose of this study was to assess the value of Tc-99m Sestamibi (MIBI) scans in the post-surgical follow up of patients with osteosarcoma. We analysed the results of 83 Tc-99m MIBI studies in 32 patients and compared these with other investigations like CT, MRI, X-ray, bone scans and also correlated with histopathology findings. Two independent observers evaluated all the scans. Sixteen out of 83 scans were found to be MIBI positive. Eleven of these 16 scans were confirmed as true positive (PPV 69%) and 5 false positive (FP). Scintiscans in 2 of these 5 patients were acquired early after surgery and in the long term follow up both became negative. The other 3 FP scans were labeled as pseudoarthrosis or graft fracture. Of the 67 negative scans, 64 were true negative (NPV 95%). Three were false negative, 2 of them were cases with MDR. It was concluded that MIBI whole body scan is a useful tool in the post-surgical follow up of patients with osteosarcoma, particularly to evaluate local or regional recurrences. A negative scan is highly predictive for no tumor recurrence. A negative baseline scan could be consistent with MDR gene expression. (author)

  1. Quality of Life in orthognathic surgery patients: post-surgical improvements in aesthetics and self-confidence.

    Rustemeyer, Jan; Gregersen, Johanne

    2012-07-01

    The objective of this prospective study was to assess changes of Quality of Life (QoL) in patients undergoing bimaxillary orthognathic surgery. Questionnaires were based on the Oral Health Impact Profile (OHIP, items OH-1-OH-14) and three additional questions (items AD-1-3), and were completed by patients (n=50; mean age 26.9±9.9 years) on average 9.1±2.4 months before surgery, and 12.1±1.4 months after surgery, using a scoring scale. Item scores describing functional limitation, physical pain, physical disability and chewing function did not change significantly, whereas item scores covering psychological discomfort and social disability domains revealed significant decreases following surgery. AD-2 "dissatisfying aesthetics" revealed the greatest difference between pre- and post-surgical scores (paesthetic improvement of facial features post-surgery, the benefit in QoL was generally high. The significant correlation of the pre- to post-surgical changes of item OH-5 "self conscious" to nearly all other item changes suggested that OH-5 was the most sensitive indicator for post-surgical improvement of QoL. Psychological factors and aesthetics exerted a strong influence on the patients' QoL, and determined major changes more than functional aspects did. Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  2. Effects of Prolonged Empirical Antibiotic Administration on Post-Surgical Intestinal Bacterial Flora of Local Dogs Undergoing Non-Laparoscopic Gastrectomy

    J.F. Akinrinmade; Gladys O. Melekwe; Adenike A.O. Ogunshe

    2015-01-01

    Prolonged post-surgical antibiotic administration may be of less advantage in prevention of post-surgical infections. This study therefore, aimed at investigating the prolonged effect of empiric administration of three most-prescribed antibiotics (amoxicillin, cefotaxime and oxytetracycline) by veterinary practices in Southwest Nigeria on intestinal bacterial population of dogs undergoing partial, non-laparoscopic gastrectomy. Using conventional quantitative and qualitative microbial culture ...

  3. Pectus excavatum postsurgical outcome based on preoperative soft body dynamics simulation

    Moreira, Antonio H. J.; Rodrigues, Pedro L.; Fonseca, Jaime; Pinho, A. C. M.; Rodrigues, Nuno F.; Correia-Pinto, Jorge; Vilaça, João L.

    2012-02-01

    Pectus excavatum is the most common congenital deformity of the anterior chest wall, in which an abnormal formation of the rib cage gives the chest a caved-in or sunken appearance. Today, the surgical correction of this deformity is carried out in children and adults through Nuss technic, which consists in the placement of a prosthetic bar under the sternum and over the ribs. Although this technique has been shown to be safe and reliable, not all patients have achieved adequate cosmetic outcome. This often leads to psychological problems and social stress, before and after the surgical correction. This paper targets this particular problem by presenting a method to predict the patient surgical outcome based on pre-surgical imagiologic information and chest skin dynamic modulation. The proposed approach uses the patient pre-surgical thoracic CT scan and anatomical-surgical references to perform a 3D segmentation of the left ribs, right ribs, sternum and skin. The technique encompasses three steps: a) approximation of the cartilages, between the ribs and the sternum, trough b-spline interpolation; b) a volumetric mass spring model that connects two layers - inner skin layer based on the outer pleura contour and the outer surface skin; and c) displacement of the sternum according to the prosthetic bar position. A dynamic model of the skin around the chest wall region was generated, capable of simulating the effect of the movement of the prosthetic bar along the sternum. The results were compared and validated with patient postsurgical skin surface acquired with Polhemus FastSCAN system.

  4. Influence of postsurgical residual tumor volume on local control in radiotherapy for maxillary sinus cancer

    Kawashima, Mitsuhiko; Ogino, Takashi; Hayashi, Ryuichi; Ishikura, Satoshi; Nihei, Keiji; Ito, Yoshinori; Ikeda, Hiroshi; Ebihara, Satoshi [National Cancer Center, Kashiwa, Chiba (Japan). Hospital East; Itai, Yuji

    2001-05-01

    The aim was to study the influence of postsurgical gross residual tumor volume on local control of maxillary sinus cancer treated with radiotherapy combined with debulking surgery. Forty-three patients who underwent combined surgery and radiotherapy (50-72 Gy, median 60 Gy) for squamous cell carcinoma of the maxillary sinus were reviewed. Gross residual tumor volume (GRTV) after surgery was measured on computed tomograms obtained during the radiotherapy planning. Patients were classified according to GRTV as follows: group AA, GRTV=0 (microscopic residual, n=2); group A, GRTV <10 cm{sup 3} (n=24); group B, 10-40 cm{sup 3} (n=9); and group C, {>=}40 cm{sup 3} (n=8). The relationship between local control and GRTV was analyzed using univariate and multivariate analysis. The 2-year local control rate for all patients was 62%. The differences in local control rates between groups AA, A and B were not significant (P<0.05), but the rate was significantly lower in group C than in the other groups (69% at 2 years vs 31% at 1 year, P<0.001). Multivariate analysis showed that GRTV (P=0.002) and histological differentiation (poorly differentiated histology was favorable, P=0.035) were independent prognostic factors and that intraarterial chemotherapy and administered total dose were not. Local control in groups A and B significantly depended on the total dose of radiotherapy, with 2-year control rates of patients receiving 50 Gy (n=6) and {>=}60 Gy (n=27) of 17% vs 79%, respectively (P<0.001). Our data suggest that adequate, not complete, debulking associated with a total radiotherapy dose of {>=}60 Gy can provide satisfactory local control for patients with squamous cell carcinoma of the maxillary sinus. (author)

  5. Developing a tool to measure pharmacoeconomic outcomes of post-surgical pain management interventions.

    Keller, Deborah S; Smalarz, Amy; Haas, Eric M

    2016-01-01

    Financial pressures have limited the ability of providers to use medication that may improve clinical outcomes and patient satisfaction. New interventions are often fraught with resistance from individual cost centers. A value realization tool (VRT) is essential for separate cost centers to communicate and comprehend the overall financial and clinical implications of post-surgical pain management medication interventions (PSMI). The goal was to describe development of a VRT. An evaluation of common in-patient PSMI approaches, impacts, and costs was performed. A multidisciplinary task force guided development of the VRT to ensure appropriate representation and relevance to clinical practice. The main outcome was an Excel-based tool that communicates the overall cost/benefit of PSMI for the post-operative patient encounter. The VRT aggregated input data on costs, clinical impact, and nursing burden of PSMI assessment and monitoring into two high-level outcome reports: Overall Cost Impact and Nurse & Patient Impact. Costs included PSMI specific medication, equipment, professional placement, labor, overall/opioid-related adverse events, re-admissions, and length of stay. Nursing impact included level of practice interference, job satisfaction, and patient care metrics. Patient impact included pain scores, opioid use, PACU time, and satisfaction. Reference data was provided for individual institutions that may not collect all variables included in the VRT. The VRT is a valuable way for administrators to assess PSMI cost/benefits and for individual cost centers to see the overall value of individual interventions. The user-friendly, decision-support tool allows the end-user to use built-in referenced or personalized outcome data, increasing relevance to their institutions. This broad picture could facilitate communication across cost centers and evidence-based decisions for appropriate use and impacts of PSMI.

  6. Variability Among Breast Radiation Oncologists in Delineation of the Postsurgical Lumpectomy Cavity

    Landis, Daniel M.; Luo Weixiu; Song Jun; Bellon, Jennifer R.; Punglia, Rinaa S.; Wong, Julia S.; Killoran, Joseph H.; Gelman, Rebecca; Harris, Jay R.

    2007-01-01

    Purpose: Partial breast irradiation (PBI) is becoming more widely used. Accurate determination of the surgical lumpectomy cavity volume is more critical with PBI than with whole breast radiation therapy. We examined the interobserver variability in delineation of the lumpectomy cavity among four academic radiation oncologists who specialize in the treatment of breast cancer. Methods and Materials: Thirty-four lumpectomy cavities in 33 consecutive patients were evaluated. Each physician contoured the cavity and a 1.5-cm margin was added to define the planning target volume (PTV). A cavity visualization score (CVS) was assigned (1-5). To eliminate bias, the physician of record was eliminated from the analysis in all cases. Three measures of variability of the PTV were developed: average shift of the center of mass (COM), average percent overlap between the PTV of two physicians (PVO), and standard deviation of the PTV. Results: Of variables examined, pathologic resection volume was significantly correlated with CVS, with larger volumes more easily visualized. Shift of the COM decreased and PVO increased significantly as CVS increased. For CVS 4 and 5 cases, the average COM shift was 3 mm and 2 mm, respectively, and PVO was 77% and 87%, respectively. In multiple linear regression, pathologic diameter >4 cm and CVS ≥3 were significantly associated with smaller COM shift. When CVS was omitted from analysis, PVO was significantly larger with pathologic diameter ≥5 cm, days to planning <36, and older age. Conclusions: Even among radiation oncologists who specialize in breast radiotherapy, there can be substantial differences in delineation of the postsurgical radiotherapy target volume. Large treatment margins may be prudent if the cavity is not clearly defined

  7. Impact of symptom burden in post-surgical non-small cell lung cancer survivors.

    Lowery, Amy E; Krebs, Paul; Coups, Elliot J; Feinstein, Marc B; Burkhalter, Jack E; Park, Bernard J; Ostroff, Jamie S

    2014-01-01

    Pain, fatigue, dyspnea, and distress are commonly reported cancer-related symptoms, but few studies have examined the effects of multiple concurrent symptoms in longer-term cancer survivors. We examined the impact of varying degrees of symptom burden on health-related quality of life (HRQOL) and performance status in surgically treated non-small cell lung cancer (NSCLC) survivors. A sample of 183 NSCLC survivors 1-6 years post-surgical treatment completed questionnaires assessing five specific symptoms (pain, fatigue, dyspnea, depression, and anxiety), HRQOL, and performance status. The number of concurrent clinically significant symptoms was calculated as an indicator of symptom burden. Most survivors (79.8 %) had some degree of symptom burden, with 30.6 % reporting one clinically significant symptom, 27.9 % reporting two symptoms, and 21.3 % reporting three or more symptoms. Physical HRQOL significantly decreased as the degree of symptom burden increased, but mental HRQOL was only significantly decreased in those with three or more symptoms. Receiver-operating characteristic (ROC) curves showed that having multiple concurrent symptoms (two or more) was most likely associated with limitations in functioning (area under a ROC curve = 0.75, sensitivity = 0.81, specificity = 0.54). Two or more clinically significant symptoms are identified as the "tipping point" for showing adverse effects on HRQOL and functioning. This highlights the need for incorporating multiple-symptom assessment into routine clinical practice. Comprehensive symptom management remains an important target of intervention for improved post-treatment HRQOL and functioning among lung cancer survivors.

  8. Iterative metal artefact reduction (MAR) in postsurgical chest CT: comparison of three iMAR-algorithms.

    Aissa, Joel; Boos, Johannes; Sawicki, Lino Morris; Heinzler, Niklas; Krzymyk, Karl; Sedlmair, Martin; Kröpil, Patric; Antoch, Gerald; Thomas, Christoph

    2017-11-01

    The purpose of this study was to evaluate the impact of three novel iterative metal artefact (iMAR) algorithms on image quality and artefact degree in chest CT of patients with a variety of thoracic metallic implants. 27 postsurgical patients with thoracic implants who underwent clinical chest CT between March and May 2015 in clinical routine were retrospectively included. Images were retrospectively reconstructed with standard weighted filtered back projection (WFBP) and with three iMAR algorithms (iMAR-Algo1 = Cardiac algorithm, iMAR-Algo2 = Pacemaker algorithm and iMAR-Algo3 = ThoracicCoils algorithm). The subjective and objective image quality was assessed. Averaged over all artefacts, artefact degree was significantly lower for the iMAR-Algo1 (58.9 ± 48.5 HU), iMAR-Algo2 (52.7 ± 46.8 HU) and the iMAR-Algo3 (51.9 ± 46.1 HU) compared with WFBP (91.6 ± 81.6 HU, p algorithms, respectively. iMAR-Algo2 and iMAR-Algo3 reconstructions decreased mild and moderate artefacts compared with WFBP and iMAR-Algo1 (p algorithms led to a significant reduction of metal artefacts and increase in overall image quality compared with WFBP in chest CT of patients with metallic implants in subjective and objective analysis. The iMARAlgo2 and iMARAlgo3 were best for mild artefacts. IMARAlgo1 was superior for severe artefacts. Advances in knowledge: Iterative MAR led to significant artefact reduction and increase image-quality compared with WFBP in CT after implementation of thoracic devices. Adjusting iMAR-algorithms to patients' metallic implants can help to improve image quality in CT.

  9. The psychology of chronic post-surgical pain: new frontiers in risk factor identification, prevention and management.

    Weinrib, Aliza Z; Azam, Muhammad A; Birnie, Kathryn A; Burns, Lindsay C; Clarke, Hance; Katz, Joel

    2017-11-01

    In an era of considerable advances in anaesthesiology and pain medicine, chronic pain after major surgery continues to be problematic. This article briefly reviews the known psychological risk and protective factors associated with the development of chronic postsurgical pain (CPSP). We begin with a definition of CPSP and then explain what we mean by a risk/protective factor. Next, we summarize known psychological risk and protective factors for CPSP. Psychological interventions that target risk factors and may impact postsurgical pain are reviewed, including the acceptance and commitment therapy (ACT)-based approach to CPSP prevention and management we use in the Transitional Pain Service (TPS) at the Toronto General Hospital. Finally, we conclude with recommendations for research in risk factor identification and psychological interventions to prevent CPSP. Several pre-surgical psychological risk factors for CPSP have been consistently identified in recent years. These include negative affective constructs, such as anxiety symptoms, depressive symptoms, pain catastrophizing and general psychological distress. In contrast, relatively few studies have examined psychological protective factors for CPSP. Psychological interventions that target known psychological risk factors while enhancing protective psychological factors may reduce new incidence of CPSP. The primary goal of our ACT intervention is to teach patients a mindful way of responding to their postsurgical pain that empowers them to interrupt the negative cycle of pain, distress, behavioural avoidance and escalating opioid use that can limit functioning and quality of life while paradoxically amplifying pain over time. Early clinical outcome data suggest that patients who receive care from TPS physicians reduce their pain and opioid use, yet patients who also receive our ACT intervention have a larger decrease in daily opioid dose while reporting less pain interference and lower depression scores.

  10. Interventions for the prediction and management of chronic postsurgical pain after total knee replacement: systematic review of randomised controlled trials.

    Beswick, Andrew D; Wylde, Vikki; Gooberman-Hill, Rachael

    2015-05-12

    Total knee replacement can be a successful operation for pain relief. However, 10-34% of patients experience chronic postsurgical pain. Our aim was to synthesise evidence on the effectiveness of applying predictive models to guide preventive treatment, and for interventions in the management of chronic pain after total knee replacement. We conducted a systematic review of randomised controlled trials using appropriate search strategies in the Cochrane Library, MEDLINE and EMBASE from inception to October 2014. No language restrictions were applied. Adult patients receiving total knee replacement. Predictive models to guide treatment for prevention of chronic pain. Interventions for management of chronic pain. Reporting of specific outcomes was not an eligibility criterion but we sought outcomes relating to pain severity. No studies evaluated the effectiveness of predictive models in guiding treatment and improving outcomes after total knee replacement. One study evaluated an intervention for the management of chronic pain. The trial evaluated the use of a botulinum toxin A injection with antinociceptive and anticholinergic activity in 49 patients with chronic postsurgical pain after knee replacement. A single injection provided meaningful pain relief for about 40 days and the authors acknowledged the need for a large trial with repeated injections. No trials of multidisciplinary interventions or individualised treatments were identified. Our systematic review highlights a lack of evidence about the effectiveness of prediction and management strategies for chronic postsurgical pain after total knee replacement. As a large number of people are affected by chronic pain after total knee replacement, development of an evidence base about care for these patients should be a research priority. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. An economic evaluation of two interventions for the prevention of post-surgical infections in cardiac surgery.

    del Diego Salas, J; Orly de Labry Lima, A; Espín Balbino, J; Bermúdez Tamayo, C; Fernández-Crehuet Navajas, J

    2016-01-01

    To conduct a cost-effectiveness analysis that compares two prophylactic protocols for treating post-surgical infections in cardiac surgery. A cost effectiveness analysis was done by using a decision tree to compare two protocols for prophylaxis of post-surgical infections (Protocol A: Those patient with positive test to methicillin-resistant Staphylococcus aureus (MRSA) colonization received muripocin (twice a day during a two-week period), with no follow-up verification. Those who tested negative did not receive the prophylaxis treatment; Protocol B: all patients received the mupirocin treatment). The number of post-surgical infections averted was the measure of effectiveness from the health system's perspective, 30 days following the surgery. The incidence of infections and complications was obtained from two cohorts of patients who underwent cardiac surgery Hospital. The times for applying the two protocols were validated by experts. They cost were calculated from the hospital's analytical accounting management system and Pharmaceutical Service. Only direct costs were taken into account, no discount rates were applied. Incremental cost-effectiveness ratio (ICER) was calculated. A probabilistic sensitivity analysis was performed. A total of 1118 patients were included (721 in Protocol A and 397 in Protocol B). No statistically significant differences were found in age, sex, diabetes, exitus or length of hospital stay between the two protocols. In the control group the rate of infection was 15.3%, compared with 11.3% in the intervention group. Protocol B proves to be more effective and at a lower cost, yielding an ICER of €32,506. Universal mupirocin prophylaxis against surgical site infections (SSI) in cardiac surgery as a dominant strategy, because it shows a lower incidence of infections and cost savings, versus the strategy to treat selectively patients according to their test results prior screening. Copyright © 2015 SECA. Published by Elsevier Espana. All

  12. Short-Term Sleep Disturbance-Induced Stress Does not Affect Basal Pain Perception, but Does Delay Postsurgical Pain Recovery.

    Wang, Po-Kai; Cao, Jing; Wang, Hongzhen; Liang, Lingli; Zhang, Jun; Lutz, Brianna Marie; Shieh, Kun-Ruey; Bekker, Alex; Tao, Yuan-Xiang

    2015-11-01

    Chronic sleep disturbance-induced stress is known to increase basal pain sensitivity. However, most surgical patients frequently report short-term sleep disturbance/deprivation during the pre- and postoperation periods and have normal pain perception presurgery. Whether this short-term sleep disturbance affects postsurgical pain is elusive. Here, we report that pre- or postexposure to rapid eye movement sleep disturbance (REMSD) for 6 hours daily for 3 consecutive days did not alter basal responses to mechanical, heat, and cold stimuli, but did delay recovery in incision-induced reductions in paw withdrawal threshold to mechanical stimulation and paw withdrawal latencies to heat and cold stimuli on the ipsilateral side of male or female rats. This short-term REMSD led to stress shown by an increase in swim immobility time, a decrease in sucrose consumption, and an increase in the level of corticosterone in serum. Blocking this stress via intrathecal RU38486 or bilateral adrenalectomy abolished REMSD-caused delay in recovery of incision-induced reductions in behavioral responses to mechanical, heat, and cold stimuli. Moreover, this short-term REMSD produced significant reductions in the levels of mu opioid receptor and kappa opioid receptor, but not Kv1.2, in the ipsilateral L4/5 spinal cord and dorsal root ganglia on day 9 after incision (but not after sham surgery). Our findings show that short-term sleep disturbance either pre- or postsurgery does not alter basal pain perception, but does exacerbate postsurgical pain hypersensitivity. The latter may be related to the reductions of mu and kappa opioid receptors in the spinal cord and dorsal root ganglia caused by REMSD plus incision. Prevention of short-term sleep disturbance may help recovery from postsurgical pain in patients. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  13. Medial and Lateral Pectoral Nerve Block with Liposomal Bupivacaine for the Management of Postsurgical Pain after Submuscular Breast Augmentation

    David Leiman, MD

    2014-12-01

    Full Text Available Summary: This report describes an ultrasound-guided medial and lateral pectoralis nerve block using liposome bupivacaine, performed before the surgical incision, in a patient undergoing submuscular breast augmentation. The anatomic basis and technique are described. This procedure may be offered to patients undergoing submuscular insertion of a breast implant or tissue expander. Advancements in ultrasound guidance allow for more precise anatomic placement of local anesthetic agents. The injection technique used for this procedure resulted in complete relaxation of the pectoralis major, facilitating the surgical dissection and markedly diminishing postsurgical pain and muscle spasms.

  14. Chest Reconstruction and Chest Dysphoria in Transmasculine Minors and Young Adults: Comparisons of Nonsurgical and Postsurgical Cohorts.

    Olson-Kennedy, Johanna; Warus, Jonathan; Okonta, Vivian; Belzer, Marvin; Clark, Leslie F

    2018-05-01

    Transmasculine youth, who are assigned female at birth but have a gender identity along the masculine spectrum, often report considerable distress after breast development (chest dysphoria). Professional guidelines lack clarity regarding referring minors (defined as people younger than 18 years) for chest surgery because there are no data documenting the effect of chest surgery on minors. To examine the amount of chest dysphoria in transmasculine youth who had had chest reconstruction surgery compared with those who had not undergone this surgery. Using a novel measure of chest dysphoria, this cohort study at a large, urban, hospital-affiliated ambulatory clinic specializing in transgender youth care collected survey data about testosterone use and chest distress among transmasculine youth and young adults. Additional information about regret and adverse effects was collected from those who had undergone surgery. Eligible youth were 13 to 25 years old, had been assigned female at birth, and had an identified gender as something other than female. Recruitment occurred during clinical visits and via telephone between June 2016 and December 2016. Surveys were collected from participants who had undergone chest surgery at the time of survey collection and an equal number of youth who had not undergone surgery. Outcomes were chest dysphoria composite score (range 0-51, with higher scores indicating greater distress) in all participants; desire for chest surgery in patients who had not had surgery; and regret about surgery and complications of surgery in patients who were postsurgical. Of 136 completed surveys, 68 (50.0%) were from postsurgical participants, and 68 (50.0%) were from nonsurgical participants. At the time of the survey, the mean (SD) age was 19 (2.5) years for postsurgical participants and 17 (2.5) years for nonsurgical participants. Chest dysphoria composite score mean (SD) was 29.6 (10.0) for participants who had not undergone chest reconstruction, which

  15. A STUDY OF POST-SURGICAL COMPLICATIONS IN ACUTE ABDOMEN CONDITIONS

    Bhooma Reddy Muthyala

    2016-09-01

    Full Text Available BACKGROUND The most common causes of the acute abdomen are acute appendicitis which may be perforated, typhoid ileal perforation, acute intestinal obstruction, gastroduodenal perforations, nonspecific abdominal pain, abdominal injuries, and acute cholecystitis. A summary of all the acute complications taken together will be the fact that all are associated with post-surgical complications. A sincere effort has been made to study the post-operative complications that a surgeon encounters while treating the acute abdomen cases. This study is intended to help the practising surgeons who deal with such complications. It also is intended to help the doctors who practice to identify such complications and thus refer the patients for immediate intervention. METHODS This study was conducted in the Department of General Surgery, Government Medical College, Nizamabad, Telangana. This study was done from June 2013 to May 2016. One hundred sixty patients who were admitted in the hospital after surgery for acute abdominal conditions were considered for the study. Thorough clinical examination was conducted and the complications that were encountered were noted and the complications were treated as per the need of the hour. The complications faced by the treating surgeon in each and every entity that was discussed earlier was duly noted and statistical analysis was conducted. All the statistical analysis was done using the latest SPSS software 2015 (California. RESULT In our study, the mean age of the study population was found to be 29.8 years. That means the majority of the patients who turn up in the Department of Emergency is young and generally in the third decade of life. In Acute Intestinal Obstruction and blunt abdominal injuries, significance of mortality is high (p<0.05. CONCLUSION The study was successful in proving that abdominal injuries are the main factors of causing morbidity and mortality in the younger generation. The surgical mode of

  16. DTI study of Children with Congenital Hydrocephalus: 1 Year Post-Surgical Outcomes

    Mangano, Francesco T.; Altaye, Mekibib; McKinstry, Robert C.; Shimony, Joshua S.; Powell, Stephanie K.; Phillips, Jannel M.; Barnard, Holly; Limbrick, David D.; Holland, Scott K.; Jones, Blaise V.; Dodd, Jonathon; Simpson, Sarah; Deanna, Mercer; Rajagopal, Akila; Bidwell, Sarah; Yuan, Weihong

    2016-01-01

    patients were found in the gCC between 3-month and 12-month post-surgery. In the PLIC, trend level longitudinal changes were found between pre-surgery and 3-month post-surgery as well as between 3-month and 12-month post-surgery. Significant correlation between DTI and developmental outcome were found at all three time points. Notably, significant correlation was found between DTI in the PLIC at 3-month post-surgery and developmental outcome at 12-month pots-surgery. Conclusion Our data showed significant WM abnormality based on DTI in both the gCC and the PLIC in children with congenital hydrocephalus before surgery and the abnormalities persisted in both the gCC and the PLIC at 3-month post-surgery. The DTI values remained significantly abnormal in the gCC at 12-month post-surgery. Longitudinal analysis showed signs of recovery in both WM structures between different time points. Combined with the significant correlation found between DTI and neuropsychological outcome, our study suggests that DTI can serve as a sensitive imaging biomarker for underlying neuroanatomical changes and post-surgical developmental outcome and even as a predictor for future outcomes. PMID:27203134

  17. Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study

    Gärtner, Rune; Cronin-Fenton, Deirdre; Hundborg, Heidi Holmager

    2010-01-01

    Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association.......Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association....

  18. Identification of pain-related psychological risk factors for the development and maintenance of pediatric chronic postsurgical pain

    Pagé MG

    2013-03-01

    Full Text Available M Gabrielle Pagé,1 Jennifer Stinson,2,3 Fiona Campbell,2,4 Lisa Isaac,2,4 Joel Katz1,4,51Department of Psychology, York University, 2Department of Anesthesia and Pain Medicine, Hospital for Sick Children, 3Lawrence S Bloomberg Faculty of Nursing, 4Department of Anesthesia, University of Toronto, 5Department of Psychology, Hospital for Sick Children, Toronto, ON, CanadaBackground: The goals of this study were to examine the trajectory of pediatric chronic postsurgical pain (CPSP over the first year after surgery and to identify acute postsurgical predictors of CPSP.Methods: Eighty-three children aged 8–18 years (mean 13.8, standard deviation 2.4 who underwent major orthopedic or general surgery completed pain and pain-related psychological measures at 48–72 hours, 2 weeks (pain anxiety and pain measures only, and 6 and 12 months after surgery.Results: Results showed that 1 year after surgery, 22% of children developed moderate to severe CPSP with minimal functional disability. Children who reported a Numeric Rating Scale pain-intensity score ≥ 3 out of 10 two weeks after discharge were more than three times as likely to develop moderate/severe CPSP at 6 months and more than twice as likely to develop moderate/severe CPSP at 12 months than those who reported a Numeric Rating Scale pain score < 3 (6-month relative risk 3.3, 95% confidence interval 1.2–9.0 and 12-month relative risk 2.5, 95% confidence interval 0.9–7.5. Pain unpleasantness predicted the transition from acute to moderate/severe CPSP, whereas anxiety sensitivity predicted the maintenance of moderate/severe CPSP from 6 to 12 months after surgery.Conclusions: This study highlights the prevalence of pediatric CPSP and the role played by psychological variables in its development/maintenance. Risk factors that are associated with the development of CPSP are different from those that maintain it.Keywords: chronic postsurgical pain, children, adolescents, anxiety sensitivity

  19. Post-surgical meningitis due to multiresistant Acinetobacter baumannii. Effective treatment with intravenous and/or intraventricular colistin and therapeutic dilemmas.

    Paramythiotou, E; Karakitsos, D; Aggelopoulou, H; Sioutos, P; Samonis, G; Karabinis, A

    2007-02-01

    Post-surgical meningitis and/or ventriculitis caused by Gram-negative bacteria may be difficult to treat due to the emergence of multiresistant strains. Two patients with multiresistant Acinetobacter baumannii central nervous system infection, successfully treated with either intravenous and/or intraventricular colistin are presented. Unresolved issues such as dose and duration of intraventricular colistin are discussed.

  20. Implantable oxygen microelectrode suitable for medium-term investigations of post-surgical tissue hypoxia and changes in tumor tissue oxygenation produced by radiotherapy

    Burke, T.R.; Johnson, R.J.; Krishnamsetty, C.B.; Sako, K.; Karakousis, C.; Wojtas, F.

    1980-01-01

    Teflon-covered platinum oxygen probes were used to monitor tissue oxygen levels in post-surgical cancer patients and those treated with radiotherapy. Progressive wound healing was usually accompanied by a decrease in tissue pO2. Radiotherapy produced a slight increase in pO2 while hyperthermia effected a significant increase in the oxygen level during 100% oxygen breathing

  1. The effect of a program to promote play to reduce children's post-surgical pain: with plush toys, it hurts less.

    Ullán, Ana M; Belver, Manuel H; Fernández, Esperanza; Lorente, Felix; Badía, Marta; Fernández, Beatriz

    2014-03-01

    Various nonpharmacological strategies to relieve hospitalized children's pain propose play as a central element. Play is considered an essential resource to improve the negative psychosocial effects of the disease and the hospitalization itself. However, the empirical research of play in health settings has not received much attention. The goal of this study was to determine the effect of a program to promote play in the hospital on postsurgical pain in pediatric patients. The research hypothesis was that children will manifest less pain if they are distracted through play during the postsurgical period. We carried out a randomized parallel trial with two groups, an experimental group and a control group. The control group did not receive any specific treatment, only the standard attention contemplated in the hospital. The parents of the children from the experimental group received instructions to play with their children in the postsurgical period and specific play material with which to play. The results obtained support the research hypothesis. On average, the children from the experimental group scored lower on a pain scale than the children from the control group. This occurred in the three postsurgical measurements of pain. It is concluded that the program to promote play can decrease children's perception of pain. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  2. Effect of anesthetic, tag size, and surgeon experience on postsurgical recovering after implantation of electronic tags in a neotropical fish: Prochilodus lineatus (Valenciennes, 1837 (Characiformes: Prochilodontidae

    João M. Lopes

    Full Text Available ABSTRACT Implantation of telemetry transmitters in fish can be affected by different parameters. This study aimed to evaluate the effect of type of anesthetic, tag size, and surgeon experience on surgical and postsurgical wound healing in the neotropical fish Prochilodus lineatus . In total, eighty fish were surgically implanted with telemetry transmitters and forty fish were kept as controls. Forty fish were implanted with a small tag and other forty were implanted with a large tag. Similarly, forty fish were anesthetized with eugenol and forty fish were anesthetized by electroanesthesia, and forty surgeries were performed by an expert surgeon and forty surgeries were performed by novice surgeons. At the end of the experimental period seventeen (21.3% tagged fish had postsurgical complications, including death (1.3%, tag expulsion (2.5%, antenna migration (2.5%, and infection (15%. Tag size was the key determinant for postsurgical complications. Surgical details and postsurgical wound healing were not affected by type of anesthetic. Incision size, duration of surgery, and wound area were significantly affected by tag size and surgeon experience, and the number of sutures was significantly affected by tag size only. The results indicate that successful implantation of telemetry transmitters is dependent upon surgeon experience and tag size.

  3. Comparison of anti-inflammatory and analgesic effects of Ginger powder and Ibuprofen in postsurgical pain model: A randomized, double-blind, case–control clinical trial

    Farshid Rayati

    2017-01-01

    Conclusion: Within the limitations of this study, it can ban be concluded that gingerpowder is as effective as ibuprofenin the management of postsurgical sequelae. Furthermore, CRP levels alone are not suggested for the assessment of anti-inflammatory effects of drugs.

  4. Navigated transcranial magnetic stimulation for glioma removal: prognostic value in motor function recovery from postsurgical neurological deficits.

    Takakura, Tomokazu; Muragaki, Yoshihiro; Tamura, Manabu; Maruyama, Takashi; Nitta, Masayuki; Niki, Chiharu; Kawamata, Takakazu

    2017-10-01

    OBJECTIVE The aim of the present study was to evaluate the usefulness of navigated transcranial magnetic stimulation (nTMS) as a prognostic predictor for upper-extremity motor functional recovery from postsurgical neurological deficits. METHODS Preoperative and postoperative nTMS studies were prospectively applied in 14 patients (mean age 39 ± 12 years) who had intraparenchymal brain neoplasms located within or adjacent to the motor eloquent area in the cerebral hemisphere. Mapping by nTMS was done 3 times, i.e., before surgery, and 1 week and 3 weeks after surgery. To assess the response induced by nTMS, motor evoked potential (nTMS-MEP) was recorded using a surface electromyography electrode attached to the abductor pollicis brevis (APB). The cortical locations that elicited the largest electromyography response by nTMS were defined as hotspots. Hotspots for APB were confirmed as positive responsive sites by direct electrical stimulation (DES) during awake craniotomy. The distances between hotspots and lesions (D HS-L ) were measured. Postoperative neurological deficits were assessed by manual muscle test and dynamometer. To validate the prognostic value of nTMS in recovery from upper-extremity paresis, the following were investigated: 1) the correlation between D HS-L and the serial grip strength change, and 2) the correlation between positive nTMS-MEP at 1 week after surgery and the serial grip strength change. RESULTS From the presurgical nTMS study, MEPs from targeted muscles were identified in 13 cases from affected hemispheres. In one case, MEP was not evoked due to a huge tumor. Among 9 cases from which intraoperative DES mapping for hand motor area was available, hotspots for APB identified by nTMS were concordant with DES-positive sites. Compared with the adjacent group (D HS-L < 10 mm, n = 6), the nonadjacent group (D HS-L ≥ 10 mm, n = 7) showed significantly better recovery of grip strength at 3 months after surgery (p < 0.01). There were

  5. Patients' perceptions of implant placement surgery, the post-surgical healing and the transitional implant prostheses: a qualitative study.

    Kashbour, Wafa A; Rousseau, Nikki; Thomason, J Mark; Ellis, Janice S

    2017-07-01

    This study aimed to explore patients' thoughts, feelings about, and experiences of, implant placement surgery (IPS), the post-surgical healing stage and the immediate post-surgical transitional implant prosthesis (TIP) (fixed and removable). A qualitative study design was chosen and 38 semi-structured telephone and face-to-face interviews were conducted with 34 patients at different stages of implant treatment. The interviews were transcribed verbatim; the data collection and coding process followed the principles of thematic analysis, which was facilitated through the use of NVivo10. Patients anticipated that surgery would be painful and unpleasant but were prepared to accept this temporary discomfort for the expected benefits of implant treatment. However, a key finding was that patients felt they had overestimated the trauma of surgery but underestimated the discomfort and difficulties of the healing phase. A number of difficulties were also identified with the TIP phase following implant surgery. Existing research has tended to focus on the longer term benefits of dental implant treatment. This qualitative study has investigated in-depth patients' perceptions of dental implant surgery, including their experiences related to sedation, and of transitional implant restoration. While patients felt their concerns were overestimated in relation to the implant surgery, they experienced greater morbidity than they expected in the healing phase. Recommendations are made for relatively small changes in care provision which might improve the overall patient experience. Partial dentate patients treated with a fixed transitional prosthesis experienced advantages more quickly than patients with an overdenture. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Polychromatic light (480-3400nm) similar to the terrestrial solar spectrum without its UV component in post-surgical immunorehabilitation of breast cancer patients.

    Zhevago, Natalia A; Zimin, Alexander A; Glazanova, Tatyana V; Davydova, Natalia I; Bychkova, Natalia V; Chubukina, Zhanna V; Buinyakova, Anna I; Ballyuzek, Marina F; Samoilova, Kira A

    2017-01-01

    To this day, two methods of phototherapy (PT) have been successfully used in post-surgical immunorehabilitation of patients with breast cancer (BC): intravenous laser irradiation of the patients' blood and reinfusion of lympholeukosuspension of BC patients after single irradiation with HeNe laser. The objective of this pilot experimental study was to verify the effectiveness of the percutaneous use of polychromatic visible light combined with polychromatic infrared (pVIS+pIR) radiation similar to the major components of natural solar spectrum in post-surgical management of BC patients. Patients with BC (adenocarcinoma) of I-II stages, n=19 who had undergone mastectomy, were divided into 2 groups. The control group of patients (n=8) underwent a conventional course of post-surgical rehabilitation and sham irradiation. Patients of the PT group (n=11) additionally received 7days of daily treatment with polychromatic light on the sacral area, D=15cm. The PT course began on the day after mastectomy (Bioptron-2 device; Switzerland, 480-3400nm, 95% polarization, 40mW/cm 2 , 24J/cm 2 ). Mastectomy produced many changes in cellular and humoral immunity, which was recorded on the 1st and 8th post-surgical days. The PT course resulted in a faster normalization of post-surgical leukocytosis and activation of cytotoxic CD8 + T-lymphocytes (Lym), reduced the elevated concentration in blood of immune complexes and in parallel promoted cytotoxic activity of CD16 + /CD56 + NK-cells. The PT up-regulated the number of NK-cells in patients with its decrease on the 1st post-surgical day and prevented the decrease in the amount of monocytes, CD19 + B-Lym, CD3 + T-Lym, CD4 + T-helpers, activated CD3 + /HLADR + T-Lym, and the decrease of the phagocytotic capability of neutrophils. PT blocked the down-regulation of the IgM, IgA concentration and abnormally sharp increase of the proinflammatory cytokine IFN-γ content. Therefore, a 7-day course with polychromatic light prevented the

  7. Biobased silver nanocolloid coating on silk fibers for prevention of post-surgical wound infections

    Dhas SP

    2015-10-01

    Full Text Available Sindhu Priya Dhas, Suruthi Anbarasan, Amitava Mukherjee, Natarajan Chandrasekaran Center for Nanobiotechnology, VIT University, Vellore, India Abstract: Bombyx mori silk fibers are an important biomaterial and are used in surgical sutures due to their remarkable biocompatibility. The major drawback to the application of biomaterials is the risk of bacterial invasion, leading to clinical complications. We have developed an easy and cost-effective method for fabrication of antibacterial silk fibers loaded with silver nanoparticles (AgNPs by an in situ and ex situ process using an aqueous extract of Rhizophora apiculata leaf. Scanning electron microscopy revealed that well dispersed nanoparticles impregnated the silk fibers both in situ and ex situ. The crystalline nature of the AgNPs in the silk fibers was demonstrated by X-ray diffraction. The thermal and mechanical properties of the silk fibers were enhanced after they were impregnated with AgNPs. The silver-coated silk fibers fabricated by the in situ and ex situ method exhibited more than 90% inhibition against Pseudomonas aeruginosa and Staphylococcus aureus. Silk fibers doped with AgNPs were found to be biocompatible with 3T3 fibroblasts. The results obtained represent an important advance towards the clinical application of biocompatible AgNP-loaded silk fibers for prevention of surgical wound infections. Keywords: silk fibers, silver nanoparticles, antibacterial activity, wound infections, cytotoxicity, 3T3 fibroblast cells

  8. MEG time-frequency analyses for pre- and post-surgical evaluation of patients with epileptic rhythmic fast activity.

    Sueda, Keitaro; Takeuchi, Fumiya; Shiraishi, Hideaki; Nakane, Shingo; Asahina, Naoko; Kohsaka, Shinobu; Nakama, Hideyuki; Otsuki, Taisuke; Sawamura, Yutaka; Saitoh, Shinji

    2010-02-01

    To evaluate the effectiveness of surgery for epilepsy, we analyzed rhythmic fast activity by magnetoencephalography (MEG) before and after surgery using time-frequency analysis. To assess reliability, the results obtained by pre-surgical MEG and intraoperative electrocorticography were compared. Four children with symptomatic localization-related epilepsy caused by circumscribed cortical lesion were examined in the present study using 204-channel helmet-shaped MEG with a sampling rate of 600Hz. One patient had dysembryoplastic neuroepithelial tumor (DNT) and three patients had focal cortical dysplasia (FCD). Aberrant areas were superimposed, to reconstruct 3D MRI images, and illustrated as moving images. In three patients, short-time Fourier transform (STFT) analyses of MEG showed rhythmic activities just above the lesion with FCD and in the vicinity of DNT. In one patient with FCD in the medial temporal lobe, rhythmic activity appeared in the ipsilateral frontal lobe and temporal lateral aspect. These findings correlate well with the results obtained by intraoperative electrocorticography. After the surgery, three patients were relieved of their seizures, and the area of rhythmic MEG activity disappeared or become smaller. One patient had residual rhythmic MEG activity, and she suffered from seizure relapse. Time-frequency analyses using STFT successfully depicted MEG rhythmic fast activity, and would provide valuable information for pre- and post-surgical evaluations to define surgical strategies for patients with epilepsy.

  9. Performance of language tasks in patients with ruptured aneurysm of the left hemisphere worses in the post-surgical evaluation

    Ana Cláudia C. Vieira

    2016-08-01

    Full Text Available ABSTRACT Sub-arachnoid hemorrhage (SAH promotes impairment of upper cortical functions. However, few information is available emphasizing changes in language after aneurismal SAH and aneurysm location influence. Objective To assess the language and verbal fluency performance in aneurismal SAH pre- and post-surgery in patients caused by an aneurysm of the anterior communicating artery (AcomA, left middle cerebral artery (L-MCA and left posterior comunicating artery (L-PcomA. Methods Assessment in 79 patients with SAH, on two occasions: pre- and post surgical treatment. They were divided into three groups by the aneurysms’ location. Results Deterioration is detected in the performance of all patients during the post-surgical period; L-MCA aneurysm patients displayed a reduction in verbal naming and fluency; L-PcomA patients deteriorated in the written language and fluency tasks. Conclusion After the surgical procedure the patients decreased in various language tasks and these differences in performance being directly related to the location of the aneurysm.

  10. Persistent extra-axial post-surgical collections and Propionibacterium acnes infection. Presentation of two cases and literature review.

    González, Pedro; Thenier, José; Galárraga, Raúl; de la Lama, Adolfo; Azevedo, Eva; Conde, Cesáreo

    It is common to observe the persistence of extra-axial collections after craniotomies. Most of these disappear in weeks or months but some remain. The onset of focal symptoms or the growth of these persistent collections months or years after surgery may indicate the presence of a chronic and latent infection by germs of low virulence such as Propionibacterium acnes (P. acnes). We present two clinical cases with persistent extra-axial collections, which required surgery years after diagnosis, in which P. acnes was isolated as an aetiological agent and we reviewed the literature published in this regard. These are two patients who, following surgical procedures (decompressive craniectomy for severe TBI and craniotomy for right parietal meningioma) and extra-axial collections were kept, which were monitored over time and then were infected and required emergency evacuation. In these collections P. acnes grew as a causal agent and required targeted antibiotics. We must consider P. acnes as an infectious agent of post-surgical collections of long evolution. Atypical presentation and radiological changes may be helpful in diagnosis. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. A service evaluation of cough reflex testing to guide dysphagia management in the postsurgical adult head and neck patient population.

    Holmes, Samantha

    2016-06-01

    The article reviews recent literature supporting the use of cough reflex testing (CRT), and outlines a service evaluation of CRT conducted with postsurgical head and neck cancer patients. There is a growing evidence base to support the use of CRT in dysphagia management to establish laryngeal sensation and screen for silent aspiration; however, there is a lack of evidence relating to using CRT within the head and neck population. Over a 3-month period, inpatients on an ear, nose and throat/maxillofacial ward underwent CRT as part of their clinical swallow evaluation. Data from these patients were collected, including their diagnoses, CRT findings, and subsequent management. The evaluation was limited by difficulties in maintaining a supply of citric acid, accessing medics to prescribe the citric acid, and staffing levels, as administration of the CRT initially required two members of staff to be present. The service evaluation findings, alongside current evidence examining noncancer mortality rates, suggests identification of silent aspiration is important in this population. CRT was useful to rationalize instrumental assessments and was easily incorporated into the swallowing evaluation. More evidence is needed to support the use of CRT within the head and neck population.

  12. Povidone-iodine induced post-surgical irritant contact dermatitis localized outside of the surgical incision area. Report of 27 cases and a literature review.

    Borrego, Leopoldo; Hernández, Noelia; Hernández, Zaida; Peñate, Yeray

    2016-05-01

    Povidone-iodine solution is an antiseptic that is used worldwide as surgical paint and is considered to have a low irritant potential. Post-surgical severe irritant dermatitis has been described after the misuse of this antiseptic in the surgical setting. Between January 2011 and June 2013, 27 consecutive patients with post-surgical contact dermatitis localized outside of the surgical incision area were evaluated. Thirteen patients were also available for patch testing. All patients developed dermatitis the day after the surgical procedure. Povidone-iodine solution was the only liquid in contact with the skin of our patients. Most typical lesions were distributed in a double lumbar parallel pattern, but they were also found in a random pattern or in areas where a protective pad or an occlusive medical device was glued to the skin. The patch test results with povidone-iodine were negative. Povidone-iodine-induced post-surgical dermatitis may be a severe complication after prolonged surgical procedures. As stated in the literature and based on the observation that povidone-iodine-induced contact irritant dermatitis occurred in areas of pooling or occlusion, we speculate that povidone-iodine together with occlusion were the causes of the dermatitis epidemic that occurred in our surgical setting. Povidone-iodine dermatitis is a problem that is easily preventable through the implementation of minimal routine changes to adequately dry the solution in contact with the skin. © 2015 The International Society of Dermatology.

  13. The effect of a perioperative ketamine infusion on the incidence of chronic postsurgical pain-a pilot study.

    Peyton, P J; Wu, C; Jacobson, T; Hogg, M; Zia, F; Leslie, K

    2017-07-01

    Chronic postsurgical pain (CPSP) is a common and debilitating complication of major surgery. We undertook a pilot study at three hospitals to assess the feasibility of a proposed large multicentre placebo-controlled randomised trial of intravenous perioperative ketamine to reduce the incidence of CPSP. Ketamine, 0.5 mg/kg pre-incision, 0.25 mg/kg/hour intraoperatively and 0.1 mg/kg/hour for 24 hours, or placebo, was administered to 80 patients, recruited over a 15-month period, undergoing abdominal or thoracic surgery under general anaesthesia. The primary endpoint was CPSP in the area of the surgery reported at six-month telephone follow-up using a structured questionnaire. Fourteen patients (17.5%) reported CPSP (relative risk [95% confidence interval] if received ketamine 1.18 [0.70 to 1.98], P =0.56). Four patients in the treatment group and three in the control group reported ongoing analgesic use to treat CPSP and two patients in each group reported their worst pain in the previous 24 hours at ≥3/10 at six months. There were no significant differences in adverse event rates, quality of recovery scores, or cumulative morphine equivalents consumption in the first 72 hours. Numeric Rating Scale pain scores (median [interquartile range, IQR]) for average pain in the previous 24 hours among those patients reporting CPSP were 17.5 [0 to 40] /100 with no difference between treatment groups. A large (n=4,000 to 5,000) adequately powered multicentre trial is feasible using this population and methodology.

  14. A systematic review and meta-analysis of ketamine for the prevention of persistent post-surgical pain.

    McNicol, E D; Schumann, R; Haroutounian, S

    2014-11-01

    While post-operative pain routinely resolves, persistent post-surgical pain (PPSP) is common in certain surgeries; it causes disability, lowers quality of life and has economic consequences. The objectives of this systematic review and meta-analysis were to evaluate the effectiveness of ketamine in reducing the prevalence and severity of PPSP and to assess safety associated with its use. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE through December 2012 for articles in any language. We included randomized, controlled trials in adults in which ketamine was administered perioperatively via any route. Seventeen studies, the majority of which administered ketamine intravenously, met all inclusion criteria. The overall risk of developing PPSP was not significantly reduced at any time point in the ketamine group vs. placebo, nor did comparisons of pain severity scores reach statistical significance. Sensitivity analysis of exclusively intravenous ketamine studies included in this meta-analysis demonstrated statistically significant reductions in risk of developing PPSP at 3 and 6 months (P = 0.01 and P = 0.04, respectively). Adverse event rates were similar between ketamine and placebo groups. The study data from our review are heterogeneous and demonstrate efficacy of intravenously administered ketamine only in comparison with placebo. Highly variable timing and dosing of ketamine in these studies suggest that no unifying effective regimen has emerged. Future research should focus on clinically relevant outcomes, should stratify patients with pre-existing pain and possible central sensitization and should enroll sufficiently large numbers to account for loss to follow-up in long-term studies. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  15. Measures and time points relevant for post-surgical follow-up in patients with inflammatory arthritis: a pilot study

    Tägil Magnus

    2009-05-01

    Full Text Available Abstract Background Rheumatic diseases commonly affect joints and other structures in the hand. Surgery is a traditional way to treat hand problems in inflammatory rheumatic diseases with the purposes of pain relief, restore function and prevent progression. There are numerous measures to choose from, and a combination of outcome measures is recommended. This study evaluated if instruments commonly used in rheumatologic clinical practice are suitable to measure outcome of hand surgery and to identify time points relevant for follow-up. Methods Thirty-one patients (median age 56 years, median disease duration 15 years with inflammatory rheumatic disease and need for post-surgical occupational therapy intervention formed this pilot study group. Hand function was assessed regarding grip strength (Grippit, pain (VAS, range of motion (ROM (Signals of Functional Impairment (SOFI and grip ability (Grip Ability Test (GAT. Activities of daily life (ADL were assessed by means of Disabilities of the Arm, Shoulder and Hand Outcome (DASH and Canadian Occupational Performance Measure (COPM. The instruments were evaluated by responsiveness and feasibility; follow-up points were 0, 3, 6 and 12 months. Results All instruments showed significant change at one or more follow-up points. Satisfaction with activities (COPM showed the best responsiveness (SMR>0.8, while ROM measured with SOFI had low responsiveness at most follow-up time points. The responsiveness of the instruments was stable between 6 and 12 month follow-up which imply that 6 month is an appropriate time for evaluating short-term effect of hand surgery in rheumatic diseases. Conclusion We suggest a core set of instruments measuring pain, grip strength, grip ability, perceived symptoms and self-defined daily activities. This study has shown that VAS pain, the Grippit instrument, GAT, DASH symptom scale and COPM are suitable outcome instruments for hand surgery, while SOFI may be a more insensitive

  16. The longitudinal trajectory of post-surgical % total weight loss among middle-aged women who had undergone bariatric surgery

    Dong-Chul Seo

    2017-03-01

    Full Text Available Middle-aged women are at a higher risk of being obese. We examined the trajectory of post-surgical % total weight loss (%TWL among middle-aged female bariatric patients. We fitted sequential generalized estimating equations models to analyze a sample of women who received bariatric surgery in 1995–2012, aged 40–65 years at the time of surgery (N = 158,292 whose pre-operative body mass index (BMI was ≥30 kg/m2 in the Bariatric Outcomes Longitudinal Database. The %TWL computed by 100% × (pre-surgery BMI − post-surgery BMI / pre-surgery BMI showed different trajectories depending on type of surgery. For gastric banding, %TWL increased rapidly right after bariatric surgery and started to decrease around 1 year after surgery. For Roux-en-Y gastric bypass (RYGB and sleeve gastrectomy, %TWL overall did not show remarkable changes from around 1 year after surgery. The highest increase in %TWL was observed in patients whose pre-operative BMI was 40 or higher and those who had undergone RYGB (ps < 0.001. Whereas the trajectories of %TWL among patients with sleeve gastrectomy and gastric banding did not differ much between different pre-operative BMI groups, the trajectories for RYGB were notably different between different pre-operative BMI groups (ps < 0.001. Middle-aged female bariatric patients are likely to achieve the highest %TWL if they receive RYGB and if their pre-operative BMI is 40 or higher. Further research is warranted to corroborate the present study's finding on the long-term effect of different types of bariatric surgery on %TWL among middle-aged women.

  17. Genetic polymorphisms and their association with the prevalence and severity of chronic postsurgical pain: a systematic review.

    Hoofwijk, D M N; van Reij, R R I; Rutten, B P; Kenis, G; Buhre, W F; Joosten, E A

    2016-12-01

    Although several patient characteristic, clinical, and psychological risk factors for chronic postsurgical pain (CPSP) have been identified, genetic variants including single nucleotide polymorphisms have also become of interest as potential risk factors for the development of CPSP. The aim of this review is to summarize the current evidence on genetic polymorphisms associated with the prevalence and severity of CPSP in adult patients. A systematic review of the literature was performed, and additional literature was obtained by reference tracking. The primary outcome was CPSP, defined as pain at least 2 months after the surgery. Studies performed exclusively in animals were excluded. Out of the 1001 identified studies, 14 studies were selected for inclusion. These studies described 5269 participants in 17 cohorts. A meta-analysis was not possible because of heterogeneity of data and data analysis. Associations with the prevalence or severity of CPSP were reported for genetic variants in the COMT gene, OPRM1, potassium channel genes, GCH1, CACNG, CHRNA6, P2X7R, cytokine-associated genes, human leucocyte antigens, DRD2, and ATXN1 CONCLUSIONS: Research on the topic of genetic variants associated with CPSP is still in its initial phase. Hypothesis-free, genome-wide association studies on large cohorts are needed in this field. In addition, future studies may also integrate genetic risk factors and patient characteristic, clinical, and psychological predictors for CPSP. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism.

    Tirabassi, G; delli Muti, N; Gioia, A; Biagioli, A; Lenzi, A; Balercia, G

    2014-04-01

    The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones. 12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 ± 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number). Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Δ-) of BMDs. Conversely, Δ-testosterone correlated positively and significantly with all studied Δ-BMDs, while Δ-FSH, Δ-estradiol, Δ-FT4, and Δ-IGF-1 did not correlate significantly with any of the Δ-BMDs. Multiple linear regression analysis, after correction for Δ-testosterone, showed that CAG repeat length was negatively and significantly associated with ∆-BMD of all measured sites. Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD.

  19. Androgen receptor gene CAG repeat polymorphism independently influences recovery of male sexual function after testosterone replacement therapy in postsurgical hypogonadotropic hypogonadism.

