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  1. Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice.

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    Zhang, Hong; Liu, Bin; Xu, Xiao-Fan; Jiang, Ting-Ting; Zhang, Xiao-Qin; Shi, Ying-Li; Chen, Yu; Liu, Fang; Gu, Jie; Zhu, Lin-Jia; Wu, Nan

    2016-03-14

    To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and

  2. Management of chronic unstable acromioclavicular joint injuries.

    Science.gov (United States)

    Cisneros, Luis Natera; Reiriz, Juan Sarasquete

    2017-12-01

    The acromioclavicular joint represents the link between the clavicle and the scapula, which is responsible for the synchronized dynamic of the shoulder girdle. Chronic acromioclavicular joint instability involves changes in the orientation of the scapula, which provokes cinematic alterations that might result in chronic pain. Several surgical strategies for the management of patients with chronic and symptomatic acromioclavicular joint instability have been described. The range of possibilities includes anatomical and non-anatomical techniques, open and arthroscopy-assisted procedures, and biological and synthetic grafts. Surgical management of chronic acromioclavicular joint instability should involve the reconstruction of the torn ligaments because it is accepted that from three weeks after the injury, these structures may lack healing potential. Here, we provide a review of the literature regarding the management of chronic acromioclavicular joint instability. Expert opinion, Level V.

  3. Low Level Laser Therapy for chronic knee joint pain patients.

    Science.gov (United States)

    Nakamura, Takashi; Ebihara, Satoru; Ohkuni, Ikuko; Izukura, Hideaki; Harada, Takashi; Ushigome, Nobuyuki; Ohshiro, Toshio; Musha, Yoshiro; Takahashi, Hiroshi; Tsuchiya, Kazuaki; Kubota, Ayako

    2014-12-27

    Chronic knee joint pain is one of the most frequent complaints which is seen in the outpatient clinic in our medical institute. In previous studies we have reported the benefits of low level laser therapy (LLLT) for chronic pain in the shoulder joints, elbow, hand, finger and the lower back. The present study is a report on the effects of LLLT for chronic knee joint pain. Over the past 5 years, 35 subjects visited the outpatient clinic with complaints of chronic knee joint pain caused by the knee osteoarthritis-induced degenerative meniscal tear. They received low level laser therapy. A 1000 mW semi-conductor laser device was used to deliver 20.1 J/cm(2) per point in continuous wave at 830nm, and four points were irradiated per session (1 treatment) twice a week for 4 weeks. A visual analogue scale (VAS) was used to determine the effects of LLLT for the chronic pain and after the end of the treatment regimen a significant improvement was observed (pknee joint range of motion. Discussions with the patients revealed that it was important for them to learn how to avoid postures that would cause them knee pain in everyday life in order to have continuous benefits from the treatment. The present study demonstrated that 830 nm LLLT was an effective form of treatment for chronic knee pain caused by knee osteoarthritis. Patients were advised to undertake training involving gentle flexion and extension of the knee.

  4. Chronic hematic cyst of the temporomandibular joint

    International Nuclear Information System (INIS)

    Orhan, K.; Delilbasi, C.; Nishiyama, H.; Furukawa, S.; Mitsunobu, K.

    2005-01-01

    Hematic cyst refers to accumulation of blood or blood breakdown products in a non epithelium-lined fibrous tissue capsule. Hepatic cyst is a term often used for deeply placed, incompletely resorbed hematoma hemorrhagic cyst, which may remain unchanged and unidentified for long periods of time. Trauma is the major causative factor, although it is often vague or totally uncalled by the patient. Chronic hematic cysts are uncommon lesions those can present diagnostic challenge. In this article we report a first case of a chronic hematic cyst of the temporomandibular joint TMJ. (author)

  5. Radiology of chronic diseases of the ankle joint

    International Nuclear Information System (INIS)

    Rand, T.; Trattnig, S.; Breitenseher, M.; Imhof, H.; Wagesreither, S.

    1999-01-01

    The etiology of chronic diseases of the ankle joint comprises a wide spectrum including chronic inflammatory processes and chronic degenerative, tumorous and neuropathic processes, as well as some specific syndromes based on chronic changes of the ankle joint. Of the inflammatory processes, chronic juvenile arthritis (JVC) is the most common disease. However, also Reiter disease, psoriasis or chronic monoarthritid diseases such as gout, as well as granulomatous diseases (tuberculosis, sarcoidosis) and fungal infections, may affect the ankle joint in a chronic course. Chronic degenerative changes are usually secondary due to abnormal positioning of the joint constituents or repetitive trauma. Neuropathic changes, as frequently seen in the course of diabetes, present with massive osseous destruction and malposition of the articular constituents. Chronic osseous as well as cartilaginous and synovial changes are seen in hemoplici patients. Chronic traumatic changes are represented by pigmented villonodular synovitis (PVNS), and chondromatosis, both with a predilection for the ankle joint. Due to the possibilities of magnetic resonance imaging (MRI), diagnosis of chronic ankle changes includes chronic ligamentous, tendinous and soft tissue changes. With the use MRI, specific syndromes can be defined which particularly affect the ankle joint in a chronic way, such as the os trigonum syndrome, the anterolateral impingement syndrome and the sinus tarsi syndrome. Nevertheless, plain film radiographs are still the basic element of any investigation. MRI, however, can be potentially used as a second investigation, saving an unnecessary cascade of investigations with ultrasound and CT. The latter investigations are used only with very specific indications, for instance CT for subtle bone structures and sonography for a limited investigation of tendons or evaluation of fluid. Particularly due to the possibilities of MRI and the development of special gradient-echo imaging or

  6. Chronic proliferative synovitis of the equine metacarpophalangeal joint

    International Nuclear Information System (INIS)

    Kannegieter, N.J.