    Tirabassi, Giacomo; Delli Muti, Nicola; Corona, Giovanni; Maggi, Mario; Balercia, Giancarlo

    2014-05-01

    Few and contradictory studies have evaluated the possible influence of androgen receptor (AR) gene CAG repeat polymorphism on male sexual function. In this study we evaluated the role of AR gene CAG repeat polymorphism in the recovery of sexual function after testosterone replacement therapy (TRT) in men affected by postsurgical hypogonadotropic hypogonadism, a condition which is often associated with hypopituitarism and in which the sexual benefits of TRT must be distinguished from those of pituitary-function replacement therapies. Fifteen men affected by postsurgical hypogonadotropic hypogonadism were retrospectively assessed before and after TRT. Main outcome measures included sexual parameters as assessed by the International Index of Erectile Function questionnaire, levels of pituitary dependent hormones (total testosterone, free T3, free T4, cortisol, insulin-like growth factor-1 [IGF-1], prolactin), and results of genetic analysis (AR gene CAG repeat number). Plasma concentrations of free T3, free T4, cortisol, and prolactin did not vary significantly between the two phases, while testosterone and IGF-1 increased significantly after TRT. A significant improvement in all sexual parameters studied was found. The number of CAG triplets was negatively and significantly correlated with changes in all the sexual parameters, while opposite correlations were found between changes in sexual parameters and changes in testosterone levels; no correlation of change in IGF1 with change in sexual parameters was reported. On multiple linear regression analysis, after correction for changes in testosterone, nearly all the associations between the number of CAG triplets and changes in sexual parameters were confirmed. Shorter length AR gene CAG repeat number is associated with the recovery of sexual function after TRT in postsurgical male hypogonadotropic hypogonadism, independently of the effects of concomitant pituitary-replacement therapies. © 2014 International Society

  20. An appraisal of innovative meloxicam mucoadhesive films for periodontal postsurgical pain control: A double-blinded, randomized clinical trial of effectiveness

    S Raja Rajeswari

    2015-01-01

    Full Text Available Background and Objective: Transmucosal analgesic delivery is a promising approach to periodontal postoperative pain management. The purpose of this clinical trial is to appraise the effectiveness of transmucosal drug delivery system with meloxicam films and to identify its minimum effective dosage via this route after periodontal flap surgery. Materials and Methods: The analgesic mucoadhesive films were formulated using meloxicam and hydroxypropyl methyl cellulose polymer by solvent casting method. The sample size consisted of 60 chronic periodontitis patients who require periodontal flap surgery. The subjects were randomized using lottery method into four groups (Group A - 45 mg; B - 30 mg; C - 20 mg; D - 10 mg meloxicam per film. After periodontal flap surgery, the respective meloxicam mucoadhesive films were placed over the surgical site and were removed on 4 th day of postsurgery. The primary outcome measure was postsurgical pain level and recorded at 1 st , 2 nd , 3 rd , 4 th , 5 th , 24 th , and 48 th h using a 0-10 mm visual analog scale with markings from 0 = no pain to 10 = extreme pain. Results: The postoperative pain control observed in Groups A and B was found to be effective, and the patient comfort level was very satisfactory. Whereas in Group C, it was found to be high in the first 3 h postsurgically, after which adequate pain relief was seen. Group D exhibited inadequate pain relief. No adverse reactions were noted after applying the film in any of the groups. Conclusion: Transmucosal delivery of meloxicam was found to be effective and safe in postsurgical pain control of periodontal flap surgery. The minimum effective dosage via this route for meloxicam was found to be with 30 mg mucoadhesive films.

  1. PLGA nanofiber membranes loaded with epigallocatechin-3-O-gallate are beneficial to prevention of postsurgical adhesions

    Shin YC

    2014-08-01

    both scavenging reactive oxygen species and extending activated partial thromboplastin time. Macroscopic observation after 1 week of surgical treatment revealed that the antiadhesion efficacy of E-PLGA nanofiber membranes was significantly superior to those of untreated controls and pure PLGA equivalents, which was comparable to that of a commercial tissue-adhesion barrier. In conclusion, the E-PLGA hybrid nanofiber can be exploited to craft strategies for the prevention of postsurgical adhesions. Keywords: nanofiber membrane, poly(lactic-co-glycolic acid, epigallocatechin-3-O-gallate, antiadhesion, tissue-adhesion barrier

  2. Corrosion inhibition

    Fisher, A O

    1965-12-29

    An acid corrosion-inhibiting composition consists essentially of a sugar, and an alkali metal salt selected from the group consisting of iodides and bromides. The weight ratio of the sugar to the alkali metal salt is between 2:1 and about 20,000:1. Also, a corrosion- inhibited phosphoric acid composition comprising at least about 20 wt% of phosphoric acid and between about 0.1 wt% and about 10 wt% of molasses, and between about 0.0005 wt% and about 1 wt% of potassium iodide. The weight ratio of molasses to iodide is greater than about 2:1. (11 claims)

  3. Impact of long-term antihypertensive and antidiabetic medications on the prognosis of post-surgical colorectal cancer: the Fujian prospective investigation of cancer (FIESTA) study.

    Peng, Feng; Hu, Dan; Lin, Xiandong; Liang, Binying; Chen, Ying; Zhang, Hejun; Xia, Yan; Lin, Jinxiu; Zheng, Xiongwei; Niu, Wenquan

    2018-05-24

    Hypertension and diabetes mellitus are common comorbidities of colorectal cancer. We designed a prospective cohort study aiming to investigate the impact of long-term antihypertensive and antidiabetic medications on colorectal cancer-specific survival and recurrence among 713 post-surgical patients. All participants received radical resection for colorectal cancer during 2000-08, and they were followed up until July 2017. Colorectal cancer patients without hypertension had better survival than those with hypertension (median survival time [MST]: 190.3 months versus 99.0 months, p colorectal cancer survival was statistically significant, that is, patients receiving antidiabetic medications had longer survival time than untreated diabetic patients (MST: 135.8 months versus 80.2 months, p : 0.007), whereas the prognosis was greatly improved in colorectal cancer patients without diabetes mellitus ( p colorectal cancer relative to those without medications, respectively. Our data indicate that long-term antidiabetic medications can significantly prolong the survival and improve the prognosis of post-surgical colorectal cancer.

  4. Neem leaf glycoprotein prevents post-surgical sarcoma recurrence in Swiss mice by differentially regulating cytotoxic T and myeloid-derived suppressor cells.

    Madhurima Sarkar

    Full Text Available Post-surgical tumor recurrence is a common problem in cancer treatment. In the present study, the role of neem leaf glycoprotein (NLGP, a novel immunomodulator, in prevention of post-surgical recurrence of solid sarcoma was examined. Data suggest that NLGP prevents tumor recurrence after surgical removal of sarcoma in Swiss mice and increases their tumor-free survival time. In NLGP-treated tumor-free mice, increased cytotoxic CD8+ T cells and a decreased population of suppressor cells, especially myeloid-derived suppressor cells (MDSCs was observed. NLGP-treated CD8+ T cells showed greater cytotoxicity towards tumor-derived MDSCs and supernatants from the same CD8+ T cell culture caused upregulation of FasR and downregulation of cFLIP in MDSCs. To elucidate the role of CD8+ T cells, specifically in association with the downregulation in MDSCs, CD8+ T cells were depleted in vivo before NLGP immunization in surgically tumor removed mice and tumor recurrence was noted. These mice also exhibited increased MDSCs along with decreased levels of Caspase 3, Caspase 8 and increased cFLIP expression. In conclusion, it can be stated that NLGP, by activating CD8+ T cells, down regulates the proportion of MDSCs. Accordingly, suppressive effects of MDSCs on CD8+ T cells are minimized and optimum immune surveillance in tumor hosts is maintained to eliminate the residual tumor mass appearing during recurrence.

  5. S3 Dorsal Root Ganglion/Nerve Root Stimulation for Refractory Postsurgical Perineal Pain: Technical Aspects of Anchorless Sacral Transforaminal Lead Placement

    X. Zuidema

    2016-01-01

    Full Text Available Chronic perineal pain limits patients in physical and sexual activities, leading to social and psychological distress. In most cases, this pain develops after surgery in the urogenital area or as a consequence of trauma. Neuromodulation is one of the options in chronic postsurgical perineal pain treatment. We present a case of refractory perineal pain after right sided surgical resection of a Bartholin’s cyst which was treated with third sacral nerve root/dorsal root ganglion stimulation using the transforaminal approach. We describe a new anchorless lead placement technique using a unique curved lead delivery sheath. We postulate that this new posterior foraminal technique of lead placement is simple, safe, and reversible and may lower the occurrence of lead related complications.

  6. CORRIGENDUM to The impact of prehabilitation on post-surgical complications in patients undergoing non-urgent cardiovascular surgical intervention: Systematic review and meta-analysis.

    2018-06-01

    The impact of prehabilitation on post-surgical complications in patients undergoing non-urgent cardiovascular surgical intervention: Systematic review and meta-analysis by F Marmelo et al. European Journal of Preventive Cardiology January 2018 25: 404-417, DOI: 2016 doi: 10.1177/2047487317752373 The third author's name, affiliation and Funding information were incorrect, the correct details are below: Daniel Moreira-Gonçalves Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Portugal CIAFEL, Faculdade de Desporto, Universidade do Porto, Portugal Funding D.M.G is supported by an individual fellowship grant from Fundação para a Ciência e Tecnologia (SFRH/BPD/90010/ 2012) This has been corrected in the online article.

  7. Age at onset in patients with medically refractory temporal lobe epilepsy and mesial temporal sclerosis: impact on clinical manifestations and postsurgical outcome.

    Asadi-Pooya, Ali A; Sperling, Michael R

    2015-08-01

    To evaluate the demographic and clinical manifestations and postsurgical outcome of childhood-onset mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) and establishing the potential differences as compared to the patients with adult-onset MTS-TLE. In this retrospective study all patients with a clinical diagnosis of medically refractory TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson comprehensive epilepsy center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. Clinical manifestations and outcome were compared between patients with childhood-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure below 10 years) and those with adult-onset MTS-TLE (i.e., age at onset of the first afebrile habitual seizure 20 years or above). One hundred and twelve patients had childhood-onset MTS-TLE and 76 had adult-onset MTS-TLE. Demographic, clinical, EEG and MRI characteristics of these two groups were similar. Postoperative outcome was not statistically different between these two groups of patients (P=0.9). Temporal lobe epilepsy due to mesial temporal sclerosis is a common cause of epilepsy that can start from early childhood to late adulthood. The etiology of MTS-TLE may be different in various age groups, but it seems that when mesial temporal sclerosis is the pathological substrate of TLE, clinical manifestations and response to surgical treatment of patients are very similar in patients with childhood-onset MTS-TLE compared to those with adult-onset disease. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  8. Multi-functional electrospun antibacterial core-shell nanofibrous membranes for prolonged prevention of post-surgical tendon adhesion and inflammation.

    Shalumon, K T; Sheu, Chialin; Chen, Chih-Hao; Chen, Shih-Heng; Jose, Gils; Kuo, Chang-Yi; Chen, Jyh-Ping

    2018-05-01

    The possibility of endowing an electrospun anti-adhesive barrier membrane with multi-functionality, such as lubrication, prevention of fibroblast attachment and anti-infection and anti-inflammation properties, is highly desirable for the management of post-surgical tendon adhesion. To this end, we fabricated core-shell nanofibrous membranes (CSNMs) with embedded silver nanoparticles (Ag NPs) in the poly(ethylene glycol) (PEG)/poly(caprolactone) (PCL) shell and hyaluronic acid (HA)/ibuprofen in the core. HA imparted a lubrication effect for smooth tendon gliding and reduced fibroblast attachment, while Ag NPs and ibuprofen functioned as anti-infection and anti-inflammation agents, respectively. CSNMs with a PEG/PCL/Ag shell (PPA) and HA core containing 0% (H/PPA), 10% (HI10/PPA), 30% (HI30/PPA) and 50% (HI50/PPA) ibuprofen were fabricated through co-axial electrospinning and assessed through microscopic, spectroscopic, thermal, mechanical and drug release analyses. Considering nutrient passage through the barrier, the microporous CSNMs exerted the same barrier effect but drastically increased the mass transfer coefficients of bovine serum albumin compared with the commercial anti-adhesive membrane SurgiWrap®. Cell attachment/focal adhesion formation of fibroblasts revealed effective reduction of initial cell attachment on the CSNM surface with minimum cytotoxicity (except HI50/PPA). The anti-bacterial effect against both Gram-negative and Gram-positive bacteria was verified to be due to the Ag NPs in the membranes. In vivo studies using H/PPA and HI30/PPA CSNMs and SurgiWrap® in a rabbit flexor tendon rupture model demonstrated the improved efficacy of HI30/PPA CSNMs in reducing inflammation and tendon adhesion formation based on gross observation, histological analysis and functional assays. We conclude that HI30/PPA CSNMs can act as a multifunctional barrier membrane to prevent peritendinous adhesion after tendon surgery. A multi-functional anti-adhesion barrier

  9. Impact of local administration of liposome bupivacaine for postsurgical analgesia on wound healing: a review of data from ten prospective, controlled clinical studies.

    Baxter, Richard; Bramlett, Kenneth; Onel, Erol; Daniels, Stephen

    2013-03-01

    Liposome bupivacaine is a liposomal formulation that allows delivery of bupivacaine for 96 hours with a single local administration. It is indicated for the management of postsurgical pain. This retrospective review of 10 clinical trials assessed the potential impact of local anesthetics on wound healing and chondrolysis. Various doses of liposome bupivacaine and bupivacaine hydrochloride (HCl) were evaluated. Primary inclusion criteria across the 10 Phase 2 and Phase 3 randomized, double-blind studies required that patients be ≥18 years of age at the screening visit and scheduled to undergo the specified surgical procedure in each study (inguinal hernia repair, total knee arthroplasty, hemorrhoidectomy, breast augmentation, or bunionectomy). Key exclusion criteria were: a history of clinically significant medical conditions (including cardiovascular, hepatic, renal, neurologic, psychiatric, or metabolic disease) or laboratory results that indicated an increased vulnerability to the study drugs and/or procedures; medical condition(s) or concurrent surgery that may have required analgesic treatment in the postoperative period for pain that was not strictly related to the study surgery; and/or any clinically significant event or condition discovered during surgery that could have complicated the patient's postsurgical course. Assessments included the clinician's overall satisfaction with the patient's wound healing, wound status (erythema, drainage, edema, and induration), and wound scarring. Adverse events (AEs) potentially manifesting as wound complications and local AEs were also assessed. In total, 823 patients received liposome bupivacaine at doses ranging from 66 to 532 mg across the 5 different surgical settings; 446 patients received bupivacaine HCl (75-200 mg), and 190 patients received placebo. Few studies showed statistically significant differences between liposome bupivacaine and the comparator (bupivacaine HCl or placebo) with regard to the clinician

  10. Conservative management of post-surgical urinary incontinence in an adolescent using applied kinesiology: a case report.

    Cuthbert, Scott C; Rosner, Anthony L

    2011-06-01

    This case report describes the successful treatment of an adolescent female suffering daily stress and occasional total urinary incontinence with applied kinesiology methods and chiropractic manipulative therapy. A 13-year-old female developed unpredictable urinary incontinence and right hip pain immediately following emergency open appendectomy surgery. The patient was forced to wear an incontinence pad throughout the day and night for 10 months because of unpredictable urinary incontinence. ASSESSMENT AND INTERVENTION: Chiropractic and applied kinesiology (AK) methods - a multi-modal diagnostic technique that utilizes manual muscle tests (MMT) for the detection of musculoskeletal impairments and specific AK techniques for correction of identified issues - were utilized to diagnose and treat this patient for muscle impairments in the lumbar spine and pelvis. Patient experienced a rapid resolution of her urinary incontinence and hip pain. A six-year follow-up confirmed complete resolution of symptoms. In this case, utilization of MMT allowed for the identification of several inhibited muscles. Utilizing the appropriate corrective techniques improved the strength of these muscles and resulted in their being graded as facilitated. Symptoms of urinary incontinence and hip pain resolved with this diagnostic and treatment approach. AK methods were useful for the discovery of a number of apparent causative factors underlying this patient's urinary incontinence and hip pain. Treatment for these pelvic-floor muscle and joint abnormalities resulted in rapid, long-lasting resolution of her urinary incontinence and hip pain.

  11. Does antimicrobial usage before meningitis lead to a higher risk of adult postsurgical Acinetobacter baumannii meningitis than that of Enterobacteriaceae meningitis?

    Demiraslan, Hayati; Ulutabanca, Halil; Ercal, Baris Derya; Metan, Gokhan; Alp, Emine

    2016-12-01

    Acinetobacter baumannii and Enterobacteriaceae are two pathogens responsible for postneurosurgical meningitis. The aim of this retrospective study was to evaluate the factors that influenced the outcomes in patients with postneurosurgical meningitis caused by A. baumannii and Enterobacteriaceae. Patients with post-surgical meningitis were identified from infection control committee charts between 2007 and 2015. Subjects over 16 years old who had positive cerebral spinal fluid cultures for A. baumannii or Enterobacteriaceae were enrolled in the study. Clinical and laboratory data for 30 patients with A. baumannii meningitis were compared with those of 12 patients with Enterobacteriaceae meningitis. The mean age of patients was 51.9 years and 57.1% were male. Eleven patients had comorbidities, the most common being diabetes mellitus. Most patients were due to intracranial haemorrhage (78.6%). The rate of the patients who received an appropriate antimicrobial therapy was 35.7%, and the crude mortality rate was 64.3%. In univariate analysis, previous antibiotic use, an infection before meningitis and mechanical ventilation had an increased risk of A. baumannii meningitis. Moreover, intrathecal antimicrobial use, inappropriate empirical antimicrobial use, antimicrobial resistance and alanine aminotransferase elevation were significantly higher in patients with A. baumannii meningitis than in those with Enterobacteriaceae meningitis. Antimicrobial use before meningitis (8.84 times) and mechanical ventilation (7.28 times) resulted in an increased risk of A. baumannii meningitis. None of the results affected 30-day mortality. Avoidance of unnecessarily prolonged antimicrobial usage may help to prevent a selection of A. baumannii.

  12. Recombinant human TSH and ablation of post-surgical thyroid remnants in differentiated thyroid cancer: the effect of pre-treatment with furosemide and furosemide plus lithium

    Barbaro, Daniele; Lapi, Paola; Pasquini, Cristina; Orsini, Paola; Turco, Anna [General Hospital of Livorno, Endocrinology Unit, Livorno (Italy); Grosso, Mariano; Boni, Giuseppe; Mariani, Giuliano [University of Pisa Medical School, Regional Center of Nuclear Medicine, Pisa (Italy); Meucci, Giuseppe [General Hospital of Livorno, Division of General Surgery, Livorno (Italy); Marzola, Maria Cristina; Rubello, Domenico [' Santa Maria della Misericordia' Hospital, Department of Nuclear Medicine, PET Centre, Rovigo (Italy); Berti, Piero; Miccoli, Paolo [University of Pisa Medical School, Department of Surgery, Pisa (Italy)

    2010-02-15

    Recombinant human TSH (rhTSH) can be used for post-surgical radioiodine (I-131) thyroid remnants ablation in differentiated thyroid cancer (DTC) patients after surgery. Debate exists in literature about the optimal amount of I-131 that should be given for obtaining an effective ablation and about the role of iodine pool during treatment. Therefore, the aim of the present study was to assess whether I-131 ablation during rhTSH stimulus can be improved by reducing the circulating iodine pool and by increasing thyroid cell uptake and retention of I-131 obtained by administering furosemide and lithium. A total of 201 consecutive DTC patients were entered in the study: they were treated by total thyroidectomy and I-131 therapy during rhTSH stimulus to ablate thyroid remnants. Patients were divided into two groups according to the TNM stage: group 1 included patients in stage I-II who were treated with a low 30-mCi I-131 dose, while group 2 included patients in stage III-IV who were treated by a high 100-mCi I-131 dose. Moreover, both groups were further subdivided into three subgroups. Subgroup (a) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-thyroxine (LT4). Subgroup (b) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-T4, and after furosemide administration (25 mg/day orally) during the 3 days before I-131. Subgroup (c) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day L-T4 withdrawal, and after administration of furosemide (25 mg/day orally) during the 3 days prior I-131 and lithium (450 mg/day orally) during the 3 days following I-131. Another group (group 3) of 20 patients characterized by a very low-risk cancer (unifocal tumor <1.0 cm in diameter, without extra-capsular extension, N0) was

  13. Post-surgical functional recovery, lumbar lordosis, and range of motion associated with MR-detectable redundant nerve roots in lumbar spinal stenosis.

    Chen, Jinshui; Wang, Juying; Wang, Benhai; Xu, Hao; Lin, Songqing; Zhang, Huihao

    2016-01-01

    T1- and T2-weighted magnetic resonance images (MRI) can reveal lumbar redundant nerve roots (RNRs), a result of chronic compression and nerve elongation associated with pathogenesis of cauda equina claudication (CEC) in degenerative lumbar canal stenosis (DLCS). The study investigated effects of lumbar lordosis angle and range of motion on functional recovery in lumbar stenosis patents with and without RNRs. A retrospective study was conducted of 93 lumbar spinal stenosis patients who underwent decompressive surgery. Eligible records were assessed by 3 independent blinded radiologists for presence or absence of RNRs on sagittal T2-weighted MR (RNR and non-RNR groups), pre- and post-operative JOA score, lumbar lordosis angle, and range of motion. Of 93 total patients, the RNR group (n=37, 21/37 female) and non-RNR group (n=56; 31/56 female) had similar preoperative conditions (JOA score) and were not significantly different in age (mean 64.19 ± 8.25 vs. 62.8 ± 9.41 years), symptom duration (30.92 ± 22.43 vs. 28.64 ± 17.40 months), or follow-up periods (17.35 ± 4.02 vs. 17.75 ± 4.29 mo) (all p>0.4). The non-RNR group exhibited significantly better final JOA score (p=0.015) and recovery rate (p=0.002). RNR group patients exhibited larger lumbar lordosis angles in the neutral position (p=0.009) and extension (p=0.021) and larger range of motion (p=0.008). Poorer surgical outcomes in patients with RNRs indicated that elevated lumbar lordosis angle and range of motion increased risks of RNR formation, which in turn may cause poorer post-surgical recovery, this information is possibly useful in prognostic assessment of lumbar stenosis complicated by RNRs. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. INHIBITION IN SPEAKING PERFORMANCE

    Humaera, Isna

    2015-01-01

    The most common problem encountered by the learner in the languageacquisition process is learner inhibition. Inhibition refers to a temperamentaltendency to display wariness, fearfulness, or restrain in response tounfamiliar people, objects, and situations. There are some factors that causeinhibition, such as lack of motivation, shyness, self-confidence, self-esteem,and language ego. There are also levels of inhibition, it refers to kinds ofinhibition and caused of inhibition itself. Teacher ...

  15. Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study

    Lash Timothy L

    2010-01-01

    Full Text Available Abstract Background Selective serotonin reuptake inhibitors (SSRI decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association. Methods We conducted a population-based study of the risk of re-operation due to post-surgical bleeding within two weeks of primary surgery among Danish women with primary breast cancer. Patients were categorised according to their use of SSRI: never users, current users (SSRI prescription within 30 days of initial breast cancer surgery, and former users (SSRI prescription more than 30 days before initial breast cancer surgery. We calculated the risk of re-operation due to post-surgical bleeding within 14 days of initial surgery, and the relative risk (RR of re-operation comparing SSRI users with never users of SSRI adjusting for potential confounders. Results 389 of 14,464 women (2.7% were re-operated. 1592 (11% had a history of SSRI use. Risk of re-operation was 2.6% among never users, 7.0% among current SSRI users, and 2.7% among former users. Current users thus had an increased risk of re-operation due to post-operative bleeding (adjusted relative risk = 2.3; 95% confidence interval (CI = 1.4, 3.9 compared with never users. There was no increased risk of re-operation associated with former use of SSRI (RR = 0.93, 95% CI = 0.66, 1.3. Conclusions Current use of SSRI is associated with an increased risk of re-operation due to bleeding after surgery for breast cancer.

  16. The associations between severity of early postoperative pain, chronic postsurgical pain and plasma concentration of stable nitric oxide products after breast surgery.

    Iohom, Gabriella

    2012-02-03

    In this study, we compared the effects of two analgesic regimens on perioperative nitric oxide index (NOx) and the likelihood of subsequent development of chronic postsurgical pain (CPSP) after breast surgery and sought to determine the association among early postoperative pain, NOx, and the likelihood of subsequent development of CPSP. Twenty-nine consecutive ASA I or II patients undergoing breast surgery with axillary clearance were randomly allocated to one of two groups. Patients in group S (n = 15) received a standard intraoperative and postoperative analgesic regimen (morphine sulfate, diclofenac, dextropropoxyphene hydrochloride + acetaminophen prn). Patients in group N (n = 14) received a continuous paravertebral block (for 48 h) and acetaminophen and parecoxib (followed by celecoxib up to 5 days). Visual analog scale pain scores at rest and on arm movement were recorded regularly until the fifth postoperative day. A telephone interview was conducted 10 wk postoperatively. The McGill Pain Questionnaire was used to characterize pain. NOx was estimated preoperatively, at the end of surgery, 30 min and 2, 4, 12, 24, 48 h postoperatively. Twelve (80%) patients in group S and no patient in group N developed CPSP (P = 0.009). Compared with patients with a pain rating index > or =1 (n = 18) 10 wk postoperatively, patients with a pain rating index = 0 (n = 11) had lesser visual analog scale pain scores on movement at each postoperative time point from 30 min until 96 h postoperatively (P < 0.005) and at rest 30 min (0.6 +\\/- 1.5 versus 30.2 +\\/- 26.8; P = 0.004), 4 h (2.3 +\\/- 7.5 versus 19.0 +\\/- 25.8; P = 0.013), 8 h (4.4 +\\/- 10.2 versus 21.4 +\\/- 27.0; P = 0.03) and 12 h (0.7 +\\/- 1.2 versus 15.4 +\\/- 27.0; P = 0.035) postoperatively. NOx values were greater in group N compared with group S 48 h postoperatively (40.6 +\\/- 20.1 versus 26.4 +\\/- 13.5; P = 0.04).

  17. Transsphenoidal hypophysectomy: postsurgical CT findings

    Dolinskas, C.A.; Simeone, F.A.

    1985-01-01

    Transsphenoidal surgery produces changes in the paranasal sinuses and sella that should be familiar to radiologists in view of frequency of this type of surgery. Some of these changes, such as soft-tissue-density debris in the sinuses, are transient. Fat and other packing material identifiable in the sinuses and sella after surgery is permanent. The procedure is associated with a variety of complications that are readily detectable by computed tomography (CT). These include bleeding, compression of parasellar structures by packing material, cerebrospinal fluid leaks, and pneumocephalus. After a transsphenoidal procedure, with or without follow-up radiation therapy, residual enhancing intrasellar and parasellar lesions may still be identified

  18. Hirschsprung's disease - Postsurgical intestinal dysmotility

    Romaneli, Mariana Tresoldi das Neves; Ribeiro, Antonio Fernando; Bustorff-Silva, Joaquim Murray; de Carvalho, Rita Barbosa; Lomazi, Elizete Aparecida

    2016-01-01

    Abstract Objective: To describe the case of an infant with Hirschsprung's disease presenting as total colonic aganglionosis, which, after surgical resection of the aganglionic segment persisted with irreversible functional intestinal obstruction; discuss the difficulties in managing this form of congenital aganglionosis and discuss a plausible pathogenetic mechanism for this case. Case description: The diagnosis of Hirschsprung's disease presenting as total colonic aganglionosis was establi...

  19. Inhibition of lactation.

    Llewellyn-Jones, D

    1975-01-01

    The mechanism and hormonal regulation of lactation is explained and illustrated with a schematic representation. Circulating estrogen above a critical amount seems to be the inhibitory factor controlling lactation during pregnancy. Once delivery occurs, the level of estrogen falls, that of prolactin rises, and lactation begins. Nonsuckling can be used to inhibit lactation. Estrogens can also be used to inhibit lactation more quickly and with less pain. The reported association between estrogens and puerperal thromboembolism cannot be considered conclusive due to defects in the reporting studies. There is no reason not to use estrogens in lactation inhibition except for women over 35 who experienced a surgical delivery. Alternative therapy is available for these women. The recently-developed drug, brom-ergocryptine, may replace other methods of lactation inhibition.

  20. Accuracy of combined maxillary and mandibular repositioning and of soft tissue prediction in relation to maxillary antero-superior repositioning combined with mandibular set back A computerized cephalometric evaluation of the immediate postsurgical outcome using the TIOPS planning system

    Donatsky, Ole; Bjørn-Jørgensen, Jens; Hermund, Niels Ulrich

    2009-01-01

    surgical planning system (TIOPS). MATERIAL AND METHODS: Out of 100 prospectively and consecutively treated patients, 52 patients manifested dentofacial deformities requiring bimaxillary orthognathic surgery with maxillary antero-superior repositioning combined with mandibular set back and so were included......AIM: The purpose of the present study was to evaluate the immediate postsurgical outcome of planned and predicted hard and soft tissue positional changes in relation to maxillary antero-superior repositioning combined with mandibular set back using the computerized, cephalometric, orthognathic...... positional changes were transferred to model surgery on a three-dimensional articulator system (SAM) and finally to surgery. Five to six weeks after surgery, the actually obtained hard and soft tissue profile changes were cephalometricly assessed. RESULTS: The mean accuracy of the planned and predicted hard...

  1. Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization

    Wang Wen-Quan

    2012-11-01

    Full Text Available Abstract Background Promotion of endothelial normalization restores tumor oxygenation and obstructs tumor cells invasion, intravasation, and metastasis. We therefore investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis by inducing vascular normalization after palliative resection (PR of hepatocellular carcinoma (HCC. Methods A liver orthotopic double-tumor xenograft model in nude mouse was established by implantation of HCCLM3 (high metastatic potential and HepG2 tumor cells. After removal of one tumor by PR, the effects of tanshinone IIA administration on metastasis, tumor vascularization, and survival were evaluated. Tube formation was examined in mouse tumor-derived endothelial cells (TECs treated with tanshinone IIA. Results PR significantly accelerated residual hepatoma metastases. Tanshinone IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and, more importantly, prolonged host survival. Tanshinone IIA alleviated residual tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT in vivo; however, it did not downregulate hypoxia-inducible factor 1α (HIF-1α or reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA directly strengthened tube formation of TECs, associated with vascular endothelial cell growth factor receptor 1/platelet derived growth factor receptor (VEGFR1/PDGFR upregulation. Although the microvessel density (MVD of residual tumor tissue increased after PR, the microvessel integrity (MVI was still low. While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI, leading to vascular normalization. Conclusions Our results demonstrate that tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR. Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization. This application demonstrates the potential clinical

  2. Enzyme inhibition by iminosugars

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  3. Quorum sensing inhibition

    Persson, T.; Givskov, Michael Christian; Nielsen, J.

    2005-01-01

    /receptor transcriptional regulator in some clinically relevant Gram-negative bacteria. The present review contains all reported compound types that are currently known to inhibit the QS transcriptional regulator in Gram-negative bacteria. These compounds are sub-divided into two main groups, one comprising structural...

  4. Cooperation for Better Inhibiting.

    Novoa, Eva Maria; Ribas de Pouplana, Lluís

    2015-06-18

    Cladosporin is an antimalarial drug that acts as an ATP-mimetic to selectively inhibit Plasmodium lysyl-tRNA synthetase. Using multiple crystal structures, Fang et al. (2015) reveal in this issue of Chemistry & Biology the fascinating mechanism responsible for cladosporin selectivity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Plastics for corrosion inhibition

    Goldade, Victor A; Makarevich, Anna V; Kestelman, Vladimir N

    2005-01-01

    The development of polymer composites containing inhibitors of metal corrosion is an important endeavour in modern materials science and technology. Corrosion inhibitors can be located in a polymer matrix in the solid, liquid or gaseous phase. This book details the thermodynamic principles for selecting these components, their compatibility and their effectiveness. The various mechanisms of metal protection – barrier, inhibiting and electromechanical – are considered, as are the conflicting requirements placed on the structure of the combined material. Two main classes of inhibited materials (structural and films/coatings) are described in detail. Examples are given of structural plastics used in friction units subjected to mechano-chemical wear and of polymer films/coatings for protecting metal objects against corrosion.

  6. Inhibiting the inevitable

    Shashoua, Yvonne

    2006-01-01

    conservation is to ‘buy time’ for the object. Inhibitive conservation of plastics involves the removal or reduction of factors causing or accelerating degradation including light, oxygen, acids, relative humidity and acidic breakdown products. Specific approaches to conservation have been developed......Once plastics objects are registered in museum collections, the institution becomes responsible for their long term preservation, until the end of their useful lifetime. Plastics appear to deteriorate faster than other materials in museum collections and have a useful lifetime between 5 and 25...... years. Preventive or inhibitive conservation involves controlling the environments in which objects are placed during storage and display, with the aim of slowing the major deterioration reactions. Once in progress, degradation of plastics cannot be stopped or reversed, so the aim of preventive...

  7. Evaluation of post-surgical healing in rats using a topical preparation based on extract of Musa sapientum L., Musaceae, epicarp

    Priscila B. Lino

    2011-04-01

    Full Text Available Considering that oral preparations made with peel green bananas (e.g. flour and extracts demonstrated healing effects on mucous membranes and skin, this study evaluated the healing and the antimicrobial property of a topical preparation based on extract of Musa sapientum L., Musaceae, (apple banana in surgically induced wounds in the skin of male Wistar rats, 100 g. The extract was obtained by decoction, the presence of tannins was detected by phytochemical screening and 10% of the extract was incorporated into the carbopol gel (CMS gel. The processes of healing and bacterial isolation were evaluated in the following experimental groups: control (no treatment, treatment with placebo or with the CMS gel. The healing of surgical wounds treated with the CMS gel was faster when compared with the control and placebo groups and the treatment with CMS gel also inhibited the growth of pyogenic bacteria and enterobacteria in the wounds. The results indicate that the extract of Musa sapientum epicarp has healing and antimicrobial properties (in vivo, probably, due to tannins.

  8. Evaluation of post-surgical healing in rats using a topical preparation based on extract of Musa sapientum L., Musaceae, epicarp

    Priscila B. Lino

    2011-06-01

    Full Text Available Considering that oral preparations made with peel green bananas (e.g. flour and extracts demonstrated healing effects on mucous membranes and skin, this study evaluated the healing and the antimicrobial property of a topical preparation based on extract of Musa sapientum L., Musaceae, (apple banana in surgically induced wounds in the skin of male Wistar rats, 100 g. The extract was obtained by decoction, the presence of tannins was detected by phytochemical screening and 10% of the extract was incorporated into the carbopol gel (CMS gel. The processes of healing and bacterial isolation were evaluated in the following experimental groups: control (no treatment, treatment with placebo or with the CMS gel. The healing of surgical wounds treated with the CMS gel was faster when compared with the control and placebo groups and the treatment with CMS gel also inhibited the growth of pyogenic bacteria and enterobacteria in the wounds. The results indicate that the extract of Musa sapientum epicarp has healing and antimicrobial properties (in vivo, probably, due to tannins.

  9. Anxiety and retrieval inhibition: support for an enhanced inhibition account.

    Nuñez, Mia; Gregory, Josh; Zinbarg, Richard E

    2017-02-01

    Retrieval inhibition of negative associations is important for exposure therapy for anxiety, but the relationship between memory inhibition and anxiety is not well understood-anxiety could either be associated with enhanced or deficient inhibition. The present study tested these two competing hypotheses by measuring retrieval inhibition of negative stimuli by related neutral stimuli. Non-clinically anxious undergraduates completed measures of trait and state anxiety and completed a retrieval induced forgetting task. Adaptive forgetting varied with state anxiety. Low levels of state anxiety were associated with no evidence for retrieval inhibition for either threatening or non-threatening categories. Participants in the middle tertile of state anxiety scores exhibited retrieval inhibition for non-threatening categories but not for threatening categories. Participants in the highest tertile of state anxiety, however, exhibited retrieval inhibition for both threatening and non-threatening categories with the magnitude of retrieval inhibition being greater for threatening than non-threatening categories. The data are in line with the avoidance aspect of the vigilance-avoidance theory of anxiety and inhibition. Implications for cognitive behavioural therapy practices are discussed.

  10. Inhibition of polyphenoloxidase by sulfite

    Sayavedra-Soto, L.A.; Montgomery, M.W.

    1986-01-01

    When polyphenoloxidase (PPO) was exposed to sulfite prior to substrate addition, inhibition was irreversible. Trials to regenerate PPO activity, using extensive dialysis, column chromatography, and addition of copper salts were not successful. Increased concentrations of sulfite and pH levels less than 5 enhanced the inhibition of PPO by sulfite. At pH 4, concentrations greater than 0.04 mg/mL completely inhibited 1000 units of PPO activity almost instantaneously. This suggested that the HSO 3 - molecule was the main component in the sulfite system inhibiting PPO. Column chromatography, extensive dialysis, and gel electrophoresis did not demonstrate 35 SO 2 bound to purified pear PPO protein. Formation of extra protein bands of sulfite inhibited purified pear PPO fractions on gel electrophoresis was demonstrated. This and other evidence suggested that the major mode of direct irreversible inhibition of PPO was modification of the protein structure, with retention of its molecular unity

  11. Efficacy and speed of onset of pain relief of fast-dissolving paracetamol on postsurgical dental pain: two randomized, single-dose, double-blind, placebo-controlled clinical studies.

    Yue, Yong; Collaku, Agron; Brown, Jean; Buchanan, William L; Reed, Kenneth; Cooper, Stephen A; Otto, James

    2013-09-01

    Paracetamol (APAP), also known as acetaminophen, is the most commonly used over-the-counter analgesic for the treatment of mild-to-moderate pain. However, the speed of onset of pain relief is limited mainly to the standard, immediate-release formulation. Efficacy and speed of onset of pain relief are critical in acute pain situations such as postsurgical dental pain, because reducing pain can improve clinical outcome and reduce the risk of transition from acute pain to more chronic pain. Efficacy and rapid onset also reduce the risk of excessive dosing with the analgesic. We sought to investigate the dose-response efficacy and speed of onset of pain relief of a fast-dissolving APAP formulation compared with lower doses of APAP and placebo in dental patients after impacted third molar extraction. Two single-center, single-dose, randomized, placebo-controlled, double-blind, double-dummy, parallel-group studies (Study I and Study II) were conducted to evaluate the efficacy and speed of onset of pain relief of different doses of a fast-dissolving APAP tablet (FD-APAP), standard APAP, and placebo in patients with postsurgical dental pain following third molar extraction. In Study I, a single dose of FD-APAP 1000 mg, FD-APAP 500 mg, or placebo was given to 300 patients; in Study II, a single dose of FD-APAP 1000 mg, standard APAP 650 mg, or placebo was given to 401 patients. All 701 patients from both studies were included in the analysis and safety assessment. FD-APAP 1000 mg demonstrated significantly greater effect compared with FD-APAP 500 mg, APAP 650 mg, and placebo for all efficacy measurements, including sum of pain relief and pain intensity difference, total pain relief, sum of pain intensity difference, pain intensity difference, and pain relief score during 6 hours after the dose. Onset of confirmed first perceptible relief in subjects treated with FD-APAP 1000 mg was 15 minutes, which was 32% and 25% significantly shorter than onset of pain relief of FD

  12. Modeling intentional inhibition of actions

    Thilakarathne, D.J.; Treur, J.

    2015-01-01

    Inspired by cognitive and neurological literature on action ownership and action awareness, in this paper a computational cognitive model for intentional inhibition (i.e.; the capacity to voluntarily suspend or inhibit an action) is introduced. The interplay between (positive) potential selection of

  13. Can Arousal Modulate Response Inhibition?

    Weinbach, Noam; Kalanthroff, Eyal; Avnit, Amir; Henik, Avishai

    2015-01-01

    The goal of the present study was to examine if and how arousal can modulate response inhibition. Two competing hypotheses can be drawn from previous literature. One holds that alerting cues that elevate arousal should result in an impulsive response and therefore impair response inhibition. The other suggests that alerting enhances processing of…

  14. Management of persistent postsurgical inguinal pain

    Werner, Mads U

    2014-01-01

    . Local anesthetic blocks, pharmacological management, and treatment with sensory stimulation methods were presented in seven studies. In spite of shortcomings, the data on surgical management demonstrate that neurectomy with or without mesh removal may provide long-lasting analgesic effects in most...... patients with severe PPP following inguinal hernia repair. The evidence base for other management methods is still fragile, although promising results appear in the neuromodulation studies. CONCLUSIONS: There is a need for improved study designs and, launching of large multicenter collaborative studies...

  15. Gastrointestinal Epithelial Organoid Cultures from Postsurgical Tissues.

    Hahn, Soojung; Yoo, Jongman

    2017-08-17

    An organoid is a cellular structure three-dimensionally (3D) cultured from self-organizing stem cells in vitro, which has a cell population, architectures, and organ specific functions like the originating organs. Recent advances in the 3D culture of isolated intestinal crypts or gastric glands have enabled the generation of human gastrointestinal epithelial organoids. Gastrointestinal organoids recapitulate the human in vivo physiology because of all the intestinal epithelial cell types that differentiated and proliferated from tissue resident stem cells. Thus far, gastrointestinal organoids have been extensively used for generating gastrointestinal disease models. This protocol describes the method of isolating a gland or crypt using stomach or colon tissue after surgery and establishing them into gastroids or colonoids.

  16. Persistent postsurgical pain: risk factors and prevention

    Kehlet, Henrik; Jensen, Troels Staehelin; Woolf, Clifford J.

    2006-01-01

    therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop...... chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk...

  17. Postsurgical telecobalt radiotherapy of mammary carcinomas

    Liebl, R.

    1980-01-01

    The first part of the study is a literature survey. The second part deals with patients and results of radiotherapy of the Klinik and Poliklinik fuer Radiologie der Universitaet Muenchen. The patients with mammary carcinomas, who were treated between 1960 and 1969 were classified according to the TNM classification or they were attributed to stage I or II or III. When the therapy was begun, the mean age of the patients was 55 years, 80% of the patients was between 40 and 60 years old, 45% of the patients were in stage I, 35% in stage II and almost 20% in stage III. (orig./MG) [de

  18. Selective inhibition of distracting input.

    Noonan, MaryAnn P; Crittenden, Ben M; Jensen, Ole; Stokes, Mark G

    2017-10-16

    We review a series of studies exploring distractor suppression. It is often assumed that preparatory distractor suppression is controlled via top-down mechanisms of attention akin to those that prepare brain areas for target enhancement. Here, we consider two alternative mechanisms: secondary inhibition and expectation suppression within a predictive coding framework. We draw on behavioural studies, evidence from neuroimaging and some animal studies. We conclude that there is very limited evidence for selective top-down control of preparatory inhibition. By contrast, we argue that distractor suppression often relies secondary inhibition of non-target items (relatively non-selective inhibition) and on statistical regularities of the environment, learned through direct experience. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  19. [Concepts of inhibition in psychiatry].

    Auroux, Y; Bourrat, M M; Brun, J P

    1978-01-01

    Following a historical approach, the authors first describe the original development of the concept of inhibition in neurophysiology and then analyze the subsequent adaptations made in psychiatry around such concept including those of: -- Pavlov, Hull, Watson and the behaviorists, -- Freud and the Freudian School, -- clinicians and psychopharmacologists. The concept of inhibition has thus various meanings in psychiatry. Although some unity is achieved on the semiological level, this aspect cannot explain the extent of the process.

  20. Inhibition of MMPs by alcohols

    Tezvergil-Mutluay, Arzu; Agee, Kelli A.; Hoshika, Tomohiro; Uchiyama, Toshikazu; Tjäderhane, Leo; Breschi, Lorenzo; Mazzoni, Annalisa; Thompson, Jeremy M.; McCracken, Courtney E.; Looney, Stephen W.; Tay, Franklin R.; Pashley, David H.

    2011-01-01

    Objectives While screening the activity of potential inhibitors of matrix metalloproteinases (MMPs), due to the limited water solubility of some of the compounds, they had to be solubilized in ethanol. When ethanol solvent controls were run, they were found to partially inhibit MMPs. Thus, the purpose of this study was to compare the MMP-inhibitory activity of a series of alcohols. Methods The possible inhibitory activity of a series of alcohols was measured against soluble rhMMP-9 and insoluble matrix-bound endogenous MMPs of dentin in completely demineralized dentin. Increasing concentrations (0.17, 0.86, 1.71 and 4.28 moles/L) of a homologous series of alcohols (i.e. methanol, ethanol, propanols, butanols, pentanols, hexanols, the ethanol ester of methacrylic acid, heptanols and octanol) were compared to ethanediol, and propanediol by regression analysis to calculate the molar concentration required to inhibit MMPs by 50% (i.e. the IC50). Results Using two different MMP models, alcohols were shown to inhibit rhMMP-9 and the endogenous proteases of dentin matrix in a dose-dependent manner. The degree of MMP inhibition by alcohols increased with chain length up to 4 methylene groups. Based on the molar concentration required to inhibit rhMMP-9 fifty percent, 2-hydroxyethylmethacrylate (HEMA), 3-hexanol, 3-heptanol and 1-octanol gave the strongest inhibition. Significance The results indicate that alcohols with 4 methylene groups inhibit MMPs more effectively than methanol or ethanol. MMP inhibition was inversely related to the Hoy's solubility parameter for hydrogen bonding forces of the alcohols (i.e. to their hydrophilicity). PMID:21676453

  1. Methanol Extract of Myelophycus caespitosus Inhibits the ...

    Methanol Extract of Myelophycus caespitosus Inhibits the Inflammatory Response in Lipopolysaccharidestimulated BV2 Microglial Cells by Downregulating NF-kB via Inhibition of the Akt Signaling Pathway.

  2. Long Noncoding RNA lncCAMTA1 Promotes Proliferation and Cancer Stem Cell-Like Properties of Liver Cancer by Inhibiting CAMTA1

    Li-Juan Ding

    2016-09-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common subtype of liver malignancy, and it is characterized by poor prognosis because of cancer stem cell (CSC-mediated high postsurgical recurrence rates. Thus, targeting CSCs, or HCC cells with CSC-like properties, is an effective strategy for HCC therapy. Here, using long noncoding RNA (lncRNA microarray analysis, we identified a novel lncRNA termed lncCAMTA1 that is increased in both liver CSCs and HCC. High lncCAMTA1 expression in HCC indicates poor clinical outcome. In vitro and in vivo functional experiments showed that overexpression of lncCAMTA1 promotes HCC cell proliferation, CSC-like properties, and tumorigenesis. Conversely, depletion of lncCAMTA1 inhibits HCC cell proliferation, CSC-like properties, and tumorigenesis. Mechanistically, we demonstrated that lncCAMTA1 physically associates with the calmodulin binding transcription activator 1 (CAMTA1 promoter, induces a repressive chromatin structure, and inhibits CAMTA1 transcription. Furthermore, CAMTA1 is required for the effects of lncCAMTA1 on HCC cell proliferation and CSC-like properties, and the expression of lncCAMTA1 and CAMTA1 is significantly negatively correlated in HCC tissues. Collectively, our study revealed the important roles and underlying molecular mechanisms of lncCAMTA1 on HCC, and suggested that lncCAMTA1 could be an effective prognostic factor and a potential therapeutic target for HCC.

  3. Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain

    Tillu Dipti V

    2012-01-01

    Full Text Available Abstract Background Despite advances in our understanding of basic mechanisms driving post-surgical pain, treating incision-induced pain remains a major clinical challenge. Moreover, surgery has been implicated as a major cause of chronic pain conditions. Hence, more efficacious treatments are needed to inhibit incision-induced pain and prevent the transition to chronic pain following surgery. We reasoned that activators of AMP-activated protein kinase (AMPK may represent a novel treatment avenue for the local treatment of incision-induced pain because AMPK activators inhibit ERK and mTOR signaling, two important pathways involved in the sensitization of peripheral nociceptors. Results To test this hypothesis we used a potent and efficacious activator of AMPK, resveratrol. Our results demonstrate that resveratrol profoundly inhibits ERK and mTOR signaling in sensory neurons in a time- and concentration-dependent fashion and that these effects are mediated by AMPK activation and independent of sirtuin activity. Interleukin-6 (IL-6 is thought to play an important role in incision-induced pain and resveratrol potently inhibited IL-6-mediated signaling to ERK in sensory neurons and blocked IL-6-mediated allodynia in vivo through a local mechanism of action. Using a model of incision-induced allodynia in mice, we further demonstrate that local injection of resveratrol around the surgical wound strongly attenuates incision-induced allodynia. Intraplantar IL-6 injection and plantar incision induces persistent nociceptive sensitization to PGE2 injection into the affected paw after the resolution of allodynia to the initial stimulus. We further show that resveratrol treatment at the time of IL-6 injection or plantar incision completely blocks the development of persistent nociceptive sensitization consistent with the blockade of a transition to a chronic pain state by resveratrol treatment. Conclusions These results highlight the importance of signaling

  4. Morbid obesity: postsurgical predictive factors and prioritization of the waiting list Obesidad mórbida: factores predictivos postquirúrgicos y priorización de la lista de espera

    F. Sabench Pereferrer

    2005-03-01

    Full Text Available Aim: to study a sample of patients with morbid obesity who are on the waiting list for a surgical intervention, to establish various scores of surgical risk (Possum and severity score, and to assess potential criteria for list prioritization. Design: we calculated physiological and surgical Possum scores for every patient, and analysed comorbidities and other associated factors to calculate the severity score. Likewise, we calculated the predictive rates of morbimortality. Differences between associated comorbidities in body mass index (BMI were also analyzed. The correlation between Possum score, prediction rates, and severity score were analyzed. Patients: fifty-two patients on the surgical waiting list in our institution (San Juan University Hospital, Reus from 26/4/02 to 5/03/04. Results: the mean qualitative score is significantly higher in the female sex. Invalidating arthropathy and socio-occupational and/or psychiatric criteria are significantly higher in women. There is a significant correlation between the severity score and Possum score. Age does not correlate with any of the variables studied. Conclusions: possum scores are significantly related to BMI, particularly in terms of morbidity rates. The degree of correlation between the Possum score and the qualitative score tells how useful the latter is to cover other determinant factors in the severity of this condition. Socio-occupational and psychiatric criteria, and invalidating arthropathy are the main variables to be taken into account for postsurgical prediction, and are directly related to BMI degree.Objetivo: estudio de una muestra de pacientes afectos de obesidad mórbida y en lista de espera para intervención quirúrgica, determinar el riesgo quirúrgico según diferentes scores (Possum y score de gravedad y valorar los posibles criterios en la priorización de dicha lista. Diseño: cálculo del Possum fisiológico y quirúrgico para cada paciente y análisis de las

  5. Homo economicus belief inhibits trust.

    Ziqiang Xin

    Full Text Available As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

  6. Homo Economicus Belief Inhibits Trust

    Xin, Ziqiang; Liu, Guofang

    2013-01-01

    As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners’ benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals’ homo economicus belief and inhibit their trust. It seems that people’s increasing homo economicus belief may serve as one cause of the worldwide decline of trust. PMID:24146907

  7. Inhibition of Retinoblastoma Protein Inactivation

    2017-11-01

    CONTRACT NUMBER Inhibition of Retinoblastoma Protein Inactivation 5b. GRANT NUMBER W81XWH-14-1-0329 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Seth M...confirmed 108 compounds as giving a dose-response curve with at least 30% inhibition at 10 µM. The flowchart of hit progression is shown on the...Cancer Research Program under Award No. W81XWH-14-1-0329 to S.M.R. Opinions, interpretations, conclusions, and recommendations are those of the author

  8. Metabolic Targeting of Lactate Efflux by Malignant Glioma Inhibits Invasiveness and Induces Necrosis: An In Vivo Study1

    Colen, Chaim B; Shen, Yimin; Ghoddoussi, Farhad; Yu, Pingyang; Francis, Todd B; Koch, Brandon J; Monterey, Michael D; Galloway, Matthew P; Sloan, Andrew E; Mathupala, Saroj P

    2011-01-01

    Glioblastoma multiforme (GBM) are the most malignant among brain tumors. They are frequently refractory to chemotherapy and radiotherapy with mean patient survival of approximately 6 months, despite surgical intervention. The highly glycolytic nature of glioblastomas describes their propensity to metabolize glucose to lactic acid at an elevated rate. To survive, GBMs efflux lactic acid to the tumor microenvironment through transmembrane transporters denoted monocarboxylate transporters (MCTs). We hypothesized that inhibition of MCT function would impair the glycolytic metabolism and affect both glioma invasiveness and survival. We examined the effect on invasiveness with α-cyano-4-hydroxy-cinnamic acid (ACCA, 4CIN, CHCA), a small-molecule inhibitor of lactate transport, through Matrigel-based and organotypic (brain) slice culture invasive assays using U87-MG and U251-MG glioma cells. We then conducted studies in immunodeficient rats by stereotaxic intracranial implantation of the glioma cells followed by programmed orthotopic application of ACCA through osmotic pumps. Effect on the implanted tumor was monitored by small-animal magnetic resonance imaging. Our assays indicated that glioma invasion was markedly impaired when lactate efflux was inhibited. Convection-enhanced delivery of inhibitor to the tumor bed caused tumor necrosis, with 50% of the animals surviving beyond the experimental end points (3 months after inhibitor exhaustion). Most importantly, control animals did not display any adverse neurologic effects during orthotopic administration of ACCA to brain through programmed delivery. These results indicate the clinical potential of targeting lactate efflux in glioma through delivery of small-molecule inhibitors of MCTs either to the tumor bed or to the postsurgical resection cavity. PMID:21750656

  9. Metabolic targeting of lactate efflux by malignant glioma inhibits invasiveness and induces necrosis: an in vivo study.

    Colen, Chaim B; Shen, Yimin; Ghoddoussi, Farhad; Yu, Pingyang; Francis, Todd B; Koch, Brandon J; Monterey, Michael D; Galloway, Matthew P; Sloan, Andrew E; Mathupala, Saroj P

    2011-07-01

    Glioblastoma multiforme (GBM) are the most malignant among brain tumors. They are frequently refractory to chemotherapy and radiotherapy with mean patient survival of approximately 6 months, despite surgical intervention. The highly glycolytic nature of glioblastomas describes their propensity to metabolize glucose to lactic acid at an elevated rate. To survive, GBMs efflux lactic acid to the tumor microenvironment through transmembrane transporters denoted monocarboxylate transporters (MCTs). We hypothesized that inhibition of MCT function would impair the glycolytic metabolism and affect both glioma invasiveness and survival. We examined the effect on invasiveness with α-cyano-4-hydroxy-cinnamic acid (ACCA, 4CIN, CHCA), a small-molecule inhibitor of lactate transport, through Matrigel-based and organotypic (brain) slice culture invasive assays using U87-MG and U251-MG glioma cells. We then conducted studies in immunodeficient rats by stereotaxic intracranial implantation of the glioma cells followed by programmed orthotopic application of ACCA through osmotic pumps. Effect on the implanted tumor was monitored by small-animal magnetic resonance imaging. Our assays indicated that glioma invasion was markedly impaired when lactate efflux was inhibited. Convection-enhanced delivery of inhibitor to the tumor bed caused tumor necrosis, with 50% of the animals surviving beyond the experimental end points (3 months after inhibitor exhaustion). Most importantly, control animals did not display any adverse neurologic effects during orthotopic administration of ACCA to brain through programmed delivery. These results indicate the clinical potential of targeting lactate efflux in glioma through delivery of small-molecule inhibitors of MCTs either to the tumor bed or to the postsurgical resection cavity.

  10. Metabolic Targeting of Lactate Efflux by Malignant Glioma Inhibits Invasiveness and Induces Necrosis: An In Vivo Study

    Chaim B Colen

    2011-07-01

    Full Text Available Glioblastoma multiforme (GBM are the most malignant among brain tumors. They are frequently refractory to chemotherapy and radiotherapy with mean patient survival of approximately 6 months, despite surgical intervention. The highly glycolytic nature of glioblastomas describes their propensity to metabolize glucose to lactic acid at an elevated rate. To survive, GBMs efflux lactic acid to the tumor microenvironment through transmembrane transporters denoted monocarboxylate transporters (MCTs. We hypothesized that inhibition of MCT function would impair the glycolytic metabolism and affect both glioma invasiveness and survival. We examined the effect on invasiveness with α-cyano-4-hydroxy-cinnamic acid (ACCA, 4CIN, CHCA, a small-molecule inhibitor of lactate transport, through Matrigel-based and organotypic (brain slice culture invasive assays using U87-MG and U251-MG glioma cells. We then conducted studies in immunodeficient rats by stereotaxic intracranial implantation of the glioma cells followed by programmed orthotopic application of ACCA through osmotic pumps. Effect on the implanted tumor was monitored by small-animal magnetic resonance imaging. Our assays indicated that glioma invasion was markedly impaired when lactate efflux was inhibited. Convection-enhanced delivery of inhibitor to the tumor bed caused tumor necrosis, with 50% of the animals surviving beyond the experimental end points (3 months after inhibitor exhaustion. Most importantly, control animals did not display any adverse neurologic effects during orthotopic administration of ACCA to brain through programmed delivery. These results indicate the clinical potential of targeting lactate efflux in glioma through delivery of small-molecule inhibitors of MCTs either to the tumor bed or to the postsurgical resection cavity.

  11. Is forgetting caused by inhibition?

    Raaijmakers, J.G.W.; Jakab, E.

    2013-01-01

    A well-known finding in memory research is the forgetting effect that occurs because of practicing some Item A on the recall of a related Item B. The traditional explanation for such interference effects is based on the notion of competition. According to the inhibition theory of forgetting,

  12. Testing of Biologically Inhibiting Surface

    Bill Madsen, Thomas; Larsen, Erup

    2003-01-01

    The main purpose of this course is to examine a newly developed biologically inhibiting material with regards to galvanic corrosion and electrochemical properties. More in detail, the concern was how the material would react when exposed to cleaning agents, here under CIP cleaning (Cleaning...

  13. Inhibiting cancer cell hallmark features through nuclear export inhibition.

    Sun, Qingxiang; Chen, Xueqin; Zhou, Qiao; Burstein, Ezra; Yang, Shengyong; Jia, Da

    2016-01-01

    Treating cancer through inhibition of nuclear export is one of the best examples of basic research translation into clinical application. Nuclear export factor chromosomal region maintenance 1 (CRM1; Xpo1 and exportin-1) controls cellular localization and function of numerous proteins that are critical for the development of many cancer hallmarks. The diverse actions of CRM1 are likely to explain the broad ranging anti-cancer potency of CRM1 inhibitors observed in pre-clinical studies and/or clinical trials (phase I-III) on both advanced-stage solid and hematological tumors. In this review, we compare and contrast the mechanisms of action of different CRM1 inhibitors, and discuss the potential benefit of unexplored non-covalent CRM1 inhibitors. This emerging field has uncovered that nuclear export inhibition is well poised as an attractive target towards low-toxicity broad-spectrum potent anti-cancer therapy.

  14. On inhibition of dental erosion.

    Rölla, Gunnar; Jonski, Grazyna; Saxegaard, Erik

    2013-11-01

    To examine the erosion-inhibiting effect of different concentrations of hydrofluoric acid. Thirty-six human molars were individually treated with 10 ml of 0.1 M citric acid for 30 min (Etch 1), acid was collected and stored until analysis. The teeth were randomly divided into six groups and then individually treated with 10 ml of one of six dilutions (from 0.1-1%) of hydrofluoric acid. The teeth were then again treated with citric acid (Etch 2). The individual acid samples from Etch 1 and 2 were analyzed for calcium by flame atomic absorption spectroscopy and difference in calcium loss was calculated. The highest erosion inhibiting effect was obtained in groups with the highest concentrations of hydrofluoric acid, where the pH was lowest, below pKa of 3.17, thus the hydrofluoric acids being mainly in an undissociated state. Diluted hydrofluoric acid is present in aqueous solution of SnF2 and TiF4 (which are known to inhibit dental erosion): SnF2 + 3H2O = Sn(OH)2 + 2HF + H2O and TiF4 + 5H2O = Ti(OH)4 + 4HF + H2O. It is also known that pure, diluted hydrofluoric acid can inhibit dental erosion. Teeth treated with hydrofluoric acid are covered by a layer of CaF2-like mineral. This mineral is acid resistant at pH acid resistant mineral, initiated by tooth enamel treatment with hydrofluoric acid. Hydrofluoric acid is different in having fluoride as a conjugated base, which provides this acid with unique properties.

  15. Entanglement and inhibited quantum evolution

    Toschek, P E; Balzer, Chr; Hannemann, Th; Wunderlich, Ch; Neuhauser, W

    2003-01-01

    The evolution of a quantum system is impeded by the system's state being observed. A test on an ensemble neither proves the causal nexus nor discloses the nature of the inhibition. Two recent experiments that make use of sequential optical or microwave-optical double resonance on an individual trapped ion disprove a dynamical effect of back action by meter or environment. They rather indicate the ionic states involved in the evolution being entangled with the potentially recorded bivalued scattered-light signal

  16. The potent, indirect adenosine monophosphate-activated protein kinase activator R419 attenuates mitogen-activated protein kinase signaling, inhibits nociceptor excitability, and reduces pain hypersensitivity in mice

    Galo L. Mejia

    2016-07-01

    Full Text Available Abstract. There is a great need for new therapeutics for the treatment of pain. A possible avenue to development of such therapeutics is to interfere with signaling pathways engaged in peripheral nociceptors that cause these neurons to become hyperexcitable. There is strong evidence that mitogen-activated protein kinases and phosphoinositide 3-kinase (PI3K/mechanistic target of rapamycin signaling pathways are key modulators of nociceptor excitability in vitro and in vivo. Activation of adenosine monophosphate-activated protein kinase (AMPK can inhibit signaling in both of these pathways, and AMPK activators have been shown to inhibit nociceptor excitability and pain hypersensitivity in rodents. R419 is one of, if not the most potent AMPK activator described to date. We tested whether R419 activates AMPK in dorsal root ganglion (DRG neurons and if this leads to decreased pain hypersensitivity in mice. We find that R419 activates AMPK in DRG neurons resulting in decreased mitogen-activated protein kinase signaling, decreased nascent protein synthesis, and enhanced P body formation. R419 attenuates nerve growth factor (NGF-induced changes in excitability in DRG neurons and blocks NGF-induced mechanical pain amplification in vivo. Moreover, locally applied R419 attenuates pain hypersensitivity in a model of postsurgical pain and blocks the development of hyperalgesic priming in response to both NGF and incision. We conclude that R419 is a promising lead candidate compound for the development of potent and specific AMPK activation to inhibit pain hypersensitivity as a result of injury.

  17. Inhibition Performance in Children with Math Disabilities

    Winegar, Kathryn Lileth

    2013-01-01

    This study examined the inhibition deficit hypothesis in children with math disabilities (MD). Children with and without MD were compared on two inhibition tasks that included the random generation of numbers and letters. The results addressed three hypotheses. Weak support was found for the first hypothesis which stated difficulties related to inhibition are significantly related to math performance. I found partial support for this hypothesis in that inhibition was related to math problem s...

  18. Entanglement and inhibited quantum evolution

    Toschek, P E; Balzer, Chr; Hannemann, Th; Wunderlich, Ch; Neuhauser, W [Universitaet Hamburg, Institut fuer Laser-Physik, Jungiusstrasse 9, D-20355 Hamburg (Germany)

    2003-03-14

    The evolution of a quantum system is impeded by the system's state being observed. A test on an ensemble neither proves the causal nexus nor discloses the nature of the inhibition. Two recent experiments that make use of sequential optical or microwave-optical double resonance on an individual trapped ion disprove a dynamical effect of back action by meter or environment. They rather indicate the ionic states involved in the evolution being entangled with the potentially recorded bivalued scattered-light signal.

  19. Behavioral inhibition and obsessive-compulsive disorder.

    Coles, Meredith E; Schofield, Casey A; Pietrefesa, Ashley S

    2006-01-01

    Behavioral inhibition is frequently cited as a vulnerability factor for development of anxiety. However, few studies have examined the unique relationship between behavioral inhibition and obsessive-compulsive disorder (OCD). Therefore, the current study addressed the relationship between behavioral inhibition and OCD in a number of ways. In a large unselected student sample, frequency of current OC symptoms was significantly correlated with retrospective self-reports of total levels of childhood behavioral inhibition. In addition, frequency of current OC symptoms was also significantly correlated with both social and nonsocial components of behavioral inhibition. Further, there was evidence for a unique relationship between behavioral inhibition and OC symptoms beyond the relationship of behavioral inhibition and social anxiety. In addition, results showed that reports of childhood levels of behavioral inhibition significantly predicted levels of OCD symptoms in adulthood. Finally, preliminary evidence suggested that behavioral inhibition may be more strongly associated with some types of OC symptoms than others, and that overprotective parenting may moderate the impact of behavioral inhibition on OC symptoms. The current findings suggest the utility of additional research examining the role of behavioral inhibition in the etiology of OCD.

  20. Self-regulation, ego depletion, and inhibition.

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Graphene: corrosion-inhibiting coating.

    Prasai, Dhiraj; Tuberquia, Juan Carlos; Harl, Robert R; Jennings, G Kane; Rogers, Bridget R; Bolotin, Kirill I

    2012-02-28

    We report the use of atomically thin layers of graphene as a protective coating that inhibits corrosion of underlying metals. Here, we employ electrochemical methods to study the corrosion inhibition of copper and nickel by either growing graphene on these metals, or by mechanically transferring multilayer graphene onto them. Cyclic voltammetry measurements reveal that the graphene coating effectively suppresses metal oxidation and oxygen reduction. Electrochemical impedance spectroscopy measurements suggest that while graphene itself is not damaged, the metal under it is corroded at cracks in the graphene film. Finally, we use Tafel analysis to quantify the corrosion rates of samples with and without graphene coatings. These results indicate that copper films coated with graphene grown via chemical vapor deposition are corroded 7 times slower in an aerated Na(2)SO(4) solution as compared to the corrosion rate of bare copper. Tafel analysis reveals that nickel with a multilayer graphene film grown on it corrodes 20 times slower while nickel surfaces coated with four layers of mechanically transferred graphene corrode 4 times slower than bare nickel. These findings establish graphene as the thinnest known corrosion-protecting coating.

  2. Action inhibition in Tourette syndrome.

    Ganos, Christos; Kühn, Simone; Kahl, Ursula; Schunke, Odette; Feldheim, Jan; Gerloff, Christian; Roessner, Veit; Bäumer, Tobias; Thomalla, Götz; Haggard, Patrick; Münchau, Alexander

    2014-10-01

    Tourette syndrome is a neuropsychiatric disorder characterized by tics. Tic generation is often linked to dysfunction of inhibitory brain networks. Some previous behavioral studies found deficiencies in inhibitory motor control in Tourette syndrome, but others suggested normal or even better-than-normal performance. Furthermore, neural correlates of action inhibition in these patients are poorly understood. We performed event-related functional magnetic resonance imaging during a stop-signal reaction-time task in 14 uncomplicated adult Tourette patients and 15 healthy controls. In patients, we correlated activations in stop-signal reaction-time task with their individual motor tic frequency. Task performance was similar in both groups. Activation of dorsal premotor cortex was stronger in the StopSuccess than in the Go condition in healthy controls. This pattern was reversed in Tourette patients. A significant positive correlation was present between motor tic frequency and activations in the supplementary motor area during StopSuccess versus Go in patients. Inhibitory brain networks differ between healthy controls and Tourette patients. In the latter the supplementary motor area is probably a key relay of inhibitory processes mediating both suppression of tics and inhibition of voluntary action. © 2014 International Parkinson and Movement Disorder Society.

  3. STIR: Assessing and Training Response Inhibition Abilities

    2014-07-30

    Learning to stop responding to alcohol cues reduces alcohol intake via reduced affective associations rather than increased response inhibition. Addiction ...requires an abstract application of the core learning principle1,2, and viable examples are often hard to find and/or assess. If exposure to non...inhibition training that expands upon previous successful “near transfer” response inhibition training efforts—such as treating alcohol addictions by

  4. Inhibition of cortiocosteroidogenesis by delta-9-tetrahydrocannabinol.

    Warner, W; Harris, L S; Carchman, R A

    1977-12-01

    ACTH, cholera toxin, cyclic AMP but not pregnenolone-induced steroidogenesis in Y-1 functional mouse adrenal tumor cells was significantly inhibited by delta-9-tetrahydrocannabinol, cannabidiol, and cannabinol. The inhibition of steroidogenesis could not be correlated with a general depression in cell function or viability. The data suggest that cannabinoids inhibit corticosteroidogenesis at a site between the synthesis of cAMP and of pregnenolone.

  5. Inhibition of apparent photosynthesis by nitrogen oxides

    Hill, A C; Bennett, J H

    1970-01-01

    The nitrogen oxides (NO/sub 2/ and NO) inhibited apparent photosynthesis of oats and alfalfa at concentrations below those required to cause visible injury. There appeared to be a threshold concentration of about 0.6 ppm for each pollutant. An additive effect in depressing apparent photosynthesis occurred when the plants were exposed to a mixture of NO and NO/sub 2/. Although NO produced a more rapid effect on the plants, lower concentrations of NO/sub 2/ were required to cause a given inhibition after 2 hour of exposure. Inhibition by nitric oxide was more closely related to its partial pressure than was inhibition by NO/sub 2/.

  6. Inhibition of photosynthesis by carbon monoxide and suspension of the carbon monoxide inhibition by light

    Gewitz, H S; Voelker, W

    1963-08-01

    The experimental subject was the autotroph Chlorella pyrenoidosa. It was found that growth conditions determine whether the alga is inhibited by carbon monoxide or not. Respiration and photosynthesis are inhibited by carbon monoxide if the cells have grown rapidly under high light intensities. The inhibition of respiration and photosynthesis found in such cells is completely reversible. The inhibition depends not only on carbon monoxide pressure, but also on the oxygen pressure prevailing at the same time. 5 references, 1 figure, 3 tables.

  7. 7-Piperazinethylchrysin inhibits melanoma cell proliferation by ...

    In B16F10 and A375 cells, treatment with PEC caused the inhibition ... Conclusion: PEC inhibited melanoma cell proliferation, apparently by blocking the cell cycle at G0/G1 .... all statistical analyses. .... Financial support from the Department of.

  8. A Qualitative Approach to Enzyme Inhibition

    Waldrop, Grover L.

    2009-01-01

    Most general biochemistry textbooks present enzyme inhibition by showing how the basic Michaelis-Menten parameters K[subscript m] and V[subscript max] are affected mathematically by a particular type of inhibitor. This approach, while mathematically rigorous, does not lend itself to understanding how inhibition patterns are used to determine the…

  9. Inhibition: Mental Control Process or Mental Resource?

    Im-Bolter, Nancie; Johnson, Janice; Ling, Daphne; Pascual-Leone, Juan

    2015-01-01

    The current study tested 2 models of inhibition in 45 children with language impairment and 45 children with normally developing language; children were aged 7 to 12 years. Of interest was whether a model of inhibition as a mental-control process (i.e., executive function) or as a mental resource would more accurately reflect the relations among…

  10. The pharmacology of visuospatial attention and inhibition

    Logemann, H.N.A.

    2013-01-01

    Attention and inhibition are of vital importance in everyday functioning. Problems of attention and inhibition are central to disorders such as Attention Deficit/Hyperactivity Disorder (ADHD). Both bias and disengagement key components of visuospatial attention. Bias refers to neuronal signals that

  11. Inhibition of ethylene production by cobaltous ion

    Lau, O.L; Yang, S.F.

    1976-01-01

    The effect of Co 2+ on ethylene production by mung bean (Phaseolus aureus Roxb.) and by apple tissues was studied. Co 2+ , depending on concentrations applied, effectively inhibited ethylene production by both tissues. It also strongly inhibited the ethylene production induced by IAA, kinetin, IAA plus kinetin, Ca 2+ , kinetin plus Ca 2+ , or Cu 2+ treatments in mung bean hypocotyl segments. While Co 2+ greatly inhibited ethylene production, it had little effect on the respiration of apple tissue, indicating that Co 2+ does not exert its inhibitory effect as a general metabolic inhibitor. Ni 2+ , which belongs to the same group as Co 2+ in the periodic table, also markedly curtailed both the basal and the induced ethylene production by apple and mung bean hypocotyl tissues. In a system in which kinetin and Ca 2+ were applied together, kinetin greatly enhanced Ca 2+ uptake, thus enhancing ethylene production. Co 2+ , however, slightly inhibited the uptake of Ca 2+ but appreciably inhibited ethylene production, either in the presence or in the absence of kinetin. Tracer experiments using apple tissue indicated that Co 2+ strongly inhibited the in vivo conversion of L-[U-- 14 C]methionine to 14 C-ethylene. These data suggested that Co 2+ inhibited ethylene production by inhibiting the conversion of methionine to ethylene, a common step which is required for ethylene formation by higher plants. Co 2+ is known to promote elongation, leaf expansion, and hook opening in excised plant parts in response to applied auxins or cytokinins.Since ethylene is known to inhibit those growth phenomena, it is suggested that Co 2+ exerts its promotive effect, at least in part, by inhibiting ethylene formation

  12. Lysophospholipase inhibition by organophosphorus toxicants

    Quistad, Gary B.; Casida, John E.

    2004-01-01

    Lysophospholipases (LysoPLAs) are a large family of enzymes for removing lysophospholipids from cell membranes. Potent inhibitors are needed to define the importance of LysoPLAs as targets for toxicants and potential therapeutics. This study considers organophosphorus (OP) inhibitors with emphasis on mouse brain total LysoPLA activity relative to the mipafox-sensitive neuropathy target esterase (NTE)-LysoPLA recently established as 17% of the total activity and important in the action of OP delayed toxicants. The most potent inhibitors of total LysoPLA in mouse brain are isopropyl dodecylphosphonofluoridate (also for LysoPLA of Vibrio bacteria), ethyl octylphosphonofluoridate (EOPF), and two alkyl-benzodioxaphosphorin 2-oxides (BDPOs)[(S)-octyl and dodecyl] (IC50 2-8 nM). OP inhibitors acting in vitro and in vivo differentiate a more sensitive portion but not a distinct NTE-LysoPLA compared with total LysoPLA activity. For 10 active inhibitors, NTE-LysoPLA is 17-fold more sensitive than total LysoPLA, but structure-activity comparisons give a good correlation (r 2 = 0.94) of IC50 values, suggesting active site structural similarity or identity. In mice 4 h after intraperitoneal treatment with discriminating doses, EOPF, tribufos (a plant defoliant), and dodecanesulfonyl fluoride inhibit 41-57% of the total brain LysoPLA and 85-99% of the NTE-LysoPLA activity. Total LysoPLA as well as NTE-LysoPLA is decreased in activity in Nte +/- -haploinsufficient mice compared to their Nte +/+ littermates. The lysolecithin level of spinal cord but not brain is elevated significantly following EOPF treatment (3 mg/kg), thereby focusing attention on localized rather than general alterations in lysophospholipid metabolism in OP-induced hyperactivity and toxicity

  13. Regulation of spatial selectivity by crossover inhibition.

    Cafaro, Jon; Rieke, Fred

    2013-04-10

    Signals throughout the nervous system diverge into parallel excitatory and inhibitory pathways that later converge on downstream neurons to control their spike output. Converging excitatory and inhibitory synaptic inputs can exhibit a variety of temporal relationships. A common motif is feedforward inhibition, in which an increase (decrease) in excitatory input precedes a corresponding increase (decrease) in inhibitory input. The delay of inhibitory input relative to excitatory input originates from an extra synapse in the circuit shaping inhibitory input. Another common motif is push-pull or "crossover" inhibition, in which increases (decreases) in excitatory input occur together with decreases (increases) in inhibitory input. Primate On midget ganglion cells receive primarily feedforward inhibition and On parasol cells receive primarily crossover inhibition; this difference provides an opportunity to study how each motif shapes the light responses of cell types that play a key role in visual perception. For full-field stimuli, feedforward inhibition abbreviated and attenuated responses of On midget cells, while crossover inhibition, though plentiful, had surprisingly little impact on the responses of On parasol cells. Spatially structured stimuli, however, could cause excitatory and inhibitory inputs to On parasol cells to increase together, adopting a temporal relation very much like that for feedforward inhibition. In this case, inhibitory inputs substantially abbreviated a cell's spike output. Thus inhibitory input shapes the temporal stimulus selectivity of both midget and parasol ganglion cells, but its impact on responses of parasol cells depends strongly on the spatial structure of the light inputs.

  14. Fear inhibition in high trait anxiety.

    Merel Kindt

    Full Text Available Trait anxiety is recognized as an individual risk factor for the development of anxiety disorders but the neurobiological mechanisms remain unknown. Here we test whether trait anxiety is associated with impaired fear inhibition utilizing the AX+/BX- conditional discrimination procedure that allows for the independent evaluation of startle fear potentiation and inhibition of fear. Sixty undergraduate students participated in the study--High Trait Anxious: n = 28 and Low Trait Anxious: n = 32. We replicated earlier findings that a transfer of conditioned inhibition for startle responses requires contingency awareness. However, contrary to the fear inhibition hypothesis, our data suggest that high trait anxious individuals show a normal fear inhibition of conditioned startle responding. Only at the cognitive level the high trait anxious individuals showed evidence for impaired inhibitory learning of the threat cue. Together with other findings where impaired fear inhibition was only observed in those PTSD patients who were either high on hyperarousal symptoms or with current anxiety symptoms, we question whether impaired fear inhibition is a biomarker for the development of anxiety disorders.

  15. Should we stop thinking about inhibition? Searching for individual and age differences in inhibition ability.

    Rey-Mermet, Alodie; Gade, Miriam; Oberauer, Klaus

    2018-04-01

    Inhibition is often conceptualized as a unitary construct reflecting the ability to ignore and suppress irrelevant information. At the same time, it has been subdivided into inhibition of prepotent responses (i.e., the ability to stop dominant responses) and resistance to distracter interference (i.e., the ability to ignore distracting information). The present study investigated the unity and diversity of inhibition as a psychometric construct, and tested the hypothesis of an inhibition deficit in older age. We measured inhibition in young and old adults with 11 established laboratory tasks: antisaccade, stop-signal, color Stroop, number Stroop, arrow flanker, letter flanker, Simon, global-local, positive and negative compatibility tasks, and n-2 repetition costs in task switching. In both age groups, the inhibition measures from individual tasks had good reliabilities, but correlated only weakly among each other. Structural equation modeling identified a 2-factor model with factors for inhibition of prepotent responses and resistance to distracter interference. Older adults scored worse in the inhibition of prepotent response, but better in the resistance to distracter interference. However, the model had low explanatory power. Together, these findings call into question inhibition as a psychometric construct and the hypothesis of an inhibition deficit in older age. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  16. Inhibition of urinary calculi -- a spectroscopic study

    Manciu, Felicia; Govani, Jayesh; Durrer, William; Reza, Layra; Pinales, Luis

    2008-10-01

    Although a considerable number of investigations have already been undertaken and many causes such as life habits, metabolic disorders, and genetic factors have been noted as sources that accelerate calculi depositions and aggregations, there are still plenty of unanswered questions regarding efficient inhibition and treatment mechanisms. Thus, in an attempt to acquire more insights, we propose here a detailed scientific study of kidney stone formation and growth inhibition based on a traditional medicine approach with Rotula Aquatica Lour (RAL) herbal extracts. A simplified single diffusion gel growth technique was used for synthesizing the samples for the present study. The unexpected Zn presence in the sample with RAL inhibitor, as revealed by XPS measurements, explains the inhibition process and the dramatic reflectance of the incident light observed in the infrared transmission studies. Raman data demonstrate potential binding of the inhibitor with the oxygen of the kidney stone. Photoluminescence results corroborate to provide additional evidence of Zn-related inhibition.

  17. Exogenously triggered response inhibition in developmental stuttering.

    Eggers, Kurt; De Nil, Luc F; Van den Bergh, Bea R H

    2018-06-01

    The purpose of the present study was to examine relations between children's exogenously triggered response inhibition and stuttering. Participants were 18 children who stutter (CWS; mean age = 9;01 years) and 18 children who not stutter (CWNS; mean age = 9;01 years). Participants were matched on age (±3 months) and gender. Response inhibition was assessed by a stop signal task (Verbruggen, Logan, & Stevens, 2008). Results suggest that CWS, compared to CWNS, perform comparable to CWNS in a task where response control is externally triggered. Our findings seem to indicate that previous questionnaire-based findings (Eggers, De Nil, & Van den Bergh, 2010) of a decreased efficiency of response inhibition cannot be generalized to all types of response inhibition. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Hypnotic suggestibility, cognitive inhibition, and dissociation.

    Dienes, Zoltán; Brown, Elizabeth; Hutton, Sam; Kirsch, Irving; Mazzoni, Giuliana; Wright, Daniel B

    2009-12-01

    We examined two potential correlates of hypnotic suggestibility: dissociation and cognitive inhibition. Dissociation is the foundation of two of the major theories of hypnosis and other theories commonly postulate that hypnotic responding is a result of attentional abilities (including inhibition). Participants were administered the Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C. Under the guise of an unrelated study, 180 of these participants also completed: a version of the Dissociative Experiences Scale that is normally distributed in non-clinical populations; a latent inhibition task, a spatial negative priming task, and a memory task designed to measure negative priming. The data ruled out even moderate correlations between hypnotic suggestibility and all the measures of dissociation and cognitive inhibition overall, though they also indicated gender differences. The results are a challenge for existing theories of hypnosis.

  19. Corrosion inhibition by lithium zinc phosphate pigment

    Alibakhshi, E.; Ghasemi, E.; Mahdavian, M.

    2013-01-01

    Highlights: •Synthesis of lithium zinc phosphate (LZP) by chemical co-precipitation method. •Corrosion inhibition activity of pigments compare with zinc phosphate (ZP). •LZP showed superior corrosion inhibition effect in EIS measurements. •Evaluation of adhesion strength and dispersion stability. -- Abstract: Lithium zinc phosphate (LZP) has been synthesized through a co-precipitation process and characterized by XRD and IR spectroscopy. The inhibitive performances of this pigment for corrosion of mild steel have been discussed in comparison with the zinc phosphate (ZP) in the pigment extract solution by means of EIS and in the epoxy coating by means of salt spray. The EIS and salt spray results revealed the superior corrosion inhibitive effect of LZP compared to ZP. Moreover, adhesion strength and dispersion stability of the pigmented epoxy coating showed the advantage of LZP compared to ZP

  20. Human milk glycoconjugates that inhibit pathogens.

    Newburg, D S

    1999-02-01

    Breast-fed infants have lower incidence of diarrhea, respiratory disease, and otitis media. The protection by human milk has long been attributed to the presence of secretory IgA. However, human milk contains large numbers and amounts of complex carbohydrates, including glycoproteins, glycolipids, glycosaminoglycans, mucins, and especially oligosaccharides. The oligosaccharides comprise the third most abundant solid constituent of human milk, and contain a myriad of structures. Complex carbohydrate moieties of glycoconjugates and oligosaccharides are synthesized by the many glycosyltransferases in the mammary gland; those with homology to cell surface glycoconjugate pathogen receptors may inhibit pathogen binding, thereby protecting the nursing infant. Several examples are reviewed: A fucosyloligosaccharide inhibits the diarrheagenic effect of stable toxin of Escherichia coli. A different fucosyloligosaccharide inhibits infection by Campylobacter jejuni. Binding of Streptococcus pneumoniae and of enteropathogenic E. coli to their respective receptors is inhibited by human milk oligosaccharides. The 46-kD glycoprotein, lactadherin, inhibits rotavirus binding and infectivity. Low levels of lactadherin in human milk are associated with a higher incidence of symptomatic rotavirus in breast-fed infants. A mannosylated glycopeptide inhibits binding by enterohemorrhagic E. coli. A glycosaminoglycan inhibits binding of gp120 to CD4, the first step in HIV infection. Human milk mucin inhibits binding by S-fimbriated E. coli. The ganglioside, GM1, reduces diarrhea production by cholera toxin and labile toxin of E. coli. The neutral glycosphingolipid, Gb3, binds to Shigatoxin. Thus, many complex carbohydrates of human milk may be novel antipathogenic agents, and the milk glycoconjugates and oligosaccharides may be a major source of protection for breastfeeding infants.

  1. Inhibition in the Human Auditory Cortex.

    Koji Inui

    Full Text Available Despite their indispensable roles in sensory processing, little is known about inhibitory interneurons in humans. Inhibitory postsynaptic potentials cannot be recorded non-invasively, at least in a pure form, in humans. We herein sought to clarify whether prepulse inhibition (PPI in the auditory cortex reflected inhibition via interneurons using magnetoencephalography. An abrupt increase in sound pressure by 10 dB in a continuous sound was used to evoke the test response, and PPI was observed by inserting a weak (5 dB increase for 1 ms prepulse. The time course of the inhibition evaluated by prepulses presented at 10-800 ms before the test stimulus showed at least two temporally distinct inhibitions peaking at approximately 20-60 and 600 ms that presumably reflected IPSPs by fast spiking, parvalbumin-positive cells and somatostatin-positive, Martinotti cells, respectively. In another experiment, we confirmed that the degree of the inhibition depended on the strength of the prepulse, but not on the amplitude of the prepulse-evoked cortical response, indicating that the prepulse-evoked excitatory response and prepulse-evoked inhibition reflected activation in two different pathways. Although many diseases such as schizophrenia may involve deficits in the inhibitory system, we do not have appropriate methods to evaluate them; therefore, the easy and non-invasive method described herein may be clinically useful.

  2. The acute-phase response and serum amyloid A inhibit the inflammatory response to Acinetobacter baumannii Pneumonia

    Renckens, Rosemarijn; Roelofs, Joris J. T. H.; Knapp, Sylvia; de Vos, Alex F.; Florquin, Sandrine; van der Poll, Tom

    2006-01-01

    BACKGROUND: Acinetobacter baumannii is an emerging pathogen in nosocomial pneumonia. Trauma and postsurgical patients display a profound acute-phase protein response and are susceptible to pneumonia. METHODS: To study the way in which the acute-phase response induced by sterile tissue injury

  3. Characterization of acetylcholinesterase-inhibition by itopride.

    Iwanaga, Y; Kimura, T; Miyashita, N; Morikawa, K; Nagata, O; Itoh, Z; Kondo, Y

    1994-11-01

    Itopride is a gastroprokinetic benzamide derivative. This agent inhibited both electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BuChE). The IC50 of itopride with AChE (2.04 +/- 0.27 microM) was, however, 100-fold less than that with BuChE, whereas in the case of neostigmine with AChE (11.3 +/- 3.4 nM), it was 10-fold less. The recovery of AChE activity inhibited by 10(-7) M neostigmine was partial, but that inhibited by up to 3 x 10(-5) M itopride was complete when the reaction mixture was subjected to ultrafiltration. Double reciprocal plots of the experimental data showed that both Km and Vmax were affected by itopride, suggesting that the inhibition is a "mixed" type, although primarily being an uncompetitive one. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE. However, in the presence of a low dose of diisopropyl fluorophosphate, just enough to inhibit BuChE but not AChE, the IC50s of itopride against ChE activities were found to be about 0.5 microM. In conclusion, itopride exerts reversible and a "mixed" type of inhibition preferably against AChE. The IC50 of itopride for electric eel and guinea pig gastrointestinal AChE inhibition was 200 times and 50 times as large as that of neostigmine, respectively.

  4. Aspartate inhibits Staphylococcus aureus biofilm formation.

    Yang, Hang; Wang, Mengyue; Yu, Junping; Wei, Hongping

    2015-04-01

    Biofilm formation renders Staphylococcus aureus highly resistant to conventional antibiotics and host defenses. Four D-amino acids (D-Leu, D-Met, D-Trp and D-Tyr) have been reported to be able to inhibit biofilm formation and disassemble established S. aureus biofilms. We report here for the first time that both D- and L-isoforms of aspartate (Asp) inhibited S. aureus biofilm formation on tissue culture plates. Similar biofilm inhibition effects were also observed against other staphylococcal strains, including S. saprophyticus, S. equorum, S. chromogenes and S. haemolyticus. It was found that Asp at high concentrations (>10 mM) inhibited the growth of planktonic N315 cells, but at subinhibitory concentrations decreased the cellular metabolic activity without influencing cell growth. The decreased cellular metabolic activity might be the reason for the production of less protein and DNA in the matrix of the biofilms formed in the presence of Asp. However, varied inhibition efficacies of Asp were observed for biofilms formed by clinical staphylococcal isolates. There might be mechanisms other than decreasing the metabolic activity, e.g. the biofilm phenotypes, affecting biofilm formation in the presence of Asp. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Simvastatin inhibits Candida albicans biofilm in vitro.

    Liu, Geoffrey; Vellucci, Vincent F; Kyc, Stephanie; Hostetter, Margaret K

    2009-12-01

    By inhibiting the conversion of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) to mevalonate, statins impair cholesterol metabolism in humans. We reasoned that statins might similarly interfere with the biosynthesis of ergosterol, the major sterol of the yeast cell membrane. As assessed by spectrophotometric and microscopic analysis, significant inhibition of biofilm production was noted after 16-h incubation with 1, 2.5, and 5 muM simvastatin, concentrations that did not affect growth, adhesion, or hyphal formation by C. albicans in vitro. Higher concentrations (10, 20, and 25 muM simvastatin) inhibited biofilm by >90% but also impaired growth. Addition of exogenous ergosterol (90 muM) overcame the effects of 1 and 2.5 muM simvastatin, suggesting that at least one mechanism of inhibition is interference with ergosterol biosynthesis. Clinical isolates from blood, skin, and mucosal surfaces produced biofilms; biofilms from bloodstream isolates were similarly inhibited by simvastatin. In the absence of fungicidal activity, simvastatin's interruption of a critical step in an essential metabolic pathway, highly conserved from yeast to man, has unexpected effects on biofilm production by a eukaryotic pathogen.

  6. Terbinafine inhibits gap junctional intercellular communication

    Lee, Ju Yeun; Yoon, Sei Mee; Choi, Eun Ju; Lee, Jinu

    2016-01-01

    Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca 2+ concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. - Highlights: • In vitro pharmacological studies were performed on FRT-Cx43 and LN215 cells. • Terbinafine inhibits gap junctional intercellular communication in both cell lines. • The inhibitory effect of terbinafine is reversible and dose-dependent. • Treatment of terbinafine does not alter Cx43 phosphorylation or cytosolic Ca 2+ concentration. • Inhibition of squalene epoxidase is not involved in this new effect of terbinafine.

  7. Terbinafine inhibits gap junctional intercellular communication

    Lee, Ju Yeun, E-mail: whitewndus@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Yoon, Sei Mee, E-mail: sei_mee@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Department of Integrated OMICS for Biomedical Sciences, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Choi, Eun Ju, E-mail: yureas@naver.com [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of); Lee, Jinu, E-mail: jinulee@yonsei.ac.kr [College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983 (Korea, Republic of)

    2016-09-15

    Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca{sup 2+} concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. - Highlights: • In vitro pharmacological studies were performed on FRT-Cx43 and LN215 cells. • Terbinafine inhibits gap junctional intercellular communication in both cell lines. • The inhibitory effect of terbinafine is reversible and dose-dependent. • Treatment of terbinafine does not alter Cx43 phosphorylation or cytosolic Ca{sup 2+} concentration. • Inhibition of squalene epoxidase is not involved in this new effect of terbinafine.

  8. Inhibition of ethylene production by putrescine alleviates aluminium-induced root inhibition in wheat plants.

    Yu, Yan; Jin, Chongwei; Sun, Chengliang; Wang, Jinghong; Ye, Yiquan; Zhou, Weiwei; Lu, Lingli; Lin, Xianyong

    2016-01-08

    Inhibition of root elongation is one of the most distinct symptoms of aluminium (Al) toxicity. Although putrescine (Put) has been identified as an important signaling molecule involved in Al tolerance, it is yet unknown how Put mitigates Al-induced root inhibition. Here, the possible mechanism was investigated by using two wheat genotypes differing in Al resistance: Al-tolerant Xi Aimai-1 and Al-sensitive Yangmai-5. Aluminium caused more root inhibition in Yangmai-5 and increased ethylene production at the root apices compared to Xi Aimai-1, whereas the effects were significantly reversed by ethylene biosynthesis inhibitors. The simultaneous exposure of wheat seedlings to Al and ethylene donor, ethephon, or ethylene biosynthesis precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), increased ethylene production and aggravated root inhibition, which was more pronounced in Xi Aimai-1. In contrast, Put treatment decreased ethylene production and alleviated Al-induced root inhibition in both genotypes, and the effects were more conspicuous in Yangmai-5. Furthermore, our results indicated that Al-induced ethylene production was mediated by ACC synthase (ACS) and ACC oxidase, and that Put decreased ethylene production by inhibiting ACS. Altogether, these findings indicate that ethylene is involved in Al-induced root inhibition and this process could be alleviated by Put through inhibiting ACS activity.

  9. Silver-Palladium Surfaces Inhibit Biofilm Formation

    Chiang, Wen-Chi; Schroll, Casper; Hilbert, Lisbeth Rischel

    2009-01-01

    Undesired biofilm formation is a major concern in many areas. In the present study, we investigated biofilm-inhibiting properties of a silver-palladium surface that kills bacteria by generating microelectric fields and electrochemical redox processes. For evaluation of the biofilm inhibition...... efficacy and study of the biofilm inhibition mechanism, the silver-sensitive Escherichia coli J53 and the silver-resistant E. coli J53[pMG101] strains were used as model organisms, and batch and flow chamber setups were used as model systems. In the case of the silver-sensitive strain, the silver......-palladium surfaces killed the bacteria and prevented biofilm formation under conditions of low or high bacterial load. In the case of the silver-resistant strain, the silver-palladium surfaces killed surface-associated bacteria and prevented biofilm formation under conditions of low bacterial load, whereas under...

  10. Inhibition of melanogenesis by Xanthium strumarium L.

    Li, Hailan; Min, Young Sil; Park, Kyoung-Chan; Kim, Dong-Seok

    2012-01-01

    Xanthium strumarium L. (Asteraceae) is traditionally used in Korea to treat skin diseases. In this study, we investigated the effects of a X. strumarium stem extract on melanin synthesis. It inhibited melanin synthesis in a concentration-dependent manner, but it did not directly inhibit tyrosinase, the rate-limiting melanogenic enzyme, and instead downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase expression. MITF, the master regulator of pigmentation, is a target of the Wnt signaling pathway, which includes glycogen synthase kinase 3β (GSK3β) and β-catenin. Hence, the influence of X. strumarium stem extract on GSK3β and β-catenin was further investigated. X. strumarium induced GSK3β phosphorylation (inactivation), but the level of β-catenin did not change. Moreover, a specific GSK3β inhibitor restored X. strumarium-induced melanin reduction. Hence, we suggest that X. strumarium inhibits melanin synthesis through downregulation of tyrosinase via GSK3β phosphorylation.

  11. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    Susan Skanderup Falkenberg

    2012-01-01

    Full Text Available 12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM and collagen- (2.0 μg/mL induced aggregations in human blood. These four species in respective extracts (in brackets were Blechnum chilense (MeOH, Luma apiculata (H2O, Amomyrtus luma (DCM : MeOH 1 : 1 and Cestrum parqui (DCM : MeOH 1 : 1. The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1, and L. apiculata (H2O were substantial and confirmed by inhibition of platelet surface activation markers.

  12. Distractor inhibition: Evidence from lateralized readiness potentials.

    Pramme, Lisa; Dierolf, Angelika M; Naumann, Ewald; Frings, Christian

    2015-08-01

    The present study investigated distractor inhibition on the level of stimulus representation. In a sequential distractor-to-distractor priming task participants had to respond to target letters flanked by distractor digits. Reaction time and stimulus-locked lateralized readiness potentials (S-LRPs) of probe responses were measured. Distractor-target onset asynchrony was varied. For RTs responses to probe targets were faster in the case of prime-distractor repetition compared to distractor changes indicating distractor inhibition. Benefits in RTs and the latency of S-LRP onsets for distractor repetition were also modulated by distractor-target onset asynchrony. For S-LRPs distractor inhibition was only present with a simultaneous onset of distractors and target. The results confirm previous results indicating inhibitory mechanisms of object-based selective attention on the level of distractor representations. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Terbinafine inhibits gap junctional intercellular communication.

    Lee, Ju Yeun; Yoon, Sei Mee; Choi, Eun Ju; Lee, Jinu

    2016-09-15

    Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca(2+) concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Inhibition of aluminum corrosion using Opuntia extract

    El-Etre, A.Y.

    2003-01-01

    The inhibitive action of the mucilage extracted from the modified stems of prickly pears, toward acid corrosion of aluminum, is tested using weight loss, thermometry, hydrogen evolution and polarization techniques. It was found that the extract acts as a good corrosion inhibitor for aluminum corrosion in 2.0 M HCl solution. The inhibition action of the extract was discussed in view of Langmuir adsorption isotherm. It was found that the adsorption of the extract on aluminum surface is a spontaneous process. The inhibition efficiency (IE) increases as the extract concentration is increased. The effect of temperature on the IE was studied. It was found that the presence of extract increases the activation energy of the corrosion reaction. Moreover, the thermodynamic parameters of the adsorption process were calculated. It was found also that the Opuntia extract provides a good protection to aluminum against pitting corrosion in chloride ion containing solutions

  15. Mapuche herbal medicine inhibits blood platelet aggregation.

    Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; Mølgaard, Per; Simonsen, Henrik Toft

    2012-01-01

    12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0 μM) and collagen- (2.0 μg/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H(2)O), Amomyrtus luma (DCM : MeOH 1 : 1) and Cestrum parqui (DCM : MeOH 1 : 1). The platelet aggregating inhibitory effects of A. luma (DCM : MeOH 1 : 1), and L. apiculata (H(2)O) were substantial and confirmed by inhibition of platelet surface activation markers.

  16. Inhibition of intestinal disaccharidase activity by pentoses

    Halschou-Jensen, Kia

    on carbohydrate- ingesting enzymes activity in vitro and possible effects on human postprandial blood response. In paper 1 the effects of sugar beet polyphenols from molasses and the potential inhibition of sucrase activity in vitro, was investigated. Two different polyphenol-rich fractions from chromatographic...... separation of molasses from sugar beets and pure ferulic acid were tested. We found no effects of the two fractions of molasses. The pure ferulic acid indicated an inhibition of sucrase in vitr. Both in vitro and in vivo studies have investigated the effects of L-arabinose and D-xylose on carbohydrate...

  17. Sprout inhibition in roots, tubers and bulbs

    Luna C, P.C.

    1992-05-01

    The treatment with ionizing radiations to low dose impedes that appear sprouts in the tubers (potatoes); bulbs (onion and garlic) and in roots like the ginger and the yucca. The purpose is to inhibit the germination during the process of manipulation and storage, and this way to avoid the lost ones post crop of these products. The radiation dose required to inhibit the germination goes to depend of: the development conditions, the differences of variety, of the storage state of the bulbs and the conditions of cured and storage. (Author)

  18. Mapuche Herbal Medicine Inhibits Blood Platelet Aggregation

    Falkenberg, Susan Skanderup; Tarnow, Inge; Guzman, Alfonso; Mølgaard, Per; Simonsen, Henrik Toft

    2012-01-01

    12 plant species traditionally used by the Mapuche people in Chile to treat wounds and inflammations have been evaluated for their direct blood platelet inhibition. Seven of the 12 tested plant species showed platelet inhibitory effect in sheep blood, and four of these were also able to inhibit the ADP- (5.0??M) and collagen- (2.0??g/mL) induced aggregations in human blood. These four species in respective extracts (in brackets) were Blechnum chilense (MeOH), Luma apiculata (H2O), Amomyrtus l...

  19. Peptide inhibition of human cytomegalovirus infection

    Morris Cindy A

    2011-02-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV is the most prevalent congenital viral infection in the United States and Europe causing significant morbidity and mortality to both mother and child. HCMV is also an opportunistic pathogen in immunocompromised individuals, including human immunodeficiency virus (HIV- infected patients with AIDS, and solid organ and allogeneic stem cell transplantation recipients. Current treatments for HCMV-associated diseases are insufficient due to the emergence of drug-induced resistance and cytotoxicity, necessitating novel approaches to limit HCMV infection. The aim of this study was to develop therapeutic peptides targeting glycoprotein B (gB, a major glycoprotein of HCMV that is highly conserved across the Herpesviridae family, that specifically inhibit fusion of the viral envelope with the host cell membrane preventing HCMV entry and infection. Results Using the Wimley-White Interfacial Hydrophobicity Scale (WWIHS, several regions within gB were identified that display a high potential to interact with lipid bilayers of cell membranes and hydrophobic surfaces within proteins. The ability of synthetic peptides analogous to WWIHS-positive sequences of HCMV gB to inhibit viral infectivity was evaluated. Human foreskin fibroblasts (HFF were infected with the Towne-GFP strain of HCMV (0.5 MOI, preincubated with peptides at a range of concentrations (78 nm to 100 μM, and GFP-positive cells were visualized 48 hours post-infection by fluorescence microscopy and analyzed quantitatively by flow cytometry. Peptides that inhibited HCMV infection demonstrated different inhibitory concentration curves indicating that each peptide possesses distinct biophysical properties. Peptide 174-200 showed 80% inhibition of viral infection at a concentration of 100 μM, and 51% and 62% inhibition at concentrations of 5 μM and 2.5 μM, respectively. Peptide 233-263 inhibited infection by 97% and 92% at concentrations of 100

  20. Inhibition of barley grain germination by light

    Roth-Bejerano, N.; Meulen, R.M. van der; Wang, M.

    1996-01-01

    Intact grains of barley (Hordeum distichum cv. Triumph) germinated rapidly in the dark or when exposed to brief daily light breaks in the temperature range 15-25°C, although germination proceeded less rapidly at low temperatures. Prolonged illumination (16 h/day) or continuous light inhibited

  1. Probenazole treatment inhibits anthocyanins biosynthesis via ...

    It has been found that anthocyanins were accumulated in Arabidopsis under drought or salt stress. In this study, such accumulation was found to be inhibited by external applied probenazole (3-allyloxy-1, 2-benzisothiazole-1,1-dioxide, PBZ), which is the active ingredient in oryzemate used for the protection of rice from ...

  2. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    Szkudlarek-Mikho, Maria; Saunders, Rudel A.; Yap, Sook Fan; Ngeow, Yun Fong; Chin, Khew-Voon

    2012-01-01

    Highlights: ► Salinomycin inhibits preadipocyte differentiation into adipocytes. ► Salinomycin inhibits transcriptional regulation of adipogenesis. ► Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  3. Illustrating Enzyme Inhibition Using Gibbs Energy Profiles

    Bearne, Stephen L.

    2012-01-01

    Gibbs energy profiles have great utility as teaching and learning tools because they present students with a visual representation of the energy changes that occur during enzyme catalysis. Unfortunately, most textbooks divorce discussions of traditional kinetic topics, such as enzyme inhibition, from discussions of these same topics in terms of…

  4. Microbial Metabolism and Inhibition Studies of Phenobarbital

    Erah

    techniques, high performance liquid chromatography (HPLC), mass spectrometry (MS) ... Keywords: Microbial metabolism, Phenobarbital, Inhibition studies, Rhizopus stolonifer, CYP 2C9, .... 24 h of incubation 0.5 ml of drug solution was ... mode, positive: spray voltage, 3.5 KV: ... Rhizopus stolonifer showed an extra peak at.

  5. Luteoloside Inhibits Proliferation of Human Chronic Myeloid ...

    Purpose: To investigate the effects of luteoloside on the proliferation of human chronic ..... Zhang N, Wang D, Zhu Y, Wang J, Lin H. Inhibition ... Han X. Protection of Luteolin-7-O-Glucoside Against ... Hwang YJ, Lee EJ, Kim HR, Hwang KA.

  6. Nickel Inhibits Mitochondrial Fatty Acid Oxidation

    Uppala, Radha; McKinney, Richard W.; Brant, Kelly A.; Fabisiak, James P.; Goetzman, Eric S.

    2015-01-01

    Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation—the pathway by which fatty acids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273

  7. Inhibiting Intuitive Thinking in Mathematics Education

    Thomas, Michael O. J.

    2015-01-01

    The papers in this issue describe recent collaborative research into the role of inhibition of intuitive thinking in mathematics education. This commentary reflects on this research from a mathematics education perspective and draws attention to some of the challenges that arise in collaboration between research fields with different cultures,…

  8. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    Szkudlarek-Mikho, Maria; Saunders, Rudel A. [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States); Yap, Sook Fan [Faculty of Medicine and Health Sciences, Department of Pre-Clinical Sciences, University of Tunku Abdul Rahman (Malaysia); Ngeow, Yun Fong [Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603 (Malaysia); Chin, Khew-Voon, E-mail: khew-voon.chin@utoledo.edu [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer Salinomycin inhibits preadipocyte differentiation into adipocytes. Black-Right-Pointing-Pointer Salinomycin inhibits transcriptional regulation of adipogenesis. Black-Right-Pointing-Pointer Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor {gamma}. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  9. Undecylenic Acid Inhibits Morphogenesis of Candida albicans

    McLain, Nealoo; Ascanio, Rhoda; Baker, Carol; Strohaver, Robert A.; Dolan, Joseph W.

    2000-01-01

    Resilient liners are frequently used to treat denture stomatitis, a condition often associated with Candida albicans infections. Of 10 liners tested, 2 were found to inhibit the switch from the yeast form to hyphae and a third was found to stimulate this switch. The inhibitor was determined to be undecylenic acid.

  10. Undecylenic acid inhibits morphogenesis of Candida albicans.

    McLain, N; Ascanio, R; Baker, C; Strohaver, R A; Dolan, J W

    2000-10-01

    Resilient liners are frequently used to treat denture stomatitis, a condition often associated with Candida albicans infections. Of 10 liners tested, 2 were found to inhibit the switch from the yeast form to hyphae and a third was found to stimulate this switch. The inhibitor was determined to be undecylenic acid.

  11. Cellulase Inhibition by High Concentrations of Monosaccharides

    Hsieh, Chia-Wen; Cannella, David; Jørgensen, Henning

    2014-01-01

    Biological degradation of biomass on an industrial scale culminates in high concentrations of end products. It is known that the accumulation of glucose and cellobiose, end products of hydrolysis, inhibit cellulases and decrease glucose yields. Aside from these end products, however, other monosa...

  12. Inhibiting Translation One Protein at a Time.

    Disney, Matthew D

    2017-06-01

    Historically, translational inhibitors have been confined to anti-bacterials that globally affect translation. Lintner et al. demonstrate that small molecules can specifically inhibit translation of a single disease-associated protein by stalling the ribosome's nascent chain [1], opening up a new therapeutic strategy for 'undruggable' proteins. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Polysulfonate suramin inhibits Zika virus infection.

    Tan, Chee Wah; Sam, I-Ching; Chong, Wei Lim; Lee, Vannajan Sanghiran; Chan, Yoke Fun

    2017-07-01

    Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log 10  PFU viral reduction with IC 50 value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Neural Synchrony during Response Production and Inhibition

    Müller, Viktor; Anokhin, Andrey P.

    2012-01-01

    Inhibition of irrelevant information (conflict monitoring) and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs) elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG) recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300–600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations. PMID:22745691

  15. WEE1 inhibition sensitizes osteosarcoma to radiotherapy

    PosthumaDeBoer, Jantine; Würdinger, Thomas; Graat, Harm CA; Beusechem, Victor W van; Helder, Marco N; Royen, Barend J van; Kaspers, Gertjan JL

    2011-01-01

    The use of radiotherapy in osteosarcoma (OS) is controversial due to its radioresistance. OS patients currently treated with radiotherapy generally are inoperable, have painful skeletal metastases, refuse surgery or have undergone an intralesional resection of the primary tumor. After irradiation-induced DNA damage, OS cells sustain a prolonged G 2 cell cycle checkpoint arrest allowing DNA repair and evasion of cell death. Inhibition of WEE1 kinase leads to abrogation of the G 2 arrest and could sensitize OS cells to irradiation induced cell death. WEE1 expression in OS was investigated by gene-expression data analysis and immunohistochemistry of tumor samples. WEE1 expression in OS cell lines and human osteoblasts was investigated by Western blot. The effect of WEE1 inhibition on the radiosensitivity of OS cells was assessed by cell viability and caspase activation analyses after combination treatment. The presence of DNA damage was visualized using immunofluorescence microscopy. Cell cycle effects were investigated by flow cytometry and WEE1 kinase regulation was analyzed by Western blot. WEE1 expression is found in the majority of tested OS tissue samples. Small molecule drug PD0166285 inhibits WEE1 kinase activity. In the presence of WEE1-inhibitor, irradiated cells fail to repair their damaged DNA, and show higher levels of caspase activation. The inhibition of WEE1 effectively abrogates the irradiation-induced G 2 arrest in OS cells, forcing the cells into premature, catastrophic mitosis, thus enhancing cell death after irradiation treatment. We show that PD0166285, a small molecule WEE1 kinase inhibitor, can abrogate the G 2 checkpoint in OS cells, pushing them into mitotic catastrophe and thus sensitizing OS cells to irradiation-induced cell death. This suggests that WEE1 inhibition may be a promising strategy to enhance the radiotherapy effect in patients with OS

  16. Neural synchrony during response production and inhibition.

    Viktor Müller

    Full Text Available Inhibition of irrelevant information (conflict monitoring and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300-600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations.

  17. Contrasting neural effects of aging on proactive and reactive response inhibition

    Bloemendaal, Mirjam; Zandbelt, Bram; Wegman, Joost; Rest, van de O.; Cools, Roshan; Aarts, Esther

    2016-01-01

    Two distinct forms of response inhibition may underlie observed deficits in response inhibition in aging. We assessed whether age-related neurocognitive impairments in response inhibition reflect deficient reactive inhibition (outright stopping) or also deficient proactive inhibition

  18. Mullerian Inhibiting Substances (MIS) Augments IFN-gamma Mediated Inhibition of Breast Cancer Cell Growth

    Gupta, Vandana

    2006-01-01

    MIS is a member of the TGF family. The purpose of this study is to test the hypothesis that MIS and IFN-gamma might be more effective in the inhibition of breast cancer cell growth than either agent alone...

  19. Mullerian Inhibiting Substance (MIS) Augments IFN-gamma Mediated Inhibition of Breast Cancer Cell Growth

    Gupta, Vandana

    2004-01-01

    Mullerian Inhibiting Substance (MIS), a member of the TGFB family regulates growth, differentiation, and apoptosis in many cell types In the male embryo, MIS causes regression of the Mullerian duct...

  20. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro

    Mahalingam, Sharada; Gao, Liying; Gonnering, Marni; Helferich, William; Flaws, Jodi A.

    2016-01-01

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24 h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. - Highlights: • Equol exposure inhibits antral follicle growth. • Equol exposure increases follicle atresia. • Equol exposure inhibits sex steroid hormone levels. • Equol exposure inhibits mRNA levels of certain steroidogenic enzymes.

  1. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro

    Mahalingam, Sharada, E-mail: mahalin2@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Gao, Liying, E-mail: lgao@uiuc.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Gonnering, Marni, E-mail: mgonne2@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Helferich, William, E-mail: helferic@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States)

    2016-03-15

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24 h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. - Highlights: • Equol exposure inhibits antral follicle growth. • Equol exposure increases follicle atresia. • Equol exposure inhibits sex steroid hormone levels. • Equol exposure inhibits mRNA levels of certain steroidogenic enzymes.

  2. Proactive modulation of long-interval intracortical inhibition during response inhibition

    Cowie, Matthew J.; MacDonald, Hayley J.; Cirillo, John

    2016-01-01

    Daily activities often require sudden cancellation of preplanned movement, termed response inhibition. When only a subcomponent of a whole response must be suppressed (required here on Partial trials), the ensuing component is markedly delayed. The neural mechanisms underlying partial response inhibition remain unclear. We hypothesized that Partial trials would be associated with nonselective corticomotor suppression and that GABAB receptor-mediated inhibition within primary motor cortex might be responsible for the nonselective corticomotor suppression contributing to Partial trial response delays. Sixteen right-handed participants performed a bimanual anticipatory response inhibition task while single- and paired-pulse transcranial magnetic stimulation was delivered to elicit motor evoked potentials in the left first dorsal interosseous muscle. Lift times, amplitude of motor evoked potentials, and long-interval intracortical inhibition were examined across the different trial types (Go, Stop-Left, Stop-Right, Stop-Both). Go trials produced a tight distribution of lift times around the target, whereas those during Partial trials (Stop-Left and Stop-Right) were substantially delayed. The modulation of motor evoked potential amplitude during Stop-Right trials reflected anticipation, suppression, and subsequent reinitiation of movement. Importantly, suppression was present across all Stop trial types, indicative of a “default” nonselective inhibitory process. Compared with blocks containing only Go trials, inhibition increased when Stop trials were introduced but did not differ between trial types. The amount of inhibition was positively correlated with lift times during Stop-Right trials. Tonic levels of inhibition appear to be proactively modulated by task context and influence the speed at which unimanual responses occur after a nonselective “brake” is applied. PMID:27281744

  3. Surgical exclusion of postsurgical pseudoaneurysm of the ascending aorta

    Barik, Ramachandra; Patnaik, Amar Narayana; Kumar, Ravintula Venkata; Mohapatra, Rudra Prasad; Medep, Vikas; Nemani, Lalita

    2014-01-01

    Pseudoaneurysm of ascending aorta after cardiac surgery is rare in children. We report a case of successful surgical exclusion of ascending aortic pseudoaneurysm in a 15-year-old boy. The neck of the aneurysm was in close proximity to the right coronary artery (RCA). PMID:24987261

  4. Surgical exclusion of postsurgical pseudoaneurysm of the ascending aorta

    Barik, Ramachandra; Patnaik, Amar Narayana [Department of Cardiology, Nizam' s Institute of Medical Sciences, Hyderabad, Andhra Pradesh (India); Kumar, Ravintula Venkata; Mohapatra, Rudra Prasad [Department of Cardiothoracic Surgery, Nizam' s Institute of Medical Sciences, Hyderabad, Andhra Pradesh (India); Medep, Vikas; Nemani, Lalita [Department of Cardiology, Nizam' s Institute of Medical Sciences, Hyderabad, Andhra Pradesh (India)

    2014-01-01

    Pseudoaneurysm of ascending aorta after cardiac surgery is rare in children. We report a case of successful surgical exclusion of ascending aortic pseudoaneurysm in a 15-year-old boy. The neck of the aneurysm was in close proximity to the right coronary artery (RCA)

  5. Surgical exclusion of postsurgical pseudoaneurysm of the ascending aorta

    Ramachandra Barik

    2014-01-01

    Full Text Available Pseudoaneurysm of ascending aorta after cardiac surgery is rare in children. We report a case of successful surgical exclusion of ascending aortic pseudoaneurysm in a 15-year-old boy. The neck of the aneurysm was in close proximity to the right coronary artery (RCA.

  6. Postsurgical Disfigurement Influences Disgust Recognition: A Case-Control Study.

    Lisan, Quentin; George, Nathalie; Hans, Stephane; Laccourreye, Ollivier; Lemogne, Cédric

    Little is known about how emotion recognition may be modified in individuals prone to elicit disgust. We sought to determine if subjects with total laryngectomy would present a modified recognition of facial expressions of disgust. A total of 29 patients presenting with a history of advanced-stage laryngeal cancer were recruited, 17 being surgically treated (total laryngectomy) and 12 treated with chemoradiation therapy only. Based on a validated set of images of facial expressions of fear, disgust, surprise, happiness, sadness and anger displayed by 6 actors, we presented participants with expressions of each emotion at 5 levels of increasing intensity and measured their ability to recognize these emotions. Participants with (vs without) laryngectomy showed a higher threshold for the recognition of disgust (3.2. vs 2.7 images needed before emotion recognition, p = 0.03) and a lower success rate of correct recognition (75.5% vs 88.9%, p = 0.03). Subjects presenting with an aesthetic impairment of the head and neck showed poorer performance in disgust recognition when compared with those without disfigurement. These findings might relate either to some perceptual adaptation, habituation phenomenon, or to some higher-level processes related to emotion regulation strategies. Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. A role for the fibrinolytic system in postsurgical adhesion formation

    Hellebrekers, Bart W. J.; Emeis, Jef J.; Kooistra, Teake; Trimbos, J. Baptist; Moore, Norma R.; Zwinderman, Koos H.; Trimbos-Kemper, Trudy C. M.

    2005-01-01

    To look for evidence of a fibrinolytic insufficiency as a cause of adhesion formation. Retrospective and prospective study. University medical center. Retrospective study: 50 patients undergoing laparoscopy, divided into patients with and without endometriosis. Prospective study: 18 patients

  8. Novel Split Chest Tube Improves Post-Surgical Thoracic Drainage

    Olivencia-Yurvati, Albert H; Cherry, Brandon H; Gurji, Hunaid A; White, Daniel W; Newton, J Tyler; Scott, Gary F; Hoxha, Besim; Gourlay, Terence; Mallet, Robert T

    2014-01-01

    Objective Conventional, separate mediastinal and pleural tubes are often inefficient at draining thoracic effusions. Description We developed a Y-shaped chest tube with split ends that divide within the thoracic cavity, permitting separate intrathoracic placement and requiring a single exit port. In this study, thoracic drainage by the split drain vs. that of separate drains was tested. Methods After sternotomy, pericardiotomy, and left pleurotomy, pigs were fitted with separate chest drains (n=10) or a split tube prototype (n=9) with internal openings positioned in the mediastinum and in the costo-diaphragmatic recess. Separate series of experiments were conducted to test drainage of D5W or 0.58 M sucrose, an aqueous solution with viscosity approximating that of plasma. One litre of fluid was infused into the thorax, and suction was applied at −20 cm H2O for 30 min. Results When D5W was infused, the split drain left a residual volume of 53 ± 99 ml (mean value ± SD) vs. 148 ± 120 for the separate drain (P=0.007), representing a drainage efficiency (i.e. drained vol/[drained + residual vol]) of 95 ± 10% vs. 86 ± 12% for the separate drains (P = 0.011). In the second series, the split drain evacuated more 0.58 M sucrose in the first minute (967 ± 129 ml) than the separate drains (680 ± 192 ml, Pdrain evacuated a similar volume of sucrose vs. the conventional drain (1089 ± 72 vs. 1056 ± 78 ml; P = 0.5). Residual volume tended to be lower (25 ± 10 vs. 62 ± 72 ml; P = 0.128) and drainage efficiency tended to be higher (98 ± 1 vs. 95 ± 6%; P = 0.111) with the split drain vs. conventional separate drains. Conclusion The split chest tube drained the thoracic cavity at least as effectively as conventional separate tubes. This new device could potentially alleviate postoperative complications. PMID:25478289

  9. Post-surgical rehabilitative approach to fragility fractures.

    Gimigliano, F; Iolascon, G; Riccio, I; Frizzi, L; Gimigliano, R

    2013-10-01

    Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. The most frequent sites of fragility fractures are the hip, the distal radius, the spine, the proximal humerus, and the ankle. In most cases, a surgical approach with subsequent rehabilitative treatment is required. The general aims of rehabilitation are to increase functioning and improve patients' activities, participation level, and quality of life.

  10. Dysphagia and laryngeal pathology in post-surgical cardiothoracic patients.

    Miles, Anna; McLellan, Naomi; Machan, Rochelle; Vokes, David; Hunting, Alexandra; McFarlane, Mary; Holmes, Jennifer; Lynn, Kelly

    2018-02-09

    Cardiothoracic surgery is known to result in dysphagia and laryngeal injury. While prevalence has been explored, extent, trajectory and longevity of symptoms are poorly understood. This retrospective, observational study explored dysphagia and laryngeal injury in patients following cardiothoracic surgery referred for instrumental swallowing assessment. Clinical notes and endoscopic recordings of 106 patients (age range 18-87yrs; mean 63yrs; SD 15yrs) (including 190 endoscopes) at one large tertiary centre were reviewed by two speech-language pathologists and a laryngologist. Standardized measures of laryngeal anatomy and physiology, New Zealand Secretion Scale, Penetration-Aspiration scale and Yale Residue Scale were rated. Prevalence of abnormality included 39% silent aspiration, 65% laryngeal edema and 61% vocal paralysis. The incidence of pneumonia was 36% with a post-operative stroke rate of 14%. Forty percent of patients were receiving a standard diet by discharge from acute care; while, 24% continued to require enteral feeding and 8% received laryngeal surgery within twelve months of discharge. Vocal fold motion impairment was significantly associated with ventilation time and tracheostomy tube duration (pdysphagia and laryngeal injury in patients following cardiothoracic surgery may allow early management and prevention of secondary complications. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Post-surgical management of pontine hemorrhage with Ayurvedic treatment

    Areekkat Manojkumar

    2013-01-01

    Full Text Available A female aged 30 years, consulted the Govt. Ayurveda Hospital, Perinthalmanna with complaints of left side of the body totally paralysed along with severe shivering of the right hand and head and the patient was bedridden for 1½ years. She was diagnosed earlier with spontaneous pontine hematoma (on 10 th Nov 2007 and had undergone midline sub occipital craniectomy (on 13 th Nov 2007 as an emergency treatment. She developed neurotrophic ulcer in the right eye with lagophthalmos post-surgery. The patient showed no improvement to treatment but further developed stromal abscess and hence paramedian tarsorraphy (4 th Jan 2008 was done. The deficits in the right eye led to diminution of vision of that eye after Allopathy treatment. The patient sought Ayurvedic treatment for a better prognosis. The patient was under Ayurvedic treatment from 5 th Mar 2009 to 24 th Nov 2009. During that period Ayurvedic treatment such as abhyaṅga (oil massage, patra poṭṭalī sveda (use of poultices and mṛdu virecana (purgation was also done. After a period of 8 months of internal medication and treatment, the shivering of the right hand and head resolved. She could move the left leg and left hand and started walking without support. There was gradual loss of vision during the course of Ayurvedic treatment. At present, the patient is able to move around and do household works on her own.

  12. [Postsurgical chylous ascites: case report and literature review].

    Olivar Roldán, J; Fernández Martínez, A; Martínez Sancho, E; Díaz Gómez, J; Martín Borge, V; Gómez Candela, C

    2009-01-01

    Chylous ascites derives from chyle leakage into the peritoneal cavity, either due to rupture or obstruction of abdominal lymphatic vessels. The main clinical sign is abdominal distention, while diagnosis requires the presence of triglycerides in ascitic fluid. Neoplasms are the most common cause of chylous ascites, although less common causes, such as abdominal surgery, should also be considered. The mainstay of therapy is hyperproteic diet with fat restriction and middle-chain triglycerides. Parenteral nutrition is reserved for cases in which dietary treatment fails to restore an optimal nutritional status or is contraindicated, whereas surgery is considered for patients that are deemed refractory to conservative therapy. We present a case of chylous ascites secondary to retroperitoneal lymphadenectomy.

  13. The unerupted maxillary canine - a post-surgical review.

    O'Dowling, Ian

    2009-10-01

    The orthodontic records of 685 patients referred for surgical exposure of an unerupted impacted maxillary canine tooth were examined. The condition was more common among females than males, slightly less than 2:1. The impacted teeth had a palatal-labial ratio of 3:1. All of the teeth were exposed using the open surgical technique and in 98% of cases the tooth erupted and was orthodontically aligned. In 2% of cases ankylosis occurred and the teeth were subsequently extracted. The presence of peg-shaped lateral incisors associated with the impacted maxillary canine tooth was 3.4% of the total number of impacted teeth and congenital absence was found in 1.7% of impacted teeth.

  14. Pre- and Postsurgical Orthodontics in Patients with Moebius Syndrome

    Marisabel Magnifico

    2017-01-01

    Full Text Available The authors report a combined orthodontic-surgical correction of an adult patient’s malocclusion affected by Moebius Syndrome (MS. The treatment was conducted at the Dentistry Unit and the Maxillofacial Surgery Unit of the University Hospital of Parma. Treatment of malocclusion was performed after the correction of facial mimic mobility with smile surgery. The postoperative stability and orthodontic results were good and the correction of the morphological problems related to the syndrome was very satisfactory.

  15. Imaging findings of liposuction with an emphasis on postsurgical complications

    You, Je Sung; Chung, Sung Phil; Kim, Myeong Jin [Dept. of mergency Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chung, Yong Eun; Baek, Song Ee [Dept. of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-12-15

    Liposuction is one of the most frequently performed cosmetic surgeries worldwide for reshaping the body contour. Although liposuction is minimally invasive and relatively safe, it is a surgical procedure, and it carries the risk of major and minor complications. These complications vary from postoperative nausea to life-threatening events. Common complications include infection, abdominal wall injury, bowel herniation, bleeding, haematoma, seroma, and lymphoedema. Life-threatening complications such as necrotizing fasciitis, deep vein thrombosis, and pulmonary embolism have also been reported. In this paper, we provide a brief introduction to liposuction with the related anatomy and present computed tomography and ultrasonography findings of a wide spectrum of postoperative complications associated with liposuction.

  16. The unerupted maxillary canine--a post-surgical review.

    O'Dowling, Ian

    2009-01-01

    The orthodontic records of 685 patients referred for surgical exposure of an unerupted impacted maxillary canine tooth were examined. The condition was more common among females than males, slightly less than 2:1. The impacted teeth had a palatal-labial ratio of 3:1. All of the teeth were exposed using the open surgical technique and in 98% of cases the tooth erupted and was orthodontically aligned. In 2% of cases ankylosis occurred and the teeth were subsequently extracted. The presence of peg-shaped lateral incisors associated with the impacted maxillary canine tooth was 3.4% of the total number of impacted teeth and congenital absence was found in 1.7% of impacted teeth.

  17. Novel Split Chest Tube Improves Post-Surgical Thoracic Drainage.

    Olivencia-Yurvati, Albert H; Cherry, Brandon H; Gurji, Hunaid A; White, Daniel W; Newton, J Tyler; Scott, Gary F; Hoxha, Besim; Gourlay, Terence; Mallet, Robert T

    2014-01-01

    Conventional, separate mediastinal and pleural tubes are often inefficient at draining thoracic effusions. We developed a Y-shaped chest tube with split ends that divide within the thoracic cavity, permitting separate intrathoracic placement and requiring a single exit port. In this study, thoracic drainage by the split drain vs. that of separate drains was tested. After sternotomy, pericardiotomy, and left pleurotomy, pigs were fitted with separate chest drains (n=10) or a split tube prototype (n=9) with internal openings positioned in the mediastinum and in the costo-diaphragmatic recess. Separate series of experiments were conducted to test drainage of D5W or 0.58 M sucrose, an aqueous solution with viscosity approximating that of plasma. One litre of fluid was infused into the thorax, and suction was applied at -20 cm H2O for 30 min. When D5W was infused, the split drain left a residual volume of 53 ± 99 ml (mean value ± SD) vs. 148 ± 120 for the separate drain (P=0.007), representing a drainage efficiency (i.e. drained vol/[drained + residual vol]) of 95 ± 10% vs. 86 ± 12% for the separate drains (P = 0.011). In the second series, the split drain evacuated more 0.58 M sucrose in the first minute (967 ± 129 ml) than the separate drains (680 ± 192 ml, Pdrain evacuated a similar volume of sucrose vs. the conventional drain (1089 ± 72 vs. 1056 ± 78 ml; P = 0.5). Residual volume tended to be lower (25 ± 10 vs. 62 ± 72 ml; P = 0.128) and drainage efficiency tended to be higher (98 ± 1 vs. 95 ± 6%; P = 0.111) with the split drain vs. conventional separate drains. The split chest tube drained the thoracic cavity at least as effectively as conventional separate tubes. This new device could potentially alleviate postoperative complications.

  18. Inhibition of COX1/2 alters the host response and reduces ECM scaffold mediated constructive tissue remodeling in a rodent model of skeletal muscle injury.

    Dearth, Christopher L; Slivka, Peter F; Stewart, Scott A; Keane, Timothy J; Tay, Justin K; Londono, Ricardo; Goh, Qingnian; Pizza, Francis X; Badylak, Stephen F

    2016-02-01

    Extracellular matrix (ECM) has been used as a biologic scaffold material to both reinforce the surgical repair of soft tissue and serve as an inductive template to promote a constructive tissue remodeling response. Success of such an approach is dependent on macrophage-mediated degradation and remodeling of the biologic scaffold. Macrophage phenotype during these processes is a predictive factor of the eventual remodeling outcome. ECM scaffolds have been shown to promote an anti-inflammatory or M2-like macrophage phenotype in vitro that includes secretion of downstream products of cycolooxygenases 1 and 2 (COX1/2). The present study investigated the effect of a common COX1/2 inhibitor (Aspirin) on macrophage phenotype and tissue remodeling in a rodent model of ECM scaffold treated skeletal muscle injury. Inhibition of COX1/2 reduced the constructive remodeling response by hindering myogenesis and collagen deposition in the defect area. The inhibited response was correlated with a reduction in M2-like macrophages in the defect area. The effects of Aspirin on macrophage phenotype were corroborated using an established in vitro macrophage model which showed a reduction in both ECM induced prostaglandin secretion and expression of a marker of M2-like macrophages (CD206). These results raise questions regarding the common peri-surgical administration of COX1/2 inhibitors when biologic scaffold materials are used to facilitate muscle repair/regeneration. COX1/2 inhibitors such as nonsteroidal anti-inflammatory drugs (NSAIDs) are routinely administered post-surgically for analgesic purposes. While COX1/2 inhibitors are important in pain management, they have also been shown to delay or diminish the healing process, which calls to question their clinical use for treating musculotendinous injuries. The present study aimed to investigate the influence of a common NSAID, Aspirin, on the constructive remodeling response mediated by an ECM scaffold (UBM) in a rat skeletal

  19. Cell Cycle Inhibition To Treat Sleeping Sickness

    Conrad L. Epting

    2017-09-01

    Full Text Available African trypanosomiasis is caused by infection with the protozoan parasite Trypanosoma brucei. During infection, this pathogen divides rapidly to high density in the bloodstream of its mammalian host in a manner similar to that of leukemia. Like all eukaryotes, T. brucei has a cell cycle involving the de novo synthesis of DNA regulated by ribonucleotide reductase (RNR, which catalyzes the conversion of ribonucleotides into their deoxy form. As an essential enzyme for the cell cycle, RNR is a common target for cancer chemotherapy. We hypothesized that inhibition of RNR by genetic or pharmacological means would impair parasite growth in vitro and prolong the survival of infected animals. Our results demonstrate that RNR inhibition is highly effective in suppressing parasite growth both in vitro and in vivo. These results support drug discovery efforts targeting the cell cycle, not only for African trypanosomiasis but possibly also for other infections by eukaryotic pathogens.

  20. Product inhibition of five Hypocrea jecorina cellulases

    Murphy, Leigh; Westh, Peter; Bohlin, Christina

    2013-01-01

    Product inhibition of cellulolytic enzymes has been deemed a critical factor in the industrial saccharification of cellulosic biomass. Several investigations have addressed this problem using crude enzyme preparations or commercial (mixed) cellulase products, but quantitative information...... on individual cellulases hydrolyzing insoluble cellulose remains insufficient. Such knowledge is necessary to pinpoint and quantify inhibitory weak-links in cellulose hydrolysis, but has proven challenging to come by. Here we show that product inhibition of mono-component cellulases hydrolyzing unmodified...... cellulose may be monitored by calorimetry. The key advantage of this approach is that it directly measures the rate of hydrolysis while being essentially blind to the background of added product. We investigated the five major cellulases from Hypocrea jecorina (anamorph: Tricoderma reesei), Cel7A (formerly...

  1. How x rays inhibit amphibian limb regeneration

    Maden, M.; Wallace, H.

    1976-01-01

    The effects of an inhibiting dose of 2,000 rad of x-rays on the regenerating limbs of axolotl larvae have been examined in a histological and cytological study. Particular attention was paid to the mitotic indices of normal and irradiated epidermal and blastemal cells. Both the characteristic pattern of epidermal mitotic stimulation which normally follows amputation and the later increase in blastemal mitoses are suppressed by irradiation. In most cells the effects are permanent, but in a small proportion a mitotic delay is induced and upon subsequent division chromosome damage in the form of micronuclei is revealed. Thus irradiated cells which do divide almost certainly die. These results are discussed in relation to other theories of x-ray inhibition of regeneration with particular reference to the view that irradiated cells can be reactivated

  2. Myrtenal inhibits acetylcholinesterase, a known Alzheimer target.

    Kaufmann, Dorothea; Dogra, Anudeep Kaur; Wink, Michael

    2011-10-01

    Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer's disease. In this study selected components of essential oils, which carry a variety of important functional groups, were tested for their in-vitro anti-acetylcholinesterase activity. In-vitro anti-acetylcholinesterase activity was measured by an adapted version of Ellman's colorimetric assay. 1,8-cineole, carvacrol, myrtenal and verbenone apparently inhibited AChE; the highest inhibitory activity was observed for myrtenal (IC50 = 0.17 mm). This is the first study showing the AChE inhibitory activity of myrtenal. Our investigations provided evidence for the efficacy of monoterpenes as inhibitors of AChE. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

  3. Theobromine inhibits sensory nerve activation and cough.

    Usmani, Omar S; Belvisi, Maria G; Patel, Hema J; Crispino, Natascia; Birrell, Mark A; Korbonits, Márta; Korbonits, Dezso; Barnes, Peter J

    2005-02-01

    Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid-induced cough in guinea-pigs in vivo. Furthermore, in a randomized, double-blind, placebo-controlled study in man, theobromine suppresses capsaicin-induced cough with no adverse effects. We also demonstrate that theobromine directly inhibits capsaicin-induced sensory nerve depolarization of guinea-pig and human vagus nerve suggestive of an inhibitory effect on afferent nerve activation. These data indicate the actions of theobromine appear to be peripherally mediated. We conclude theobromine is a novel and promising treatment, which may form the basis for a new class of antitussive drugs.

  4. Direct renin inhibition in chronic kidney disease

    Persson, Frederik; Rossing, Peter; Parving, Hans-Henrik

    2013-01-01

    that renin inhibition could hold potential for improved treatment in patients with chronic kidney disease, with diabetic nephropathy as an obvious group of patients to investigate, as the activity of the renin-angiotensin-aldosterone system is enhanced in these patients and as there is an unmet need....... In addition, combination treatment seemed safe and effective also in patients with impaired kidney function. These initial findings formed the basis for the design of a large morbidity and mortality trial investigating aliskiren as add-on to standard treatment. The study has just concluded, but was terminated...... early as a beneficial effect was unlikely and there was an increased frequency of side effects. Also in non-diabetic kidney disease a few intervention studies have been carried out, but there is no ongoing hard outcome study. In this review we provide the current evidence for renin inhibition in chronic...

  5. Extinction Generates Outcome-Specific Conditioned Inhibition.

    Laurent, Vincent; Chieng, Billy; Balleine, Bernard W

    2016-12-05

    Extinction involves altering a previously established predictive relationship between a cue and its outcome by repeatedly presenting that cue alone. Although it is widely accepted that extinction generates some form of inhibitory learning [1-4], direct evidence for this claim has been lacking, and the nature of the associative changes induced by extinction have, therefore, remained a matter of debate [5-8]. In the current experiments, we used a novel behavioral approach that we recently developed and that provides a direct measure of conditioned inhibition [9] to compare the influence of extinguished and non-extinguished cues on choice between goal-directed actions. Using this approach, we provide direct evidence that extinction generates outcome-specific conditioned inhibition. Furthermore, we demonstrate that this inhibitory learning is controlled by the infralimbic cortex (IL); inactivation of the IL using M4 DREADDs abolished outcome-specific inhibition and rendered the cue excitatory. Importantly, we found that context modulated this inhibition. Outside its extinction context, the cue was excitatory and functioned as a specific predictor of its previously associated outcome, biasing choice toward actions earning the same outcome. In its extinction context, however, the cue acted as a specific inhibitor and biased choice toward actions earning different outcomes. Context modulation of these excitatory and inhibitory memories was mediated by the dorsal hippocampus (HPC), suggesting that the HPC and IL act in concert to control the influence of conditioned inhibitors on choice. These findings demonstrate for the first time that extinction turns a cue into a net inhibitor that can influence choice via counterfactual action-outcome associations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Fermentation of lignocellulosic hydrolysates: Inhibition and detoxification

    Palmqvist, E.

    1998-02-01

    The ethanol yield and productivity obtained during fermentation of lignocellulosic hydrolysates is decreased due to the presence of inhibiting compounds, such as weak acids, furans and phenolic compounds produced during hydrolysis. Evaluation of the effect of various biological, physical and chemical detoxification treatments by fermentation assays using Saccharomyces cerevisiae was used to characterise inhibitors. Inhibition of fermentation was decreased after removal of the non-volatile compounds, pre-fermentation by the filamentous fungus Trichoderma reesei, treatment with the lignolytic enzyme laccase, extraction with ether, and treatment with alkali. Yeast growth in lignocellulosic hydrolysates was inhibited below a certain fermentation pH, most likely due to high concentrations of undissociated weak acids. The effect of individual compounds were studied in model fermentations. Furfural is reduced to furfuryl alcohol by yeast dehydrogenases, thereby affecting the intracellular redox balance. As a result, acetaldehyde accumulated during furfural reduction, which most likely contributed to inhibition of growth. Acetic acid (10 g 1{sup -1}) and furfural (3 g 1{sup -1}) interacted antagonistically causing decreased specific growth rate, whereas no significant individual or interaction effects were detected by the lignin-derived compound 4-hydroxybenzoic acid (2 g 1{sup -1}). By maintaining a high cell mass density in the fermentor, the process was less sensitive to inhibitors affecting growth and to fluctuations in fermentation pH, and in addition the depletion rate of bioconvertible inhibitors was increased. A theoretical ethanol yield and high productivity was obtained in continuous fermentation of spruce hydrolysate when the cell mass concentration was maintained at a high level by applying cell recirculation 164 refs, 16 figs, 5 tabs

  7. Osthole inhibits bone metastasis of breast cancer

    Wu, Chunyu; Sun, Zhenping; Guo, Baofeng; Ye, Yiyi; Han, Xianghui; Qin, Yuenong; Liu, Sheng

    2017-01-01

    Bone is one of the most common sites for breast cancer metastasis, which greatly contributes to patient morbidity and mortality. Osthole, a major extract from Cnidium monnieri (L.), exhibits many biological and pharmacological activities, however, its potential as a therapeutic agent in the treatment of breast cancer bone metastases remain poorly understood. In this study, we set out to investigate whether osthole could inhibit breast cancer metastasis to bone in mice and clarified the potent...

  8. Fermented Broth in Tyrosinase- and Melanogenesis Inhibition

    Chin-Feng Chan; Ching-Cheng Huang; Ming-Yuan Lee; Yung-Sheng Lin

    2014-01-01

    Fermented broth has a long history of applications in the food, pharmaceutical and cosmetic industries. Recently, the use of fermented broth in skin care products is in ascendance. This review investigates the efficacy of fermented broth in inhibiting tyrosinase and melanogenesis. Possible active ingredients and hypopigmentation mechanisms of fermented broth are discussed, and potential applications of fermented broth in the cosmetic industry are also addressed.

  9. Fermented Broth in Tyrosinase- and Melanogenesis Inhibition

    Chin-Feng Chan

    2014-08-01

    Full Text Available Fermented broth has a long history of applications in the food, pharmaceutical and cosmetic industries. Recently, the use of fermented broth in skin care products is in ascendance. This review investigates the efficacy of fermented broth in inhibiting tyrosinase and melanogenesis. Possible active ingredients and hypopigmentation mechanisms of fermented broth are discussed, and potential applications of fermented broth in the cosmetic industry are also addressed.

  10. Many Putative Endocrine Disruptors Inhibit Prostaglandin Synthesis

    Kristensen, David M.; Skalkam, Maria L.; Audouze, Karine Marie Laure

    2011-01-01

    Background: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine disrupting compounds (EDCs) share a high...... suggest a hitherto unknown mode of action by EDCs through inhibition of the PG pathway and suggest new avenues to investigate effects of EDCs on reproductive and immunological disorders that have become increasingly common in recent decades....

  11. Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase

    Petr Dobes

    2013-05-01

    Full Text Available Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE and/or, butyrylcholinesterase (BChE, the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon’s plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, Ki, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as Ki was found to be 175 ± 9 µmol/L. The predicted free energy of binding was −6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed.

  12. Inhibition of methane production by Methanobacterium formicicum

    Hobson, P N; Shaw, B G

    1976-01-01

    The effects of volatile fatty acids, ammonia and copper on methane production by growing cultures of Methanobacterium formicicum were studied. Acetate and butyrate were not inhibitory, but propionate was inhibitory above certain concentrations, as was ammonia. Copper was inhibitory, but inhibitory concentrations are difficult to define as varying amounts may be precipitated as the sulphide. The results are compared with those from piggery-waste digesters and it is suggested that failure of farm-waste digesters from such inhibitions is unlikely.

  13. Evidence of dopaminergic processing of executive inhibition.

    Rajendra D Badgaiyan

    Full Text Available Inhibition of unwanted response is an important function of the executive system. Since the inhibitory system is impaired in patients with dysregulated dopamine system, we examined dopamine neurotransmission in the human brain during processing of a task of executive inhibition. The experiment used a recently developed dynamic molecular imaging technique to detect and map dopamine released during performance of a modified Eriksen's flanker task. In this study, young healthy volunteers received an intravenous injection of a dopamine receptor ligand ((11C-raclopride after they were positioned in the PET camera. After the injection, volunteers performed the flanker task under Congruent and Incongruent conditions in a single scan session. They were required to inhibit competing options to select an appropriate response in the Incongruent but not in the Congruent condition. The PET data were dynamically acquired during the experiment and analyzed using two variants of the simplified reference region model. The analysis included estimation of a number of receptor kinetic parameters before and after initiation of the Incongruent condition. We found increase in the rate of ligand displacement (from receptor sites and decrease in the ligand binding potential in the Incongruent condition, suggesting dopamine release during task performance. These changes were observed in small areas of the putamen and caudate bilaterally but were most significant on the dorsal aspect of the body of left caudate. The results provide evidence of dopaminergic processing of executive inhibition and demonstrate that neurochemical changes associated with cognitive processing can be detected and mapped in a single scan session using dynamic molecular imaging.

  14. Inhibition of enveloped viruses infectivity by curcumin.

    Tzu-Yen Chen

    Full Text Available Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter than for the pseudorabies virus (approximately 180 nm and the vaccinia virus (roughly 335 × 200 × 200 nm. These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses.

  15. Imitation inhibition in children with Tourette syndrome.

    Brandt, Valerie Cathérine; Moczydlowski, Agnes; Jonas, Melanie; Boelmans, Kai; Bäumer, Tobias; Brass, Marcel; Münchau, Alexander

    2017-08-12

    Echopraxia, that is, the open and automatic imitation of other peoples' actions, is common in patients with Gilles de la Tourette syndrome, autism spectrum disorder, and also those with frontal lobe lesions. While systematic reaction time tasks have confirmed increased automatic imitation in the latter two groups, adult patients with Tourette syndrome appear to compensate for automatic imitation tendencies by an overall slowing in response times. However, whether children with Tourette syndrome are already able to inhibit automatic imitation tendencies has not been investigated. Fifteen children with Tourette syndrome and 15 healthy children (aged 7-12 years) performed an imitation inhibition paradigm. Participants were asked to respond to an auditory cue by lifting their index finger or their little finger. Participants were simultaneously presented with either compatible or incompatible visual stimuli. Overall responses in children with Tourette syndrome were slower than in healthy children. Although responses were faster in compatible than in incompatible trials in both groups, this 'interference effect' was smaller in children with Tourette syndrome. Children with Tourette syndrome have a smaller interference effect than healthy children, indicating an enhanced ability to behaviourally control automatic imitation tendencies at the cost of reacting slower. The results suggest that children with Tourette syndrome already employ different or additional inhibition strategies compared to healthy children. © 2017 The British Psychological Society.

  16. Inhibition of Enveloped Viruses Infectivity by Curcumin

    Wen, Hsiao-Wei; Ou, Jun-Lin; Chiou, Shyan-Song; Chen, Jo-Mei; Wong, Min-Liang; Hsu, Wei-Li

    2013-01-01

    Curcumin, a natural compound and ingredient in curry, has antiinflammatory, antioxidant, and anticarcinogenic properties. Previously, we reported that curcumin abrogated influenza virus infectivity by inhibiting hemagglutination (HA) activity. This study demonstrates a novel mechanism by which curcumin inhibits the infectivity of enveloped viruses. In all analyzed enveloped viruses, including the influenza virus, curcumin inhibited plaque formation. In contrast, the nonenveloped enterovirus 71 remained unaffected by curcumin treatment. We evaluated the effects of curcumin on the membrane structure using fluorescent dye (sulforhodamine B; SRB)-containing liposomes that mimic the viral envelope. Curcumin treatment induced the leakage of SRB from these liposomes and the addition of the influenza virus reduced the leakage, indicating that curcumin disrupts the integrity of the membranes of viral envelopes and of liposomes. When testing liposomes of various diameters, we detected higher levels of SRB leakage from the smaller-sized liposomes than from the larger liposomes. Interestingly, the curcumin concentration required to reduce plaque formation was lower for the influenza virus (approximately 100 nm in diameter) than for the pseudorabies virus (approximately 180 nm) and the vaccinia virus (roughly 335 × 200 × 200 nm). These data provide insights on the molecular antiviral mechanisms of curcumin and its potential use as an antiviral agent for enveloped viruses. PMID:23658730

  17. Scaling Up Cortical Control Inhibits Pain

    Jahrane Dale

    2018-05-01

    Full Text Available Summary: Acute pain evokes protective neural and behavioral responses. Chronic pain, however, disrupts normal nociceptive processing. The prefrontal cortex (PFC is known to exert top-down regulation of sensory inputs; unfortunately, how individual PFC neurons respond to an acute pain signal is not well characterized. We found that neurons in the prelimbic region of the PFC increased firing rates of the neurons after noxious stimulations in free-moving rats. Chronic pain, however, suppressed both basal spontaneous and pain-evoked firing rates. Furthermore, we identified a linear correlation between basal and evoked firing rates of PFC neurons, whereby a decrease in basal firing leads to a nearly 2-fold reduction in pain-evoked response in chronic pain states. In contrast, enhancing basal PFC activity with low-frequency optogenetic stimulation scaled up prefrontal outputs to inhibit pain. These results demonstrate a cortical gain control system for nociceptive regulation and establish scaling up prefrontal outputs as an effective neuromodulation strategy to inhibit pain. : Dale et al. find that acute pain increases activity levels in the prefrontal cortex. Chronic pain reduces both basal spontaneous and pain-evoked activity in this region, whereas neurostimulation to restore basal activities can in turn enhance nociception-evoked prefrontal activities to inhibit pain. Keywords: chronic pain, neuromodulation, prefrontal cortex, PFC, cortical gain control

  18. Pharmacological inhibition of feline immunodeficiency virus (FIV).

    Mohammadi, Hakimeh; Bienzle, Dorothee

    2012-05-01

    Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats.

  19. Wnt signaling inhibits CTL memory programming.

    Xiao, Zhengguo; Sun, Zhifeng; Smyth, Kendra; Li, Lei

    2013-12-01

    Induction of functional CTLs is one of the major goals for vaccine development and cancer therapy. Inflammatory cytokines are critical for memory CTL generation. Wnt signaling is important for CTL priming and memory formation, but its role in cytokine-driven memory CTL programming is unclear. We found that wnt signaling inhibited IL-12-driven CTL activation and memory programming. This impaired memory CTL programming was attributed to up-regulation of eomes and down-regulation of T-bet. Wnt signaling suppressed the mTOR pathway during CTL activation, which was different to its effects on other cell types. Interestingly, the impaired memory CTL programming by wnt was partially rescued by mTOR inhibitor rapamycin. In conclusion, we found that crosstalk between wnt and the IL-12 signaling inhibits T-bet and mTOR pathways and impairs memory programming which can be recovered in part by rapamycin. In addition, direct inhibition of wnt signaling during CTL activation does not affect CTL memory programming. Therefore, wnt signaling may serve as a new tool for CTL manipulation in autoimmune diseases and immune therapy for certain cancers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Response inhibition in motor conversion disorder.

    Voon, Valerie; Ekanayake, Vindhya; Wiggs, Edythe; Kranick, Sarah; Ameli, Rezvan; Harrison, Neil A; Hallett, Mark

    2013-05-01

    Conversion disorders (CDs) are unexplained neurological symptoms presumed to be related to a psychological issue. Studies focusing on conversion paralysis have suggested potential impairments in motor initiation or execution. Here we studied CD patients with aberrant or excessive motor movements and focused on motor response inhibition. We also assessed cognitive measures in multiple domains. We compared 30 CD patients and 30 age-, sex-, and education-matched healthy volunteers on a motor response inhibition task (go/no go), along with verbal motor response inhibition (color-word interference) and measures of attention, sustained attention, processing speed, language, memory, visuospatial processing, and executive function including planning and verbal fluency. CD patients had greater impairments in commission errors on the go/no go task (P conversion. Patients with nonepileptic seizures, a different form of conversion disorder, are commonly reported to have lower IQ and multiple cognitive deficits. Our results point toward potential differences between conversion disorder subgroups. © 2013 Movement Disorder Society. Copyright © 2013 Movement Disorder Society.

  1. The Kinetics of Carrier Transport Inhibition

    Rosenberg, T.; Wilbrandt, Robert Walter

    1962-01-01

    The kinetical treatment of enzymatic carrier transports as given in previous communications has been extended to conditions of inhibition. Various possible types of inhibitors have been considered differing in the site of attack (enzyme or carrier), in the mode of action (competing with the subst......The kinetical treatment of enzymatic carrier transports as given in previous communications has been extended to conditions of inhibition. Various possible types of inhibitors have been considered differing in the site of attack (enzyme or carrier), in the mode of action (competing...... with the substrate for the enzyme or the carrier or for both, competing with the carrier for the enzyme, or non-competitive) and in the ability of penetrating the membrane. Experiments are reported on the inhibition of glucose and fructose transport across the human red cell membrane by phlorizine, phloretine...... and polyphloretinephosphate. The results of the analysis for these inhibitors indicate a substrate competitive mode of action. The effect of reversing the transport direction by interchanging the substrate concentration has been treated for the case of a non-penetrating substrate competitive inhibitor in the external medium...

  2. Trace element inhibition of phytase activity.

    Santos, T; Connolly, C; Murphy, R

    2015-02-01

    Nowadays, 70 % of global monogastric feeds contains an exogenous phytase. Phytase supplementation has enabled a more efficient utilisation of phytate phosphorous (P) and reduction of P pollution. Trace minerals, such as iron (Fe), zinc (Zn), copper (Cu) and manganese (Mn) are essential for maintaining health and immunity as well as being involved in animal growth, production and reproduction. Exogenous sources of phytase and trace elements are regularly supplemented to monogastric diets and usually combined in a premix. However, the possibility for negative interaction between individual components within the premix is high and is often overlooked. Therefore, this initial study focused on assessing the potential in vitro interaction between inorganic and organic chelated sources of Fe, Zn, Cu and Mn with three commercially available phytase preparations. Additionally, this study has investigated if the degree of enzyme inhibition was dependent of the type of chelated sources. A highly significant relationship between phytase inhibition, trace mineral type as well as mineral source and concentration, p phytases for Fe and Zn, as well as for Cu with E. coli and Aspergillus niger phytases. Different chelate trace mineral sources demonstrated diversifying abilities to inhibit exogenous phytase activity.

  3. Bioassays for the determination of nitrification inhibition

    Grunditz, Camilla

    1999-07-01

    Requirements for nitrogen reduction in wastewater treatment plants were introduced in Sweden in the early 1990's. This was a governmental move to reduce the nitrogen discharges to the Baltic and Kattegat in order to prevent eutrophication. The nitrification process in wastewater treatment plants is performed by nitrifying bacteria. These are susceptible to inhibition and it is of great importance that the influent water does not contain toxic compounds. Therefore, there is a need for assays for the determination of nitrification inhibition. This thesis describes the development and applications of such bioassays. Pure cultures of Nitrosomonas sp. and Nitrobacter sp. were isolated from activated sludge of a wastewater treatment plant. These cultures were used as test organisms in the development of bioassays for nitrification inhibition measurements. The assays are based on two different principles; cell suspensions of the bacteria, performed in test tubes, and mediated amperometric biosensors with the bacteria immobilised. Ammonia oxidation and nitrite oxidation are studied separately without interference from other organisms, which makes it easier to interpret the results. The cell suspension assays were applied to samples of industrial and municipal wastewater. The Nitrosomonas and Nitrobacter assays showed to have different inhibition patterns. A large percentage of the Swedish municipal wastewater treatment plants were found to receive inhibitory influent water, but the inhibition level was generally low. Compared to an assay based on activated sludge, the screening method, the pure culture assays found more samples of influent water strongly inhibitory or stimulating. The highest correlation was found between the screening method and the Nitrosomonas assay. The Nitrobacter assay was found to be the most sensitive method. Assessment of toxicity of a number of chemical substances was studied using the biosensors, together with the cell suspension assays

  4. Inhibition of Breast Cancer Metastasis by Heregulin-Beta 1

    Yu, Dihua

    1999-01-01

    The major goal of this Idea proposal is to determine whether and how HRG-Beta1 inhibits breast cancer metastasis and to identify the functional domains that are sufficient for inhibition of breast cancer metastasis...

  5. A specific bioassay for the inhibition of flowering.

    Blake, J

    1972-06-01

    A bioassay for the inhibition of flowering involving the in vitro culture of excised, partially-induced, apices of Viscaria candida is described. This bioassay has been used to detect flowering inhibition in extracts from Kalanchoe blossfeldiana.

  6. Differential effects of cognitive inhibition and intelligence on creativity

    Benedek, Mathias; Franz, Fabiola; Heene, Moritz; Neubauer, Aljoscha C.

    2012-01-01

    There are different conceptions about how cognitive inhibition is related to creativity. Creativity has either been associated with effective inhibition, or with disinhibition, or with an adaptive engagement of inhibition. In this study, we examined the relationship of cognitive inhibition, assessed by means of the random motor generation task, with different measures of creativity. We also analyzed whether this relation is mediated by intelligence. We generally found a positive correlation o...

  7. Attention Inhibition Training Can Reduce Betel-Nut Chewing Time

    Ho, Ming-Chou; Li, Ren-Hau; Tang, Tze-Chun

    2011-01-01

    Betel nut (or areca) is the fourth most commonly used drug worldwide after tobacco, alcohol, and caffeine. Many chemical ingredients of betel nut are carcinogenic. We examined whether the manipulation of attentional inhibition toward the areca-related stimuli could affect betel-nut chewing time. Three matched groups of habitual chewers were recruited: inhibit-areca, inhibit-non-areca, and control. This study consisted of a Go/No-Go task for inhibition training, followed by a taste test for ob...

  8. Use of bacillus subtilis strains to inhibit postharvest pathogenic fungi

    Arras, G.; Gambella, F.; Demontis, S.; Petretto, A.

    1995-01-01

    An isolate (87) of the bacillus subtilis strains isolated from cold stored citrus fruit 13 proved to inhibit the growth in vitro of the penicillium italicum used in the experiment (from 50.6% to 92.2%) and to inhibit botrytis cinerea (from 65.3% to 95.9%). A further test, superimposing on plates containing PDA strains Nos. 13, 173, and 160, totally inhibited the fungi. Tested in vivo on artificially bruised oranges, they significantly inhibited two fungi

  9. The development of children's inhibition: Does parenting matter?

    Roskam, I.; Stievenart, Marie; Meunier, J.-C.; Noël, M.-P.

    2014-01-01

    Whereas a large body of research has investigated the maturation of inhibition in relation to the prefrontal cortex, far less research has been devoted to environmental factors that could contribute to inhibition improvement. The aim of the current study was to test whether and to what extent parenting matters for inhibition development from 2 to 8. years of age. Data were collected from 421 families, with 348 mother-child dyads and 342 father-child dyads participating. Children's inhibition ...

  10. Contour detection based on nonclassical receptive field inhibition

    Grigorescu, Cosmin; Petkov, Nicolai; Westenberg, Michel A.

    We propose a biologically motivated computational step, called nonclassical receptive field (non-CRF) inhibition, more generally surround inhibition or suppression, to improve contour detection in machine vision. Non-CRF inhibition is exhibited by 80% of the orientation-selective neurons in the

  11. The Effectiveness of Reward and Punishment Contingencies on Response Inhibition

    Costantini, Arthur F.; Hoving, Kenneth L.

    1973-01-01

    The relative effectiveness of reward and punishment on the development of response inhibition was evaluated developmentally with kindergarteners and second graders. Removal of positive reinforcers was apparently more effective than reward in producing inhibiting at both age levels. Transfer of inhibition training was also evaluated. (DP)

  12. Effect of Adenine Concentration on the Corrosion Inhibition of Aisi ...

    This gave a surface coverage of 0.8956 and corrosion penetration rate of 0.022132mm/yr. Hence, the best adenine concentration for the corrosion inhibition of alloys 304L in 1.0M sulphuric acid solution to obtain optimum inhibition efficiency is 0.011M. Keywords: Corrosion, AISI 304L Steel, Inhibition efficiency, Degree of ...

  13. Inhibition of acetylcholinesterase activity by essential oil from Citrus paradisi.

    Miyazawa, M; Tougo, H; Ishihara, M

    2001-01-01

    Inhibition of acetylcholinesterase (AChE) activity by essential oils of Citrus paradisi (grapefruit pink in USA) was studied. Inhibition of AChE was measured by the colorimetric method. Nootkatone and auraptene were isolated from C. paradisi oil and showed 17-24% inhibition of AChE activity at the concentration of 1.62 microg/mL.

  14. Inhibition and Adsorption impact of Leave Extracts of Cnidoscolus ...

    Corrosion inhibition in the presence of alokaloid and non alkaloid extracts of Cnidoscolus aconitifolius in 1M HCl was studied using the weight loss and hydrogen evolution techniques at 303, 313 and 333 K. The results obtained revealed that the inhibition efficiency decreased with increase in temperature. Inhibition ...

  15. A fusion-inhibiting peptide against Rift Valley fever virus inhibits multiple, diverse viruses.

    Jeffrey W Koehler

    Full Text Available For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III based on the protein sequence and structure. For Rift Valley fever virus (RVFV, the glycoprotein Gc (Class II fusion protein mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus, Class II (Andes virus, or Class III (vesicular stomatitis virus fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors.

  16. Inhibition of oxygen scavengers realized by peritoneal macrophages: an adhesion prevention target?

    Mynbaev OA

    2014-11-01

    Full Text Available Ospan A Mynbaev,1–4 Marina Yu Eliseeva,1,2 Oktay T Kadayifci,1,5 Tahar Benhidjeb,1,6 Michael Stark1,41The International Translational Medicine and Biomodeling Research team, MIPT center for human physiology studies, Laboratory of Cellular and Molecular Technologies, The Department of Applied Mathematics, Moscow Institute of Physics and Technology (State University, Moscow Region, Russia; 2The Department of Obstetrics, Gynecology and Reproductive Medicine, Peoples’ Friendship University of Russia, Moscow, Russia; 3Laboratory of Pilot Projects, Moscow State University of Medicine and Dentistry, Moscow, Russia; 4The New European Surgical Academy, Berlin, Germany; 5Onkim Stem Cell Technologies Inc., Istanbul, Turkey; 6Department of Surgery, Burjeel Hospital, Abu Dhabi, United Arab EmiratesOur team, general surgeons and gynecologists look constantly for ways to prevent postsurgical adhesions, and hence, we appreciate the platform you have established through multiple publications.1–3 This is especially because postsurgical adhesions may result in several complications such as the small bowel obstruction, secondary infertility, dyspareunia, chronic abdominal/pelvic pain and many others.Prevention of postsurgical adhesions is still an unsolved problem in spite of the suggested modifications of current surgical methods and application of various barriers, sprays, and use of other antiadhesive medications. We have already pointed out that a design of ideal nanoparticles should become a target of personalized adhesion prevention strategy in the future4,5 and therefore, we read with great interest the article by Shin et al that was recently published in your journal.6 This article explores the potential of postoperative adhesion prevention by nanofibers of poly(lactic-co-glycolic acid (PLGA loaded with epigallocatechin-3-O-gallate (EGCG, which is the most bioactive polyphenolic compound extracted from green tea.Read the original article by Shin and

  17. Curcumin inhibits aggregation of alpha-synuclein.

    Pandey, Neeraj; Strider, Jeffrey; Nolan, William C; Yan, Sherry X; Galvin, James E

    2008-04-01

    Aggregation of amyloid-beta protein (Abeta) is a key pathogenic event in Alzheimer's disease (AD). Curcumin, a constituent of the Indian spice Turmeric is structurally similar to Congo Red and has been demonstrated to bind Abeta amyloid and prevent further oligomerization of Abeta monomers onto growing amyloid beta-sheets. Reasoning that oligomerization kinetics and mechanism of amyloid formation are similar in Parkinson's disease (PD) and AD, we investigated the effect of curcumin on alpha-synuclein (AS) protein aggregation. In vitro model of AS aggregation was developed by treatment of purified AS protein (wild-type) with 1 mM Fe3+ (Fenton reaction). It was observed that the addition of curcumin inhibited aggregation in a dose-dependent manner and increased AS solubility. The aggregation-inhibiting effect of curcumin was next investigated in cell culture utilizing catecholaminergic SH-SY5Y cell line. A model system was developed in which the red fluorescent protein (DsRed2) was fused with A53T mutant of AS and its aggregation examined under different concentrations of curcumin. To estimate aggregation in an unbiased manner, a protocol was developed in which the images were captured automatically through a high-throughput cell-based screening microscope. The obtained images were processed automatically for aggregates within a defined dimension of 1-6 microm. Greater than 32% decrease in mutant alpha-synuclein aggregation was observed within 48 h subsequent to curcumin addition. Our data suggest that curcumin inhibits AS oligomerization into higher molecular weight aggregates and therefore should be further explored as a potential therapeutic compound for PD and related disorders.

  18. Interferon-γ Inhibits Ebola Virus Infection.

    Bethany A Rhein

    Full Text Available Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  19. Interferon-γ Inhibits Ebola Virus Infection.

    Rhein, Bethany A; Powers, Linda S; Rogers, Kai; Anantpadma, Manu; Singh, Brajesh K; Sakurai, Yasuteru; Bair, Thomas; Miller-Hunt, Catherine; Sinn, Patrick; Davey, Robert A; Monick, Martha M; Maury, Wendy

    2015-01-01

    Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option. Using mouse-adapted Ebola virus, we found that murine interferon gamma administered 24 hours before or after infection robustly protects lethally-challenged mice and reduces morbidity and serum viral titers. Furthermore, we demonstrated that interferon gamma profoundly inhibits Ebola virus infection of macrophages, an early cellular target of infection. As early as six hours following in vitro infection, Ebola virus RNA levels in interferon gamma-treated macrophages were lower than in infected, untreated cells. Addition of the protein synthesis inhibitor, cycloheximide, to interferon gamma-treated macrophages did not further reduce viral RNA levels, suggesting that interferon gamma blocks life cycle events that require protein synthesis such as virus replication. Microarray studies with interferon gamma-treated human macrophages identified more than 160 interferon-stimulated genes. Ectopic expression of a select group of these genes inhibited Ebola virus infection. These studies provide new potential avenues for antiviral targeting as these genes that have not previously appreciated to inhibit negative strand RNA viruses and specifically Ebola virus infection. As treatment of interferon gamma robustly protects mice from lethal Ebola virus infection, we propose that interferon gamma should be further evaluated for its efficacy as a prophylactic and/or therapeutic strategy against filoviruses. Use of this FDA-approved drug could rapidly be deployed during future outbreaks.

  20. Cannabidiol inhibits angiogenesis by multiple mechanisms.

    Solinas, M; Massi, P; Cantelmo, A R; Cattaneo, M G; Cammarota, R; Bartolini, D; Cinquina, V; Valenti, M; Vicentini, L M; Noonan, D M; Albini, A; Parolaro, D

    2012-11-01

    Several studies have demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on various tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumours in vitro and in vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favourable pharmacological and toxicological profile, here, we evaluated the ability of CBD to modulate tumour angiogenesis. Firstly, we evaluated the effect of CBD on human umbilical vein endothelial cell (HUVEC) proliferation and viability - through [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS analysis - and in vitro motility - both in a classical Boyden chamber test and in a wound-healing assay. We next investigated CBD effects on different angiogenesis-related proteins released by HUVECs, using an angiogenesis array kit and an ELISA directed at MMP2. Then we evaluated its effects on in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels, and further characterized its effects in vivo using a Matrigel sponge model of angiogenesis in C57/BL6 mice. CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion and sprouting in vitro, and angiogenesis in vivo in Matrigel sponges. These effects were associated with the down-modulation of several angiogenesis-related molecules. This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumour and endothelial cells supports the hypothesis that CBD has potential as an effective agent in cancer therapy. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  1. Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication

    Jan, Yi-Hua [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States); Richardson, Jason R., E-mail: jricha3@eohsi.rutgers.edu [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States); Baker, Angela A. [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States); Mishin, Vladimir [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Health Science, New York Medical College, Valhalla, NY (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Laskin, Jeffrey D., E-mail: jlaskin@eohsi.rutgers.edu [Department of Environmental and Occupational Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ (United States)

    2015-10-01

    Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40 mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation. - Highlights: • Menadione redox cycles with cytochrome P450 reductase and generates reactive oxygen species. • Redox cycling inhibits cytochrome P450-mediated parathion metabolism. • Short term administration of menadione inhibits parathion toxicity by inhibiting paraoxon formation.

  2. Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication

    Jan, Yi-Hua; Richardson, Jason R.; Baker, Angela A.; Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2015-01-01

    Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40 mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation. - Highlights: • Menadione redox cycles with cytochrome P450 reductase and generates reactive oxygen species. • Redox cycling inhibits cytochrome P450-mediated parathion metabolism. • Short term administration of menadione inhibits parathion toxicity by inhibiting paraoxon formation.

  3. Saw palmetto ethanol extract inhibits adipocyte differentiation.

    Villaverde, Nicole; Galvis, Adriana; Marcano, Adriana; Priestap, Horacio A; Bennett, Bradley C; Barbieri, M Alejandro

    2013-07-01

    The fruits of saw palmetto have been used for the treatment of a variety of urinary and reproductive system problems. In this study we investigated whether the fruit extracts affect in vitro adipogenesis. Saw palmetto ethanol extract inhibited the lipid droplet accumulation by induction media in a dose-dependent manner, and it also attenuated the protein expressions of C-EBPα and PPARγ. Phosphorylation of Erk1/2 and Akt1 were also decreased by saw palmetto ethanol extract. This report suggests that saw palmetto extracts selectively affect the adipocyte differentiation through the modulation of several key factors that play a critical role during adipogenesis.

  4. Irradiation inhibits the regeneration of aneurogenic limbs

    Wallace, H.; Maden, M.

    1976-01-01

    The developing arms of axolotl larvae from the 2-digit stage onward and the aneurogenic arms of surgically denervated larvae maintained in parabiosis are able to regenerate after amputation. Such regeneration is uniformly inhibited by local irradiation of the arm, whether innervated or not. This demonstration refutes a recent hypothesis that x-rays interfere with a special activity of nerves required for regeneration, and supports the earlier concept that x-rays act directly on those cells which must proliferate to form the regenerated tissues

  5. Inhibition of sulfate reduction in paddy soils

    Vamos, R

    1958-12-13

    The hydrogen sulfide formed in waterlogged soils is a serious problem in rice cultivation. It inhibits the uptake of water and nutrients and may even cause root-rot. Results can best be obtained by preventing the formation of hydrogen sulfide. It is formed mainly by reduction of sulfate for which the cellulose-butyric acid fermentation provides the hydrogen source. Addition of ammonium or potassium nitrate prevents the formation of H/sub 2/S. The hydrogen produced by butyric acid fermentation is used to reduce nitrate and consequently cannot be utilized by the sulfate-reducing bacteria as a source of energy. 6 references.

  6. Vaginal Lactobacillus isolates inhibit uropathogenic Escherichia coli.

    Atassi , Fabrice; Brassart , Dominique; Grob , Philipp; Graf , Federico; Servin , Alain ,

    2006-01-01

    The purpose of this study was to investigate the antibacterial activities of Lactobacillus jensenii KS119.1 and KS121.1, and Lactobacillus gasserii KS120.1 and KS124.3 strains isolated from the vaginal microflora of healthy women, against uropathogenic, diffusely adhering Afa/Dr Escherichia coli (Afa/Dr DAEC) strains IH11128 and 7372 involved in recurrent cystitis. We observed that some of the Lactobacillus isolates inhibited the growth and decreased the viability of E. coli IH11128 and 7372....

  7. Research on inhibition of corneal neovascularization

    Zhang-Hui Yang

    2015-12-01

    Full Text Available Corneal transparency is the basis of the normal physiological functions.However, corneal neovascularization(CNVmay occur in the infection, mechanical and chemical injury or under other pathological conditions,which make the cornea lose original transparency and severe visual impairment. In recent years, along with the development of immunology, molecular biology, biochemistry and other disciplines, there is more in-depth understanding on the CNV, and clinical treatment of CNV has made new breakthroughs. This article provides an overview of the inhibition of CNV.

  8. Na+/K+-ATPase: Activity and inhibition

    Čolović, M.; Krstić, D.; Krinulović, K.; Momić, T.; Savić, J.; Vujačić, A.; Vasić, V.

    2009-09-01

    The aim of the study was to give an overview of the mechanism of inhibition of Na+/K+-ATPase activity induced by some specific and non specific inhibitors. For this purpose, the effects of some ouabain like compounds (digoxin, gitoxin), noble metals complexes ([PtCl2DMSO2], [AuCl4]-, [PdCl4]2-, [PdCl(dien)]+, [PdCl(Me4dien)]+), transition metal ions (Cu2+, Zn2+, Fe2+, Co2+), and heavy metal ions (Hg2+, Pb2+, Cd2+) on the activity of Na+/K+-ATPase from rat synaptic plasma membranes (SPM), porcine cerebral cortex and human erythrocytes were discussed.

  9. Inhibition of human aromatase complex (CYP19) by antiepileptic drugs

    Jacobsen, Naja Wessel; Halling-Sørensen, Bent; Birkved, Franziska Maria A Kramer

    2008-01-01

    of 1.4-49.7 mM. Carbamazepine, gabapentin, primidone, topiramate and vigabatrin showed no inhibition. Additionally, binary drug combinations were tested to investigate if combination therapy could potentiate the aromatase inhibition. Additive inhibition was seen in combination experiments...... with valproate and phenobarbital. When adding carbamazepine to a range of valproate concentrations no additional inhibition was seen. The data for some of the AEDs show that side effects on steroid synthesis in humans due to inhibition of aromatase should be considered....

  10. Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing

    Tropea, J.E.; Molyneux, R.J.; Kaushal, G.P.; Pan, Y.T.; Mitchell, M.; Elbein, A.D.

    1989-01-01

    Australine is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, the authors tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the α-glucosidase amyloglucosidase (50% inhibition at 5.8 μM), but it did not inhibit β-glucosidase, α- or β-mannosidase, or α- or β-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc 3 Man 7-9 (GlcNAc) 2 -oligosaccharides

  11. Sprouting inhibition of rhizomes by gamma irradiation

    Hilmy, Nazly; Chosdu, Rahayu

    1985-01-01

    Sprouting inhibition by gamma irradiation to prolong the storage life of 4 species of rhizomes, namely curcuma domestica, kaemferia galanga, curcuma xanthoriza and curcuma aeruginosa, has been carried out. Two groups of samples were used, freshly harvested rhizomes and fresh rhizomes which have been stored for about two weeks. The samples were packed in a plastic net bag, each contained about 100 grams of rhizomes. Irradiation was carried out at room temperature at the doses of 0, 0.02, 0.04, 0.06, 0.08, 0.10, 0.15, 0.20 and 0.25 kGy. Post irradiation storage was done at room temperature with relative humidity ranging between 85 and 95%. The results showed that irradiation doses of 0.06 to 0.08 kGy was sufficient to inhibit sprouting of freshly harvested rhizomes and prolonged its storage life for 6 weeks, while in the other group sprouting still occured at the dose of 0.25 kGy. Irradiation dose up to 0.25 kGy did not cause significant effect on moisture and volatile oil contents, as well as volatile oil characteristics of the samples. About 50% of weight losses were found either in irradiated or unirradiated samples after being stored for 8 weeks. Odour and texture were evaluated organoleptically while mould growth and insect damage were observed visually. (author)

  12. Inhibition of DNA replication by ultraviolet light

    Edenberg, H.J.

    1976-01-01

    DNA replication in ultraviolet-irradiated HeLa cells was studied by two different techniques: measurements of the kinetics of semiconservative DNA synthesis, and DNA fiber autoradiography. In examining the kinetics of semiconservative DNA synthesis, density label was used to avoid measuring the incorporation due to repair replication. The extent of inhibition varied with time. After doses of less than 10 J/m 2 the rate was initially depressed but later showed some recovery. After higher doses, a constant, low rate of synthesis was seen for at least the initial 6 h. An analysis of these data indicated that the inhibition of DNA synthesis could be explained by replication forks halting at pyrimidine dimers. DNA fiber autoradiography was used to further characterize replication after ultraviolet irradiation. The average length of labeled segments in irradiated cells increased in the time immediately after irradiation, and then leveled off. This is the predicted pattern if DNA synthesis in each replicon continued at its previous rate until a lesion is reached, and then halted. The frequency of lesions that block synthesis is approximately the same as the frequency of pyrimidine dimers

  13. Soluble Aβ aggregates can inhibit prion propagation.

    Sarell, Claire J; Quarterman, Emma; Yip, Daniel C-M; Terry, Cassandra; Nicoll, Andrew J; Wadsworth, Jonathan D F; Farrow, Mark A; Walsh, Dominic M; Collinge, John

    2017-11-01

    Mammalian prions cause lethal neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and consist of multi-chain assemblies of misfolded cellular prion protein (PrP C ). Ligands that bind to PrP C can inhibit prion propagation and neurotoxicity. Extensive prior work established that certain soluble assemblies of the Alzheimer's disease (AD)-associated amyloid β-protein (Aβ) can tightly bind to PrP C , and that this interaction may be relevant to their toxicity in AD. Here, we investigated whether such soluble Aβ assemblies might, conversely, have an inhibitory effect on prion propagation. Using cellular models of prion infection and propagation and distinct Aβ preparations, we found that the form of Aβ assemblies which most avidly bound to PrP in vitro also inhibited prion infection and propagation. By contrast, forms of Aβ which exhibit little or no binding to PrP were unable to attenuate prion propagation. These data suggest that soluble aggregates of Aβ can compete with prions for binding to PrP C and emphasize the bidirectional nature of the interplay between Aβ and PrP C in Alzheimer's and prion diseases. Such inhibitory effects of Aβ on prion propagation may contribute to the apparent fall-off in the incidence of sporadic CJD at advanced age where cerebral Aβ deposition is common. © 2017 The Authors.

  14. Ketose induced respiratory inhibition in isolated hepatocytes.

    Martínez, P; Carrascosa, J M; Núñez de Castro, I

    1987-06-01

    The addition of 10 mM fructose or 10 mM tagatose to a suspension of hepatocytes caused respiratory inhibition, whereas no change in oxygen uptake was observed following the addition of glucose. However, incubations in the presence of fructose showed a high, aerobic glycolytic activity. Tagatose is phosphorylated to tagatose 1-phosphate but is not further metabolized by cell free liver extract. Moreover, the addition of fructose to glucagon treated cells also caused the Crabtree-like effect. The concentration of adenine nucleotides and inorganic phosphate (Pi) in the mitochondrial and cytosolic compartments during incubation (time 30 min) was determined by the digitonin fractionation procedure. In the presence of 10 mM fructose or tagatose, the total adenine nucleotide pools decreased by 40%; however, glucose produced no change. The addition of ketoses diminished the asymmetric distribution of extramitochondrial (ATP/ADP)e ratio and intramitochondrial (ATP/ADP)i ratio. At the same time the total mitochondrial Pi fell from 17 mM to 6-7 mM. The mitochondrial membrane potential (-161 mV) in the presence of fructose showed no changes during the 30 min experimental period. An increase in the NADH/NAD+ ratio was observed. These results suggest that in hepatocytes the inhibition of respiration is not necessarily linked with the enhanced aerobic glycolysis, by competition for common substrates.

  15. Lactam inhibiting Streptococcus mutans growth on titanium

    Xavier, J.G.; Geremias, T.C.; Montero, J.F.D. [Center for Research on Dental Implants (CEPID), School of Dentistry (ODT), Federal University of Santa Catarina - UFSC, Florianópolis/SC, 88040-900 (Brazil); Vahey, B.R. [Herman Ostrow School of Dentistry of USC, 925 W 34 St, Los Angeles, CA 90089 (United States); Benfatti, C.A.M.; Souza, J.C.M.; Magini, R.S. [Center for Research on Dental Implants (CEPID), School of Dentistry (ODT), Federal University of Santa Catarina - UFSC, Florianópolis/SC, 88040-900 (Brazil); Pimenta, A.L., E-mail: andrea@intelab.ufsc.br [Department of Biologia, ERRMECe, Université de Cergy Pontoise, 2, Av. Adolphe Chauvin 95302 Cergy, Pontoise (France); Integrated Laboratories Technologies (InteLab), Dept. Chemical and Food Engineering (EQA), Federal University of Santa Catarina - UFSC, Florianópolis/SC, 88040-970 (Brazil)

    2016-11-01

    The aim of this work was to analyze the activity of novel synthetic lactams on preventing biofilm formation on titanium surfaces. Titanium (Ti6Al4V) samples were exposed to Streptococcus mutans cultures in the presence or absence of a synthetic lactam. After 48 h incubation, planktonic growth was determined by spectrophotometry. Biofilm was evaluated by crystal violet staining and colony forming units (CFU·ml{sup −1}), followed by scanning electron microscopy (SEM). Results showed that the average of adhered viable cells was approximately 1.5 × 10{sup 2} CFU/ml in the presence of lactam and 4 × 10{sup 2} CFU/ml in its absence. This novel compound was considerable active in reducing biofilm formation over titanium surfaces, indicating its potential for the development of antimicrobial drugs targeting the inhibition of the initial stages of bacterial biofilms on dental implants abutments. - Highlights: • A novel synthetic compound is tested on preventing biofilm formation on titanium surfaces • Biofilm inhibition has been achieved on titanium surfaces containing the novel compound. • Planktonic growth of S. mutans was not affected by the presence of lactams on titanium.

  16. Universal water-dilutable inhibited protective lubricants

    Mamtseva, M.V.; Kardash, N.V.; Latynina, M.B.

    1993-01-01

    In the interest of environmental protection, improvement of working conditions, and reduced fire hazard in production operations, water-based protective lubricants are now available in a wide assortment, and the production volume has increased greatly. The term water-dilutable inhibited protective lubricants (WDIPL) means water-soluble, water-emulsifiable, or water-dispersible products with the dual function of reducing friction and wear and protecting metal surfaces against corrosion for specified periods of time. According to the standard Unified System of Protection Against Corrosion and Aging (COST 9.103-78), WDIPLs are classed as products for the temporary corrosion protection of metals and end-items. In the general class of WDIPLs one can identify water-dilutable combination corrosion inhibitors, film-forming inhibited petroleum compositions (FIPC-d), detergent-preservative fluids, operational-preservative lubricating-cooling process compounds (ICPC), and, finally, universal multifunctional products. Combined corrosion inhibitors may consist of water-soluble organic and inorganic compounds; water/oil and oil-soluble surfactants - corrosion inhibitors of the chemisorption type or donor and/or acceptor types; shielding inhibitors of the adsorption type; and fast-acting water-displacing components. 23 refs

  17. Salinomycin, A Polyether Ionophoric Antibiotic, Inhibits Adipogenesis

    Szkudlarek-Mikho, Maria; Saunders, Rudel A.; Yap, Sook Fan; Ngeow, Yun Fong; Chin, Khew-Voon

    2012-01-01

    The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy. PMID:23123626

  18. Structural basis of kynurenine 3-monooxygenase inhibition.

    Amaral, Marta; Levy, Colin; Heyes, Derren J; Lafite, Pierre; Outeiro, Tiago F; Giorgini, Flaviano; Leys, David; Scrutton, Nigel S

    2013-04-18

    Inhibition of kynurenine 3-monooxygenase (KMO), an enzyme in the eukaryotic tryptophan catabolic pathway (that is, kynurenine pathway), leads to amelioration of Huntington's-disease-relevant phenotypes in yeast, fruitfly and mouse models, as well as in a mouse model of Alzheimer's disease. KMO is a flavin adenine dinucleotide (FAD)-dependent monooxygenase and is located in the outer mitochondrial membrane where it converts l-kynurenine to 3-hydroxykynurenine. Perturbations in the levels of kynurenine pathway metabolites have been linked to the pathogenesis of a spectrum of brain disorders, as well as cancer and several peripheral inflammatory conditions. Despite the importance of KMO as a target for neurodegenerative disease, the molecular basis of KMO inhibition by available lead compounds has remained unknown. Here we report the first crystal structure of Saccharomyces cerevisiae KMO, in the free form and in complex with the tight-binding inhibitor UPF 648. UPF 648 binds close to the FAD cofactor and perturbs the local active-site structure, preventing productive binding of the substrate l-kynurenine. Functional assays and targeted mutagenesis reveal that the active-site architecture and UPF 648 binding are essentially identical in human KMO, validating the yeast KMO-UPF 648 structure as a template for structure-based drug design. This will inform the search for new KMO inhibitors that are able to cross the blood-brain barrier in targeted therapies against neurodegenerative diseases such as Huntington's, Alzheimer's and Parkinson's diseases.

  19. PD-1 checkpoint inhibition: Toxicities and management.

    Hahn, Andrew W; Gill, David M; Agarwal, Neeraj; Maughan, Benjamin L

    2017-12-01

    With the recent approval of 5 PD-1/PD-L1 inhibitors for a number of malignancies, PD-1 axis inhibition is drastically changing the treatment landscape of immunotherapy in cancer. As PD-1/PD-L1 are involved in peripheral immune tolerance, inhibition of this immune checkpoint has led to novel immune-related adverse events including colitis, hepatitis, pneumonitis, rash, and endocrinopathies among many others. In this seminar, we will analyze the incidence of immune-related adverse events for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. Then, we will discuss the specific management of the most common immune-mediated adverse events including colitis, hepatitis, pneumonitis, rash, endocrinopathies, nephritis, and neurologic toxicities. Immune-related adverse events are frequently treated with immunosuppressive medication such as steroids and mycofenolate mofetil. There are specific immune-related adverse events which are frequently seen by the treating oncologist from checkpoint inhibitors. It is essential to understand the recommended treatment options to minimize toxicity and mortality from this important class of anti-neoplastic therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Platelets Inhibit Migration of Canine Osteosarcoma Cells.

    Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

    2017-01-01

    The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

  1. Kaempferol inhibits thrombosis and platelet activation.

    Choi, Jun-Hui; Park, Se-Eun; Kim, Sung-Jun; Kim, Seung

    2015-08-01

    The objectives of the present study were to investigate whether kaempferol affects pro-coagulant proteinase activity, fibrin clot formation, blood clot and thrombin (or collagen/epinephrine)-stimulated platelet activation, thrombosis, and coagulation in ICR (Imprinting Control Region) mice and SD (Sprague-Dawley) rats. Kaempferol significantly inhibited the enzymatic activities of thrombin and FXa by 68 ± 1.6% and 52 ± 2.4%, respectively. Kaempferol also inhibited fibrin polymer formation in turbidity. Microscopic analysis was performed using a fluorescent conjugate. Kaempferol completely attenuated phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and phosphoinositide 3-kinase (PI3K)/PKB (AKT) in thrombin-stimulated platelets and delayed aggregation time (clotting) by 34.6% in an assay of collagen/epinephrine-stimulated platelet activation. Moreover, kaempferol protected against thrombosis development in 3 animal models, including collagen/epinephrine- and thrombin-induced acute thromboembolism models and an FeCl3-induced carotid arterial thrombus model. The ex vivo anticoagulant effect of kaempferol was further confirmed in ICR mice. This study demonstrated that kaempferol may be clinically useful due to its ability to reduce or prevent thrombotic challenge. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  2. Lactam inhibiting Streptococcus mutans growth on titanium

    Xavier, J.G.; Geremias, T.C.; Montero, J.F.D.; Vahey, B.R.; Benfatti, C.A.M.; Souza, J.C.M.; Magini, R.S.; Pimenta, A.L.

    2016-01-01

    The aim of this work was to analyze the activity of novel synthetic lactams on preventing biofilm formation on titanium surfaces. Titanium (Ti6Al4V) samples were exposed to Streptococcus mutans cultures in the presence or absence of a synthetic lactam. After 48 h incubation, planktonic growth was determined by spectrophotometry. Biofilm was evaluated by crystal violet staining and colony forming units (CFU·ml −1 ), followed by scanning electron microscopy (SEM). Results showed that the average of adhered viable cells was approximately 1.5 × 10 2 CFU/ml in the presence of lactam and 4 × 10 2 CFU/ml in its absence. This novel compound was considerable active in reducing biofilm formation over titanium surfaces, indicating its potential for the development of antimicrobial drugs targeting the inhibition of the initial stages of bacterial biofilms on dental implants abutments. - Highlights: • A novel synthetic compound is tested on preventing biofilm formation on titanium surfaces • Biofilm inhibition has been achieved on titanium surfaces containing the novel compound. • Planktonic growth of S. mutans was not affected by the presence of lactams on titanium.

  3. Periostin Limits Tumor Response to VEGFA Inhibition.

    Keklikoglou, Ioanna; Kadioglu, Ece; Bissinger, Stefan; Langlois, Benoît; Bellotti, Axel; Orend, Gertraud; Ries, Carola H; De Palma, Michele

    2018-03-06

    Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs) under extended vascular-endothelial growth factor A (VEGFA) blockade are dependent on periostin (POSTN), a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA + stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy. POSTN deficiency also impeded the upregulation of basic fibroblast growth factor (FGF2), an adaptive mechanism previously implicated in PNET evasion from antiangiogenic therapy. Higher POSTN expression correlated with markers of M2-like macrophages in human PNETs, and depleting macrophages with a colony-stimulating factor 1 receptor (CSF1R) antibody inhibited PNET revascularization and progression under VEGFA blockade despite continued POSTN production. These findings suggest a role for POSTN in orchestrating resistance to anti-VEGFA therapy in PNETs. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Heat enhances radiation inhibition of wound healing

    Twomey, P.; Hill, S.; Joiner, M.; Hobson, B.; Denekamp, J.

    1987-01-01

    To study the effect of hyperthermia on the inhibition of healing by radiation, the authors used 2 models of wound tensile strength in mice. In one, tensile strength of 1 cm strips of wounded skin was measured. In the other, strength was measured on 2 by 1 by .3 cm surgical prosthetic sponges of polyvinyl alcohol which has been cut, resutured, and implanted subcutaneously. Granulation tissue grows into the pores of the sponges which gradually fill with collagen. Tensile strength in both models was measured on day 14 using a constant strain extensiometer. The wounds were given graduated doses of ortho-voltage radiation with or without hyperthermia. Maximum radiation sensitivity occurred during the period of rapid neovascularization in the first 5 days after wounding, when a loss of 80% in wound strength occurred with doses less than 20 gray. For single radiation doses given 48 hours after wounding, the authors found a steep dose-response curve with half maximum reduction in strength occurring in both models at approximately 10 gray. Hyperthermia was produced in two ways. Skin wounds were heated in a circulating water bath. In the sponge model, more uniform heating occurs with an RF generator scaled to the mouse. At a dose of 43 C for 30 minutes, no inhibition of healing by heat alone was found. However the combination of heat and radiation produced definite enhancement of radiation damage, with thermal enhancement ratios of up to 1.9 being observed

  5. Periostin Limits Tumor Response to VEGFA Inhibition

    Ioanna Keklikoglou

    2018-03-01

    Full Text Available Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs under extended vascular-endothelial growth factor A (VEGFA blockade are dependent on periostin (POSTN, a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA+ stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy. POSTN deficiency also impeded the upregulation of basic fibroblast growth factor (FGF2, an adaptive mechanism previously implicated in PNET evasion from antiangiogenic therapy. Higher POSTN expression correlated with markers of M2-like macrophages in human PNETs, and depleting macrophages with a colony-stimulating factor 1 receptor (CSF1R antibody inhibited PNET revascularization and progression under VEGFA blockade despite continued POSTN production. These findings suggest a role for POSTN in orchestrating resistance to anti-VEGFA therapy in PNETs.

  6. Inhibition by acrolein of light-induced stomatal opening through inhibition of inward-rectifying potassium channels in Arabidopsis thaliana.

    Islam, Md Moshiul; Ye, Wenxiu; Matsushima, Daiki; Khokon, Md Atiqur Rahman; Munemasa, Shintaro; Nakamura, Yoshimasa; Murata, Yoshiyuki

    2015-01-01

    Acrolein is a reactive α,β-unsaturated aldehyde derived from lipid peroxides, which are produced in plants under a variety of stress. We investigated effects of acrolein on light-induced stomatal opening using Arabidopsis thaliana. Acrolein inhibited light-induced stomatal opening in a dose-dependent manner. Acrolein at 100 μM inhibited plasma membrane inward-rectifying potassium (Kin) channels in guard cells. Acrolein at 100 μM inhibited Kin channel KAT1 expressed in a heterologous system using Xenopus leaves oocytes. These results suggest that acrolein inhibits light-induced stomatal opening through inhibition of Kin channels in guard cells.

  7. 3-Bromopyruvate inhibits human gastric cancer tumor growth in nude mice via the inhibition of glycolysis.

    Xian, Shu-Lin; Cao, Wei; Zhang, Xiao-Dong; Lu, Yun-Fei

    2015-02-01

    Tumor cells primarily depend upon glycolysis in order to gain energy. Therefore, the inhibition of glycolysis may inhibit tumor growth. Our previous study demonstrated that 3-bromopyruvate (3-BrPA) inhibited gastric cancer cell proliferation in vitro . However, the ability of 3-BrPA to suppress tumor growth in vivo, and its underlying mechanism, have yet to be elucidated. The aim of the present study was to investigate the inhibitory effect of 3-BrPA in an animal model of gastric cancer. It was identified that 3-BrPA exhibited strong inhibitory effects upon xenograft tumor growth in nude mice. In addition, the antitumor function of 3-BrPA exhibited a dose-effect association, which was similar to that of the chemotherapeutic agent, 5-fluorouracil. Furthermore, 3-BrPA exhibited low toxicity in the blood, liver and kidneys of the nude mice. The present study hypothesized that the inhibitory effect of 3-BrPA is achieved through the inhibition of hexokinase activity, which leads to the downregulation of B-cell lymphoma 2 (Bcl-2) expression, the upregulation of Bcl-2-associated X protein expression and the subsequent activation of caspase-3. These data suggest that 3-BrPA may be a novel therapy for the treatment of gastric cancer.

  8. Does SGLT2 inhibition with dapagliflozin overcome individual therapy resistance to RAAS inhibition?

    Petrykiv, Sergei; Laverman, Gozewijn D.; de Zeeuw, Dick; Heerspink, Hiddo J. L.

    Individual patients show a large variation in their response to renin-angiotensin-aldosteron system (RAAS) inhibition (RAASi), both in surrogates such as albuminuria and in hard renal outcomes. Sodium-glucose co-transporter 2 inhibitors (SGLT2) have been shown to lower albuminuria and to confer

  9. Ketoconazole inhibits the cellular uptake of anandamide via inhibition of FAAH at pharmacologically relevant concentrations.

    Emmelie Björklund

    Full Text Available The antifungal compound ketoconazole has, in addition to its ability to interfere with fungal ergosterol synthesis, effects upon other enzymes including human CYP3A4, CYP17, lipoxygenase and thromboxane synthetase. In the present study, we have investigated whether ketoconazole affects the cellular uptake and hydrolysis of the endogenous cannabinoid receptor ligand anandamide (AEA.The effects of ketoconazole upon endocannabinoid uptake were investigated using HepG2, CaCo2, PC-3 and C6 cell lines. Fatty acid amide hydrolase (FAAH activity was measured in HepG2 cell lysates and in intact C6 cells. Ketoconazole inhibited the uptake of AEA by HepG2 cells and CaCo2 cells with IC50 values of 17 and 18 µM, respectively. In contrast, it had modest effects upon AEA uptake in PC-3 cells, which have a low expression of FAAH. In cell-free HepG2 lysates, ketoconazole inhibited FAAH activity with an IC50 value (for the inhibitable component of 34 µM.The present study indicates that ketoconazole can inhibit the cellular uptake of AEA at pharmacologically relevant concentrations, primarily due to its effects upon FAAH. Ketoconazole may be useful as a template for the design of dual-action FAAH/CYP17 inhibitors as a novel strategy for the treatment of prostate cancer.

  10. Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis.

    Li, Qingli; Lambrechts, Mark J; Zhang, Qiuyang; Liu, Sen; Ge, Dongxia; Yin, Rutie; Xi, Mingrong; You, Zongbing

    2013-01-01

    Glycine is a nonessential amino acid that is reversibly converted from serine intracellularly by serine hydroxymethyltransferase. Glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), are analogs to glycine, thus they may inhibit serine hydroxymethyltransferase to decrease intracellular glycine synthesis. In this study, we found that glyphosate and AMPA inhibited cell growth in eight human cancer cell lines but not in two immortalized human normal prostatic epithelial cell lines. AMPA arrested C4-2B and PC-3 cancer cells in the G1/G0 phase and inhibited entry into the S phase of the cell cycle. AMPA also promoted apoptosis in C4-2B and PC-3 cancer cell lines. AMPA upregulated p53 and p21 protein levels as well as procaspase 9 protein levels in C4-2B cells, whereas it downregulated cyclin D3 protein levels. AMPA also activated caspase 3 and induced cleavage of poly (adenosine diphosphate [ADP]-ribose) polymerase. This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy.

  11. Inhibition of autophagy induced by proteasome inhibition increases cell death in human SHG-44 glioma cells.

    Ge, Peng-Fei; Zhang, Ji-Zhou; Wang, Xiao-Fei; Meng, Fan-Kai; Li, Wen-Chen; Luan, Yong-Xin; Ling, Feng; Luo, Yi-Nan

    2009-07-01

    The ubiquitin-proteasome system (UPS) and lysosome-dependent macroautophagy (autophagy) are two major intracellular pathways for protein degradation. Recent studies suggest that proteasome inhibitors may reduce tumor growth and activate autophagy. Due to the dual roles of autophagy in tumor cell survival and death, the effect of autophagy on the destiny of glioma cells remains unclear. In this study, we sought to investigate whether inhibition of the proteasome can induce autophagy and the effects of autophagy on the fate of human SHG-44 glioma cells. The proteasome inhibitor MG-132 was used to induce autophagy in SHG-44 glioma cells, and the effect of autophagy on the survival of SHG-44 glioma cells was investigated using an autophagy inhibitor 3-MA. Cell viability was measured by MTT assay. Apoptosis and cell cycle were detected by flow cytometry. The expression of autophagy related proteins was determined by Western blot. MG-132 inhibited cell proliferation, induced cell death and cell cycle arrest at G(2)/M phase, and activated autophagy in SHG-44 glioma cells. The expression of autophagy-related Beclin-1 and LC3-I was significantly up-regulated and part of LC3-I was converted into LC3-II. However, when SHG-44 glioma cells were co-treated with MG-132 and 3-MA, the cells became less viable, but cell death and cell numbers at G(2)/M phase increased. Moreover, the accumulation of acidic vesicular organelles was decreased, the expression of Beclin-1 and LC3 was significantly down-regulated and the conversion of LC3-II from LC3-I was also inhibited. Inhibition of the proteasome can induce autophagy in human SHG-44 glioma cells, and inhibition of autophagy increases cell death. This discovery may shed new light on the effect of autophagy on modulating the fate of SHG-44 glioma cells.Acta Pharmacologica Sinica (2009) 30: 1046-1052; doi: 10.1038/aps.2009.71.

  12. Inhibition of GRP78 abrogates radioresistance in oropharyngeal carcinoma cells after EGFR inhibition by cetuximab.

    Chaonan Sun

    Full Text Available The EGFR-specific mAb cetuximab is one of the most effective treatments for oropharyngeal carcinoma, while patient responses to EGFR inhibitors given alone are modest. Combination treatment with radiation can improve the efficacy of treatment through increasing radiosensitivity, while resistance to radiation after administration of cetuximab limits its efficiency. Radiation and drugs can damage the endoplasmic reticulum (ER homeostatic state and result in ER stress (ERS, subsequently causing resistance to radiation and drugs. Whether the ERS pathway is involved in radioresistance after administration of cetuximab has not been reported. Herein, we show that cetuximab could increase the radiosensitivity of FaDu cells but not Detroit562 cells. In addition, cetuximab inhibited the radiation-induced activation of the ERS signalling pathway IRE1α/ATF6-GRP78 in FaDu cells, while this effect was absent in Detroit562 cells. Silencing GRP78 increased the radiosensitivity of oropharyngeal carcinoma cells and inhibited radiation-induced DNA double-strand-break (DSB repair and autophagy. More interestingly, silencing GRP78 abrogated resistance to cetuximab and radiation in Detroit562 cells and had a synergistic effect with cetuximab in increasing the radiosensitivity of FaDu cells. Immunohistochemistry showed that overexpression of both GRP78 and EGFR was associated with a poor prognosis in oropharyngeal carcinoma patients (P<0.05. Overall, the results of this study show that radioresistance after EGFR inhibition by cetuximab is mediated by the ERS signalling pathway IRE1α/ATF6-GRP78. This suppression was consequently unable to inhibit radiation-induced DSB repair and autophagy in oropharyngeal carcinoma cells, which conferred resistance to radiotherapy and cetuximab. These results suggest that the cooperative effects of radiotherapy and cetuximab could be further improved by inhibiting GRP78 in non-responsive oropharyngeal carcinoma patients.

  13. A novel approach to inhibit bone resorption

    Panwar, Preety; Søe, Kent; Guido, Rafael VC

    2016-01-01

    BACKGROUND AND PURPOSE: Cathepsin K (CatK) is a major drug target for the treatment of osteoporosis. Potent active site-directed inhibitors have been developed and showed variable success in clinical trials. These inhibitors block the entire activity of CatK and thus may interfere with other...... pathways. The present study investigates the antiresorptive effect of an exosite inhibitor that selectively inhibits only the therapeutically relevant collagenase activity of CatK. EXPERIMENTAL APPROACH: Human osteoclasts and fibroblasts were used to analyse the effect of the exosite inhibitor, ortho......-dihydrotanshinone (DHT1), and the active site inhibitor, odanacatib (ODN), on bone resorption and TGF-ß1 degradation. Cell cultures, Western blot, light and scanning electron microscopy as well as energy dispersive X-ray spectroscopy, molecular modelling and enzymatic assays were used to evaluate the inhibitors. KEY...

  14. Diclofenac inhibits 27-hydroxycholesterol-induced inflammation.

    Kim, Bo-Young; Son, Yonghae; Eo, Seong-Kug; Park, Young Chul; Kim, Koanhoi

    2016-09-23

    27-Hydroxycholesterol (27OHChol) is a cholesterol oxidation product that induces inflammation. In the current study we investigated the effects of diclofenac on inflammatory responses caused by 27OHChol using human monocyte/macrophage (THP-1) cells. Transcription and secretion of CCL2, CCL3, and CCL4 chemokines enhanced by 27OHChol were significantly attenuated by diclofenac in a concentration dependent manner. Migrations of monocytic cells and CCR5-positive Jurkat T cells were reduced proportionally to the concentrations of diclofenac. Superproduction of CCL2 and monocytic cell migration induced by 27OHChol plus LPS were significantly attenuated by diclofenac. Diclofenac also attenuated transcription of MMP-9 and release of its active gene product. These results indicate that diclofenac inhibits 27OHChol-induced inflammatory responses, thereby suppressing inflammation in a milieu rich in cholesterol oxidation products. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Isoform-specific inhibition of cyclophilins.

    Daum, Sebastian; Schumann, Michael; Mathea, Sebastian; Aumüller, Tobias; Balsley, Molly A; Constant, Stephanie L; de Lacroix, Boris Féaux; Kruska, Fabian; Braun, Manfred; Schiene-Fischer, Cordelia

    2009-07-07

    Cyclophilins belong to the enzyme class of peptidyl prolyl cis-trans isomerases which catalyze the cis-trans isomerization of prolyl bonds in peptides and proteins in different folding states. Cyclophilins have been shown to be involved in a multitude of cellular functions like cell growth, proliferation, and motility. Among the 20 human cyclophilin isoenzymes, the two most abundant members of the cyclophilin family, CypA and CypB, exhibit specific cellular functions in several inflammatory diseases, cancer development, and HCV replication. A small-molecule inhibitor on the basis of aryl 1-indanylketones has now been shown to discriminate between CypA and CypB in vitro. CypA binding of this inhibitor has been characterized by fluorescence anisotropy- and isothermal titration calorimetry-based cyclosporin competition assays. Inhibition of CypA- but not CypB-mediated chemotaxis of mouse CD4(+) T cells by the inhibitor provided biological proof of discrimination in vivo.

  16. Inhibition of cellular oxidation by fluoride

    Borei, H

    1945-01-01

    An attempt has been made to investigate the inhibition by fluoride of the oxidative processes which occur in the cell by way of the cytochrome oxidase-cytochrome system. Some chemical and physical properties of the fluoride ion are discussed, together with certain quantitative methods for the determination of fluoride. An exhaustive review of the literature concerning the effect of fluoride on enzymic processes has been compiled. The experiments have shown that the point of the attack by fluoride is to be found among the cytochromes. The inhibitory mechanism appears to be such that the haemoprotein is prevented from taking part in the preceding and succeeding links in the reaction chain. The blocking action leaves the prosthetic group of the haemoprotein completely unchanged. The experimental results indicate the formation of a fluorophosphoprotein complex, analogous to that found in the case of enolase. Magnesium may possibly play a part in this process.

  17. Inhibition of Neurogenesis by Zika virus Infection.

    Ahmad, Fahim; Siddiqui, Amna; Kamal, Mohammad A; Sohrab, Sayed S

    2018-02-01

    The association between Zika virus infection and neurological disorder has raised urgent global alarm. The ongoing epidemic has triggered quick responses in the scientific community. The first case of Zika virus was reported in 2015 from Brazil and now has spread over 30 countries. Nearly four hundred cases of travel-associated Zika virus infection have also been reported in the United States. Zika virus is primarily transmitted by mosquito belongs to the genus Aedes that are widely distributed throughout the world including the Southern United States. Additionally, the virus can also be transmitted from males to females by sexual contact. The epidemiological investigations during the current outbreak found a causal link between infection in pregnant women and development of microcephaly in their unborn babies. This finding is a cause for grave concern since microcephaly is a serious neural developmental disorder that can lead to significant post-natal developmental abnormalities and disabilities. Recently, published data indicate that Zika virus infection affects the growth of fetal neural progenitor cells and cerebral neurons that results in malformation of cerebral cortex leading to microcephaly. Recently, it has been reported that Zika virus infection deregulates the signaling pathway of neuronal cell and inhibit the neurogenesis resulting into dementia. In this review we have discussed about the information about cellular and molecular mechanisms in neurodegeneration of human neuronal cells and inhibit the neurogenesis. Additionally, this information will be very helpful further not only in neuro-scientific research but also designing and development of management strategies for microcephaly and other mosquito borne disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Spice phenolics inhibit human PMNL 5-lipoxygenase.

    Prasad, N Satya; Raghavendra, R; Lokesh, B R; Naidu, K Akhilender

    2004-06-01

    A wide variety of phenolic compounds and flavonoids present in spices possess potent antioxidant, antimutagenic and anticarcinogenic activities. We examined whether 5-lipoxygenase (5-LO), the key enzyme involved in biosynthesis of leukotrienes is a possible target for the spices. Effect of aqueous extracts of turmeric, cloves, pepper, chili, cinnamon, onion and also their respective active principles viz., curcumin, eugenol, piperine, capsaicin, cinnamaldehyde, quercetin, and allyl sulfide were tested on human PMNL 5-LO activity by spectrophotomeric and HPLC methods. The formation of 5-LO product 5-HETE was significantly inhibited in a concentration-dependent manner with IC(50) values of 0.122-1.44 mg for aqueous extracts of spices and 25-83 microM for active principles, respectively. The order of inhibitory activity was of quercetin>eugenol>curcumin>cinnamaldehyde>piperine>capsaicin>allyl sulfide. Quercetin, eugenol and curcumin with one or more phenolic ring and methoxy groups in their structure showed high inhibitory effect, while the non-phenolic spice principle allyl sulfide showed least inhibitory effect on 5-LO. The inhibitory effect of quercetin, curcumin and eugenol was similar to that of synthetic 5-LO inhibitors-phenidone and NDGA. Moreover, the inhibitory potency of aqueous extracts of spice correlated with the active principles of their respective spices. The synergistic or antagonistic effect of mixtures of spice active principles and spice extracts were investigated and all the combinations of spice active principles/extracts exerted synergistic effect in inhibiting 5-LO activity. These findings clearly suggest that phenolic compounds present in spices might have physiological role in modulating 5-LO pathway.

  19. Inhibition of Zika Virus Replication by Silvestrol

    Fabian Elgner

    2018-03-01

    Full Text Available The Zika virus (ZIKV outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A which is required to unwind structured 5´-untranslated regions (5′-UTRs of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5′-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted.

  20. Notch Inhibits Osteoblast Differentiation and Causes Osteopenia

    Zanotti, Stefano; Smerdel-Ramoya, Anna; Stadmeyer, Lisa; Durant, Deena; Radtke, Freddy; Canalis, Ernesto

    2008-01-01

    Notch receptors are determinants of cell fate decisions. To define the role of Notch in the adult skeleton, we created transgenic mice overexpressing the Notch intracellular domain (NICD) under the control of the type I collagen promoter. First-generation transgenics were small and osteopenic. Bone histomorphometry revealed that NICD caused a decrease in bone volume, secondary to a reduction in trabecular number; osteoblast and osteoclast number were decreased. Low fertility of founder mice and lethality of young pups did not allow the complete establishment of transgenic lines. To characterize the effect of Notch overexpression in vitro, NICD was induced in osteoblasts and stromal cells from Rosanotch mice, in which a STOP cassette flanked by loxP sites is upstream of NICD, by transduction with an adenoviral vector expressing Cre recombinase (Cre) under the control of the cytomegalovirus (CMV) promoter (Ad-CMV-Cre). NICD impaired osteoblastogenesis and inhibited Wnt/β-catenin signaling. To determine the effects of notch1 deletion in vivo, mice in which notch1 was flanked by loxP sequences (notch1loxP/loxP) were mated with mice expressing Cre recombinase under the control of the osteocalcin promoter. Conditional null notch1 mice had no obvious skeletal phenotype, possibly because of rescue by notch2; however, 1-month-old females exhibited a modest increase in osteoclast surface and eroded surface. Osteoblasts from notch1loxP/loxP mice, transduced with Ad-CMV-Cre and transfected with Notch2 small interfering RNA, displayed increased alkaline phosphatase activity. In conclusion, Notch signaling in osteoblasts causes osteopenia and impairs osteo-blastogenesis by inhibiting the Wnt/β-catenin pathway. PMID:18420737

  1. Cartilage proteoglycans inhibit fibronectin-mediated adhesion

    Rich, A. M.; Pearlstein, E.; Weissmann, G.; Hoffstein, S. T.

    1981-09-01

    Normal tissues and organs show, on histological examination, a pattern of cellular and acellular zones that is characteristic and unique for each organ or tissue. This pattern is maintained in health but is sometimes destroyed by disease. For example, in mobile joints, the articular surfaces consist of relatively acellular hyaline cartilage, and the joint space is enclosed by a capsule of loose connective tissue with a lining of fibroblasts and macrophages. In the normal joint these cells are confined to the synovial lining and the articular surface remains acellular. In in vitro culture, macrophages and their precursor monocytes are very adhesive, and fibroblasts can migrate and overgrow surfaces such as collagen or plastic used for tissue culture. The fibroblasts adhere to collagen by means of fibronectin, which they synthesize and secrete1. Because the collagen of cartilage is capable of binding serum fibronectin2 and fibronectin is present in cartilage during its development3, these cells should, in theory, slowly migrate from the synovial lining to the articular surface. It is their absence from the articular cartilage in normal circumstances, and then presence in such pathological states as rheumatoid arthritis, that is striking. We therefore set out to determine whether a component of cartilage could prevent fibroblast adherence in a defined adhesion assay. As normal cartilage is composed of 50% proteoglycans and 50% collagen by dry weight4, we tested the possibility that the proteoglycans in cartilage inhibit fibroblast adhesion to collagen. We present here evidence that fibroblast spreading and adhesion to collagenous substrates is inhibited by cartilage proteoglycans.

  2. Inhibition of MAO by fractions and constituents of hypericum extract.

    Bladt, S; Wagner, H

    1994-10-01

    The inhibition of monoamine oxidase (MAO) by six fractions from hypericum extract and three characteristic constituents (as pure substances) were analyzed in vitro and ex vivo to study the antidepressive mechanism of action. Rat brain homogenates were used as the in vitro model, while the ex vivo analysis was performed after intraperitoneal application of the test substances to albino rats. Massive inhibition of MAO-A could be shown with the total extract and all fractions only at the concentration of 10(-3) mol/L. At 10(-4) mol/L, one fraction rich in flavonoides showed an inhibition of 39%, and all other fractions demonstrated less than 25% inhibition. Using pure hypericin as well as in all ex vivo experiments, no relevant inhibiting effects could be shown. From the results it can be concluded that the clinically proven antidepressive effect of hypericum extract cannot be explained in terms of MAO inhibition.

  3. Gliclazide directly inhibits arginine-induced glucagon release

    Cejvan, Kenan; Coy, David H; Holst, Jens Juul

    2002-01-01

    Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of glicl......Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect....... In islet perifusions with DC-41-33, arginine-induced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell....

  4. Molecular mechanisms of DNA repair inhibition by caffeine

    Selby, C.P.; Sancar, A. (Univ. of North Carolina School of Medicine, Chapel Hill (USA))

    1990-05-01

    Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA.

  5. Inhibition of Action, Thought, and Emotion: A Selective Neurobiological Review

    Dillon, Daniel; Pizzagalli, Diego

    2007-01-01

    The neural bases of inhibitory function are reviewed, covering data from paradigms assessing inhibition of motor responses (antisaccade, go/nogo, stop-signal), cognitive sets (e.g., Wisconsin Card Sort Test), and emotion (fear extinction). The frontal cortex supports performance on these paradigms, but the specific neural circuitry varies: response inhibition depends upon fronto-basal ganglia networks, inhibition of cognitive sets is supported by orbitofrontal cortex, and retention of fear ex...

  6. High molecular weight polysaccharide that binds and inhibits virus

    Konowalchuk, Thomas W

    2014-01-14

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods on inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  7. Inhibition of poliovirus RNA synthesis by brefeldin A.

    Maynell, L A; Kirkegaard, K; Klymkowsky, M W

    1992-01-01

    Brefeldin A (BFA), a fungal metabolite that blocks transport of newly synthesized proteins from the endoplasmic reticulum, was found to inhibit poliovirus replication 10(5)- to 10(6)-fold. BFA does not inhibit entry of poliovirus into the cell or translation of viral RNA. Poliovirus RNA synthesis, however, is completely inhibited by BFA. A specific class of membranous vesicles, with which the poliovirus replication complex is physically associated, is known to proliferate in poliovirus-infect...

  8. Chemical mechanism of the fluoride-inhibition of fermentation

    Warburg, O; Christian, W

    1941-08-01

    Among the fluoride-sensitive fermentation elements, enolase is the most sensitive. An investigation was made, quantitatively, of fluoride inhibition for chemically pure magnesium-enolase using an optical enolase test. Data show that the effective compound for fluoride inhibition is a complex magnesium-fluoro-phosphate and that the magnesium-fluoro-phosphate inhibits fermentation by combining proportionally to its concentration with the ferment-protein in a dissociating manner.

  9. High molecular weight polysaccharide that binds and inhibits virus

    Konowalchuk, Thomas W.; Konowalchuk, Jack

    2017-07-18

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods of inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further includes methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  10. A speculated cause of respiratory inhibition in infants.

    Minowa, Hideki; Arai, Ikuyo; Yasuhara, Hajime; Ebisu, Reiko; Ohgitani, Ayako

    2018-10-01

    In our previous studies, we documented that threatened premature labor and asymmetrical intrauterine growth restriction were risk factors for respiratory inhibition. The goal of this study was to determine the cause of respiratory inhibition by considering perinatal risk factors. We examined 1497 infants with a gestational age of 36 weeks or greater. All infants were monitored using pulse oximetry and examined via cranial sonography. Respiratory inhibition was defined as severe hypoxemia caused by respiratory inhibition immediately after crying or gastroesophageal reflux or as a respiratory pause during feeding. We examined the relationships between respiratory inhibition and perinatal factors and speculated on the cause of respiratory inhibition. The median gestational age, birth weight, Apgar score at 1 min, and Apgar score at 5 min of the subjects were 38.9 weeks, 2930 g, 8.0 points, and 9.0 points, respectively. Respiratory inhibition was observed in 422 infants. Lateral ventricle enlargement and increased echogenicity in the ganglionic eminence were observed in 417 and 516 infants, respectively. Respiratory inhibition was significantly correlated with shorter gestational periods, twin pregnancies, lateral ventricle enlargement, and increased echogenicity in the ganglionic eminence. We speculate that umbilical cord compression is a major cause of respiratory inhibition.

  11. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

    Chen, Ying-Nan P.; LaMarche, Matthew J.; Chan, Ho Man; Fekkes, Peter; Garcia-Fortanet, Jorge; Acker, Michael G.; Antonakos, Brandon; Chen, Christine Hiu-Tung; Chen, Zhouliang; Cooke, Vesselina G.; Dobson, Jason R.; Deng, Zhan; Fei, Feng; Firestone, Brant; Fodor, Michelle; Fridrich, Cary; Gao, Hui; Grunenfelder, Denise; Hao, Huai-Xiang; Jacob, Jaison; Ho, Samuel; Hsiao, Kathy; Kang, Zhao B.; Karki, Rajesh; Kato, Mitsunori; Larrow, Jay; La Bonte, Laura R.; Lenoir, Francois; Liu, Gang; Liu, Shumei; Majumdar, Dyuti; Meyer, Matthew J.; Palermo, Mark; Perez, Lawrence; Pu, Minying; Price, Edmund; Quinn, Christopher; Shakya, Subarna; Shultz, Michael D.; Slisz, Joanna; Venkatesan, Kavitha; Wang, Ping; Warmuth, Markus; Williams, Sarah; Yang, Guizhi; Yuan, Jing; Zhang, Ji-Hu; Zhu, Ping; Ramsey, Timothy; Keen, Nicholas J.; Sellers, William R.; Stams, Travis; Fortin , Pascal D. (Novartis)

    2016-06-29

    The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase1. Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma1, 2, 3, 4, 5. SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS–ERK signalling pathway2, 3. It is also a key mediator of the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) immune checkpoint pathways6, 7. Reduction of SHP2 activity suppresses tumour cell growth and is a potential target of cancer therapy8, 9. Here we report the discovery of a highly potent (IC50 = 0.071 μM), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHP2 in an auto-inhibited conformation. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models. Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers.

  12. Arctigenin Inhibits Liver Cancer Tumorigenesis by Inhibiting Gankyrin Expression via C/EBPα and PPARα

    Ying Sun; Ying Sun; Yu-jun Tan; Yu-jun Tan; Zhan-zhao Lu; Zhan-zhao Lu; Bing-bing Li; Bing-bing Li; Cheng-hong Sun; Cheng-hong Sun; Tao Li; Tao Li; Li-li Zhao; Li-li Zhao; Zhong Liu

    2018-01-01

    Burdock (Arctium lappa) is a popular vegetable in China and Japan that is consumed for its general health benefits. The principal active component of burdock is arctigenin, which shows a range of bioactivities in vivo and in vitro. Here, we investigated the potential anti-tumor effects of arctigenin using two human hepatocellular carcinoma (HCC) cell lines, HepG2 and Hep3B, and sought to elucidate its potential mechanisms of action. Our results showed that arctigenin treatment inhibited cell ...

  13. Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis

    Li Q

    2013-07-01

    Full Text Available Qingli Li,1,2 Mark J Lambrechts,1 Qiuyang Zhang,1 Sen Liu,1 Dongxia Ge,1 Rutie Yin,2 Mingrong Xi,2 Zongbing You1 1Departments of Structural and Cellular Biology and Orthopaedic Surgery, Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane Center for Stem Cell Research and Regenerative Medicine, and Tulane Center for Aging, Tulane University Health Sciences Center, New Orleans, LA, USA; 2Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Glycine is a nonessential amino acid that is reversibly converted from serine intracellularly by serine hydroxymethyltransferase. Glyphosate and its degradation product, aminomethylphosphonic acid (AMPA, are analogs to glycine, thus they may inhibit serine hydroxymethyltransferase to decrease intracellular glycine synthesis. In this study, we found that glyphosate and AMPA inhibited cell growth in eight human cancer cell lines but not in two immortalized human normal prostatic epithelial cell lines. AMPA arrested C4-2B and PC-3 cancer cells in the G1/G0 phase and inhibited entry into the S phase of the cell cycle. AMPA also promoted apoptosis in C4-2B and PC-3 cancer cell lines. AMPA upregulated p53 and p21 protein levels as well as procaspase 9 protein levels in C4-2B cells, whereas it downregulated cyclin D3 protein levels. AMPA also activated caspase 3 and induced cleavage of poly (adenosine diphosphate [ADP]-ribose polymerase. This study provides the first evidence that glyphosate and AMPA can inhibit proliferation and promote apoptosis of cancer cells but not normal cells, suggesting that they have potentials to be developed into a new anticancer therapy. Keywords: serine hydroxymethyltransferase, prostate cancer, apoptosis

  14. Ketamine inhibits 45Ca influx and catecholamine secretion by inhibiting 22Na influx in cultured bovine adrenal medullary cells

    Takara, Hiroshi; Wada, Akihiko; Arita, Masahide; Izumi, Futoshi; Sumikawa, Koji

    1986-01-01

    The effects of ketamine, an intravenous anesthetic, on 22 Na influx, 45 Ca influx and catecholamine secretion were investigated in cultured bovine adrenal medullary cells. Ketamine inhibited carbachol-induced 45 Ca influx and catecholamine secretion in a concentration-dependent manner with a similar potency. Ketamine also reduced veratridine-induced 45 Ca influx and catecholamine secretion. The influx of 22 Na caused by carbachol or by veratridine was suppressed by ketamine with a concentration-inhibition curve similar to that of 45 Ca influx and catecholamine secretion. Inhibition by ketamine of the carbachol-induced influx of 22 Na, 45 Ca and secretion of catecholamines was not reversed by the increased concentrations of carbachol. These observations indicate that ketamine, at clinical concentrations, can inhibit nicotinic receptor-associated ionic channels and that the inhibition of Na influx via the receptor-associated ionic channels is responsible for the inhibition of carbachol-induced Ca influx and catecholamine secretion. (Auth.)

  15. Fluoxetine-induced inhibition of synaptosomal [3H]5-HT release: Possible Ca2+-channel inhibition

    Stauderman, K.A.; Gandhi, V.C.; Jones, D.J.

    1992-01-01

    Fluoxetine, a selective 5-Ht uptake inhibitor, inhibited 15 mM K + -induced [ 3 H]5-HT release from rat spinal cord and cortical synaptosomes at concentrations > 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K + used to depolarize the synaptosomes and the concentration of external Ca 2+ . Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of [ 3 H]5-HT release induced by the Ca 2+ -ionophore A 23187 or Ca 2+ -independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K + -induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca 2+ channels and Ca 2+ entry

  16. Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism and inhibits parathion intoxication.

    Jan, Yi-Hua; Richardson, Jason R; Baker, Angela A; Mishin, Vladimir; Heck, Diane E; Laskin, Debra L; Laskin, Jeffrey D

    2015-10-01

    Parathion, a widely used organophosphate insecticide, is considered a high priority chemical threat. Parathion toxicity is dependent on its metabolism by the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon causes the accumulation of acetylcholine in synapses and overstimulation of nicotinic and muscarinic cholinergic receptors, leading to characteristic signs of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon represents a potential approach to counter parathion toxicity. Herein, we demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase that preferentially uses electrons from NADPH at the expense of their supply to the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes, menadione was found to inhibit the formation of paraoxon from parathion. Administration of menadione bisulfite (40mg/kg, ip) to rats also reduced parathion-induced inhibition of brain cholinesterase activity, as well as parathion-induced tremors and the progression of other signs and symptoms of parathion poisoning. These data suggest that redox cycling compounds, such as menadione, have the potential to effectively mitigate the toxicity of organophosphorus pesticides including parathion which require cytochrome P450-mediated activation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Inhibition of chrysin on xanthine oxidase activity and its inhibition mechanism.

    Lin, Suyun; Zhang, Guowen; Liao, Yijing; Pan, Junhui

    2015-11-01

    Chrysin, a bioactive flavonoid, was investigated for its potential to inhibit the activity of xanthine oxidase (XO), a key enzyme catalyzing xanthine to uric acid and finally causing gout. The kinetic analysis showed that chrysin possessed a strong inhibition on XO ability in a reversible competitive manner with IC50 value of (1.26±0.04)×10(-6)molL(-1). The results of fluorescence titrations indicated that chrysin bound to XO with high affinity, and the interaction was predominately driven by hydrogen bonds and van der Waals forces. Analysis of circular dichroism demonstrated that chrysin induced the conformational change of XO with increases in α-helix and β-sheet and reductions in β-turn and random coil structures. Molecular simulation revealed that chrysin interacted with the amino acid residues Leu648, Phe649, Glu802, Leu873, Ser876, Glu879, Arg880, Phe1009, Thr1010, Val1011 and Phe1013 located within the active cavity of XO. The mechanism of chrysin on XO activity may be the insertion of chrysin into the active site occupying the catalytic center of XO to avoid the entrance of xanthine and causing conformational changes in XO. Furthermore, the interaction assays indicated that chrysin and its structural analog apigenin exhibited an additive effect on inhibition of XO. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Inhibition of lignin-derived phenolic compounds to cellulase.

    Qin, Lei; Li, Wen-Chao; Liu, Li; Zhu, Jia-Qing; Li, Xia; Li, Bing-Zhi; Yuan, Ying-Jin

    2016-01-01

    Lignin-derived phenolic compounds are universal in the hydrolysate of pretreated lignocellulosic biomass. The phenolics reduce the efficiency of enzymatic hydrolysis and increase the cost of ethanol production. We investigated inhibition of phenolics on cellulase during enzymatic hydrolysis using vanillin as one of the typical lignin-derived phenolics and Avicel as cellulose substrate. As vanillin concentration increased from 0 to 10 mg/mL, cellulose conversion after 72-h enzymatic hydrolysis decreased from 53 to 26 %. Enzyme deactivation and precipitation were detected with the vanillin addition. The enzyme concentration and activity consecutively decreased during hydrolysis, but the inhibition degree, expressed as the ratio of the cellulose conversion without vanillin to the conversion with vanillin (A 0 /A), was almost independent on hydrolysis time. Inhibition can be mitigated by increasing cellulose loading or cellulase concentration. The inhibition degree showed linear relationship with the vanillin concentration and exponential relationship with the cellulose loading and the cellulase concentration. The addition of calcium chloride, BSA, and Tween 80 did not release the inhibition of vanillin significantly. pH and temperature for hydrolysis also showed no significant impact on inhibition degree. The presence of hydroxyl group, carbonyl group, and methoxy group in phenolics affected the inhibition degree. Besides phenolics concentration, other factors such as cellulose loading, enzyme concentration, and phenolic structure also affect the inhibition of cellulose conversion. Lignin-blocking agents have little effect on the inhibition effect of soluble phenolics, indicating that the inhibition mechanism of phenolics to enzyme is likely different from insoluble lignin. The inhibition of soluble phenolics can hardly be entirely removed by increasing enzyme concentration or adding blocking proteins due to the dispersity and multiple binding sites of phenolics

  19. Altered cortical processing of motor inhibition in schizophrenia.

    Lindberg, Påvel G; Térémetz, Maxime; Charron, Sylvain; Kebir, Oussama; Saby, Agathe; Bendjemaa, Narjes; Lion, Stéphanie; Crépon, Benoît; Gaillard, Raphaël; Oppenheim, Catherine; Krebs, Marie-Odile; Amado, Isabelle

    2016-12-01

    Inhibition is considered a key mechanism in schizophrenia. Short-latency intracortical inhibition (SICI) in the motor cortex is reduced in schizophrenia and is considered to reflect locally deficient γ-aminobutyric acid (GABA)-ergic modulation. However, it remains unclear how SICI is modulated during motor inhibition and how it relates to neural processing in other cortical areas. Here we studied motor inhibition Stop signal task (SST) in stabilized patients with schizophrenia (N = 28), healthy siblings (N = 21) and healthy controls (n = 31) matched in general cognitive status and educational level. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were used to investigate neural correlates of motor inhibition. SST performance was similar in patients and controls. SICI was modulated by the task as expected in healthy controls and siblings but was reduced in patients with schizophrenia during inhibition despite equivalent motor inhibition performance. fMRI showed greater prefrontal and premotor activation during motor inhibition in schizophrenia. Task-related modulation of SICI was higher in subjects who showed less inhibition-related activity in pre-supplementary motor area (SMA) and cingulate motor area. An exploratory genetic analysis of selected markers of inhibition (GABRB2, GAD1, GRM1, and GRM3) did not explain task-related differences in SICI or cortical activation. In conclusion, this multimodal study provides direct evidence of a task-related deficiency in SICI modulation in schizophrenia likely reflecting deficient GABA-A related processing in motor cortex. Compensatory activation of premotor areas may explain similar motor inhibition in patients despite local deficits in intracortical processing. Task-related modulation of SICI may serve as a useful non-invasive GABAergic marker in development of therapeutic strategies in schizophrenia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Pharmacologic inhibition of lactate production prevents myofibroblast differentiation.

    Kottmann, Robert Matthew; Trawick, Emma; Judge, Jennifer L; Wahl, Lindsay A; Epa, Amali P; Owens, Kristina M; Thatcher, Thomas H; Phipps, Richard P; Sime, Patricia J

    2015-12-01

    Myofibroblasts are one of the primary cell types responsible for the accumulation of extracellular matrix in fibrosing diseases, and targeting myofibroblast differentiation is an important therapeutic strategy for the treatment of pulmonary fibrosis. Transforming growth factor-β (TGF-β) has been shown to be an important inducer of myofibroblast differentiation. We previously demonstrated that lactate dehydrogenase and its metabolic product lactic acid are important mediators of myofibroblast differentiation, via acid-induced activation of latent TGF-β. Here we explore whether pharmacologic inhibition of LDH activity can prevent TGF-β-induced myofibroblast differentiation. Primary human lung fibroblasts from healthy patients and those with pulmonary fibrosis were treated with TGF-β and or gossypol, an LDH inhibitor. Protein and RNA were analyzed for markers of myofibroblast differentiation and extracellular matrix generation. Gossypol inhibited TGF-β-induced expression of the myofibroblast marker α-smooth muscle actin (α-SMA) in a dose-dependent manner in both healthy and fibrotic human lung fibroblasts. Gossypol also inhibited expression of collagen 1, collagen 3, and fibronectin. Gossypol inhibited LDH activity, the generation of extracellular lactic acid, and the rate of extracellular acidification in a dose-dependent manner. Furthermore, gossypol inhibited TGF-β bioactivity in a dose-dependent manner. Concurrent treatment with an LDH siRNA increased the ability of gossypol to inhibit TGF-β-induced myofibroblast differentiation. Gossypol inhibits TGF-β-induced myofibroblast differentiation through inhibition of LDH, inhibition of extracellular accumulation of lactic acid, and inhibition of TGF-β bioactivity. These data support the hypothesis that pharmacologic inhibition of LDH may play an important role in the treatment of pulmonary fibrosis. Copyright © 2015 the American Physiological Society.

  1. Saberes e práticas de acompanhantes sobre complicações respiratórias pós-cirúrgicas no idoso, compartilhados com a enfermeira Conocimientos y prácticas de acompañantes sobre complicaciones respiratorias posquirúrgicas en ancianos, compartidas con la enfermera Knowledge and experiences of caregivers for post-surgical respiratory complications in elderly people, shared with the nurse

    Maria da Luz Ferreira Xavier

    2012-09-01

    conocimientos y prácticas de los acompañantes con los de la enfermera/investigadora en la visita preoperatoria. Resultaron en nuevas o revisitadas prácticas, culminando en un cuidado congruente a las reales necesidades de los clientes y sus acompañantes, tornándolos compañeros en el proceso de cuidar.This is a convergent-assistance research, whose goal was to analyze the knowledge and experiences of caregivers focused on the prevention for post-surgical respiratory in the elderly people, in order to develop a care plan to be implemented with these clients. The theoretical and conceptual bases founded on the Critical Pedagogy of Freire. The subjects were 14 caregivers of elderly on a pre-surgical period. The technique used was individual interviews, participant observation and the analysis of a thematic content. The results showed that the caregivers accumulate knowledge, concerning to the basic care in the post-surgical, able to prevent respiratory problems. Through the dialogue it was developed a shared care plan to be realized with the elderly, as a result from the integration of the knowledge and experiences from the caregivers and from the nurse-researcher on a pre-surgical visit. The result was the new or revisited practices, culminating into a congruent care to the real needs of the clients and theirs companions, becoming partners in the care process.

  2. High outgroup entitativity can inhibit intergroup retribution.

    Newheiser, Anna-Kaisa; Dovidio, John F

    2015-06-01

    Understanding the psychological processes that are involved in the perpetuation and escalation of intergroup conflict remains an important goal for intergroup relations research. In the present research, we examined perceived outgroup entitativity as a potential determinant of intergroup hostility. In intergroup conflict situations, high-entitative outgroups are perceived as particularly deserving of retribution; however, high-entitative outgroups are also perceived as efficacious and capable of retaliating successfully, suggesting that people may inhibit hostility against high-entitative (vs. low-entitative) outgroups that are in a position to retaliate. We tested this prediction in two studies. In Study 1, we manipulated intergroup provocation and outgroup entitativity, and found that higher negative mood predicted greater aggression against a low-entitative provoker outgroup, but failed to predict aggression against a high-entitative provoker outgroup that was plausibly in a position to retaliate. In Study 2, we held provocation constant while manipulating outgroup entitativity and the possibility of retaliation by the outgroup, and found that people acted in a retributive manner against a high-entitative provoker outgroup only when the outgroup was not in a position to retaliate. Implications for intergroup conflict are discussed. © 2014 The British Psychological Society.

  3. Poxviruses Utilize Multiple Strategies to Inhibit Apoptosis

    Nichols, Daniel Brian; De Martini, William; Cottrell, Jessica

    2017-01-01

    Cells have multiple means to induce apoptosis in response to viral infection. Poxviruses must prevent activation of cellular apoptosis to ensure successful replication. These viruses devote a substantial portion of their genome to immune evasion. Many of these immune evasion products expressed during infection antagonize cellular apoptotic pathways. Poxvirus products target multiple points in both the extrinsic and intrinsic apoptotic pathways, thereby mitigating apoptosis during infection. Interestingly, recent evidence indicates that poxviruses also hijack cellular means of eliminating apoptotic bodies as a means to spread cell to cell through a process called apoptotic mimicry. Poxviruses are the causative agent of many human and veterinary diseases. Further, there is substantial interest in developing these viruses as vectors for a variety of uses including vaccine delivery and as oncolytic viruses to treat certain human cancers. Therefore, an understanding of the molecular mechanisms through which poxviruses regulate the cellular apoptotic pathways remains a top research priority. In this review, we consider anti-apoptotic strategies of poxviruses focusing on three relevant poxvirus genera: Orthopoxvirus, Molluscipoxvirus, and Leporipoxvirus. All three genera express multiple products to inhibit both extrinsic and intrinsic apoptotic pathways with many of these products required for virulence. PMID:28786952

  4. Inhibition of oxidation in nuclear graphite

    Winston, Philip L.; Sterbentz, James W.; Windes, William E.

    2015-01-01

    Graphite is a fundamental material of high-temperature gas-cooled nuclear reactors, providing both structure and neutron moderation. Its high thermal conductivity, chemical inertness, thermal heat capacity, and high thermal structural stability under normal and off-normal conditions contribute to the inherent safety of these reactor designs. One of the primary safety issues for a high-temperature graphite reactor core is the possibility of rapid oxidation of the carbon structure during an off-normal design basis event where an oxidising atmosphere (air ingress) can be introduced to the hot core. Although the current Generation IV high-temperature reactor designs attempt to mitigate any damage caused by a postulated air ingress event, the use of graphite components that inhibit oxidation is a logical step to increase the safety of these reactors. Recent experimental studies of graphite containing between 5.5 and 7 wt% boron carbide (B 4 C) indicate that oxidation is dramatically reduced even at prolonged exposures at temperatures up to 900 deg. C. The proposed addition of B 4 C to graphite components in the nuclear core would necessarily be enriched in B-11 isotope in order to minimise B-10 neutron absorption and graphite swelling. The enriched boron can be added to the graphite during billet fabrication. Experimental oxidation rate results and potential applications for borated graphite in nuclear reactor components will be discussed. (authors)

  5. Conditioned inhibition in the spatial domain.

    Sansa, J; Rodrigo, T; Santamaría, J J; Manteiga, R D; Chamizo, V D

    2009-10-01

    Using a variation on the standard procedure of conditioned inhibition (Trials A+ and AX-), rats (Rattus norvegicus) in a circular pool were trained to find a hidden platform that was located in a specific spatial position in relation to 2 individual landmarks (Trials A --> platform and B --> platform; Experiments 1a and 1b) and to 2 configurations of landmarks (Trials ABC --> platform and FGH --> platform; Experiment 2a). The rats also underwent inhibitory trials (Experiment 1: Trials AZ --> no platform; Experiment 2a: Trials CDE --> no platform) interspersed with these excitatory trials. In both experiments, subsequent test trials without the platform showed both a summation effect and retardation of excitatory conditioning, and in Experiment 2a rats learned to avoid the CDE quadrant over the course of the experiment. Two further experiments established that these results could not be attributed to any difference in salience between the conditioned inhibitors and the control stimuli. All these results contribute to the growing body of evidence consistent with the idea that there is a general mechanism of learning that is associative in nature. PsycINFO Database Record (c) 2009 APA, all rights reserved.

  6. Inhibition of RAS in diabetic nephropathy

    Yacoub R

    2015-04-01

    Full Text Available Rabi Yacoub, Kirk N Campbell Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY, USA Abstract: Diabetic kidney disease (DKD is a progressive proteinuric renal disorder in patients with type 1 or type 2 diabetes mellitus. It is a common cause of end-stage kidney disease worldwide, particularly in developed countries. Therapeutic targeting of the renin–angiotensin system (RAS is the most validated clinical strategy for slowing disease progression. DKD is paradoxically a low systematic renin state with an increased intrarenal RAS activity implicated in its pathogenesis. Angiotensin II (AngII, the main peptide of RAS, is not only a vasoactive peptide but functions as a growth factor, activating interstitial fibroblasts and mesangial and tubular cells, while promoting the synthesis of extracellular matrix proteins. AngII also promotes podocyte injury through increased calcium influx and the generation of reactive oxygen species. Blockade of the RAS using either angiotensin converting enzyme inhibitors, or angiotensin receptor blockers can attenuate progressive glomerulosclerosis in animal models, and slows disease progression in humans with DKD. In this review, we summarize the role of intrarenal RAS activation in the pathogenesis and progression of DKD and the rationale for RAS inhibition in this population. Keywords: renin–angiotensin system, diabetic kidney disease, angiotensin II, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers

  7. Insulin-Inducible SMILE Inhibits Hepatic Gluconeogenesis.

    Lee, Ji-Min; Seo, Woo-Young; Han, Hye-Sook; Oh, Kyoung-Jin; Lee, Yong-Soo; Kim, Don-Kyu; Choi, Seri; Choi, Byeong Hun; Harris, Robert A; Lee, Chul-Ho; Koo, Seung-Hoi; Choi, Hueng-Sik

    2016-01-01

    The role of a glucagon/cAMP-dependent protein kinase-inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner-interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis. Here, we show that hepatic SMILE expression was induced by feeding in normal mice but not in db/db and high-fat diet (HFD)-fed mice. Interestingly, SMILE expression was induced by insulin in mouse primary hepatocyte and liver. Hepatic SMILE expression was not altered by refeeding in liver-specific insulin receptor knockout (LIRKO) or PKB β-deficient (PKBβ(-/-)) mice. At the molecular level, SMILE inhibited hepatocyte nuclear factor 4-mediated transcriptional activity via direct competition with PGC-1α. Moreover, ablation of SMILE augmented gluconeogenesis and increased blood glucose levels in mice. Conversely, overexpression of SMILE reduced hepatic gluconeogenic gene expression and ameliorated hyperglycemia and glucose intolerance in db/db and HFD-fed mice. Therefore, SMILE is an insulin-inducible corepressor that suppresses hepatic gluconeogenesis. Small molecules that enhance SMILE expression would have potential for treating hyperglycemia in diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. Efficacy of ALK5 inhibition in myelofibrosis

    Zhao, Wanke; Ho, Wanting Tina; Han, Ying; Murdun, Cem; Mailloux, Adam W.; Zhang, Ling; Wang, Xuefeng; Budhathoki, Anjali; Pradhan, Kith; Rapaport, Franck; Wang, Huaquan; Shao, Zonghong; Ren, Xiubao; Steidl, Ulrich; Levine, Ross L.; Zhao, Zhizhuang Joe; Verma, Amit; Epling-Burnette, Pearlie K.

    2017-01-01

    Myelofibrosis (MF) is a bone marrow disorder characterized by clonal myeloproliferation, aberrant cytokine production, extramedullary hematopoiesis, and bone marrow fibrosis. Although somatic mutations in JAK2, MPL, and CALR have been identified in the pathogenesis of these diseases, inhibitors of the Jak2 pathway have not demonstrated efficacy in ameliorating MF in patients. TGF-β family members are profibrotic cytokines and we observed significant TGF-β1 isoform overexpression in a large cohort of primary MF patient samples. Significant overexpression of TGF-β1 was also observed in murine clonal MPLW515L megakaryocytic cells. TGF-β1 stimulated the deposition of excessive collagen by mesenchymal stromal cells (MSCs) by activating the TGF-β receptor I kinase (ALK5)/Smad3 pathway. MSCs derived from MPLW515L mice demonstrated sustained overproduction of both collagen I and collagen III, effects that were abrogated by ALK5 inhibition in vitro and in vivo. Importantly, use of galunisertib, a clinically active ALK5 inhibitor, significantly improved MF in both MPLW515L and JAK2V617F mouse models. These data demonstrate the role of malignant hematopoietic stem cell (HSC)/TGF-β/MSC axis in the pathogenesis of MF, and provide a preclinical rationale for ALK5 blockade as a therapeutic strategy in MF. PMID:28405618

  9. Inhibition of lignifying processes by sulfur dioxide

    Pfanz, H.; Oppmann, B.

    1991-01-01

    Intercellular washing fluids (IWF) from spruce needles (Picea abies L. Karst.) contain peroxidases 1-2% of total IWF protein. These apoplastic enzymes show the ability to polymerize monophenols or phenylpropanes to form lignin precursors in vitro. In the presence of potentially acidic air pollutants like NO 2 , HF(20 mM of salts in solution), and in the presence of Pb-, Cd- (0.5 mM) or Al-salts (8 mM) no inhibitory effect on the polymerization reactions examined was detectable. In contrast, the anions of SO 2 (sulfite and bisulfite) revealed a strong inhibition on the dimerization of ferulic and caffeic acid (Ki ca. 1 mM), and on the dehydration of syringaldazine (Ki ca. 8 μM). Polymerization of coniferyl alcohol, on the other hand, seemed to be enhanced. Maier-Maercker and Koch (1986) demonstrated that the cell walls of guard cells from undamaged spruce needles are properly lignified, whereas those of damaged needles seem to be affected. It is therefore assumed that cell wall lignification, and concomitantly stomatal regulation of coniferous needles are disturbed in regions with high atmospheric SO 2 pollution (e.g. Ore Mountains in CSFR)

  10. Bioelectronic sniffer for nicotine using enzyme inhibition.

    Mitsubayashi, Kohji; Nakayama, Kazumi; Taniguchi, Midori; Saito, Hirokazu; Otsuka, Kimio; Kudo, Hiroyuki

    2006-07-28

    A novel bioelectronic sniffer for nicotine in the gas phase was developed with enzyme inhibition principle to butyrylcholinesterase activity. The bioelectronic devices for nicotine in the gas and liquid phases were constructed using a Clark-type dissolved oxygen electrode and a membrane immobilized butyrylcholinesterase and choline oxidase. After the assessment of the sensor performances to choline and butyrylcholine as pre-examinations, the characteristics of the biosensor and bio-sniffer for nicotine were evaluated in the liquid and gas phases, respectively. The sensor signal of the bio-devices with 300 micromol l(-1) of butyrylcholine decreased quickly following application of nicotine and reached to the steady-state current, thus relating the concentration of nicotine in the liquid and gas phases. The biosensor was used to measure nicotine solution from 10 to 300 micromol l(-1). In the gas-phase experiment, the current signal of the bio-sniffer was also found to be linearly to the nicotine concentration over the range of 10.0-1000 ppb including 75.0 ppb as threshold limit value (TLV) by American Conference of Governmental Industrial Hygienists (ACGIH).

  11. Radiation metagenesis and inhibition of DNA synthesis

    Dubinina, L.G.; Sergievskaya, S.P.; Kurashova, Z.I.; Dubinin, N.P.

    1983-01-01

    The study of modification of radiation mutagenesis and inhibition of the DNA synthesis by means of 1-β-D arabinofuranosylcytosine (ara-C) is carried out. It is shown that ara-C-acting on chromosomes in the G 1 phase and G 2 phase does not cause mutations in the C capillaris cells. The modification by means of ara-C radiation effect in the G 1 phase and G 2 phase correlates with duration and time of administering ara-C before and after irradiation. A new form of ara-C DNA synthesis inhibitor interaction with mutation processes has been found out. Protective effect of the DNA synthesis inhibitor (ara-C) from mutageneous radiation effect is stressed. Sensibilization of the radiation mutagenesis during cell treafment by the DNA synthesis inhibitor (ara-C) is shown. It is pointed out that emergence of sensibilization or protective effect, i. e. antimutagenesis phenomenon depends on conditions under which the synthesis inhibitor acted in G 1 and G 2 phases

  12. Lycopene Inhibits Propagation of Chlamydia Infection

    Naylia A. Zigangirova

    2017-01-01

    Full Text Available Chlamydiaceae is a family of obligate intracellular pathogenic bacteria with similar developmental cycles and cell biology responsible for a wide range of diseases in different hosts including genital and eye inflammatory diseases, arthritis, and inflammatory diseases of the respiratory and cardiovascular systems. In the present paper, we report that lycopene, one of the main dietary carotenoids, which is present in tomato and some other fruits, has a strong inhibitory effect on C. trachomatis and C. pneumoniae infections in alveolar macrophages. This finding was documented by both immunofluorescence analysis and electron microscopy. It was noted that lycopene treatment inhibited intracellular phase of the chlamydial developmental cycle and resulted in a significant loss of infectious progeny. The antichlamydial effect of lycopene was also confirmed in a clinical setting. There was a significant reduction of IgG antibodies against C. pneumoniae in the serum of volunteers treated for a month with oral ingestion of 7 mg of lycopene. Additional studies are needed to further explore the antichlamydial activity of lycopene and its possible effect on C. pneumoniae in relation to antichlamydial activity of lycopene to mechanisms of atherosclerosis.

  13. Clofilium inhibits Slick and Slack potassium channels.

    de Los Angeles Tejada, Maria; Stolpe, Kathleen; Meinild, Anne-Kristine; Klaerke, Dan A

    2012-01-01

    Slick and Slack high-conductance potassium channels have been recently discovered, and are found in the central nervous system and in the heart. Both channels are activated by Na(+) and Cl(-), and Slick channels are also inhibited by adenosine triphospate (ATP). An important role of setting the resting membrane potential and controlling the basal excitability of neurons has been suggested for these channels. In addition, no specific blockers for these channels are known up to the present. With the purpose of studying the pharmacological characteristics of Slick and Slack channels, the effects of exposure to the antiarrhythmic compound clofilium were evaluated. Clofilium was able to modulate the activity of Slick and Slack channels effectively, with a stronger effect on Slack than Slick channels. In order to evaluate the pharmacological behavior of Slick and Slack channels further, 38 commonly used potassium channel blockers were tested. Screening of these compounds did not reveal any modulators of Slick and Slack channels, except for clofilium. The present study provides a first approach towards elucidating the pharmacological characteristics of Slick and Slack channels and could be the basis for future studies aimed at developing potent and specific blockers and activators for these channels.

  14. Linking algal growth inhibition to chemical activity

    Schmidt, Stine N.; Mayer, Philipp

    Unitless chemical activity, expressing the energetic level of a compound relative to its energetic level in pure liquid [0-1], has proven useful to quantify the effective exposure to hydrophobic organic compounds through both aerial and aqueous media. Several studies have linked toxicity to chemi......Unitless chemical activity, expressing the energetic level of a compound relative to its energetic level in pure liquid [0-1], has proven useful to quantify the effective exposure to hydrophobic organic compounds through both aerial and aqueous media. Several studies have linked toxicity...... to chemical activity, as opposed to e.g. the total concentration. Baseline toxicity (narcosis) for neutral hydrophobic organic compounds has been shown to initiate in the narrow chemical activity range of 0.01 to 0.1. This presentation focuses on linking algal growth inhibition to chemical activity......-polar liquids were applied to challenge the chemical activity range for baseline toxicity. For each compound, the effective activity (Ea50) was estimated as the ratio of the effective concentration (EC50) and water solubility. Of these ratios, 90% were within the expected chemical activity range of 0.01 to 0...

  15. Peliminary examination of herbal extracts on the inhibition of ...

    Methods: The activity was quantitatively assessed on the basis of the inhibition zone, and their activity index was also calculated along with the MIC method. Results: All the plants demonstrated antimicrobial activity against H. pylori with zone of inhibition diameters ranging from 0 - 30 mm and minimum inhibitory ...

  16. Attention Inhibition Training Can Reduce Betel-Nut Chewing Time

    Ming-Chou Ho

    2011-05-01

    Full Text Available Betel nut (or areca is the fourth most commonly used drug worldwide after tobacco, alcohol, and caffeine. Many chemical ingredients of betel nut are carcinogenic. We examined whether the manipulation of attentional inhibition toward the areca-related stimuli could affect betel-nut chewing time. Three matched groups of habitual chewers were recruited: inhibit-areca, inhibit-non-areca, and control. This study consisted of a Go/No-Go task for inhibition training, followed by a taste test for observing chewing behavior. The Go/No-Go task constituted three phases (pretest, training and posttest. In the taste test, the habitual chewers were asked to rate the flavors of one betel nut and one gum. The purpose (blind to the chewers of this taste test was to observe whether their picking order and chewing time were affected by experimental manipulation. Results from the Go/No-Go task showed successful training. Further, the training groups (the inhibit-areca and inhibit-non-areca groups showed a significant reduction in betel nut chewing time, in comparison to the control group. Since both training groups showed reduced chewing time, the inhibition training may affect general control ability, in regardless of the stimulus (areca or not to be inhibited. Reduced chewing time is important for reducing areca-related diseases.

  17. Cohort-Sequential Study of Conflict Inhibition during Middle Childhood

    Rollins, Leslie; Riggins, Tracy

    2017-01-01

    This longitudinal study examined developmental changes in conflict inhibition and error correction in three cohorts of children (5, 7, and 9 years of age). At each point of assessment, children completed three levels of Luria's tapping task (1980), which requires the inhibition of a dominant response and maintenance of task rules in working…

  18. Optogenetic inhibition of chemically induced hypersynchronized bursting in mice

    Berglind, Fredrik; Ledri, Marco; Sørensen, Andreas Toft

    2014-01-01

    hyperpolarization and thereby inactivation of a principal neuronal population in the hippocampus is effectively attenuating seizure activity caused by disconnected network inhibition both in vitro and in vivo. Our data suggest that epileptiform activity in the hippocampus caused by impaired inhibition may...

  19. The role of non-CRF inhibition in contour detection

    Grigorescu, C.; Petkov, N.; Westenberg, M.A.

    2003-01-01

    We propose a biologically motivated computational step, called non-classical receptive field (non-CRF) inhibition, to improve the performance of contour detectors. Non-CRF inhibition is exhibited by 80% of the orientation selective neurons in the primary visual cortex of macaque monkeys and has been

  20. Pseudomonas aeruginosa inhibits the growth of Cryptococcus species.

    Rella, Antonella; Yang, Mo Wei; Gruber, Jordon; Montagna, Maria Teresa; Luberto, Chiara; Zhang, Yong-Mei; Del Poeta, Maurizio

    2012-06-01

    Pseudomonas aeruginosa is a ubiquitous and opportunistic bacterium that inhibits the growth of different microorganisms, including Gram-positive bacteria and fungi such as Candida spp. and Aspergillus fumigatus. In this study, we investigated the interaction between P. aeruginosa and Cryptococcus spp. We found that P. aeruginosa PA14 and, to a lesser extent, PAO1 significantly inhibited the growth of Cryptococcus spp. The inhibition of growth was observed on solid medium by the visualization of a zone of inhibition of yeast growth and in liquid culture by viable cell counting. Interestingly, such inhibition was only observed when P. aeruginosa and Cryptococcus were co-cultured. Minimal inhibition was observed when cell-cell contact was prevented using a separation membrane, suggesting that cell contact is required for inhibition. Using mutant strains of Pseudomonas quinoline signaling, we showed that P. aeruginosa inhibited the growth of Cryptococcus spp. by producing antifungal molecules pyocyanin, a redox-active phenazine, and 2-heptyl-3,4-dihydroxyquinoline (PQS), an extracellular quorum-sensing signal. Because both P. aeruginosa and Cryptococcus neoformans are commonly found in lung infections of immunocompromised patients, this study may have important implication for the interaction of these microbes in both an ecological and a clinical point of view.

  1. Stuttering Inhibition via Altered Auditory Feedback during Scripted Telephone Conversations

    Hudock, Daniel; Kalinowski, Joseph

    2014-01-01

    Background: Overt stuttering is inhibited by approximately 80% when people who stutter read aloud as they hear an altered form of their speech feedback to them. However, levels of stuttering inhibition vary from 60% to 100% depending on speaking situation and signal presentation. For example, binaural presentations of delayed auditory feedback…

  2. Menadione inhibits MIBG uptake in two neuroendocrine cell lines

    Cornelissen, J.; Tytgat, G. A.; van den Brug, M.; van Kuilenburg, A. B.; Voûte, P. A.; van Gennip, A. H.

    1997-01-01

    In this paper we report on our studies of the effect of menadione on the uptake of MIBG in the neuroendocrine cell lines PC12 and SK-N-SH. Menadione inhibits the uptake of MIBG in both cell lines in a dose-dependent manner. Inhibition of MIBG uptake is most pronounced in the PC12 cell line.

  3. Methanol Extract of Hydroclathrus clathratus Inhibits Production of ...

    Methanol Extract of Hydroclathrus clathratus Inhibits Production of Nitric Oxide, Prostaglandin E2 and Tumor Necrosis Factor-α in Lipopolysaccharidestimulated BV2 Microglial Cells via Inhibition of NF-κB Activity. RGPT Jayasooriya, D-O Moon, YH Chol, C-H Yoon, G-Y Kim ...

  4. Trichilia monadelpha Bark Extracts Inhibit Carrageenan-Induced ...

    The present study was undertaken to evaluate the anti-inflammatory properties of aqueous (TWE), alcoholic (TAE) and petroleum ether extract (TPEE) of T. ... The reference anti-inflammatory drugs (diclofenac and dexamethasone) inhibited the chick-carrageenan-induced footpad oedema, with maximal inhibitions of ...

  5. Social inhibition sense of belonging and vulnerability to internalizing problems

    de Moor, E.L.; Denollet, J.; Laceulle, O.M.

    2018-01-01

    Background The aim of this study was to provide a conceptual test of how social inhibition, sense of belonging and internalizing problems are related, and whether sense of belonging moderates or mediates the relation between social inhibition and internalizing problems. Methods Data were used from

  6. The Affective Consequences of Cognitive Inhibition: Devaluation or Neutralization?

    Frischen, Alexandra; Ferrey, Anne E.; Burt, Dustin H. R.; Pistchik, Meghan; Fenske, Mark J.

    2012-01-01

    Affective evaluations of previously ignored visual stimuli are more negative than those of novel items or prior targets of attention or response. This has been taken as evidence that inhibition has negative affective consequences. But inhibition could act instead to attenuate or "neutralize" preexisting affective salience, predicting opposite…

  7. Distractor Inhibition: Principles of Operation during Selective Attention

    Wyatt, Natalie; Machado, Liana

    2013-01-01

    Research suggests that although target amplification acts as the main determinant of the efficacy of selective attention, distractor inhibition contributes under some circumstances. Here we aimed to gain insight into the operating principles that regulate the use of distractor inhibition during selective attention. The results suggest that, in…

  8. Study of electroplated silver-palladium biofouling inhibiting coating

    Chiang, Wen-Chi; Hilbert, Lisbeth Rischel; Schroll, Casper

    2008-01-01

    Biofouling can cause many undesirable effects in industrial and medical settings. In this study, a new biofouling inhibiting Ag-Pd surface was designed to form an inhibiting effect by itself. This design was based on silver combined with nobler palladium, both with catalytic properties. Owing to ...

  9. Corrosion Inhibition of Aluminium by Capparis deciduas in Acidic Media

    P. Arora

    2007-01-01

    Full Text Available The inhibition efficiency of ethanolic extract of different parts of Capparis deciduas (Ker in acidic medium has been evaluated by mass loss and thermometric methods. Values of inhibition efficiency obtained from the two methods are in good agreement and are dependent upon the concentration of inhibitor and acid.

  10. Corrosion Inhibition of Aluminium by Capparis deciduas in Acidic Media

    P. Arora; S. Kumar; M. K. Sharma; S. P. Mathur

    2007-01-01

    The inhibition efficiency of ethanolic extract of different parts of Capparis deciduas (Ker) in acidic medium has been evaluated by mass loss and thermometric methods. Values of inhibition efficiency obtained from the two methods are in good agreement and are dependent upon the concentration of inhibitor and acid.

  11. Experimental and quantum chemical studies on corrosion inhibition ...

    Abstract. The corrosion inhibition effect of fluconazole (FLU) was investigated on steel in 1 M hydrochloric acid solution. Weight loss measurements and atomic force microscope analysis were utilized to investigate the corrosion inhibition properties and film formation behaviour of FLU. Quantum chemical approach was also ...

  12. Belief Inhibition in Children's Reasoning: Memory-Based Evidence

    Steegen, Sara; Neys, Wim De

    2012-01-01

    Adult reasoning has been shown as mediated by the inhibition of intuitive beliefs that are in conflict with logic. The current study introduces a classic procedure from the memory field to investigate belief inhibition in 12- to 17-year-old reasoners. A lexical decision task was used to probe the memory accessibility of beliefs that were cued…

  13. Inhibition of Snl6 expression for biofuel production

    Bart, Rebecca; Chern, Mawsheng; Ronald, Pamela; Vega-Sanchez, Miguel

    2018-04-03

    The invention provides compositions and methods for inhibiting the expression of the gene Snl6 in plants. Plants with inhibited expression of Snl6 have use in biofuel production, e.g., by increasing the amount of soluble sugar that can be extracted from the plant.

  14. Apigenin inhibits proliferation and migratory properties of Barrett's ...

    dependent fashion, with an IC50 of 75 µM, after 72 h of incubation, and also induced apoptosis, with modulation of pro- and anti-apoptotic genes. Furthermore, apigenin inhibited the motility of OE33 by targeting PI3K/Akt/mTOR signaling. Conclusion: Apigenin effectively inhibits the oncogenicity of OE33 cells by targeting ...

  15. Cognitive Inhibition in Students with and without Dyslexia and Dyscalculia

    Wang, Li-Chih; Tasi, Hung-Ju; Yang, Hsien-Ming

    2012-01-01

    The present study presents a comparison of the cognitive inhibition abilities of dyslexic, dyscalculic, and control students. The participants were 45 dyslexic students, 45 dyscalculic students, and 45 age-, gender-, and IQ-matched control students. The major evaluation tools included six cognitive inhibition tasks which were restructured during…

  16. Inhibition of autophagy initiation potentiates chemosensitivity in mesothelioma.

    Follo, Carlo; Cheng, Yao; Richards, William G; Bueno, Raphael; Broaddus, Virginia Courtney

    2018-03-01

    The benefits of inhibiting autophagy in cancer are still controversial, with differences in outcome based on the type of tumor, the context and the particular stage of inhibition. Here, we investigated the impact of inhibiting autophagy at different stages on chemosensitivity using 3-dimensional (3D) models of mesothelioma, including ex vivo human tumor fragment spheroids. As shown by LC3B accumulation, we successfully inhibited autophagy using either an early stage ULK1/2 inhibitor (MRT 68921) or a late stage inhibitor (hydroxychloroquine). We found that inhibition of autophagy at the early stage, but not at late stage, potentiated chemosensitivity. This effect was seen only in those spheroids with high autophagy and active initiation at steady state. Inhibition of autophagy alone, at either early or late stage, did not cause cell death, showing that the inhibitors were non-toxic and that mesothelioma did not depend on autophagy at baseline, at least over 24 h. Using ATG13 puncta analysis, we found that autophagy initiation identified tumors that are more chemosensitive at baseline and after autophagy inhibition. Our results highlight a potential role of autophagy initiation in supporting mesothelioma cells during chemotherapy. Our work also highlights the importance of testing the inhibition of different stages in order to uncover the role of autophagy and the potential of its modulation in the treatment of cancer. © 2017 Wiley Periodicals, Inc.

  17. Experimental and quantum chemical studies on corrosion inhibition

    The corrosion inhibition effect of fluconazole (FLU) was investigated on steel in 1 M hydrochloric acid solution. Weight loss measurements and atomic force microscope analysis were utilized to investigate the corrosion inhibition properties and film formation behaviour of FLU. Quantum chemical approach was also used to ...

  18. Probe substrate and enzyme source-dependent inhibition of UDP ...

    Background: Drug-metabolizing enzymes (DMEs) inhibition based drug-drug interaction and herb-drug interaction severely challenge the R&D process of drugs or herbal ingredients. Objective: To evaluate the inhibition potential of wogonin (an important flavonoid isolated from the root of Scutellaria baicalensis) towards ...

  19. Sulindac Sulfide, but Not Sulindac Sulfone, Inhibits Colorectal Cancer Growth

    Christopher S. Williams

    1999-06-01

    Full Text Available Sulindac sulfide, a metabolite of the nonsteroidal antiinflammatory drug (NSAID sulindac sulfoxide, is effective at reducing tumor burden in both familial adenomatous polyposis patients and in animals with colorectal cancer. Another sulindac sulfoxide metabolite, sulindac sulfone, has been reported to have antitumor properties without inhibiting cyclooxygenase activity. Here we report the effect of sulindac sulfone treatment on the growth of colorectal carcinoma cells. We observed that sulindac sulfide or sulfone treatment of HCA-7 cells led to inhibition of prostaglandin E2 production. Both sulindac sulfide and sulfone inhibited HCA-7 and HCT-116 cell growth in vitro. Sulindac sulfone had no effect on the growth of either HCA-7 or HCT-116 xenografts, whereas the sulfide derivative inhibited HCA-7 growth in vivo. Both sulindac sulfide and sulfone inhibited colon carcinoma cell growth and prostaglandin production in vitro, but sulindac sulfone had no effect on the growth of colon cancer cell xenografts in nude mice.

  20. Feedforward somatosensory inhibition is normal in cervical dystonia.

    Ferrè, Elisa R; Ganos, Christos; Bhatia, Kailash P; Haggard, Patrick

    2015-03-01

    Insufficient cortical inhibition is a key pathophysiological finding in dystonia. Subliminal sensory stimuli were reported to transiently inhibit somatosensory processing. Here we investigated whether such subliminal feedforward inhibition is reduced in patients with cervical dystonia. Sixteen cervical dystonia patients and 16 matched healthy controls performed a somatosensory detection task. We measured the drop in sensitivity to detect a threshold-level digital nerve shock when it was preceded by a subliminal conditioning shock, compared to when it was not. Subliminal conditioning shocks reduced sensitivity to threshold stimuli to a similar extent in both patients and controls, suggesting that somatosensory subliminal feedforward inhibition is normal in cervical dystonia. Somatosensory feedforward inhibition was normal in this group of cervical dystonia patients. Our results qualify previous concepts of a general dystonic deficit in sensorimotor inhibitory processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Effect of overall feedback inhibition in unbranched biosynthetic pathways.

    Alves, R; Savageau, M A

    2000-11-01

    We have determined the effects of control by overall feedback inhibition on the systemic behavior of unbranched metabolic pathways with an arbitrary pattern of other feedback inhibitions by using a recently developed numerical generalization of Mathematically Controlled Comparisons, a method for comparing the function of alternative molecular designs. This method allows the rigorous determination of the changes in systemic properties that can be exclusively attributed to overall feedback inhibition. Analytical results show that the unbranched pathway can achieve the same steady-state flux, concentrations, and logarithmic gains with respect to changes in substrate, with or without overall feedback inhibition. The analytical approach also shows that control by overall feedback inhibition amplifies the regulation of flux by the demand for end product while attenuating the sensitivity of the concentrations to the same demand. This approach does not provide a clear answer regarding the effect of overall feedback inhibition on the robustness, stability, and transient time of the pathway. However, the generalized numerical method we have used does clarify the answers to these questions. On average, an unbranched pathway with control by overall feedback inhibition is less sensitive to perturbations in the values of the parameters that define the system. The difference in robustness can range from a few percent to fifty percent or more, depending on the length of the pathway and on the metabolite one considers. On average, overall feedback inhibition decreases the stability margins by a minimal amount (typically less than 5%). Finally, and again on average, stable systems with overall feedback inhibition respond faster to fluctuations in the metabolite concentrations. Taken together, these results show that control by overall feedback inhibition confers several functional advantages upon unbranched pathways. These advantages provide a rationale for the prevalence of this

  2. Targeting fibroblast growth factor receptor signaling inhibits prostate cancer progression.

    Feng, Shu; Shao, Longjiang; Yu, Wendong; Gavine, Paul; Ittmann, Michael

    2012-07-15

    Extensive correlative studies in human prostate cancer as well as studies in vitro and in mouse models indicate that fibroblast growth factor receptor (FGFR) signaling plays an important role in prostate cancer progression. In this study, we used a probe compound for an FGFR inhibitor, which potently inhibits FGFR-1-3 and significantly inhibits FGFR-4. The purpose of this study is to determine whether targeting FGFR signaling from all four FGFRs will have in vitro activities consistent with inhibition of tumor progression and will inhibit tumor progression in vivo. Effects of AZ8010 on FGFR signaling and invasion were analyzed using immortalized normal prostate epithelial (PNT1a) cells and PNT1a overexpressing FGFR-1 or FGFR-4. The effect of AZ8010 on invasion and proliferation in vitro was also evaluated in prostate cancer cell lines. Finally, the impact of AZ8010 on tumor progression in vivo was evaluated using a VCaP xenograft model. AZ8010 completely inhibits FGFR-1 and significantly inhibits FGFR-4 signaling at 100 nmol/L, which is an achievable in vivo concentration. This results in marked inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and invasion in PNT1a cells expressing FGFR-1 and FGFR-4 and all prostate cancer cell lines tested. Treatment in vivo completely inhibited VCaP tumor growth and significantly inhibited angiogenesis and proliferation and increased cell death in treated tumors. This was associated with marked inhibition of ERK phosphorylation in treated tumors. Targeting FGFR signaling is a promising new approach to treating aggressive prostate cancer.

  3. Magnolol Inhibits the Growth of Non-Small Cell Lung Cancer via Inhibiting Microtubule Polymerization

    Jia Shen

    2017-07-01

    Full Text Available Background: The tubulin/microtubule system, which is an integral component of the cytoskeleton, plays an essential role in mitosis. Targeting mitotic progression by disturbing microtubule dynamics is a rational strategy for cancer treatment. Methods: Microtubule polymerization assay was performed to examine the effect of Magnolol (a novel natural phenolic compound isolated from Magnolia obovata on cellular microtubule polymerization in human non-small cell lung cancer (NSCLC cells. Cell cycle analysis, mitotic index assay, cell proliferation assay, colony formation assay, western blotting analysis of cell cycle regulators, Annexin V-FITC/PI staining, and live/dead viability staining were carried out to investigate the Magnolol’s inhibitory effect on proliferation and viability of NSCLS cells in vitro. Xenograft model of human A549 NSCLC tumor was used to determine the Magnolol’s efficacy in vivo. Results: Magnolol treatment effectively inhibited cell proliferation and colony formation of NSCLC cells. Further study proved that Magnolol induced the mitotic phase arrest and inhibited G2/M progression in a dose-dependent manner, which were mechanistically associated with expression alteration of a series of cell cycle regulators. Furthermore, Magnolol treatment disrupted the cellular microtubule organization via inhibiting the polymerization of microtubule. We also found treatment with NSCLC cells with Magnolol resulted in apoptosis activation through a p53-independent pathway, and autophgy induction via down-regulation of the Akt/mTOR pathway. Finally, Magnolol treatment significantly suppressed the NSCLC tumor growth in mouse xenograft model in vivo. Conclusion: These findings identify Magnolol as a promising candidate with anti-microtubule polymerization activity for NSCLC treatment.

  4. Global inhibition of reactive oxygen species (ROS inhibits paclitaxel-induced painful peripheral neuropathy.

    Mehmet Fidanboylu

    Full Text Available Paclitaxel (Taxol® is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS, the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6, the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13 completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day -1 to 12 did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals

  5. Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition

    Hubers, Scott A.; Brown, Nancy J.

    2016-01-01

    Heart failure affects approximately 5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the FDA approved the first of a new class of drugs for the treatment of heart failure; valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses two of the pathophysiologic mechanisms of heart failure - activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared to enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacologic properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension. PMID:26976916

  6. Iron inhibits hydroxyapatite crystal growth in vitro.

    Guggenbuhl, Pascal; Filmon, Robert; Mabilleau, Guillaume; Baslé, Michel F; Chappard, Daniel

    2008-07-01

    Hemochromatosis is a known cause of osteoporosis in which the pathophysiology of bone loss is largely unknown and the role of iron remains questionable. We have investigated the effects of iron on the growth of hydroxyapatite crystals in vitro on carboxymethylated poly(2-hydroxyethyl methacrylate) pellets. This noncellular and enzyme-independent model mimics the calcification of woven bone (composed of calcospherites made of hydroxyapatite crystals). Polymer pellets were incubated with body fluid containing iron at increasing concentrations (20, 40, 60 micromol/L). Hydroxyapatite growth was studied by chemical analysis, scanning electron microscopy, and Raman microscopy. When incubated in body fluid containing iron, significant differences were observed with control pellets. Iron was detected at a concentration of 5.41- to 7.16-fold that of controls. In pellets incubated with iron, there was a approximately 3- to 4-fold decrease of Ca and P and a approximately 1.3- to 1.4-fold increase in the Ca/P ratio. There was no significant difference among the iron groups of pellets, but a trend to a decrease of Ca with the increase of iron concentration was noted. Calcospherite diameters were significantly lower on pellets incubated with iron. Raman microspectroscopy showed a decrease in crystallinity (measured by the full width of the half height of the 960 Deltacm(-1) band) with a significant increase in carbonate substitution (measured by the intensity ratio of 1071 to 960 Deltacm(-1) band). Energy dispersive x-ray analysis identified iron in the calcospherites. In vitro, iron is capable to inhibit bone crystal growth with significant changes in crystallinity and carbonate substitution.

  7. Adrenergic manipulation inhibits pavlovian conditioned approach behaviors.

    Pasquariello, Kyle Z; Han, Marina; Unal, Cagla; Meyer, Paul J

    2018-02-26

    Environmental rewards and Pavlovian reward cues can acquire incentive salience, thereby eliciting incentive motivational states and instigate reward-seeking. In rats, the incentive salience of food cues can be measured during a Pavlovian conditioned approach paradigm, in which rats engage in cue-directed approach ("sign-tracking") or approach the food delivery location ("goal-tracking"). While it has been shown that dopamine signaling is necessary for sign-tracking, some studies have suggested that norepinephrine is involved in learning to sign-track as well. Thus, in order to investigate the influence of norepinephrine in Pavlovian conditioned approach, we administered three adrenergic drugs while rats learned that a food cue (an illuminated, retractable lever) preceded the delivery of banana-flavored food pellets into a food-cup. We found that pre-session injections of disulfiram (a dopamine-β-hydroxylase inhibitor) inhibited the development of sign-tracking, but goal-tracking was only affected at the high dose. In one experiment, post-session injections of disulfiram blocked the development of sign-tracking, although this effect was not replicated in a separate set of rats. Post-session injections of prazosin (an α1-adrenergic receptor antagonist) and propranolol (a β-adrenergic receptor antagonist) also blocked the development of sign-tracking but not goal-tracking. Taken together, these results suggest that adrenergic transmission mediates the acquisition of sign-tracking but not goal-tracking, and thus plays a selective role in the attribution of incentive salience food cues. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Reactor design for minimizing product inhibition during enzymatic lignocellulose hydrolysis II. Quantification of inhibition and suitability of membrane reactors

    Andric, Pavle; Meyer, Anne S.; Jensen, Peter Arendt

    2010-01-01

    conversion are required for alleviation of glucose product inhibition. Supported by numerous calculations this review assesses the quantitative aspects of glucose product inhibition on enzyme-catalyzed cellulose degradation rates. The significance of glucose product inhibition on dimensioning of different......Product inhibition of cellulolytic enzymes affects the efficiency of the biocatalytic conversion of lignocellulosic biomass to ethanol and other valuable products. New strategies that focus on reactor designs encompassing product removal, notably glucose removal, during enzymatic cellulose...... reactor features, including system set-up, dilution rate, glucose output profile, and the problem of cellobiose are examined to illustrate the quantitative significance of the glucose product inhibition and the total glucose concentration on the cellulolytic conversion rate. Comprehensive overviews...

  9. Neural correlates of central inhibition during physical fatigue.

    Masaaki Tanaka

    Full Text Available Central inhibition plays a pivotal role in determining physical performance during physical fatigue. Classical conditioning of central inhibition is believed to be associated with the pathophysiology of chronic fatigue. We tried to determine whether classical conditioning of central inhibition can really occur and to clarify the neural mechanisms of central inhibition related to classical conditioning during physical fatigue using magnetoencephalography (MEG. Eight right-handed volunteers participated in this study. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause central inhibition. Participants underwent MEG recording during imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The next day, neural activities during imagery of maximum grips of the right hand guided by metronome sounds were measured for 10 min. Levels of fatigue sensation and sympathetic nerve activity on the second day were significantly higher relative to those of the first day. Equivalent current dipoles (ECDs in the posterior cingulated cortex (PCC, with latencies of approximately 460 ms, were observed in all the participants on the second day, although ECDs were not identified in any of the participants on the first day. We demonstrated that classical conditioning of central inhibition can occur and that the PCC is involved in the neural substrates of central inhibition related to classical conditioning during physical fatigue.

  10. The somatotopy of tic inhibition: Where and how much?

    Ganos, Christos; Bongert, Jens; Asmuss, Luisa; Martino, Davide; Haggard, Patrick; Münchau, Alexander

    2015-08-01

    Tics are the hallmark feature of Tourette syndrome. The basic phenomenological and neurophysiological characteristics of tics have been widely investigated. Interestingly, the spatial distribution of tics across different body parts has received little attention. No previous study has investigated whether the capacity for voluntary tic inhibition also varies across body parts. We analyzed video sequences of 26 adolescents with Tourette syndrome in a "tic freely" condition, and in a "voluntary tic inhibition" condition, to obtain absolute tic counts for different body parts. Two measures of the spatial distribution of tics were then analyzed. Linear regression analyses were employed to investigate the relation between the contribution of each body part to overall tic behavior and the ability to inhibit tics in that body part, averaged over our patient group. Tic distribution across patients showed a characteristic somatotopic pattern, with the face most strongly represented. A significant negative relation was found between the ability to inhibit tics and pooled tic frequency across body parts. The body parts that exhibited the fewest tics were the ones for which tic inhibition was most effective. Our data are consistent with the idea that tic recruitment order reflects a "tic generator" spreading across a somatotopic map in the brain. Voluntary tic inhibition did not simply cause a proportional reduction of tics in each body part. Rather, the least affected body parts showed most effective voluntary tic inhibition. The results are discussed in terms of signal and noise within cortical-subcortical motor loops. © 2015 International Parkinson and Movement Disorder Society.

  11. Harmane inhibits serotonergic dorsal raphe neurons in the rat.

    Touiki, Khalid; Rat, Pascal; Molimard, Robert; Chait, Abderrahman; de Beaurepaire, Renaud

    2005-11-01

    Harmane and norharmane (two beta-carbolines) are tobacco components or products. The effects of harmane and norharmane on serotonergic raphe neurons remain unknown. Harmane and norharmane are inhibitors of the monoamine oxidases A (MAO-A) and B (MAO-B), respectively. To study the effects of harmane, norharmane, befloxatone (MAOI-A), and selegiline (MAOI-B) on the firing of serotonergic neurons. To compare the effects of these compounds to those of nicotine (whose inhibitory action on serotonergic neurons has been previously described). The effects of cotinine, a metabolite of nicotine known to interact with serotonergic systems, are also tested. In vivo electrophysiological recordings of serotonergic dorsal raphe neurons in the anaesthetized rat. Nicotine, harmane, and befloxatone inhibited serotonergic dorsal raphe neurons. The other compounds had no effects. The inhibitory effect of harmane (rapid and long-lasting inhibition) differed from that of nicotine (short and rapidly reversed inhibition) and from that of befloxatone (slow, progressive, and long-lasting inhibition). The inhibitory effects of harmane and befloxatone were reversed by the 5-HT1A antagonist WAY 100 635. Pretreatment of animals with p-chlorophenylalanine abolished the inhibitory effect of befloxatone, but not that of harmane. Nicotine, harmane, and befloxatone inhibit the activity of raphe serotonergic neurons. Therefore, at least two tobacco compounds, nicotine and harmane, inhibit the activity of serotonergic neurons. The mechanism by which harmane inhibits serotonergic dorsal raphe neurons is likely unrelated to a MAO-A inhibitory effect.

  12. Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing

    Tropea, J.E.; Molyneux, R.J.; Kaushal, G.P.; Pan, Y.T.; Mitchell, M.; Elbein, A.D. (Univ. of Texas Health Science Center, San Antonio (USA))

    1989-03-07

    Australine is a polyhydroxylated pyrrolizidine alkaloid that was isolated from the seeds of the Australian tree Castanospermum australe and characterized by NMR and X-ray diffraction analysis. Since swainsonine and catanospermine are polyhydroxylated indolizidine alkaloids that inhibit specific glycosidases, the authors tested australine against a variety of exoglycosidases to determine whether it would inhibit any of these enzymes. This alkaloid proved to be a good inhibitor of the {alpha}-glucosidase amyloglucosidase (50% inhibition at 5.8 {mu}M), but it did not inhibit {beta}-glucosidase, {alpha}- or {beta}-mannosidase, or {alpha}- or {beta}-galactosidase. The inhibition of amyloglucosidase was of a competitive nature. Australine also inhibited the glycoprotein processing enzyme glucosidase I, but had only slight activity toward glucosidase II. When incubated with cultured cells, this alkaloid inhibited glycoprotein processing at the glucosidase I step and caused the accumulation of glycoproteins with Glc{sub 3}Man{sub 7-9}(GlcNAc){sub 2}-oligosaccharides.

  13. The development of children's inhibition: does parenting matter?

    Roskam, Isabelle; Stievenart, Marie; Meunier, Jean-Christophe; Noël, Marie-Pascale

    2014-06-01

    Whereas a large body of research has investigated the maturation of inhibition in relation to the prefrontal cortex, far less research has been devoted to environmental factors that could contribute to inhibition improvement. The aim of the current study was to test whether and to what extent parenting matters for inhibition development from 2 to 8years of age. Data were collected from 421 families, with 348 mother-child dyads and 342 father-child dyads participating. Children's inhibition capacities and parenting behaviors were assessed in a three-wave longitudinal data collection. The main analyses examined the impact of parenting on the development of children's inhibition capacities. They were conducted using a multilevel modeling (MLM) framework. The results lead to the conclusion that both mothers and fathers contribute through their child-rearing behavior to their children's executive functioning, even when controlling for age-related improvement (maturation) and important covariates such as gender, verbal IQ, and place of enrollment. More significant relations between children's inhibition development and parenting were displayed for mothers than for fathers. More precisely, parenting behaviors that involve higher monitoring, lower discipline, inconsistency and negative controlling, and a positive parenting style are associated with good development of inhibition capacities in children. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Andrographolide inhibits multiple myeloma cells by inhibiting the TLR4/NF-κB signaling pathway.

    Gao, Hui; Wang, Jianrong

    2016-02-01

    Andrographolide is an active component from the extract of Andrographis paniculata [(Burm.f) Nees], a medicinal plant from the Acanthaceae family. Pharmacological studies have revealed that andrographolide possesses anti-bacterial, anti-inflammatory, anti-viral, immune regulatory and hepatoprotective properties, and is efficacious in the treatment of cardiovascular diseases, while exhibiting low toxicity and low cost. The present study aimed to determine the inhibitory effects of andrographolide on the growth of multiple myeloma (MM) cells and its possible impact on the Toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling pathway. Cell proliferation was detected using an MTT assay, cellular apoptosis was measured using flow cytometry, and caspase-9/3 activation were assessed using colorimetric assay kits. Furthermore, TLR4 and NF-κB protein expression was determined by western blot analysis. The results revealed that andrographolide reduced the proliferation, while increasing cellular apoptosis and caspase-9/3 activation of MM cells, in addition to downregulating the expression of TLR4 and NF-κB protein. Of note, TLR4- or NF-κB-targeting small-interfering (si)RNA enhanced the andrographolide-induced inhibition of cell proliferation and induction of apoptosis of MM cells. The results of the present study therefore suggested that andrographolide inhibited multiple myeloma cells via the TLR4/NF-κB signaling pathway.

  15. BET bromodomain inhibition promotes neurogenesis while inhibiting gliogenesis in neural progenitor cells

    Jingjun Li

    2016-09-01

    Full Text Available Neural stem cells and progenitor cells (NPCs are increasingly appreciated to hold great promise for regenerative medicine to treat CNS injuries and neurodegenerative diseases. However, evidence for effective stimulation of neuronal production from endogenous or transplanted NPCs for neuron replacement with small molecules remains limited. To identify novel chemical entities/targets for neurogenesis, we had established a NPC phenotypic screen assay and validated it using known small-molecule neurogenesis inducers. Through screening small molecule libraries with annotated targets, we identified BET bromodomain inhibition as a novel mechanism for enhancing neurogenesis. BET bromodomain proteins, Brd2, Brd3, and Brd4 were found to be downregulated in NPCs upon differentiation, while their levels remain unaltered in proliferating NPCs. Consistent with the pharmacological study using bromodomain selective inhibitor (+-JQ-1, knockdown of each BET protein resulted in an increase in the number of neurons with simultaneous reduction in both astrocytes and oligodendrocytes. Gene expression profiling analysis demonstrated that BET bromodomain inhibition induced a broad but specific transcription program enhancing directed differentiation of NPCs into neurons while suppressing cell cycle progression and gliogenesis. Together, these results highlight a crucial role of BET proteins as epigenetic regulators in NPC development and suggest a therapeutic potential of BET inhibitors in treating brain injuries and neurodegenerative diseases.

  16. Sex differences in emotional contexts modulation on response inhibition.

    Ramos-Loyo, Julieta; Angulo-Chavira, Armando; Llamas-Alonso, Luis A; González-Garrido, Andrés A

    2016-10-01

    The aim of the present study was to explore sex differences in the effects that emotional contexts exert on the temporal course of response inhibition using event-related potentials (ERP). Participants performed a Go-NoGo response inhibition task under 3 context conditions: with 1) neutral background stimuli, and 2) pleasant, and 3) unpleasant emotional contexts. No sex differences were found in relation to accuracy. Women showed higher N2NoGo amplitudes than men in both emotional contexts; whereas during inhibition men tended to show higher P3NoGo amplitudes than women in the unpleasant context. Both groups experienced a relevant effect of the presence of the unpleasant context during inhibition processing, as shown by the enhancement of the N2NoGo amplitudes in frontal regions compared to results from the neutral and pleasant conditions. In addition, women showed differences between the pleasant and unpleasant contexts, with the latter inducing higher amplitude values. Only in men did inhibition accuracy correlate with higher N2NoGo and lower P3NoGo amplitudes in the emotional context conditions. These findings suggest that when an inhibition task is performed in an emotionally-neutral background context no sex differences are observed in either accuracy or ERP components. However, when the emotional context was introduced -especially the unpleasant one- some gender differences did become evident. The higher N2NoGo amplitude at the presence of the unpleasant context may reflect an effect on attention and conflict monitoring. In addition, results suggest that during earlier processing stages, women invested more resources to process inhibition than men. Furthermore, men who invested more neural resources during earlier stages showed better response inhibition than those who did it during later processing stages, more closely-related to cognitive and motor inhibition processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Lactate dehydrogenase activity is inhibited by methylmalonate in vitro.

    Saad, Laura O; Mirandola, Sandra R; Maciel, Evelise N; Castilho, Roger F

    2006-04-01

    Methylmalonic acidemia (MMAemia) is an inherited metabolic disorder of branched amino acid and odd-chain fatty acid metabolism, involving a defect in the conversion of methylmalonyl-coenzyme A to succinyl-coenzyme A. Systemic and neurological manifestations in this disease are thought to be associated with the accumulation of methylmalonate (MMA) in tissues and biological fluids with consequent impairment of energy metabolism and oxidative stress. In the present work we studied the effect of MMA and two other inhibitors of mitochondrial respiratory chain complex II (malonate and 3-nitropropionate) on the activity of lactate dehydrogenase (LDH) in tissue homogenates from adult rats. MMA potently inhibited LDH-catalyzed conversion of lactate to pyruvate in liver and brain homogenates as well as in a purified bovine heart LDH preparation. LDH was about one order of magnitude less sensitive to inhibition by MMA when catalyzing the conversion of pyruvate to lactate. Kinetic studies on the inhibition of brain LDH indicated that MMA inhibits this enzyme competitively with lactate as a substrate (K (i)=3.02+/-0.59 mM). Malonate and 3-nitropropionate also strongly inhibited LDH-catalyzed conversion of lactate to pyruvate in brain homogenates, while no inhibition was observed by succinate or propionate, when present in concentrations of up to 25 mM. We propose that inhibition of the lactate/pyruvate conversion by MMA contributes to lactate accumulation in blood, metabolic acidemia and inhibition of gluconeogenesis observed in patients with MMAemia. Moreover, the inhibition of LDH in the central nervous system may also impair the lactate shuttle between astrocytes and neurons, compromising neuronal energy metabolism.

  18. Metalloproteinase inhibition prevents acute respiratory distress syndrome.

    Carney, D E; McCann, U G; Schiller, H J; Gatto, L A; Steinberg, J; Picone, A L; Nieman, G F

    2001-08-01

    -3 prevented lung injury in our model of endotoxin-induced ARDS. The proposed mechanism of COL-3 is a synergistic inhibition of the terminal neutrophil effectors MMPs and NE. Similar to the universal practice of prophylaxis against gastric stress ulceration and deep venous thromboses in trauma patients, chemically modified tetracyclines may likewise be administered to prevent acute lung injury in critically injured patients at risk of developing ARDS. Copyright 2001 Academic Press.

  19. Curcumin inhibits amygdaloid kindled seizures in rats.

    DU, Peng; Li, Xin; Lin, Hao-Jie; Peng, Wei-Feng; Liu, Jian-Ying; Ma, Yu; Fan, Wei; Wang, Xin

    2009-06-20

    Curcumin can reduce the severity of seizures induced by kainate acid (KA), but the role of curcumin in amygdaloid kindled models is still unknown. This study aimed to explore the effect of curcumin on the development of kindling in amygdaloid kindled rats. With an amygdaloid kindled Sprague-Dawley (SD) rat model and an electrophysiological method, different doses of curcumin (10 mgxkg(-1)xd(-1) and 30 mgxkg(-1)xd(-1) as low dose groups, 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1) as high dose groups) were administrated intraperitoneally during the whole kindling days, by comparison with the course of kindling, afterdischarge (AD) thresholds and the number of ADs to reach the stages of class I to V seizures in the rats between control and experimental groups. One-way or two-way ANOVA and Fisher's least significant difference post hoc test were used for statistical analyses. Curcumin (both 100 mgxkg(-1)xd(-1) and 300 mgxkg(-1)xd(-1)) significantly inhibited the behavioral seizure development in the (19.80 +/- 2.25) and (21.70 +/- 2.21) stimulations respectively required to reach the kindled state. Rats treated with 100 mgxkg(-1)xd(-1) curcumin 30 minutes before kindling stimulation showed an obvious increase in the stimulation current intensity required to evoke AD from (703.3 +/- 85.9) microA to (960.0 +/- 116.5) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin showed a significant increase in the stimulation current intensity required to evoke AD from (735.0 +/- 65.2) microA to (867.0 +/- 93.4) microA during the progression to class V seizures. Rats treated with 300 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class both IV (as (199.83 +/- 12.47) seconds) and V seizures (as (210.66 +/- 10.68) seconds). Rats treated with 100 mgxkg(-1)xd(-1) curcumin required much more evoked ADs to reach the stage of class V seizures (as (219.56 +/- 18.24) seconds). Our study suggests that curcumin has

  20. Inhibition of PTEN and activation of Akt by menadione

    Yoshikawa, Kyoko; Nigorikawa, Kiyomi; Tsukamoto, Mariko; Tamura, Namiko; Hazeki, Kaoru; Hazeki, Osamu

    2007-01-01

    Menadione (vitamin K3) has been shown to activate Erk in several cell lines. This effect has been shown to be due to the activation of EGF receptors (EGFR) as a result of inhibition of some protein tyrosine phosphatases. In the present study, we examined the effects of menadione on Akt in Chinese hamster ovary cells. The phosphorylation of Akt by menadione was not inhibited by AG1478, an inhibitor of EGFR. Menadione inhibited the lipid phosphatase activity of PTEN in a cell-free system. In an...

  1. Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

    Sliutz, G; Speiser, P; Schultz, A M; Spona, J; Zeillinger, R

    1993-05-01

    In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

  2. Measuring Feedforward Inhibition and Its Impact on Local Circuit Function.

    Hull, Court

    2017-05-01

    This protocol describes a series of approaches to measure feedforward inhibition in acute brain slices from the cerebellar cortex. Using whole-cell voltage and current clamp recordings from Purkinje cells in conjunction with electrical stimulation of the parallel fibers, these methods demonstrate how to measure the relationship between excitation and inhibition in a feedforward circuit. This protocol also describes how to measure the impact of feedforward inhibition on Purkinje cell excitability, with an emphasis on spike timing. © 2017 Cold Spring Harbor Laboratory Press.

  3. Spike propagation in driven chain networks with dominant global inhibition

    Chang Wonil; Jin, Dezhe Z.

    2009-01-01

    Spike propagation in chain networks is usually studied in the synfire regime, in which successive groups of neurons are synaptically activated sequentially through the unidirectional excitatory connections. Here we study the dynamics of chain networks with dominant global feedback inhibition that prevents the synfire activity. Neural activity is driven by suprathreshold external inputs. We analytically and numerically demonstrate that spike propagation along the chain is a unique dynamical attractor in a wide parameter regime. The strong inhibition permits a robust winner-take-all propagation in the case of multiple chains competing via the inhibition.

  4. Inhibition of hepatic lipogenesis by 2-tetradecylglycidic acid.

    McCune, S A; Nomura, T; Harris, R A

    1979-10-01

    2-Tetradecylglycidic acid (TDGA), a hypoglycemic agent, has been found to be a very effective inhibitor of de novo fatty acid synthesis by isolated hepatocytes. A comparison was made between the effectiveness of TDGA and 5-(tetradecyloxy)-2-furoic acid (TOFA), a hypolipidemic agent, on the metabolic processes of isolated hepatocytes. These compounds are structurally related and both inhibit fatty acid synthesis; however, they have opposite effects from each other on the oxidation and esterification of fatty acids. TDGA inhibits whereas TOFA stimulates fatty acid oxidation. TDGA stimulates whereas TOFA inhibits fatty acid esterification.

  5. Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism.

    Cullen, Joseph J; Hinkhouse, Marilyn M; Grady, Matthew; Gaut, Andrew W; Liu, Jingru; Zhang, Yu Ping; Weydert, Christine J Darby; Domann, Frederick E; Oberley, Larry W

    2003-09-01

    NADPH:quinone oxidoreductase (NQO(1)), a homodimeric, ubiquitous, flavoprotein, catalyzes the two-electron reduction of quinones to hydroquinones. This reaction prevents the one-electron reduction of quinones by cytochrome P450 reductase and other flavoproteins that would result in oxidative cycling with generation of superoxide (O(2)(.-)). NQO(1) gene regulation may be up-regulated in some tumors to accommodate the needs of rapidly metabolizing cells to regenerate NAD(+). We hypothesized that pancreatic cancer cells would exhibit high levels of this enzyme, and inhibiting it would suppress the malignant phenotype. Reverse transcription-PCR, Western blots, and activity assays demonstrated that NQO(1) was up-regulated in the pancreatic cancer cell lines tested but present in very low amounts in the normal human pancreas. To determine whether inhibition of NQO(1) would alter the malignant phenotype, MIA PaCa-2 pancreatic cancer cells were treated with a selective inhibitor of NQO(1), dicumarol. Dicumarol increased intracellular production of O(2)(.-), as measured by hydroethidine staining, and inhibited cell growth. Both of these effects were blunted with infection of an adenoviral vector containing the cDNA for manganese superoxide dismutase. Dicumarol also inhibited cell growth, plating efficiency, and growth in soft agar. We conclude that inhibition of NQO(1) increases intracellular O(2)(.-) production and inhibits the in vitro malignant phenotype of pancreatic cancer. These mechanisms suggest that altering the intracellular redox environment of pancreatic cancer cells may inhibit growth and delineate a potential strategy directed against pancreatic cancer.

  6. Inhibiting prenylation augments chemotherapy efficacy in renal cell carcinoma through dual inhibition on mitochondrial respiration and glycolysis.

    Huang, Jiangrong; Yang, Xiaoyu; Peng, Xiaochun; Huang, Wei

    2017-11-18

    Prenylation is a posttranslational lipid modification required for the proper functions of a number of proteins involved in cell regulation. Here, we show that prenylation inhibition is important for renal cell carcinoma (RCC) growth, survival and response to chemotherapy, and its underlying mechanism may be contributed to mitochondrial dysfunction. We first demonstrated that a HMG-CoA reductase inhibitor pitavastatin inhibited mevalonate pathway and thereby prenylation in RCC cells. In addition, pitavastatin is effective in inhibiting growth and inducing apoptosis in a panel of RCC cell lines. Combination of pitavastatin and paclitaxel is significantly more effective than pitavastatin or paclitaxel alone as shown by both in vitro cell culture system and in vivo RCC xenograft model. Importantly, pitavastatin treatment inhibits mitochondrial respiration via suppressing mitochondrial complex I and II enzyme activities. Interestingly, different from mitochondrial inhibitor phenformin that inhibits mitochondrial respiration but activates glycolytic rate in RCC cells, pitavastatin significantly decreases glycolytic rate. The dual inhibitory action of pitavastatin on mitochondrial respiration and glycolysis results in remarkable energy depletion and oxidative stress in RCC cells. In addition, inhibition of prenylation by depleting Isoprenylcysteine carboxylmethyltransferase (Icmt) also mimics the inhibitory effects of pitavastatin in RCC cells. Our work demonstrates the previously unappreciated association between prenylation inhibition and energy metabolism in RCC, which can be therapeutically exploited, likely in tumors that largely rely on energy metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Control of CA3 output by feedforward inhibition despite developmental changes in the excitation-inhibition balance.

    Torborg, Christine L; Nakashiba, Toshiaki; Tonegawa, Susumu; McBain, Chris J

    2010-11-17

    In somatosensory cortex, the relative balance of excitation and inhibition determines how effectively feedforward inhibition enforces the temporal fidelity of action potentials. Within the CA3 region of the hippocampus, glutamatergic mossy fiber (MF) synapses onto CA3 pyramidal cells (PCs) provide strong monosynaptic excitation that exhibit prominent facilitation during repetitive activity. We demonstrate in the juvenile CA3 that MF-driven polysynaptic IPSCs facilitate to maintain a fixed EPSC-IPSC ratio during short-term plasticity. In contrast, in young adult mice this MF-driven polysynaptic inhibitory input can facilitate or depress in response to short trains of activity. Transgenic mice lacking the feedback inhibitory loop continue to exhibit both facilitating and depressing polysynaptic IPSCs, indicating that this robust inhibition is not caused by the secondary engagement of feedback inhibition. Surprisingly, eliminating MF-driven inhibition onto CA3 pyramidal cells by blockade of GABA(A) receptors did not lead to a loss of temporal precision of the first action potential observed after a stimulus but triggered in many cases a long excitatory plateau potential capable of triggering repetitive action potential firing. These observations indicate that, unlike other regions of the brain, the temporal precision of single MF-driven action potentials is dictated primarily by the kinetics of MF EPSPs, not feedforward inhibition. Instead, feedforward inhibition provides a robust regulation of CA3 PC excitability across development to prevent excessive depolarization by the monosynaptic EPSP and multiple action potential firings.

  8. Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

    Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Wani, Mohan R., E-mail: mohanwani@nccs.res.in [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India)

    2010-09-03

    Research highlights: {yields} IL-3 inhibits receptor activator of NF-{kappa}B ligand (RANKL)-induced osteoclastogenesis. {yields} IL-3 inhibits RANKL-induced JNK activation. {yields} IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. {yields} IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. {yields} IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-{kappa}B (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

  9. Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

    Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T.; Wani, Mohan R.

    2010-01-01

    Research highlights: → IL-3 inhibits receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. → IL-3 inhibits RANKL-induced JNK activation. → IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. → IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. → IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-κB (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

  10. Arctigenin Inhibits Liver Cancer Tumorigenesis by Inhibiting Gankyrin Expression via C/EBPα and PPARα

    Sun, Ying; Tan, Yu-jun; Lu, Zhan-zhao; Li, Bing-bing; Sun, Cheng-hong; Li, Tao; Zhao, Li-li; Liu, Zhong; Zhang, Gui-min; Yao, Jing-chun; Li, Jie

    2018-01-01

    Burdock (Arctium lappa) is a popular vegetable in China and Japan that is consumed for its general health benefits. The principal active component of burdock is arctigenin, which shows a range of bioactivities in vivo and in vitro. Here, we investigated the potential anti-tumor effects of arctigenin using two human hepatocellular carcinoma (HCC) cell lines, HepG2 and Hep3B, and sought to elucidate its potential mechanisms of action. Our results showed that arctigenin treatment inhibited cell growth in both HepG2 and Hep3B cell lines (IC50 of 4.74 nM for HepG2 cells, and of 59.27 nM for Hep3B cells). In addition, migration, invasion, and colony formation by HepG2 cells were significantly inhibited by arctigenin. By contrast, treatment of Hep3B cells with arctigenin did not alter these parameters. Arctigenin also significantly reduced the levels of gankyrin mRNA and protein in HepG2 cells, but not in Hep3B cells. A luciferase assay indicated that arctigenin targeted the -450 to -400 region of the gankyrin promoter. This region is also the potential binding site for both C/EBPα and PPARα, as predicted and confirmed by an online software analysis and ChIP assay. Additionally, a co-immunoprecipitation (Co-IP) assay showed that binding between C/EBPα and PPARα was increased in the presence of arctigenin. However, arctigenin did not increase the expression of C/EBPα or PPARα protein. A binding screening assay and liquid chromatography–mass spectrometry (LC–MS) were performed to identify the mechanisms by which arctigenin regulates gankyrin expression. The results suggested that arctigenin could directly increase C/EBPα binding to the gankyrin promoter (-432 to -422 region), but did not affect PPARα binding. Expression of gankyrin, C/EBPα, and PPARα were analyzed in tumor tissues of patients using real-time PCR. Both C/EBPα and PPARα showed negative correlations with gankyrin. In tumor-bearing mice, arctigenin had a significant inhibitory effect on HCC

  11. Arctigenin Inhibits Liver Cancer Tumorigenesis by Inhibiting Gankyrin Expression via C/EBPα and PPARα

    Ying Sun

    2018-03-01

    Full Text Available Burdock (Arctium lappa is a popular vegetable in China and Japan that is consumed for its general health benefits. The principal active component of burdock is arctigenin, which shows a range of bioactivities in vivo and in vitro. Here, we investigated the potential anti-tumor effects of arctigenin using two human hepatocellular carcinoma (HCC cell lines, HepG2 and Hep3B, and sought to elucidate its potential mechanisms of action. Our results showed that arctigenin treatment inhibited cell growth in both HepG2 and Hep3B cell lines (IC50 of 4.74 nM for HepG2 cells, and of 59.27 nM for Hep3B cells. In addition, migration, invasion, and colony formation by HepG2 cells were significantly inhibited by arctigenin. By contrast, treatment of Hep3B cells with arctigenin did not alter these parameters. Arctigenin also significantly reduced the levels of gankyrin mRNA and protein in HepG2 cells, but not in Hep3B cells. A luciferase assay indicated that arctigenin targeted the -450 to -400 region of the gankyrin promoter. This region is also the potential binding site for both C/EBPα and PPARα, as predicted and confirmed by an online software analysis and ChIP assay. Additionally, a co-immunoprecipitation (Co-IP assay showed that binding between C/EBPα and PPARα was increased in the presence of arctigenin. However, arctigenin did not increase the expression of C/EBPα or PPARα protein. A binding screening assay and liquid chromatography–mass spectrometry (LC–MS were performed to identify the mechanisms by which arctigenin regulates gankyrin expression. The results suggested that arctigenin could directly increase C/EBPα binding to the gankyrin promoter (-432 to -422 region, but did not affect PPARα binding. Expression of gankyrin, C/EBPα, and PPARα were analyzed in tumor tissues of patients using real-time PCR. Both C/EBPα and PPARα showed negative correlations with gankyrin. In tumor-bearing mice, arctigenin had a significant inhibitory

  12. Arctigenin Inhibits Liver Cancer Tumorigenesis by Inhibiting Gankyrin Expression via C/EBPα and PPARα.

    Sun, Ying; Tan, Yu-Jun; Lu, Zhan-Zhao; Li, Bing-Bing; Sun, Cheng-Hong; Li, Tao; Zhao, Li-Li; Liu, Zhong; Zhang, Gui-Min; Yao, Jing-Chun; Li, Jie

    2018-01-01

    Burdock ( Arctium lappa ) is a popular vegetable in China and Japan that is consumed for its general health benefits. The principal active component of burdock is arctigenin, which shows a range of bioactivities in vivo and in vitro . Here, we investigated the potential anti-tumor effects of arctigenin using two human hepatocellular carcinoma (HCC) cell lines, HepG2 and Hep3B, and sought to elucidate its potential mechanisms of action. Our results showed that arctigenin treatment inhibited cell growth in both HepG2 and Hep3B cell lines (IC 50 of 4.74 nM for HepG2 cells, and of 59.27 nM for Hep3B cells). In addition, migration, invasion, and colony formation by HepG2 cells were significantly inhibited by arctigenin. By contrast, treatment of Hep3B cells with arctigenin did not alter these parameters. Arctigenin also significantly reduced the levels of gankyrin mRNA and protein in HepG2 cells, but not in Hep3B cells. A luciferase assay indicated that arctigenin targeted the -450 to -400 region of the gankyrin promoter. This region is also the potential binding site for both C/EBPα and PPARα, as predicted and confirmed by an online software analysis and ChIP assay. Additionally, a co-immunoprecipitation (Co-IP) assay showed that binding between C/EBPα and PPARα was increased in the presence of arctigenin. However, arctigenin did not increase the expression of C/EBPα or PPARα protein. A binding screening assay and liquid chromatography-mass spectrometry (LC-MS) were performed to identify the mechanisms by which arctigenin regulates gankyrin expression. The results suggested that arctigenin could directly increase C/EBPα binding to the gankyrin promoter (-432 to -422 region), but did not affect PPARα binding. Expression of gankyrin, C/EBPα , and PPARα were analyzed in tumor tissues of patients using real-time PCR. Both C/EBPα and PPARα showed negative correlations with gankyrin. In tumor-bearing mice, arctigenin had a significant inhibitory effect on HCC

  13. Pathological histone acetylation in Parkinson's disease: Neuroprotection and inhibition of microglial activation through SIRT 2 inhibition.

    Harrison, Ian F; Smith, Andrew D; Dexter, David T

    2018-02-14

    Parkinson's disease (PD) is associated with degeneration of nigrostriatal neurons due to intracytoplasmic inclusions composed predominantly of a synaptic protein called α-synuclein. Accumulations of α-synuclein are thought to 'mask' acetylation sites on histone proteins, inhibiting the action of histone acetyltransferase (HAT) enzymes in their equilibrium with histone deacetylases (HDACs), thus deregulating the dynamic control of gene transcription. It is therefore hypothesised that the misbalance in the actions of HATs/HDACs in neurodegeneration can be rectified with the use of HDAC inhibitors, limiting the deregulation of transcription and aiding neuronal homeostasis and neuroprotection in disorders such as PD. Here we quantify histone acetylation in the Substantia Nigra pars compacta (SNpc) in the brains of control, early and late stage PD cases to determine if histone acetylation is a function of disease progression. PD development is associated with Braak-dependent increases in histone acetylation. Concurrently, we show that as expected disease progression is associated with reduced markers of dopaminergic neurons and increased markers of activated microglia. We go on to demonstrate that in vitro, degenerating dopaminergic neurons exhibit histone hypoacetylation whereas activated microglia exhibit histone hyperacetylation. This suggests that the disease-dependent increase in histone acetylation observed in human PD cases is likely a combination of the contributions of both degenerating dopaminergic neurons and infiltrating activated microglia. The HDAC SIRT 2 has become increasingly implicated as a novel target for mediation of neuroprotection in PD: the neuronal and microglial specific effects of its inhibition however remain unclear. We demonstrate that SIRT 2 expression in the SNpc of PD brains remains relatively unchanged from controls and that SIRT 2 inhibition, via AGK2 treatment of neuronal and microglial cultures, results in neuroprotection of

  14. Inhibition Effect of Deanol on Mild Steel Corrosion in Dilute ...

    NICOLAAS

    2014-06-23

    Jun 23, 2014 ... allows for extensive use as the material of construction in petro- leum industries .... steel specimens was investigated after mass-loss analysis ..... Ogbuliec, Inhibition of pseudo-anaerobic corrosion of oil pipeline steel in ...

  15. Melanogenesis inhibition activity of floralginsenoside A from Panax ginseng berry

    Dae Young Lee

    2017-10-01

    Conclusion: FGA showed the most potent inhibition of melanogenesis in both in vitro and in vivo studies. This study suggests that FGA purified from P. ginseng may be an effective melanogenesis inhibitor.

  16. Automatic motion inhibit system for a nuclear power generating system

    Musick, C.R.; Torres, J.M.

    1977-01-01

    Disclosed is an automatic motion inhibit system for a nuclear power generating system for inhibiting automatic motion of the control elements to reduce reactor power in response to a turbine load reduction. The system generates a final reactor power level setpoint signal which is continuously compared with a reactor power signal. The final reactor power level setpoint is a setpoint within the capacity of the bypass valves to bypass steam which in no event is lower in value than the lower limit of automatic control of the reactor. If the final reactor power level setpoint is greater than the reactor power, an inhibit signal is generated to inhibit automatic control of the reactor. 6 claims, 5 figures

  17. Noninvasive optical inhibition with a red-shifted microbial rhodopsin

    Chuong, Amy S; Miri, Mitra L; Busskamp, Volker

    2014-01-01

    Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium......) salinarum (strain Shark) and engineered to result in red light-induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also...... demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied...

  18. Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by ...

    Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway.

  19. Functional inhibition of UQCRB suppresses angiogenesis in zebrafish

    Cho, Yoon Sun; Jung, Hye Jin [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Seok, Seung Hyeok [Department of Microbiology and Immunology, Institute for Experimental Animals, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Payumo, Alexander Y.; Chen, James K. [Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305 (United States); Kwon, Ho Jeong, E-mail: kwonhj@yonsei.ac.kr [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2013-04-19

    Highlights: ► This is the first functional characterization of UQCRB in vivo model. ► Angiogenesis is inhibited with UQCRB loss of function in zebrafish. ► UQCRB is introduced as a prognostic marker for mitochondria- and angiogenesis-related diseases. -- Abstract: As a subunit of mitochondrial complex III, UQCRB plays an important role in complex III stability, electron transport, and cellular oxygen sensing. Herein, we report UQCRB function regarding angiogenesis in vivo with the zebrafish (Danio rerio). UQCRB knockdown inhibited angiogenesis in zebrafish leading to the suppression of VEGF expression. Moreover, the UQCRB-targeting small molecule terpestacin also inhibited angiogenesis and VEGF levels in zebrafish, supporting the role of UQCRB in angiogenesis. Collectively, UQCRB loss of function by either genetic and pharmacological means inhibited angiogenesis, indicating that UQCRB plays a key role in this process and can be a prognostic marker of angiogenesis- and mitochondria-related diseases.

  20. Inhibiting DNA Polymerases as a Therapeutic Intervention against Cancer

    Anthony J. Berdis

    2017-11-01

    Full Text Available Inhibiting DNA synthesis is an important therapeutic strategy that is widely used to treat a number of hyperproliferative diseases including viral infections, autoimmune disorders, and cancer. This chapter describes two major categories of therapeutic agents used to inhibit DNA synthesis. The first category includes purine and pyrmidine nucleoside analogs that directly inhibit DNA polymerase activity. The second category includes DNA damaging agents including cisplatin and chlorambucil that modify the composition and structure of the nucleic acid substrate to indirectly inhibit DNA synthesis. Special emphasis is placed on describing the molecular mechanisms of these inhibitory effects against chromosomal and mitochondrial DNA polymerases. Discussions are also provided on the mechanisms associated with resistance to these therapeutic agents. A primary focus is toward understanding the roles of specialized DNA polymerases that by-pass DNA lesions produced by DNA damaging agents. Finally, a section is provided that describes emerging areas in developing new therapeutic strategies targeting specialized DNA polymerases.

  1. Inhibition of trypsin by condensed tannins and wine.

    Gonçalves, Rui; Soares, Susana; Mateus, Nuno; de Freitas, Victor

    2007-09-05

    Phenolic compounds are abundant vegetable secondary metabolites in the human diet. The ability of procyanidin oligomers and wine polyphenols to inhibit trypsin activity was studied using a versatile and reliable in vitro method. The hydrolysis of the chromogenic substrate N-benzoyl-d,l-arginine-p-nitroanilide (BApNA) by trypsin was followed by spectrophotometry in the presence and absence of condensed tannins and wine. A clear relationship between the degree of polymerization of procyanidins and enzymatic inhibition was observed. Trypsin activity inhibition was also detected in several types of wine. In general, the inhibition increased with the concentration of phenolic compounds in wines. These results may be relevant when considering these compounds as antinutritional factors, thereby contributing to a reduced absorption of nutrients.

  2. Ginsenoside Rb1 Reduces Nitric Oxide Production via Inhibition of ...

    Inhibition of Nuclear Factor-κB Activation in Interleukin-1β- ... 20, 40, 80 µM ginsenoside Rb1. NO concentration was assessed by the Griess reaction. ... International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, ...

  3. Transcriptome dynamics of the microRNA inhibition response

    Wen, Jiayu; Leucci, Elenora; Vendramin, Roberto

    2015-01-01

    We report a high-resolution time series study of transcriptome dynamics following antimiR-mediated inhibition of miR-9 in a Hodgkin lymphoma cell-line-the first such dynamic study of the microRNA inhibition response-revealing both general and specific aspects of the physiological response. We show...... validate the key observations with independent time series qPCR and we experimentally validate key predicted miR-9 targets. Methodologically, we developed sensitive functional data analytic predictive methods to analyse the weak response inherent in microRNA inhibition experiments. The methods...... of this study will be applicable to similar high-resolution time series transcriptome analyses and provides the context for more accurate experimental design and interpretation of future microRNA inhibition studies....

  4. Inhibition of human lung adenocarcinoma growth using survivint34a ...

    Prakash

    knockdown, survivin-directed vaccines (Pisarev et al. 2003), ... Endotoxin levels of the plasmid DNA prepared were determined by .... power fields/slide). ... inhibition of angiogenesis and directly increase apoptosis of .... α-induced apoptosis.

  5. Functional inhibition of UQCRB suppresses angiogenesis in zebrafish

    Cho, Yoon Sun; Jung, Hye Jin; Seok, Seung Hyeok; Payumo, Alexander Y.; Chen, James K.; Kwon, Ho Jeong

    2013-01-01

    Highlights: ► This is the first functional characterization of UQCRB in vivo model. ► Angiogenesis is inhibited with UQCRB loss of function in zebrafish. ► UQCRB is introduced as a prognostic marker for mitochondria- and angiogenesis-related diseases. -- Abstract: As a subunit of mitochondrial complex III, UQCRB plays an important role in complex III stability, electron transport, and cellular oxygen sensing. Herein, we report UQCRB function regarding angiogenesis in vivo with the zebrafish (Danio rerio). UQCRB knockdown inhibited angiogenesis in zebrafish leading to the suppression of VEGF expression. Moreover, the UQCRB-targeting small molecule terpestacin also inhibited angiogenesis and VEGF levels in zebrafish, supporting the role of UQCRB in angiogenesis. Collectively, UQCRB loss of function by either genetic and pharmacological means inhibited angiogenesis, indicating that UQCRB plays a key role in this process and can be a prognostic marker of angiogenesis- and mitochondria-related diseases

  6. Nitric oxide inhibits glycogen synthesis in isolated rat hepatocytes

    Sprangers, F.; Sauerwein, H. P.; Romijn, J. A.; van Woerkom, G. M.; Meijer, A. J.

    1998-01-01

    There is increasing evidence for the existence of intrahepatic regulation of glucose metabolism by Kupffer cell products. Nitric oxide (NO) is known to inhibit gluconeogenic flux through pyruvate carboxylase and phosphoenolpyruvate carboxykinase. However, NO may also influence glucose metabolism at

  7. Inhibition of glutathione S-transferases (GSTs) activity from cowpea ...

    STORAGESEVER

    2009-10-19

    Oct 19, 2009 ... Inhibition effect of the plant extracts on the GST was studied by spectrophotometric method. The ... of assuring food security in developing countries like ..... studies on African cat fish (Clarias gariepinus) liver glutathione s-.

  8. Impaired face recognition is associated with social inhibition.

    Avery, Suzanne N; VanDerKlok, Ross M; Heckers, Stephan; Blackford, Jennifer U

    2016-02-28

    Face recognition is fundamental to successful social interaction. Individuals with deficits in face recognition are likely to have social functioning impairments that may lead to heightened risk for social anxiety. A critical component of social interaction is how quickly a face is learned during initial exposure to a new individual. Here, we used a novel Repeated Faces task to assess how quickly memory for faces is established. Face recognition was measured over multiple exposures in 52 young adults ranging from low to high in social inhibition, a core dimension of social anxiety. High social inhibition was associated with a smaller slope of change in recognition memory over repeated face exposure, indicating participants with higher social inhibition showed smaller improvements in recognition memory after seeing faces multiple times. We propose that impaired face learning is an important mechanism underlying social inhibition and may contribute to, or maintain, social anxiety. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. IN VITRO STUDY ON INHIBITION OF GLYCOSYLATION OF ...

    Administrator

    complications of diabetes mellitus (Makita et al., 1991). Apart from protein ... enzymes; inhibition of regulatory molecule binding; crosslinking of glycosylated .... further investigation specific bio active compound responsible for such activities.

  10. Hyperoxia Inhibits T Cell Activation in Mice

    Hughes-Fulford, M.; Meissler, J.; Aguayo, E. T.; Globus, R.; Aguado, J.; Candelario, T.

    2013-02-01

    , spleens were removed and the splenocytes were isolated and kept as individual biological samples. We have also examined transcription factors (JASPAR) and pathways of the immune system to help us understand the mechanism of regulation. Results: Our recent mouse immunology experiment aboard STS-131 suggests that the early T cell immune response was inhibited in animals that have been exposed to spaceflight, even 24 hours after return to earth. Moreover, recent experiments in hyperoxic mice show that many of the same genes involved in early T cell activation were altered. Specifically, expression of IL-2Rα, Cxcl2, TNFα, FGF2, LTA and BCL2 genes are dysregulated in mice exposed to hyperoxia. Conclusions: If these hyperoxia-induced changes of gene expression in early T cell activation are additive to the changes seen in the microgravity of spaceflight, there could be an increased infection risk to EVA astronauts, which should be addressed prior to conducting a Mars or other long-term mission.

  11. Study of oxygen inhibition effect on radiation curing

    Xiao Bin; Yang Xuemei; Zhao Pengji; Zeng Shuqing; Jiang Bo; Zhou Yong; Huang Wei; Zhou Youyi

    1995-01-01

    Michacl addition reaction product was used in the research of oxygen inhibition effect of radiation curing. The experimental results was measured by the content of gel and percentage of double bonds. It was proved that 9% of Michacl addition product could speed up 1.2 times of the radiation curing rate at 30 kGy of EB irradiation. This kind of formulation can withstand oxygen inhibition effect obviously, so it was the foundation of application for radiation curing in atmospheric condition

  12. Antiangiogenic and Antitumor Effects of Src Inhibition in Ovarian Carcinoma

    Han, Liz Y.; Landen, Charles N.; Trevino, Jose G.; Halder, Jyotsnabaran; Lin, Yvonne G.; Kamat, Aparna A.; Kim, Tae-Jin; Merritt, William M.; Coleman, Robert L.; Gershenson, David M.; Shakespeare, William C.; Wang, Yihan; Sundaramoorth, Raji; Metcalf, Chester A.; Dalgarno, David C.; Sawyer, Tomi K.; Gallick, Gary E.; Sood, Anil K.

    2011-01-01

    Src, a nonreceptor tyrosine kinase, is a key mediator for multiple signaling pathways that regulate critical cellular functions and is often aberrantly activated in a number of solid tumors, including ovarian carcinoma. The purpose of this study was to determine the role of activated Src inhibition on tumor growth in an orthotopic murine model of ovarian carcinoma. In vitro studies on HeyA8 and SKOV3ip1 cell lines revealed that Src inhibition by the Src-selective inhibitor, AP23846, occurred within 1 hour and responded in a dose-dependent manner. Furthermore, Src inhibition enhanced the cytotoxicity of docetaxel in both chemosensitive and chemoresistant ovarian cancer cell lines, HeyA8 and HeyA8-MDR, respectively. In vivo, Src inhibition by AP23994, an orally bioavailable analogue of AP23846, significantly decreased tumor burden in HeyA8 (P = 0.02), SKOV3ip1 (P = 0.01), as well as HeyA8-MDR (P < 0.03) relative to the untreated controls. However, the greatest effect on tumor reduction was observed in combination therapy with docetaxel (P < 0.001, P = 0.002, and P = 0.01, for the above models, respectively). Proliferating cell nuclear antigen staining showed that Src inhibition alone (P = 0.02) and in combination with docetaxel (P = 0.007) significantly reduced tumor proliferation. In addition, Src inhibition alone and in combination with docetaxel significantly down-regulated tumoral production of vascular endothelial growth factor and interleukin 8, whereas combination therapy decreased the microvessel density (P = 0.02) and significantly affected vascular permeability (P < 0.05). In summary, Src inhibition with AP23994 has potent antiangiogenic effects and significantly reduces tumor burden in preclinical ovarian cancer models. Thus, Src inhibition may be an attractive therapeutic approach for patients with ovarian carcinoma. PMID:16951177

  13. Hili Inhibits HIV Replication in Activated T Cells.

    Peterlin, B Matija; Liu, Pingyang; Wang, Xiaoyun; Cary, Daniele; Shao, Wei; Leoz, Marie; Hong, Tian; Pan, Tao; Fujinaga, Koh

    2017-06-01

    P-element-induced wimpy-like (Piwil) proteins restrict the replication of mobile genetic elements in the germ line. They are also expressed in many transformed cell lines. In this study, we discovered that the human Piwil 2 (Hili) protein can also inhibit HIV replication, especially in activated CD4 + T cells that are the preferred target cells for this virus in the infected host. Although resting cells did not express Hili, its expression was rapidly induced following T cell activation. In these cells and transformed cell lines, depletion of Hili increased levels of viral proteins and new viral particles. Further studies revealed that Hili binds to tRNA. Some of the tRNAs represent rare tRNA species, whose codons are overrepresented in the viral genome. Targeting tRNA Arg (UCU) with an antisense oligonucleotide replicated effects of Hili and also inhibited HIV replication. Finally, Hili also inhibited the retrotransposition of the endogenous intracysternal A particle (IAP) by a similar mechanism. Thus, Hili joins a list of host proteins that inhibit the replication of HIV and other mobile genetic elements. IMPORTANCE Piwil proteins inhibit the movement of mobile genetic elements in the germ line. In their absence, sperm does not form and male mice are sterile. This inhibition is thought to occur via small Piwi-interacting RNAs (piRNAs). However, in some species and in human somatic cells, Piwil proteins bind primarily to tRNA. In this report, we demonstrate that human Piwil proteins, especially Hili, not only bind to select tRNA species, including rare tRNAs, but also inhibit HIV replication. Importantly, T cell activation induces the expression of Hili in CD4 + T cells. Since Hili also inhibited the movement of an endogenous retrovirus (IAP), our finding shed new light on this intracellular resistance to exogenous and endogenous retroviruses as well as other mobile genetic elements. Copyright © 2017 American Society for Microbiology.

  14. Novel Antimicrobial Peptides That Inhibit Gram Positive Bacterial Exotoxin Synthesis

    Merriman, Joseph A.; Nemeth, Kimberly A.; Schlievert, Patrick M.

    2014-01-01

    Gram-positive bacteria, such as Staphylococcus aureus, cause serious human illnesses through combinations of surface virulence factors and secretion of exotoxins. Our prior studies using the protein synthesis inhibitor clindamycin and signal transduction inhibitors glycerol monolaurate and α-globin and β-globin chains of hemoglobin indicate that their abilities to inhibit exotoxin production by S. aureus are separable from abilities to inhibit growth of the organism. Additionally, our previous studies suggest that inhibition of exotoxin production, in absence of ability to kill S. aureus and normal flora lactobacilli, will prevent colonization by pathogenic S. aureus, while not interfering with lactobacilli colonization. These disparate activities may be important in development of novel anti-infective agents that do not alter normal flora. We initiated studies to explore the exotoxin-synthesis-inhibition activity of hemoglobin peptides further to develop potential agents to prevent S. aureus infections. We tested synthesized α-globin chain peptides, synthetic variants of α-globin chain peptides, and two human defensins for ability to inhibit exotoxin production without significantly inhibiting S. aureus growth. All of these peptides were weakly or not inhibitory to bacterial growth. However, the peptides were inhibitory to exotoxin production with increasing activity dependent on increasing numbers of positively-charged amino acids. Additionally, the peptides could be immobilized on agarose beads or have amino acid sequences scrambled and still retain exotoxin-synthesis-inhibition. The peptides are not toxic to human vaginal epithelial cells and do not inhibit growth of normal flora L. crispatus. These peptides may interfere with plasma membrane signal transduction in S. aureus due to their positive charges. PMID:24748386

  15. The contribution of forward masking to saccadic inhibition of return.

    Souto, David; Born, Sabine; Kerzel, Dirk

    2018-03-08

    Inhibition of return is the name typically given to the prolonged latency of motor responses directed to a previously cued target location. There is intense debate about the origins of this effect and its function, but most take for granted (despite lack of evidence) that it depends little on forward masking. Therefore, we re-examined the role of forward masking in inhibition of return. Forward masking was indexed by slower saccadic reaction times (SRTs) when the target orientation repeated the cue orientation at the same location. We confirmed effects of orientation repetition in the absence of an attentional bias when cues were presented on both sides of fixation (bilateral presentation). The effect of orientation repetition was reduced with high target contrast, consistent with a low-level origin such as contrast gain control in early visual areas. When presenting cues on only one side of fixation (unilateral presentation), we obtained inhibition of return with longer cue-target intervals and facilitation with targets presented shortly after the cue. The effect of orientation repetition was reduced when facilitation was observed, but was as strong as with bilateral cues when inhibition of return was observed. Therefore, forward masking may contribute to the inhibition of return effect by delaying reaction times to repeated features at the same location, but is not a principal cause of inhibition of return; in agreement with previous views. The saccadic inhibition of return effect is a reaction-time cost when responding to a pre-cued location. Additional object updating costs are typically invoked to explain reaction-time costs observed when cue and target have the same shape. Yet, lower-level, forward masking of the target by the cue can not be ruled out. Importantly, we show an effect of orientation repetition that is consistent with low-level forward masking rather than object updating costs and that does not interact with inhibition of return.

  16. Buprofezin inhibits acetylcholinesterase activity in B-biotype Bemisia tabaci.

    Cottage, Emma L A; Gunning, Robin V

    2006-01-01

    B-biotype Bemisia tabaci is a severe insect pest worldwide in many ornamental, agricultural, and horticultural industries. Control of this insect is hampered by resistance to many acetylcholinesterase (AChE)-inhibiting insecticides, such as organophosphates and carbamates. Consequently, insect growth regulators such as buprofezin, which act by inhibiting chitin synthesis, are being investigated for use against B-biotype B. tabaci in Australia. This study discusses the effects of buprofezin on B. tabaciAChE.

  17. Influence of norepinephrine transporter inhibition on hemodynamic response to hypergravitation

    Strempel, Sebastian

    2011-01-01

    Background: Sympathetically-mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness (g-LOC). Norepinephrine transporter (NET) inhibition prevents neurally-mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus, it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. Methods. We performed a double-blind, randomized...

  18. Cantharidin biosynthesis in a blister beetle: inhibition by 6-fluoromevalonate causes chemical disarmament.

    Carrel, J E; Doom, J P; McCormick, J P

    1986-07-15

    Biosynthesis of cantharidin in a blister beetle, Lytta polita, is effectively inhibited by 6-fluoromevalonate. Inhibition is attributed specifically to the fluorine substituent. Biochemical inhibition has not been demonstrated previously for an arthropod's defensive substance.

  19. Prepotent response inhibition predicts treatment outcome in attention deficit/hyperactivity disorder

    van der Oord, S.; Geurts, H.M.; Prins, P.J.M.; Emmelkamp, P.M.G.; Oosterlaan, J.

    2012-01-01

    Objective: Inhibition deficits, including deficits in prepotent response inhibition and interference control, are core deficits in ADHD. The predictive value of prepotent response inhibition and interference control was assessed for outcome in a 10-week treatment trial with methylphenidate. Methods:

  20. Substrate and product inhibition of hydrogen production by the extreme thermophile, Caldicellulosiruptor saccharolyticus

    Niel, van E.W.J.; Claassen, P.A.M.; Stams, A.J.M.

    2003-01-01

    Substrate and product inhibition of hydrogen production during sucrose fermentation by the extremely thermophilic bacterium Caldicellulosiruptor saccharolyticus was studied. The inhibition kinetics were analyzed with a noncompetitive, nonlinear inhibition model. Hydrogen was the most severe

  1. Beyond Behavioral Inhibition: A Computer Avatar Task Designed to Assess Behavioral Inhibition Extends to Harm Avoidance

    Michael Todd Allen

    2017-09-01

    Full Text Available Personality factors such as behavioral inhibition (BI, a temperamental tendency for avoidance in the face of unfamiliar situations, have been identified as risk factors for anxiety disorders. Personality factors are generally identified through self-report inventories. However, this tendency to avoid may affect the accuracy of these self-report inventories. Previously, a computer based task was developed in which the participant guides an on-screen “avatar” through a series of onscreen events; performance on the task could accurately predict participants’ BI, measured by a standard paper and pencil questionnaire (Adult Measure of Behavioral Inhibition, or AMBI. Here, we sought to replicate this finding as well as compare performance on the avatar task to another measure related to BI, the harm avoidance (HA scale of the Tridimensional Personality Questionnaire (TPQ. The TPQ includes HA scales as well as scales assessing reward dependence (RD, novelty seeking (NS and persistence. One hundred and one undergraduates voluntarily completed the avatar task and the paper and pencil inventories in a counter-balanced order. Scores on the avatar task were strongly correlated with BI assessed via the AMBI questionnaire, which replicates prior findings. Females exhibited higher HA scores than males, but did not differ on scores on the avatar task. There was a strong positive relationship between scores on the avatar task and HA scores. One aspect of HA, fear of uncertainty was found to moderately mediate the relationship between AMBI scores and avatar scores. NS had a strong negative relationship with scores on the avatar task, but there was no significant relationship between RD and scores on the avatar task. These findings indicate the effectiveness of the avatar task as a behavioral alternative to self-report measures to assess avoidance. In addition, the use of computer based behavioral tasks are a viable alternative to paper and pencil self

  2. DMSO inhibits human platelet activation through cyclooxygenase-1 inhibition. A novel agent for drug eluting stents?

    Asmis, Lars; Tanner, Felix C.; Sudano, Isabella; Luescher, Thomas F.; Camici, Giovanni G.

    2010-01-01

    Background: DMSO is routinely infused together with hematopoietic cells in patients undergoing myeloablative therapy and was recently found to inhibit smooth muscle cells proliferation and arterial thrombus formation in the mouse by preventing tissue factor (TF), a key activator of the coagulation cascade. This study was designed to investigate whether DMSO prevents platelet activation and thus, whether it may represent an interesting agent to be used on drug eluting stents. Methods and results: Human venous blood from healthy volunteers was collected in citrated tubes and platelet activation was studied by cone and platelet analyzer (CPA) and rapid-platelet-function-assay (RPFA). CPA analysis showed that DMSO-treated platelets exhibit a lower adherence in response to shear stress (-15.54 ± 0.9427%, n = 5, P < 0.0001 versus control). Additionally, aggregometry studies revealed that DMSO-treated, arachidonate-stimulated platelets had an increased lag phase (18.0% ± 4.031, n = 9, P = 0.0004 versus control) as well as a decreased maximal aggregation (-6.388 ± 2.212%, n = 6, P = 0.0162 versus control). Inhibitory action of DMSO could be rescued by exogenous thromboxane A2 and was mediated, at least in part, by COX-1 inhibition. Conclusions: Clinically relevant concentrations of DMSO impair platelet activation by a thromboxane A2-dependent, COX-1-mediated effect. This finding may be crucial for the previously reported anti-thrombotic property displayed by DMSO. Our findings support a role for DMSO as a novel drug to prevent not only proliferation, but also thrombotic complications of drug eluting stents.

  3. SGLT2 inhibition in the diabetic kidney – an update

    Novikov, Aleksandra; Vallon, Volker

    2016-01-01

    Purpose of review The sodium glucose cotransporter SGLT2 reabsorbs most of the glucose filtered by the kidneys. SGLT2 inhibitors reduce glucose reabsorption thereby lowering blood glucose levels and have been approved as new anti-hyperglycemic drugs. While the therapeutic strategy is very promising, many questions remain. Recent findings Using validated antibodies SGLT2 expression was localized to the brush border of the early proximal tubule in human kidney and was found upregulated in genetic murine models of type 1 and 2 diabetes. SGLT2 may functionally interact with the Na/H exchanger NHE3 in the proximal tubule. SGLT1-mediated reabsorption explains the fractional glucose reabsorption of 40–50% during SGLT2 inhibition. SGLT2 is expressed on pancreatic alpha cells where its inhibition induces glucagon secretion. SGLT2 inhibition lowers GFR in hyperfiltering diabetic patients consistent with the tubular hypothesis of diabetic hyperfiltration. New data indicate a potential of SGLT2 inhibition for renal medullary hypoxia and ketoacidosis, but also for blood glucose effect-dependent and independent nephroprotective actions, renal gluconeogenesis inhibition, reduction in cardiovascular mortality, and cancer therapy. Summary The findings expand and refine our understanding of SGLT2 and its inhibition, have relevance for clinical practice, and will help interpret ongoing clinical trials on the long-term safety and cardiovascular effects of SGLT2 inhibitors. PMID:26575393

  4. Acrolein in cigarette smoke inhibits T-cell responses.

    Lambert, Cherie; McCue, Jesica; Portas, Mary; Ouyang, Yanli; Li, JiMei; Rosano, Thomas G; Lazis, Alexander; Freed, Brian M

    2005-10-01

    Cigarette smoking inhibits T-cell responses in the lungs, but the immunosuppressive compounds have not been fully identified. Cigarette smoke extracts inhibit IL-2, IFN-gamma, and TNF-alpha production in stimulated lymphocytes obtained from peripheral blood, even when the extracts were diluted 100-fold to 1000-fold. The objective of these studies was to identify the immunosuppressive compounds found in cigarette smoke. Gas chromatography/mass spectroscopy and HPLC were used to identify and quantitate volatile compounds found in cigarette smoke extracts. Bioactivity was measured by viability and production of cytokine mRNA and protein levels in treated human lymphocytes. The vapor phase of the cigarette smoke extract inhibited cytokine production, indicating that the immunosuppressive compounds were volatile. Among the volatile compounds identified in cigarette smoke extracts, only the alpha,beta-unsaturated aldehydes, acrolein (inhibitory concentration of 50% [IC50] = 3 micromol/L) and crotonaldehyde (IC50 = 6 micromol/L), exhibited significant inhibition of cytokine production. Although the levels of aldehydes varied 10-fold between high-tar (Camel) and ultralow-tar (Carlton) extracts, even ultralow-tar cigarettes produced sufficient levels of acrolein (34 micromol/L) to suppress cytokine production by >95%. We determined that the cigarette smoke extract inhibited transcription of cytokine genes. The inhibitory effects of acrolein could be blocked with the thiol compound N-acetylcysteine. The vapor phase from cigarette smoke extracts potently suppresses cytokine production. The compound responsible for this inhibition appears to be acrolein.

  5. Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals

    Tzu-Yu Lin

    2015-03-01

    Full Text Available The effect of palmitoylethanolamide (PEA, an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes was investigated. PEA inhibited the Ca2+-dependent release of glutamate, which was triggered by exposing synaptosomes to the potassium channel blocker 4-aminopyridine. This release inhibition was concentration dependent, associated with a reduction in cytosolic Ca2+ concentration, and not due to a change in synaptosomal membrane potential. The glutamate release-inhibiting effect of PEA was prevented by the Cav2.1 (P/Q-type channel blocker ω-agatoxin IVA or the protein kinase A inhibitor H89, not affected by the intracellular Ca2+ release inhibitors dantrolene and CGP37157, and partially antagonized by the cannabinoid CB1 receptor antagonist AM281. Based on these results, we suggest that PEA exerts its presynaptic inhibition, likely through a reduction in the Ca2+ influx mediated by Cav2.1 (P/Q-type channels, thereby inhibiting the release of glutamate from rat cortical nerve terminals. This release inhibition might be linked to the activation of presynaptic cannabinoid CB1 receptors and the suppression of the protein kinase A pathway.

  6. Response inhibition under alcohol: effects of cognitive and motivational conflict.

    Fillmore, M T; Vogel-Sprott, M

    2000-03-01

    This experiment tested the effect of cognitive and motivational conflict on response inhibition under alcohol. Fifty-six male social drinkers were randomly assigned to one of eight groups (n = 8). Four pairs of groups received 0.62 g/kg of alcohol, or a placebo, and each pair performed a go/stop choice reaction time task under one of four conflict conditions. One condition (C) produced cognitive conflict by presenting "go" and "stop" signals in the task. Another condition (IR) added motivational conflict by administering an equal monetary reward for inhibiting responses to stop-signals, and for responding to go-signals. The remaining two conditions resolved the motivational conflict by administering the monetary reward only for inhibitions (I), or only for responses (R). Compared with placebo, alcohol reduced inhibitions (i.e., impaired inhibitory control) under cognitive conflict (C; p = .041) and under motivational conflict (IR; p = .012). No significant effect of alcohol on inhibitions was observed in conditions where conflict was resolved (i.e., I and R). The study shows that alcohol can reduce the ability to inhibit a response. However, impaired inhibitory control is not an inevitable outcome of the drug action, because it can be counteracted by the consequences of behavior in the situation.

  7. Inhibition of PTEN and activation of Akt by menadione.

    Yoshikawa, Kyoko; Nigorikawa, Kiyomi; Tsukamoto, Mariko; Tamura, Namiko; Hazeki, Kaoru; Hazeki, Osamu

    2007-04-01

    Menadione (vitamin K(3)) has been shown to activate Erk in several cell lines. This effect has been shown to be due to the activation of EGF receptors (EGFR) as a result of inhibition of some protein tyrosine phosphatases. In the present study, we examined the effects of menadione on Akt in Chinese hamster ovary cells. The phosphorylation of Akt by menadione was not inhibited by AG1478, an inhibitor of EGFR. Menadione inhibited the lipid phosphatase activity of PTEN in a cell-free system. In an intact cell system, menadione inhibited the effect of transfected PTEN on Akt. Thus, one mechanism of its action was considered the accelerated activation of Akt through inhibition of PTEN. This was not the sole mechanism responsible for the EGFR-independent activation of Akt, because menadione attenuated the rate of Akt dephosphorylation even in PTEN-null PC3 cells. The decelerated inactivation of Akt, probably through inhibition of some tyrosine phosphatases, was considered another mechanism of its action.

  8. Lipid-Lowering Pharmaceutical Clofibrate Inhibits Human Sweet Taste

    Kochem, Matthew

    2017-01-01

    T1R2-T1R3 is a heteromeric receptor that binds sugars, high potency sweeteners, and sweet taste blockers. In rodents, T1R2-T1R3 is largely responsible for transducing sweet taste perception. T1R2-T1R3 is also expressed in non-taste tissues, and a growing body of evidence suggests that it helps regulate glucose and lipid metabolism. It was previously shown that clofibric acid, a blood lipid-lowering drug, binds T1R2-T1R3 and inhibits its activity in vitro. The purpose of this study was to determine whether clofibric acid inhibits sweetness perception in humans and is, therefore, a T1R2-T1R3 antagonist in vivo. Fourteen participants rated the sweetness intensity of 4 sweeteners (sucrose, sucralose, Na cyclamate, acesulfame K) across a broad range of concentrations. Each sweetener was prepared in solution neat and in mixture with either clofibric acid or lactisole. Clofibric acid inhibited sweetness of every sweetener. Consistent with competitive binding, inhibition by clofibric acid was diminished with increasing sweetener concentration. This study provides in vivo evidence that the lipid-lowering drug clofibric acid inhibits sweetness perception and is, therefore, a T1R carbohydrate receptor inhibitor. Our results are consistent with previous in vitro findings. Given that T1R2-T1R3 may in part regulate glucose and lipid metabolism, future studies should investigate the metabolic effects of T1R inhibition. PMID:27742692

  9. Iron chelators ICL670 and 311 inhibit HIV-1 transcription

    Debebe, Zufan; Ammosova, Tatyana; Jerebtsova, Marina; Kurantsin-Mills, Joseph; Niu, Xiaomei; Charles, Sharroya; Richardson, Des R.; Ray, Patricio E.; Gordeuk, Victor R.; Nekhai, Sergei

    2007-01-01

    HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2. Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics

  10. Inhibition of AMPK catabolic action by GSK3

    Suzuki, Tsukasa; Bridges, Dave; Nakada, Daisuke; Skiniotis, Georgios; Morrison, Sean J.; Lin, Jiandie; Saltiel, Alan R.; Inoki, Ken

    2013-01-01

    SUMMARY AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis by inhibiting anabolic and activating catabolic processes. While AMPK activation has been extensively studied, mechanisms that inhibit AMPK remain elusive. Here we report that glycogen synthase kinase 3 (GSK3) inhibits AMPK function. GSK3 forms a stable complex with AMPK through interactions with the AMPK β regulatory subunit and phosphorylates the AMPK α catalytic subunit. This phosphorylation enhances the accessibility of the activation loop of the α subunit to phosphatases, thereby inhibiting AMPK kinase activity. Surprisingly, PI3K-Akt signaling, which is a major anabolic signaling and normally inhibits GSK3 activity, promotes GSK3 phosphorylation and inhibition of AMPK, thus revealing how AMPK senses anabolic environments in addition to cellular energy levels. Consistently, disrupting GSK3 function within the AMPK complex sustains higher AMPK activity and cellular catabolic processes even under anabolic conditions, indicating that GSK3 acts as a critical sensor for anabolic signaling to regulate AMPK. PMID:23623684

  11. Gingival tissue-produced inhibition of platelet aggregation and the loss of inhibition in streptozotocin-induced diabetic rats

    Kawamura, Keiichiroh; Tamai, Kazuharu; Shirakawa, Masaharu; Okamoto, Hiroshi; Dohi, Toshihiro; Tsujimoto, Akira

    1988-01-01

    Addition of medium incubated with normal rat gingival tissue to platelet-rich plasma inhibited ADP-induced platelet aggregation. The ability of rat gingiva to produce activity inhibiting platelet aggregation was enhanced by the addition of arachidonic acid. Diabetic rat gingiva failed to inhibit platelet aggregation but did produce the anti-platelet aggregating activity in the presence of arachidonic acid. Indomethacin blocked the production of anti-platelet aggregating activity. There was no difference in conversion of (1-/sup 14/C)arachidonic acid to prostaglandins by normal and diabetic rat gingiva. These results suggest that an arachidonic acid metabolite released from gingiva during incubation inhibits platelet aggregation, and the synthesis of the metabolite is impaired in diabetic rat gingiva. A decrease in availability of arachidonic acid may be a causal factor of the defect in diabetic rat gingiva.

  12. Gingival tissue-produced inhibition of platelet aggregation and the loss of inhibition in streptozotocin-induced diabetic rats

    Kawamura, Keiichiroh; Tamai, Kazuharu; Shirakawa, Masaharu; Okamoto, Hiroshi; Dohi, Toshihiro; Tsujimoto, Akira

    1988-01-01

    Addition of medium incubated with normal rat gingival tissue to platelet-rich plasma inhibited ADP-induced platelet aggregation. The ability of rat gingiva to produce activity inhibiting platelet aggregation was enhanced by the addition of arachidonic acid. Diabetic rat gingiva failed to inhibit platelet aggregation but did produce the anti-platelet aggregating activity in the presence of arachidonic acid. Indomethacin blocked the production of anti-platelet aggregating activity. There was no difference in conversion of [1- 14 C]arachidonic acid to prostaglandins by normal and diabetic rat gingiva. These results suggest that an arachidonic acid metabolite released from gingiva during incubation inhibits platelet aggregation, and the synthesis of the metabolite is impaired in diabetic rat gingiva. A decrease in availability of arachidonic acid may be a causal factor of the defect in diabetic rat gingiva. (author)

  13. Allosteric Inhibition of Factor XIIIa. Non-Saccharide Glycosaminoglycan Mimetics, but Not Glycosaminoglycans, Exhibit Promising Inhibition Profile.

    Rami A Al-Horani

    Full Text Available Factor XIIIa (FXIIIa is a transglutaminase that catalyzes the last step in the coagulation process. Orthostery is the only approach that has been exploited to design FXIIIa inhibitors. Yet, allosteric inhibition of FXIIIa is a paradigm that may offer a key advantage of controlled inhibition over orthosteric inhibition. Such an approach is likely to lead to novel FXIIIa inhibitors that do not carry bleeding risks. We reasoned that targeting a collection of basic amino acid residues distant from FXIIIa's active site by using sulfated glycosaminoglycans (GAGs or non-saccharide GAG mimetics (NSGMs would lead to the discovery of the first allosteric FXIIIa inhibitors. We tested a library of 22 variably sulfated GAGs and NSGMs against human FXIIIa to discover promising hits. Interestingly, although some GAGs bound to FXIIIa better than NSGMs, no GAG displayed any inhibition. An undecasulfated quercetin analog was found to inhibit FXIIIa with reasonable potency (efficacy of 98%. Michaelis-Menten kinetic studies revealed an allosteric mechanism of inhibition. Fluorescence studies confirmed close correspondence between binding affinity and inhibition potency, as expected for an allosteric process. The inhibitor was reversible and at least 9-fold- and 26-fold selective over two GAG-binding proteins factor Xa (efficacy of 71% and thrombin, respectively, and at least 27-fold selective over a cysteine protease papain. The inhibitor also inhibited the FXIIIa-mediated polymerization of fibrin in vitro. Overall, our work presents the proof-of-principle that FXIIIa can be allosterically modulated by sulfated non-saccharide agents much smaller than GAGs, which should enable the design of selective and safe anticoagulants.

  14. A rhodanine derivative CCR-11 inhibits bacterial proliferation by inhibiting the assembly and GTPase activity of FtsZ.

    Singh, Parminder; Jindal, Bhavya; Surolia, Avadhesha; Panda, Dulal

    2012-07-10

    A perturbation of FtsZ assembly dynamics has been shown to inhibit bacterial cytokinesis. In this study, the antibacterial activity of 151 rhodanine compounds was assayed using Bacillus subtilis cells. Of 151 compounds, eight strongly inhibited bacterial proliferation at 2 μM. Subsequently, we used the elongation of B. subtilis cells as a secondary screen to identify potential FtsZ-targeted antibacterial agents. We found that three compounds significantly increased bacterial cell length. One of the three compounds, namely, CCR-11 [(E)-2-thioxo-5-({[3-(trifluoromethyl)phenyl]furan-2-yl}methylene)thiazolidin-4-one], inhibited the assembly and GTPase activity of FtsZ in vitro. CCR-11 bound to FtsZ with a dissociation constant of 1.5 ± 0.3 μM. A docking analysis indicated that CCR-11 may bind to FtsZ in a cavity adjacent to the T7 loop and that short halogen-oxygen, H-bonding, and hydrophobic interactions might be important for the binding of CCR-11 with FtsZ. CCR-11 inhibited the proliferation of B. subtilis cells with a half-maximal inhibitory concentration (IC(50)) of 1.2 ± 0.2 μM and a minimal inhibitory concentration of 3 μM. It also potently inhibited proliferation of Mycobacterium smegmatis cells. Further, CCR-11 perturbed Z-ring formation in B. subtilis cells; however, it neither visibly affected nucleoid segregation nor altered the membrane integrity of the cells. CCR-11 inhibited HeLa cell proliferation with an IC(50) value of 18.1 ± 0.2 μM (∼15 × IC(50) of B. subtilis cell proliferation). The results suggested that CCR-11 inhibits bacterial cytokinesis by inhibiting FtsZ assembly, and it can be used as a lead molecule to develop FtsZ-targeted antibacterial agents.

  15. CORROSION INHIBITION OF ALUMINUM ALLOY 3SR IN HCl BY POLYVINYLPYRROLIDONE AND POLYACRYLAMIDE: EFFECT OF MOLECULAR STRUCTURE ON INHIBITION EFFICIENCY

    S. A. UMOREN

    2009-01-01

    The inhibitive performance of two water soluble polymers–polyacrylamide (PA) and polyvinylpyrrolidone (PVP) on the corrosion behavior of aluminum alloy 3SR in HCl solution was investigated using weight loss, hydrogen evolution, and thermometric methods at 30–60°C. Results obtained indicate that both polymers inhibited acid-induced corrosion of aluminum at the temperatures studied. PVP was found to be a better corrosion inhibitor than PA. All measurements from the three techniques show that in...

  16. Method of inhibiting the onset of acute radiation syndrome and also inhibiting the onset of septicemia and a composition therefor

    Ribi, E E

    1986-01-14

    A method is described for inhibiting the onset of acute radiation syndrome caused by the exposure of warm-blooded animals to a whole body dose of at least 100 rads of x-radiation. Also described is a method for inhibiting the onset of septicemia. The methods comprise administering to a warm-blooded animal an effective amount of a pharmaceutical preparation containing refined detoxified endotoxin in combination with a pharmaceutically acceptable carrier.

  17. Inhibition of carbachol-induced formation of inositolphosphates in isolated pancreatic islets

    Kardasz, A.M.J.; Capito, Kirsten; Hansen, Svend Erik

    1991-01-01

    Medicinsk biokemi, feed-back inhibition, phospholipase C, pancreatic islets, Calcium, proteinkinase C......Medicinsk biokemi, feed-back inhibition, phospholipase C, pancreatic islets, Calcium, proteinkinase C...

  18. Chlorpromazine inhibits tumour necrosis factor synthesis and cytotoxicity in vitro.

    Zinetti, M; Galli, G; Demitri, M T; Fantuzzi, G; Minto, M; Ghezzi, P; Alzani, R; Cozzi, E; Fratelli, M

    1995-11-01

    Chlorpromazine (CPZ) has been previously shown to protect against endotoxin [lipopolysaccharide (LPS)] lethality and inhibit the release of tumour necrosis factor in vivo. We investigated at the cellular level whether this was due to direct inhibition of tumour necrosis factor-alpha (TNF-alpha) synthesis, using LPS-stimulated THP-1 human monocytic leukemia cells. We also studied the effect of CPZ on human TNF-alpha action by assessing TNF-alpha cytotoxicity on mouse fibrosarcoma L929 cells. CPZ (1-100 microM) inhibited TNF-alpha production in THP-1 cells in a dose dependent manner by a maximum of 80%. This effect was comparable to that of two well-known inhibitory drugs, dexamethasone and cyclicAMP. Inhibition was also evident at the mRNA level. On the other hand CPZ (10-25 microM) also inhibited TNF-alpha activity: in fact it reduced the cytotoxicity of TNF-alpha on L929 cells (EC50 was increased four times) and could provide protection even as a post-treatment. CPZ inhibited TNF-induced apoptosis in L929 cells, as detected by analysis of nuclear morphology. However, since we showed that apoptosis was very limited, and was not the main mode of cell death in our conditions, this could not explain the overall protection. Since CPZ did not interfere with either the oligomerization state of TNF-alpha or its receptor binding, our data suggest that it reduced cytotoxicity by inhibiting some steps in the TNF-alpha signalling pathways.

  19. High Concentrations of Tranexamic Acid Inhibit Ionotropic Glutamate Receptors.

    Lecker, Irene; Wang, Dian-Shi; Kaneshwaran, Kirusanthy; Mazer, C David; Orser, Beverley A

    2017-07-01

    The antifibrinolytic drug tranexamic acid is structurally similar to the amino acid glycine and may cause seizures and myoclonus by acting as a competitive antagonist of glycine receptors. Glycine is an obligatory co-agonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Thus, it is plausible that tranexamic acid inhibits NMDA receptors by acting as a competitive antagonist at the glycine binding site. The aim of this study was to determine whether tranexamic acid inhibits NMDA receptors, as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate subtypes of ionotropic glutamate receptors. Tranexamic acid modulation of NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptors was studied using whole cell voltage-clamp recordings of current from cultured mouse hippocampal neurons. Tranexamic acid rapidly and reversibly inhibited NMDA receptors (half maximal inhibitory concentration = 241 ± 45 mM, mean ± SD; 95% CI, 200 to 281; n = 5) and shifted the glycine concentration-response curve for NMDA-evoked current to the right. Tranexamic acid also inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (half maximal inhibitory concentration = 231 ± 91 mM; 95% CI, 148 to 314; n = 5 to 6) and kainate receptors (half maximal inhibitory concentration = 90 ± 24 mM; 95% CI, 68 to 112; n = 5). Tranexamic acid inhibits NMDA receptors likely by reducing the binding of the co-agonist glycine and also inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors. Receptor blockade occurs at high millimolar concentrations of tranexamic acid, similar to the concentrations that occur after topical application to peripheral tissues. Glutamate receptors in tissues including bone, heart, and nerves play various physiologic roles, and tranexamic acid inhibition of these receptors may contribute to adverse drug effects.

  20. Digestion products of the PH20 hyaluronidase inhibit remyelination.

    Preston, Marnie; Gong, Xi; Su, Weiping; Matsumoto, Steven G; Banine, Fatima; Winkler, Clayton; Foster, Scott; Xing, Rubing; Struve, Jaime; Dean, Justin; Baggenstoss, Bruce; Weigel, Paul H; Montine, Thomas J; Back, Stephen A; Sherman, Larry S

    2013-02-01

    Oligodendrocyte progenitor cells (OPCs) recruited to demyelinating lesions often fail to mature into oligodendrocytes (OLs) that remyelinate spared axons. The glycosaminoglycan hyaluronan (HA) accumulates in demyelinating lesions and has been implicated in the failure of OPC maturation and remyelination. We tested the hypothesis that OPCs in demyelinating lesions express a specific hyaluronidase, and that digestion products of this enzyme inhibit OPC maturation. Mouse OPCs grown in vitro were analyzed for hyaluronidase expression and activity. Gain of function studies were used to define the hyaluronidases that blocked OPC maturation. Mouse and human demyelinating lesions were assessed for hyaluronidase expression. Digestion products from different hyaluronidases and a hyaluronidase inhibitor were tested for their effects on OPC maturation and functional remyelination in vivo. OPCs demonstrated hyaluronidase activity in vitro and expressed multiple hyaluronidases, including HYAL1, HYAL2, and PH20. HA digestion by PH20 but not other hyaluronidases inhibited OPC maturation into OLs. In contrast, inhibiting HA synthesis did not influence OPC maturation. PH20 expression was elevated in OPCs and reactive astrocytes in both rodent and human demyelinating lesions. HA digestion products generated by the PH20 hyaluronidase but not another hyaluronidase inhibited remyelination following lysolecithin-induced demyelination. Inhibition of hyaluronidase activity lead to increased OPC maturation and promoted increased conduction velocities through lesions. We determined that PH20 is elevated in demyelinating lesions and that increased PH20 expression is sufficient to inhibit OPC maturation and remyelination. Pharmacological inhibition of PH20 may therefore be an effective way to promote remyelination in multiple sclerosis and related conditions. Copyright © 2012 American Neurological Association.

  1. Mechanisms of caffeine-induced inhibition of UVB carcinogenesis

    Allan H Conney

    2013-06-01

    Full Text Available Sunlight-induced nonmelanoma skin cancer is the most prevalent cancer in the United States with more than 2 million cases per year. Several studies have shown an inhibitory effect of caffeine administration on UVB-induced skin cancer in mice, and these studies are paralleled by epidemiology studies that indicate an inhibitory effect of coffee drinking on nonmelanoma skin cancer in humans. Strikingly, decaffeinated coffee consumption had no such inhibitory effect.Mechanism studies indicate that caffeine has a sunscreen effect that inhibits UVB-induced formation of thymine dimers and sunburn lesions in the epidermis of mice. In addition, caffeine administration has a biological effect that enhances UVB-induced apoptosis thereby enhancing the elimination of damaged precancerous cells, and caffeine administration also enhances apoptosis in tumors. Caffeine administration enhances UVB-induced apoptosis by p53-dependent and p53-independent mechanisms. Exploration of the p53-independent effect indicated that caffeine administration enhanced UVB-induced apoptosis by inhibiting the UVB-induced increase in ATR-mediated formation of phospho-Chk1 (Ser345 and abolishing the UVB-induced decrease in cyclin B1 which resulted in caffeine-induced premature and lethal mitosis in mouse skin. In studies with cultured primary human keratinocytes, inhibition of ATR with siRNA against ATR inhibited Chk1 phosphorylation and enhanced UVB-induced apoptosis. Transgenic mice with decreased epidermal ATR function that were irradiated chronically with UVB had 69% fewer tumors at the end of the study compared with irradiated littermate controls with normal ATR function. These results, which indicate that genetic inhibition of ATR (like pharmacologic inhibition of ATR via caffeine inhibits UVB-induced carcinogenesis and supports the concept that ATR-mediated phosphorylation of Chk1 is an important target for caffeine’s inhibitory effect on UVB-induced carcinogenesis.

  2. Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

    Magdalena Markowicz-Piasecka

    2017-01-01

    Full Text Available The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM may predispose to Alzheimer’s disease (AD. The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition and BuChE (IC50 = 28 nmol/mL, mixed type inhibition, while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL. Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.

  3. Norepinephrine transporter inhibition alters the hemodynamic response to hypergravitation.

    Strempel, Sebastian; Schroeder, Christoph; Hemmersbach, Ruth; Boese, Andrea; Tank, Jens; Diedrich, André; Heer, Martina; Luft, Friedrich C; Jordan, Jens

    2008-03-01

    Sympathetically mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness. Norepinephrine transporter (NET) inhibition prevents neurally mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. We performed a double-blind, randomized, placebo-controlled crossover study in 11 healthy men (26 +/- 1 yr, body mass index 24 +/- 1 kg/m2), who ingested the selective NET inhibitor reboxetine (4 mg) or matching placebo 25, 13, and 1 h before testing on separate days. We monitored heart rate, blood pressure, and thoracic impedance in three different body positions (supine, seated, standing) and during a graded centrifuge run (incremental steps of 0.5 g for 3 min each, up to a maximal vertical acceleration load of 3 g). NET inhibition increased supine blood pressure and heart rate. With placebo, blood pressure increased in the seated position and was well maintained during standing. However, with NET inhibition, blood pressure decreased in the seated and standing position. During hypergravitation, blood pressure increased in a graded fashion with placebo. With NET inhibition, the increase in blood pressure during hypergravitation was profoundly diminished. Conversely, the tachycardic responses to sitting, standing, and hypergravitation all were greatly increased with NET inhibition. In contrast to our expectation, short-term NET inhibition did not improve tolerance to hypergravitation. Redistribution of sympathetic activity to the heart or changes in baroreflex responses could explain the excessive tachycardia that we observed.

  4. Aspergillus ficuum phytase activity is inhibited by cereal grain components.

    Bekalu, Zelalem Eshetu; Madsen, Claus Krogh; Dionisio, Giuseppe; Brinch-Pedersen, Henrik

    2017-01-01

    In the current study, we report for the first time that grain components of barley, rice, wheat and maize can inhibit the activity of Aspergillus ficuum phytase. The phytase inhibition is dose dependent and varies significantly between cereal species, between cultivars of barley and cultivars of wheat and between Fusarium graminearum infected and non-infected wheat grains. The highest endpoint level of phytase activity inhibition was 90%, observed with grain protein extracts (GPE) from F. graminearum infected wheat. Wheat GPE from grains infected with F. graminearum inhibits phytase activity significantly more than GPE from non-infected grains. For four barley cultivars studied, the IC50 value ranged from 0.978 ± 0.271 to 3.616 ± 0.087 mg×ml-1. For two non-infected wheat cultivars investigated, the IC50 values were varying from 2.478 ± 0.114 to 3.038 ± 0.097 mg×ml-1. The maize and rice cultivars tested gaveIC50 values on 0.983 ± 0.205 and 1.972 ± 0.019 mg×ml-1, respectively. After purifying the inhibitor from barley grains via Superdex G200, an approximately 30-35 kDa protein was identified. No clear trend for the mechanism of inhibition could be identified via Michaelis-Menten kinetics and Lineweaver-Burk plots. However, testing of the purified phytase inhibitor together with the A. ficuum phytase and the specific protease inhibitors pepstatin A, E64, EDTA and PMSF revealed that pepstatin A repealed the phytase inhibition. This indicates that the observed inhibition of A. ficuum phytase by cereal grain extracts is caused by protease activity of the aspartic proteinase type.

  5. Menthol binding and inhibition of α7-nicotinic acetylcholine receptors.

    Abrar Ashoor

    Full Text Available Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca(2+-dependent Cl(- channels, since menthol inhibition remained unchanged by intracellular injection of the Ca(2+ chelator BAPTA and perfusion with Ca(2+-free bathing solution containing Ba(2+. Furthermore, increasing ACh concentrations did not reverse menthol inhibition and the specific binding of [(125I] α-bungarotoxin was not attenuated by menthol. Studies of α7- nACh receptors endogenously expressed in neural cells demonstrate that menthol attenuates α7 mediated Ca(2+ transients in the cell body and neurite. In conclusion, our results suggest that menthol inhibits α7-nACh receptors in a noncompetitive manner.

  6. Mutant p53 protein localized in the cytoplasm inhibits autophagy.

    Morselli, Eugenia; Tasdemir, Ezgi; Maiuri, Maria Chiara; Galluzzi, Lorenzo; Kepp, Oliver; Criollo, Alfredo; Vicencio, José Miguel; Soussi, Thierry; Kroemer, Guido

    2008-10-01

    The knockout, knockdown or chemical inhibition of p53 stimulates autophagy. Moreover, autophagy-inducing stimuli such as nutrient depletion, rapamycin or lithium cause the depletion of cytoplasmic p53, which in turn is required for the induction of autophagy. Here, we show that retransfection of p53(-/-) HCT 116 colon carcinoma cells with wild type p53 decreases autophagy down to baseline levels. Surprisingly, one third among a panel of 22 cancer-associated p53 single amino acid mutants also inhibited autophagy when transfected into p53(-/-) cells. Those variants of p53 that preferentially localize to the cytoplasm effectively repressed autophagy, whereas p53 mutants that display a prominently nuclear distribution failed to inhibit autophagy. The investigation of a series of deletion mutants revealed that removal of the DNA-binding domain from p53 fails to interfere with its role in the regulation of autophagy. Altogether, these results identify the cytoplasmic localization of p53 as the most important feature for p53-mediated autophagy inhibition. Moreover, the structural requirements for the two biological activities of extranuclear p53, namely induction of apoptosis and inhibition of autophagy, are manifestly different.

  7. Stereoselective effects of MDMA on inhibition of monoamine uptake

    Steele, T.D.; Nichols, D.E.; Yim, G.K.W.

    1986-01-01

    The R(-)-isomers of hallucinogenic phenylisopropylamines are most active, whereas the S(+)-enantiomers of amphetamine (AMPH) and methylenedioxymethamphetamine (MDMA) are more potent centrally. To determine if MDMA exhibits stereoselective effects at the biochemical level that resemble either those of amphetamine or the potent hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM), the ability of the isomers of MDMA, AMPH and DOM to inhibit uptake of radiolabelled monoamines into synaptosomes was measured. AMPH was more potent than MDMA in inhibiting uptake of 3 H-norepinephrine (NE) into hypothalamic synaptosomes and 3 H-dopamine (DA) into striatal synaptosomes. The S(+)-isomer was more active in each case. MDMA was more potent than AMPH in inhibiting uptake of 3 H-serotonin (5-HT) into hippocampal synaptosomes and exhibited a high degree of stereoselectivity, in favor of the S(+)-isomer. DOM showed only minimal activity in inhibiting uptake of any monoamine (IC 50 > 10 -5 M). These results suggest that MDMA exhibits stereoselective effects similar to those of amphetamine on monoamine uptake inhibition, a parameter that is unrelated to the mechanism of action of the hallucinogen DOM

  8. AI-2 of Aggregatibacter actinomycetemcomitans Inhibits Candida albicans Biofilm Formation

    Endang W. Bachtiar

    2014-07-01

    Full Text Available Aggregatibacter actinomycetemcomitans, a Gram-negative bacterium, and Candida albicans, a polymorphic fungus, are both commensals of the oral cavity but both are opportunistic pathogens that can cause oral diseases. A. actinomycetemcomitans produces a quorum-sensing molecule called autoinducer-2 (AI-2, synthesized by LuxS, that plays an important role in expression of virulence factors, in intra- but also in interspecies communication. The aim of this study was to investigate the role of AI-2 based signaling in the interactions between C. albicans and A. actinomycetemcomitans. A. actinomycetemcomitans adhered to C. albicans and inhibited biofilm formation by means of a molecule that was secreted during growth. C. albicans biofilm formation increased significantly when co-cultured with A. actinomycetemcomitans luxS, lacking AI-2 production. Addition of wild-type-derived spent medium or synthetic AI-2 to spent medium of the luxS strain, restored inhibition of C. albicans biofilm formation to wild-type levels. Addition of synthetic AI-2 significantly inhibited hypha formation of C. albicans possibly explaining the inhibition of biofilm formation. AI-2 of A. actinomycetemcomitans is synthesized by LuxS, accumulates during growth and inhibits C. albicans hypha- and biofilm formation. Identifying the molecular mechanisms underlying the interaction between bacteria and fungi may provide important insight into the balance within complex oral microbial communities.

  9. Lactobacillus plantarum lipoteichoic acid inhibits biofilm formation of Streptococcus mutans

    Ahn, Ki Bum; Baik, Jung Eun; Park, Ok-Jin; Yun, Cheol-Heui

    2018-01-01

    Dental caries is a biofilm-dependent oral disease and Streptococcus mutans is the known primary etiologic agent of dental caries that initiates biofilm formation on tooth surfaces. Although some Lactobacillus strains inhibit biofilm formation of oral pathogenic bacteria, the molecular mechanisms by which lactobacilli inhibit bacterial biofilm formation are not clearly understood. In this study, we demonstrated that Lactobacillus plantarum lipoteichoic acid (Lp.LTA) inhibited the biofilm formation of S. mutans on polystyrene plates, hydroxyapatite discs, and dentin slices without affecting the bacterial growth. Lp.LTA interferes with sucrose decomposition of S. mutans required for the production of exopolysaccharide, which is a main component of biofilm. Lp.LTA also attenuated the biding of fluorescein isothiocyanate-conjugated dextran to S. mutans, which is known to have a high affinity to exopolysaccharide on S. mutans. Dealanylated Lp.LTA did not inhibit biofilm formation of S. mutans implying that D-alanine moieties in the Lp.LTA structure were crucial for inhibition. Collectively, these results suggest that Lp.LTA attenuates S. mutans biofilm formation and could be used to develop effective anticaries agents. PMID:29420616

  10. THE INHIBITION OF DEOXYRIBONUCLEASS I BY HYDEOXY-PIPHENYLS

    Gottesfeld, J.M.; Adams, N.H.; El-Badry, A.M.; Moses, V.; Calvin,M.

    1970-09-01

    DNA extracted with certain commercial brands of phenol is resistant to hydrolysis by the endonuclease DNAase I, while DNA extracted with other brands, or prepared by sodium chloride extraction, is susceptible to hydrolysis. The agent responsible for inhibition has been shown to be an oxidation product produced in some phenols. The inhibitor has been separated from other impurities in phenol by paper chromatography, and, by means of infrared and ultraviolet spectroscopy, it has been identified as o-hydroxybiphenyl. The kinetics of inhibition have been studied, and it was found that inhibition arises from direct action on the DNA rather than on the enzyme. Several hydroxybiphenyls and related compounds have been tested for inhibition, and a theory of molecular structure versus inhibitory effectiveness is suggested from this data. From studies on the chemical reversal of inhibition, as well as from ultraviolet spectral studies (in both absorption and circular dichroism), it appears that the mode of action of the inhibitors is hydrogen bonding to, and intercalation between, the basis of the nucleic acid.

  11. Inhibition of cardiac sodium currents by toluene exposure

    Cruz, Silvia L; Orta-Salazar, Gerardo; Gauthereau, Marcia Y; Millan-Perez Peña, Lourdes; Salinas-Stefanón, Eduardo M

    2003-01-01

    Toluene is an industrial solvent widely used as a drug of abuse, which can produce sudden sniffing death due to cardiac arrhythmias. In this paper, we tested the hypothesis that toluene inhibits cardiac sodium channels in Xenopus laevis oocytes transfected with Nav1.5 cDNA and in isolated rat ventricular myocytes. In oocytes, toluene inhibited sodium currents (INa+) in a concentration-dependent manner, with an IC50 of 274 μM (confidence limits: 141–407μM). The inhibition was complete, voltage-independent, and slowly reversible. Toluene had no effect on: (i) the shape of the I–V curves; (ii) the reversal potential of Na+; and (iii) the steady-state inactivation. The slow recovery time constant from inactivation of INa+ decreased with toluene exposure, while the fast recovery time constant remained unchanged. Block of INa+ by toluene was use- and frequency-dependent. In rat cardiac myocytes, 300 μM toluene inhibited the sodium current (INa+) by 62%; this inhibition was voltage independent. These results suggest that toluene binds to cardiac Na+ channels in the open state and unbinds either when channels move between inactivated states or from an inactivated to a closed state. The use- and frequency-dependent block of INa+ by toluene might be responsible, at least in part, for its arrhythmogenic effect. PMID:14534149

  12. Recruitment of Perisomatic Inhibition during Spontaneous Hippocampal Activity In Vitro.

    Anna Beyeler

    Full Text Available It was recently shown that perisomatic GABAergic inhibitory postsynaptic potentials (IPSPs originating from basket and chandelier cells can be recorded as population IPSPs from the hippocampal pyramidal layer using extracellular electrodes (eIPSPs. Taking advantage of this approach, we have investigated the recruitment of perisomatic inhibition during spontaneous hippocampal activity in vitro. Combining intracellular and extracellular recordings from pyramidal cells and interneurons, we confirm that inhibitory signals generated by basket cells can be recorded extracellularly, but our results suggest that, during spontaneous activity, eIPSPs are mostly confined to the CA3 rather than CA1 region. CA3 eIPSPs produced the powerful time-locked inhibition of multi-unit activity expected from perisomatic inhibition. Analysis of the temporal dynamics of spike discharges relative to eIPSPs suggests significant but moderate recruitment of excitatory and inhibitory neurons within the CA3 network on a 10 ms time scale, within which neurons recruit each other through recurrent collaterals and trigger powerful feedback inhibition. Such quantified parameters of neuronal interactions in the hippocampal network may serve as a basis for future characterisation of pathological conditions potentially affecting the interactions between excitation and inhibition in this circuit.

  13. Curcumin synergizes with resveratrol to inhibit colon cancer.

    Majumdar, Adhip P N; Banerjee, Sanjeev; Nautiyal, Jyoti; Patel, Bhaumik B; Patel, Vaishali; Du, Jianhua; Yu, Yingjie; Elliott, Althea A; Levi, Edi; Sarkar, Fazlul H

    2009-01-01

    Development and progression of many malignancies, including colorectal cancer, are associated with activation of multiple signaling pathways. Therefore, inhibition of these signaling pathways with noncytotoxic natural products represents a logical preventive and/or therapeutic approach for colon cancer. Curcumin and resveratrol, both of which inhibit the growth of transformed cells and colon carcinogenesis, were selected to examine whether combining them would be an effective preventive and/or therapeutic strategy for colon cancer. Indeed, the combination of curcumin and resveratrol was found to be more effective in inhibiting growth of p53-positive (wt) and p53-negative colon cancer HCT-116 cells in vitro and in vivo in SCID xenografts of colon cancer HCT-116 (wt) cells than either agent alone. Analysis by Calcusyn software showed synergism between curcumin and resveratrol. The inhibition of tumors in response to curcumin and/or resveratrol was associated with the reduction in proliferation and stimulation of apoptosis accompanied by attenuation of NF-kappaB activity. In vitro studies have further demonstrated that the combinatorial treatment caused a greater inhibition of constitutive activation of EGFR and its family members as well as IGF-1R. Our current data suggest that the combination of curcumin and resveratrol could be an effective preventive/therapeutic strategy for colon cancer.

  14. IGF-1 receptor inhibition by picropodophyllin in medulloblastoma

    Ohshima-Hosoyama, Sachiko; Hosoyama, Tohru; Nelon, Laura D. [Greehey Children' s Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Keller, Charles, E-mail: keller@ohsu.edu [Greehey Children' s Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Department of Pediatrics, University of Texas Health Science Center, San Antonio, TX 78229 (United States); Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229 (United States)

    2010-09-03

    Research highlights: {yields} Igf1r is overexpressed and activated in a Sonic Hedgehog driven model of medulloblastoma. {yields} Picropodophyllin targets and abrogates IGF signaling in medulloblastoma. {yields} Picropodophyllin inhibits medulloblastoma tumor cell growth by induction of apoptosis. -- Abstract: The insulin-like growth factor-1 receptor (Igf1r) is a multifunctional membrane-associated tyrosine kinase associated with regulation of transformation, proliferation, differentiation and apoptosis. Increased IGF pathway activity has been reported in human and murine medulloblastoma. Tumors from our genetically-engineered medulloblastoma mouse model over-express Igf1r, and thus this mouse model is a good platform with which to study the role of Igf1r in tumor progression. We hypothesize that inhibition of IGF pathway in medulloblastoma can slow or inhibit tumor growth and metastasis. To test our hypothesis, we tested the role of IGF in tumor growth in vitro by treatment with the tyrosine kinase small molecule inhibitor, picropodophyllin (PPP), which strongly inhibits the IGF pathway. Our results demonstrate that PPP-mediated downregulation of the IGF pathway inhibits mouse tumor cell growth and induces apoptotic cell death in vitro in primary medulloblastoma cultures that are most reflective of tumor cell behavior in vivo.

  15. Ligninolytic system of Phanerochaete chrysosporium: inhibition by o-phthalate

    Fenn, P.; Kirk, T.K.

    1979-01-01

    The degradation rate of (synthetic/sup 14/C)-lignin to /sup 14/CO/sub 2/ by Phanerochaete chrysosporium in cultures buffered with 0.01 M 2,2-dimethylsuccinate (DMS) was twice that in 0.01 M o-phthalate-buffered cultures. This difference could be totally accounted for by o-phthalate inhibition of the activity of the ligninolytic system. /sup 14/CO/sub 2/ production from ring-, sidechain-, and methoyxl-labled lignins was inhibited, the degree of inhibition being dependent on o-phthalate concentration. Oxidations of /sup 14/C-glucose, /sup 14/C-acetovanillone, and /sup 14/C-apocynol were not inhibited; thus o-phthalate is not a general inhibitor, and might inhibit activities involved in attach of the lignin polymer. DMS is a suitable buffer for the ligninolytic system. Degradation rates of ring-labeled lignin to /sup 14/CO/sub 2/ of 10 to 15% in 24 h were obtained consistently over the pH range 3.6 to 4.5, with an optimum near pH 4.0.

  16. Inhibition of growth of Trichophyton tonsurans by Lactobacillus reuteri.

    Guo, J; Mauch, A; Galle, S; Murphy, P; Arendt, E K; Coffey, A

    2011-08-01

    The aims of this study were to identify antifungal lactic acid bacteria (LAB) and characterize their activity against the dermatophyte Trichophyton tonsurans. A total of 165 different LAB were isolated and initially screened for anti-Penicillium expansum activity. Five strains, which exhibited strong inhibitory activity, were then tested against the dermatophyte T. tonsurans DSM12285, where they also caused inhibition as observed by large fungal clearing on agar surface. The strongest inhibition was seen with Lactobacillus reuteri R2. When freeze-dried cell-free supernatant powder from this strain was incorporated in culture medium at concentrations >1%, growth of fungal colony was inhibited. Conidia germination was also inhibited under these conditions as determined by microscopy. The anti-T. tonsurans activity of Lact. reuteri R2 was not affected neither by heat treatment nor by proteolytic treatment using pronase E and proteinase K, indicating that the responsible agent(s) were nonproteinaceous in nature. Lactobacillus reuteri R2 was identified as having strong inhibitory activity against the dermatophyte T. tonsurans DSMZ12285. LAB are naturally associated with many foods and are well recognized for their biopreservative properties. The use of these and/or their products may well provide alternative safe approaches for the inhibition of dermatophytic fungi. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

  17. IGF-1 receptor inhibition by picropodophyllin in medulloblastoma

    Ohshima-Hosoyama, Sachiko; Hosoyama, Tohru; Nelon, Laura D.; Keller, Charles

    2010-01-01

    Research highlights: → Igf1r is overexpressed and activated in a Sonic Hedgehog driven model of medulloblastoma. → Picropodophyllin targets and abrogates IGF signaling in medulloblastoma. → Picropodophyllin inhibits medulloblastoma tumor cell growth by induction of apoptosis. -- Abstract: The insulin-like growth factor-1 receptor (Igf1r) is a multifunctional membrane-associated tyrosine kinase associated with regulation of transformation, proliferation, differentiation and apoptosis. Increased IGF pathway activity has been reported in human and murine medulloblastoma. Tumors from our genetically-engineered medulloblastoma mouse model over-express Igf1r, and thus this mouse model is a good platform with which to study the role of Igf1r in tumor progression. We hypothesize that inhibition of IGF pathway in medulloblastoma can slow or inhibit tumor growth and metastasis. To test our hypothesis, we tested the role of IGF in tumor growth in vitro by treatment with the tyrosine kinase small molecule inhibitor, picropodophyllin (PPP), which strongly inhibits the IGF pathway. Our results demonstrate that PPP-mediated downregulation of the IGF pathway inhibits mouse tumor cell growth and induces apoptotic cell death in vitro in primary medulloblastoma cultures that are most reflective of tumor cell behavior in vivo.

  18. Two mechanisms of oral malodor inhibition by zinc ions.

    Suzuki, Nao; Nakano, Yoshio; Watanabe, Takeshi; Yoneda, Masahiro; Hirofuji, Takao; Hanioka, Takashi

    2018-01-18

    The aim of this study was to reveal the mechanisms by which zinc ions inhibit oral malodor. The direct binding of zinc ions to gaseous hydrogen sulfide (H2S) was assessed in comparison with other metal ions. Nine metal chlorides and six metal acetates were examined. To understand the strength of H2S volatilization inhibition, the minimum concentration needed to inhibit H2S volatilization was determined using serial dilution methods. Subsequently, the inhibitory activities of zinc ions on the growth of six oral bacterial strains related to volatile sulfur compound (VSC) production and three strains not related to VSC production were evaluated. Aqueous solutions of ZnCl2, CdCl2, CuCl2, (CH3COO)2Zn, (CH3COO)2Cd, (CH3COO)2Cu, and CH3COOAg inhibited H2S volatilization almost entirely. The strengths of H2S volatilization inhibition were in the order Ag+ > Cd2+ > Cu2+ > Zn2+. The effect of zinc ions on the growth of oral bacteria was strain-dependent. Fusobacterium nucleatum ATCC 25586 was the most sensitive, as it was suppressed by medium containing 0.001% zinc ions. Zinc ions have an inhibitory effect on oral malodor involving the two mechanisms of direct binding with gaseous H2S and suppressing the growth of VSC-producing oral bacteria.

  19. Antisense inhibition of hyaluronan synthase-2 in human osteosarcoma cells inhibits hyaluronan retention and tumorigenicity

    Nishida, Yoshihiro; Knudson, Warren; Knudson, Cheryl B.; Ishiguro, Naoki

    2005-01-01

    Osteosarcoma is a common malignant bone tumor associated with childhood and adolescence. The results of numerous studies have suggested that hyaluronan plays an important role in regulating the aggressive behavior of various types of cancer cells. However, no studies have addressed hyaluronan with respect to osteosarcomas. In this investigation, the mRNA expression copy number of three mammalian hyaluronan synthases (HAS) was determined using competitive RT-PCR in the osteoblastic osteosarcoma cell line, MG-63. MG-63 are highly malignant osteosarcoma cells with an abundant hyaluronan-rich matrix. The results demonstrated that HAS-2 is the predominant HAS in MG-63. Accumulation of intracellular hyaluronan increased in association with the proliferative phase of these cells. The selective inhibition of HAS-2 mRNA in MG-63 cells by antisense phosphorothioate oligonucleotides resulted in reduced hyaluronan accumulation by these cells. As expected, the reduction in hyaluronan disrupted the assembly of cell-associated matrices. However, of most interest, coincident with the reduction in hyaluronan, there was a substantial decrease in cell proliferation, a decrease in cell motility and a decrease in cell invasiveness. These data suggest that hyaluronan synthesized by HAS-2 in MG-63 plays a crucial role in osteosarcoma cell proliferation, motility, and invasion

  20. Depletion of Pokemon gene inhibits hepatocellular carcinoma cell growth through inhibition of H-ras.

    Zhang, Quan-Le; Tian, De-An; Xu, Xiang-Jiang

    2011-01-01

    Pokemon is a transcription repressor which plays a critical role in cell transformation and malignancy. However, little is known about its effect on the development and progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression of Pokemon in human HCC tissues and the biological behavior of Pokemon in HCC cells in which it is overexpressed. We also explored the expression of potential downstream cofactors of Pokemon. Reverse transcription polymerase chain reaction and Western blot analysis were used to investigate the expression of Pokemon in tissues of 30 HCC patients. We then examined cell proliferation or apoptosis and β-catenin or H-ras expression in Pokemon-depleted HepG(2) cells using DNA vector-based RNA interference technology. Pokemon was markedly expressed in 22/30 (73.3%) HCC tissues, with expression levels higher than in adjacent normal liver tissues (p Pokemon inhibited proliferation of HepG(2) or induced apoptosis. Also, H-ras expression decreased to a large extent. Pokemon exerts its oncogenic activity in the development of HCC by promoting cancer cell growth and reducing apoptosis, and the effect may be mediated by H-ras. Copyright © 2011 S. Karger AG, Basel.

  1. Inhibition of 5-Lipoxygenase Pathway Attenuates Acute Liver Failure by Inhibiting Macrophage Activation

    Lu Li

    2014-01-01

    Full Text Available This study aimed to investigate the role of 5-lipoxygenase (5-LO in acute liver failure (ALF and changes in macrophage activation by blocking it. ALF was induced in rats by administration of D-galactosamine (D-GalN/lipopolysaccharide (LPS. Rats were injected intraperitoneally with AA-861 (a specific 5-LO inhibitor, 24 hr before D-GalN/LPS administration. After D-GalN/LPS injection, the liver tissue was collected for assessment of histology, macrophage microstructure, macrophage counts, 5-LO mRNA formation, protein expression, and concentration of leukotrienes. Serum was collected for detecting alanine aminotransferase (ALT, aspartate transaminase (AST, total bilirubin (Tbil, and tumor necrosis factor- (TNF-α. Twenty-four hours after injection, compared with controls, ALF rats were characterized by widespread hepatocyte necrosis and elevated ALT, AST, and Tbil, and 5-LO protein expression reached a peak. Liver leukotriene B4 was also significantly elevated. However, 5-LO mRNA reached a peak 8 hr after D-GalN/LPS injection. Simultaneously, the microstructure of macrophages was changed most significantly and macrophages counts were increased significantly. Moreover, serum TNF-α was also elevated. By contrast, AA-861 pretreatment significantly decreased liver necrosis as well as all of the parameters compared with the rats without pretreatment. Macrophages, via the 5-LO pathway, play a critical role in ALF, and 5-LO inhibitor significantly alleviates ALF, possibly related to macrophage inhibition.

  2. Vanadate-induced inhibition of renin secretion is unrelated to inhibition Na,K-ATPase activity

    Churchill, P.C.; Rossi, N.F.; Churchill, M.C.; Ellis, V.R. (Wayne State Univ. School of Medicine, Detroit, MI (USA))

    1990-01-01

    There is evidence that three inhibitors of Na,K-ATPase activity-ouabain, K-free extracellular fluid, and vanadate--inhibit renin secretion by increasing Ca{sup 2+} concentration in juxtaglomerular cells, but in the case of vanadate, it is uncertain whether the increase in Ca{sup 2+} is due to a decrease in Ca{sup 2+} efflux or to an increase in Ca{sup 2+} influx through potential operated Ca channels. In the present experiments, the rat renal cortical slice preparation was used to compare and contrast the effects of ouabain, of K-free fluid, and of vanadate on renin secretion, in the absence and presence of methoxyverapamil, A Ca channel blocker. Basal renin secretory rate averaged 7.7 {plus minus} 0.3 GU/g/60 min, and secretory rate was reduced to nearly zero by 1 mM ouabain, by K-free fluid, by 0.5 mM vanadate, and by K-depolarization. Although 0.5 {mu}M methoxyverapamil completely blocked the inhibitory effect of K-depolarization, it failed to antagonize the inhibitory effects of ouabain, of K-free fluid, and of vanadate.

  3. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    Hannon, Patrick R., E-mail: phannon2@illinois.edu; Brannick, Katherine E., E-mail: kbran@illinois.edu; Wang, Wei, E-mail: Wei.Wang2@covance.com; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  4. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    Hannon, Patrick R.; Brannick, Katherine E.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

    2015-01-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  5. Do motivational incentives reduce the inhibition deficit in ADHD?

    Shanahan, Michelle A; Pennington, Bruce F; Willcutt, Erik W

    2008-01-01

    The primary goal of this study was to test three competing theories of ADHD: the inhibition theory, the motivational theory, and a dual deficit theory. Previous studies have produced conflicting findings about the effects of incentives on executive processes in ADHD. In the present study of 25 children with ADHD and 30 typically developing controls, motivation was manipulated within the Stop Task. Stop signal reaction time was examined, as well as reaction time, its variability, and the number of errors in the primary choice reaction time task. Overall, the pattern of results supported the inhibition theory over the motivational or dual deficit hypotheses, as main effects of group were found for most key variables (ADHD group was worse), whereas the group by reward interaction predicted by the motivational and dual deficit accounts was not found. Hence, as predicted by the inhibition theory, children with ADHD performed worse than controls irrespective of incentives.

  6. Complete inhibition of creatine kinase in isolated perfused rat hearts

    Fossel, E.T.; Hoefeler, H.

    1987-01-01

    Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts are able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. 31 P-NMR of the heart was carried out

  7. Molecular basis of cyclooxygenase enzymes (COXs) selective inhibition

    Limongelli, Vittorio; Bonomi, Massimiliano; Marinelli, Luciana; Gervasio, Francesco Luigi; Cavalli, Andrea; Novellino, Ettore; Parrinello, Michele

    2010-01-01

    The widely used nonsteroidal anti-inflammatory drugs block the cyclooxygenase enzymes (COXs) and are clinically used for the treatment of inflammation, pain, and cancers. A selective inhibition of the different isoforms, particularly COX-2, is desirable, and consequently a deeper understanding of the molecular basis of selective inhibition is of great demand. Using an advanced computational technique we have simulated the full dissociation process of a highly potent and selective inhibitor, SC-558, in both COX-1 and COX-2. We have found a previously unreported alternative binding mode in COX-2 explaining the time-dependent inhibition exhibited by this class of inhibitors and consequently their long residence time inside this isoform. Our metadynamics-based approach allows us to illuminate the highly dynamical character of the ligand/protein recognition process, thus explaining a wealth of experimental data and paving the way to an innovative strategy for designing new COX inhibitors with tuned selectivity. PMID:20215464

  8. Aedes aegypti D7 Saliva Protein Inhibits Dengue Virus Infection.

    Michael J Conway

    2016-09-01

    Full Text Available Aedes aegypti is the primary vector of several medically relevant arboviruses including dengue virus (DENV types 1-4. Ae. aegypti transmits DENV by inoculating virus-infected saliva into host skin during probing and feeding. Ae. aegypti saliva contains over one hundred unique proteins and these proteins have diverse functions, including facilitating blood feeding. Previously, we showed that Ae. aegypti salivary gland extracts (SGEs enhanced dissemination of DENV to draining lymph nodes. In contrast, HPLC-fractionation revealed that some SGE components inhibited infection. Here, we show that D7 proteins are enriched in HPLC fractions that are inhibitory to DENV infection, and that recombinant D7 protein can inhibit DENV infection in vitro and in vivo. Further, binding assays indicate that D7 protein can directly interact with DENV virions and recombinant DENV envelope protein. These data reveal a novel role for D7 proteins, which inhibits arbovirus transmission to vertebrates through a direct interaction with virions.

  9. BACE inhibition-dependent repair of Alzheimer's pathophysiology.

    Keskin, Aylin D; Kekuš, Maja; Adelsberger, Helmuth; Neumann, Ulf; Shimshek, Derya R; Song, Beomjong; Zott, Benedikt; Peng, Tingying; Förstl, Hans; Staufenbiel, Matthias; Nelken, Israel; Sakmann, Bert; Konnerth, Arthur; Busche, Marc Aurel

    2017-08-08

    Amyloid-β (Aβ) is thought to play an essential pathogenic role in Alzheimer´s disease (AD). A key enzyme involved in the generation of Aβ is the β-secretase BACE, for which powerful inhibitors have been developed and are currently in use in human clinical trials. However, although BACE inhibition can reduce cerebral Aβ levels, whether it also can ameliorate neural circuit and memory impairments remains unclear. Using histochemistry, in vivo Ca 2+ imaging, and behavioral analyses in a mouse model of AD, we demonstrate that along with reducing prefibrillary Aβ surrounding plaques, the inhibition of BACE activity can rescue neuronal hyperactivity, impaired long-range circuit function, and memory defects. The functional neuronal impairments reappeared after infusion of soluble Aβ, mechanistically linking Aβ pathology to neuronal and cognitive dysfunction. These data highlight the potential benefits of BACE inhibition for the effective treatment of a wide range of AD-like pathophysiological and cognitive impairments.

  10. Physiological markers of motor inhibition during human behavior

    Duque, Julie; Greenhouse, Ian; Labruna, Ludovica; Ivry, Richard B.

    2017-01-01

    Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another. PMID:28341235

  11. Survivin inhibition via EZN-3042 in canine lymphoma and osteosarcoma.

    Shoeneman, J K; Ehrhart, E J; Charles, J B; Thamm, D H

    2016-06-01

    Canine lymphoma (LSA) and osteosarcoma (OS) have high mortality rates and remain in need of more effective therapeutic approaches. Survivin, an inhibitor of apoptosis (IAP) family member protein that inhibits apoptosis and drives cell proliferation, is commonly elevated in human and canine cancer. Survivin expression is a negative prognostic factor in dogs with LSA and OS, and canine LSA and OS cell lines express high levels of survivin. In this study, we demonstrate that survivin downregulation in canine LSA and OS cells using a clinically applicable locked nucleic acid antisense oligonucleotide (EZN-3042, Enzon Pharmaceuticals, Piscataway Township, NJ, USA) inhibits growth, induces apoptosis and enhances chemosensitivity in vitro, and inhibits survivin transcription and protein production in orthotopic canine OS xenografts. Our findings strongly suggest that survivin-directed therapies might be effective in treatment of canine LSA and OS and support evaluation of EZN-3042 in dogs with cancer. © 2014 John Wiley & Sons Ltd.

  12. Inhibition of hippocampal synaptic transmission by impairment of Ral function

    Owe-Larsson, Björn; Chaves-Olarte, Esteban; Chauhan, Ashok

    2005-01-01

    Large clostridial cytotoxins and protein overexpression were used to probe for involvement of Ras-related GTPases (guanosine triphosphate) in synaptic transmission in cultured rat hippocampal neurons. The toxins TcdA-10463 (inactivates Rho, Rac, Cdc42, Rap) and TcsL-1522 (inactivates Ral, Rac, Ras......, R-Ras, Rap) both inhibited autaptic responses. In a proportion of the neurons (25%, TcdA-10463; 54%, TcsL-1522), the inhibition was associated with a shift from activity-dependent depression to facilitation, indicating that the synaptic release probability was reduced. Overexpression of a dominant...... negative Ral mutant, Ral A28N, caused a strong inhibition of autaptic responses, which was associated with a shift to facilitation in a majority (80%) of the neurons. These results indicate that Ral, along with at least one other non-Rab GTPase, participates in presynaptic regulation in hippocampal neurons....

  13. Corrosion Inhibition of High Speed Steel by Biopolymer HPMC Derivatives

    Shih-Chen Shi

    2016-07-01

    Full Text Available The corrosion inhibition characteristics of the derivatives of biopolymer hydroxypropyl methylcellulose (HPMC, hydroxypropyl methylcellulose phthalate (HPMCP, and hydroxypropyl methylcellulose acetate succinate (HPMCAS film are investigated. Based on electrochemical impedance spectroscopic measurements and potentiodynamic polarization, the corrosion inhibition performance of high speed steel coated with HPMC derivatives is evaluated. The Nyquist plot and Tafel polarization demonstrate promising anti-corrosion performance of HPMC and HPMCP. With increasing film thickness, both materials reveal improvement in corrosion inhibition. Moreover, because of a hydrophobic surface and lower moisture content, HPMCP shows better anti-corrosion performance than HPMCAS. The study is of certain importance for designing green corrosion inhibitors of high speed steel surfaces by the use of biopolymer derivatives.

  14. Gold Nanoparticles and Microwave Irradiation Inhibit Beta-Amyloid Amyloidogenesis

    Bastus Neus

    2008-01-01

    Full Text Available Abstract Peptide-Gold nanoparticles selectively attached to β-amyloid protein (Aβ amyloidogenic aggregates were irradiated with microwave. This treatment produces dramatic effects on the Aβ aggregates, inhibiting both the amyloidogenesis and the restoration of the amyloidogenic potential. This novel approach offers a new strategy to inhibit, locally and remotely, the amyloidogenic process, which could have application in Alzheimer’s disease therapy. We have studied the irradiation effect on the amyloidogenic process in the presence of conjugates peptide-nanoparticle by transmission electronic microscopy observations and by Thioflavine T assays to quantify the amount of fibrils in suspension. The amyloidogenic aggregates rather than the amyloid fibrils seem to be better targets for the treatment of the disease. Our results could contribute to the development of a new therapeutic strategy to inhibit the amyloidogenic process in Alzheimer’s disease.

  15. Corrosion inhibition of aluminum 6063 using some pharmaceutical compounds

    Fouda, A.S.; Al-Sarawy, A.A.; Ahmed, F.Sh.; El-Abbasy, H.M.

    2009-01-01

    The corrosion inhibition characteristics of some pharmaceutical compounds on aluminum 6063 in 0.5 mol l -1 H 3 PO 4 has been studied using weight loss and galvanostatic polarization techniques. Results showed that the inhibition occurs through adsorption of the inhibitor molecules on the metal surface. The inhibition efficiency increased with increasing inhibitor concentration, but decreased with increasing temperature. The adsorption of first group pharmaceutical compounds on the metal surface is found to obey Frumkin's adsorption isotherm, but the adsorption of second group pharmaceutical compounds is found to obey Temkin's adsorption isotherm. Thermodynamic parameters for adsorption process were determined. Galvanostatic polarization studies showed that first and second groups' pharmaceutical compounds are mixed-type inhibitors and the results obtained from the two techniques are in good agreement

  16. Delivering the lateral inhibition punchline: it's all about the timing.

    Axelrod, Jeffrey D

    2010-10-26

    Experimental and theoretical biologists have long been fascinated with the emergence of self-organizing patterns in developing organisms, and much attention has focused on Notch-mediated lateral inhibition. Within sheets of cells that may adopt either of two possible cell fates, lateral inhibition establishes patterns through the activity of a negative intercellular feedback loop involving the receptor, Notch, and its ligands Delta or Serrate. Despite a long history of intensive study in Drosophila, where the mechanism was first described, as well as in other organisms, new work continues to yield important insights. Mathematical modeling, combined with biological analyses, has now shed light on two features of the process: how antagonistic and activating ligand-receptor interactions work together to accelerate inhibition and ensure fidelity, and how filopodial dynamics contribute to the observed pattern refinement and spacing.

  17. Repellents inhibit P450 enzymes in Stegomyia (Aedes aegypti.

    Gloria Isabel Jaramillo Ramirez

    Full Text Available The primary defence against mosquitoes and other disease vectors is often the application of a repellent. Despite their common use, the mechanism(s underlying the activity of repellents is not fully understood, with even the mode of action of DEET having been reported to be via different mechanisms; e.g. interference with olfactory receptor neurones or actively detected by olfactory receptor neurones on the antennae or maxillary palps. In this study, we discuss a novel mechanism for repellence, one of P450 inhibition. Thirteen essential oil extracts from Colombian plants were assayed for potency as P450 inhibitors, using a kinetic fluorometric assay, and for repellency using a modified World Health Organisation Pesticide Evaluations Scheme (WHOPES arm-in cage assay with Stegomyia (Aedes aegypti mosquitoes. Bootstrap analysis on the inhibition analysis revealed a significant correlation between P450-inhibition and repellent activity of the oils.

  18. Inhibition of the mixed leukocyte reaction by alloantisera in man

    Jonker, M.; Leeuwen, A. van; Rood, J.J. van

    1977-01-01

    The incidence of MLC(mixed leukocyte culture)-inhibiting antibodies was determined in 42 pregnancy sera. MLC's were carried out between the cells from the serum donor and her husband in the presence of nonimmune AB serum and the test serum. Fifty per cent of the sera reduced the MLC response to less than 40% of the control values. Only four sera had lymphocytotoxic activity. The inhibition was strong against the specific immunizor, less strong against random unrelated cells and weak against cells which were SD(serologically defined)-identical with the serum donor. Absorptions with lymphocytes and platelets were carried out. Lymphocytes removed activity in three of the four sera tested. Platelets removed activity from one serum. It was concluded that both anti-LD(lymphocyte defined) and anti-SD antibodies were able to inhibit the MLR (mixed leukocyte reaction) at the stimulator cell level. (author)

  19. Neural signature of behavioural inhibition in women with bulimia nervosa.

    Skunde, Mandy; Walther, Stephan; Simon, Joe J; Wu, Mudan; Bendszus, Martin; Herzog, Wolfgang; Friederich, Hans-Christoph

    2016-08-01

    Impaired inhibitory control is considered a behavioural phenotype in patients with bulimia nervosa. However, the underlying neural correlates of impaired general and food-specific behavioural inhibition are largely unknown. Therefore, we investigated brain activation during the performance of behavioural inhibition to general and food-related stimuli in adults with bulimia nervosa. Women with bulimia and healthy control women underwent event-related fMRI while performing a general and a food-specific no-go task. We included 28 women with bulimia nervosa and 29 healthy control women in our study. On a neuronal level, we observed significant group differences in response to general no-go stimuli in women with bulimia nervosa with high symptom severity; compared with healthy controls, the patients showed reduced activation in the right sensorimotor area (postcentral gyrus, precentral gyrus) and right dorsal striatum (caudate nucleus, putamen). The present results are limited to adult women with bulimia nervosa. Furthermore, it remains unclear whether impaired behavioural inhibition in patients with this disorder are a cause or consequence of chronic illness. Our findings suggest that diminished frontostriatal brain activation in patients with bulimia nervosa contribute to the severity of binge eating symptoms. Gaining further insight into the neural mechanisms of behavioural inhibition problems in individuals with this disorder may inform brain-directed treatment approaches and the development of response inhibition training approaches to improve inhibitory control in patients with bulimia nervosa. The present study does not support greater behavioural and neural impairments to food-specific behavioural inhibition in these patients.

  20. Intraglomerular inhibition maintains mitral cell response contrast across input frequencies.

    Shao, Zuoyi; Puche, Adam C; Shipley, Michael T

    2013-11-01

    Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON) synapses onto mitral/tufted cells (MTCs) and external tufted cells (ETCs); ETCs provide additional feed-forward excitation to MTCs. Both are strongly regulated by intraglomerular inhibition that can last up to 1 s and, when blocked, dramatically increases ON-evoked MC spiking. Intraglomerular inhibition thus limits the magnitude and duration of MC spike responses to sensory input. In vivo, sensory input is repetitive, dictated by sniffing rates from 1 to 8 Hz, potentially summing intraglomerular inhibition. To investigate this, we recorded MTC responses to 1- to 8-Hz ON stimulation in slices. Inhibitory postsynaptic current area (charge) following each ON stimulation was unchanged from 1 to 5 Hz and modestly paired-pulse attenuated at 8 Hz, suggesting there is no summation and only limited decrement at the highest input frequencies. Next, we investigated frequency independence of intraglomerular inhibition on MC spiking. MCs respond to single ON shocks with an initial spike burst followed by reduced spiking decaying to baseline. Upon repetitive ON stimulation peak spiking is identical across input frequencies but the ratio of peak-to-minimum rate before the stimulus (max-min) diminishes from 30:1 at 1 Hz to 15:1 at 8 Hz. When intraglomerular inhibition is selectively blocked, peak spike rate is unchanged but trough spiking increases markedly decreasing max-min firing ratios from 30:1 at 1 Hz to 2:1 at 8 Hz. Together, these results suggest intraglomerular inhibition is relatively frequency independent and can "sharpen" MC responses to input across the range of frequencies. This suggests that glomerular circuits can maintain "contrast" in MC encoding during sniff-sampled inputs.