    1990-01-01

    Chronic proliferative synovitis of 27 metacarpophalangeal joints in 16 horses is described. The diagnosis was based on a history of lameness and, or, poor performance, pain on flexion of the metacarpophalangeal joint, the response to intra-articular anaesthesia, and plain and contrast radiography. Radiographic findings included concavity of the distal dorsal metacarpus proximal to the sagittal ridge, and an increase in size of the synovial tissue adjacent to the proximal, dorsal attachment of the joint capsule. Mineralisation of the synovial tissue was present in some joints, and chip fractures from the dorsal aspect of the proximal phalanx were also occasionally seen. Treatment by arthroscopic resection of the tissue gave excellent results

  7. Diffuse skin hyperpigmentation associated with chronic minocycline use in a patient with prosthetic joint infection

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    Hadi Berbari

    2017-01-01

    Full Text Available Cutaneous hyperpigmentation is a recognized adverse effect of chronic minocycline use occurring in up to 50% of patients. In this report we present a rare case of extensive skin hyperpigmentation involving both lower extremities in a patient receiving long term minocycline. The patient was receiving minocycline as suppression for chronic prosthetic joint infection. Risk factors associated with minocycline-induced cutaneous pigmentation (MICH will be reviewed.

  8. Minimally invasive arthrodesis for chronic sacroiliac joint dysfunction using the SImmetry SI Joint Fusion system.

    Science.gov (United States)

    Miller, Larry E; Block, Jon E

    2014-01-01

    Chronic sacroiliac (SI) joint-related low back pain (LBP) is a common, yet under-diagnosed and undertreated condition due to difficulties in accurate diagnosis and highly variable treatment practices. In patients with debilitating SI-related LBP for at least 6 months duration who have failed conservative management, arthrodesis is a viable option. The SImmetry(®) SI Joint Fusion System is a novel therapy for SI joint fusion, not just fixation, which utilizes a minimally invasive surgical approach, instrumented fixation for immediate stability, and joint preparation with bone grafting for a secure construct in the long term. The purpose of this report is to describe the minimally invasive SI Joint Fusion System, including patient selection criteria, implant characteristics, surgical technique, postoperative recovery, and biomechanical testing results. Advantages and limitations of this system will be discussed.

  9. A Study of Acute and Chronic Tissue Changes in Surgical and Traumatically-Induced Experimental Models of Knee Joint Injury Using Magnetic Resonance Imaging and Micro-Computed Tomography

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    Fischenich, Kristine M.; Pauly, Hannah M.; Button, Keith D.; Fajardo, Ryan S.; DeCamp, Charles E.; Haut, Roger C.; Haut Donahue, Tammy L.

    2016-01-01

    Objective The objective of this study was to monitor the progression of joint damage in two animal models of knee joint trauma using two non-invasive, clinically available imaging modalities. Methods A 3-T clinical magnet and micro-computed tomography (mCT) was used to document changes immediately following injury (acute) and post-injury (chronic) at time points of 4, 8, or 12 weeks. Joint damage was recorded at dissection and compared to the chronic magnetic resonance imaging (MRI) record. Fifteen Flemish Giant rabbits were subjected to a single tibiofemoral compressive impact (ACLF), and 18 underwent a combination of anterior cruciate ligament (ACL) and meniscal transection (mACLT). Results All ACLF animals experienced ACL rupture, and 13 also experienced acute meniscal damage. All ACLF and mACLT animals showed meniscal and articular cartilage damages at dissection. Meniscal damage was documented as early as 4 weeks and worsened in 87% of the ACLF animals and 71% of the mACLT animals. Acute cartilage damage also developed further and increased in occurrence with time in both models. A progressive decrease in bone quantity and quality was documented in both models. The MRI data closely aligned with dissection notes suggesting this clinical tool may be a non-invasive method for documenting joint damage in lapine models of knee joint trauma. Conclusions The study investigates the acute to chronic progression of meniscal and cartilage damage at various time points, and chronic changes to the underlying bone in two models of posttraumatic osteoarthritis (PTOA), and highlights the dependency of the model on the location, type, and progression of damage over time. PMID:27756698

  10. Arthrography of the ankle joint in chronic instability

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    Dory, M.A.

    1986-05-01

    Papers on arthrography of injuries of the lateral ligaments of the ankle relate mainly to recent distortion of the joint. Arthrography performed at a later stage after injury generally is considered useless. In fact, changes in chronic instability are observed; they are subtle and consist either of small recesses adjacent to the lateral malleolus or communication of the joint with the peroneal tendon sheaths. Arthrography was assessed in 61 cases of recurrent lateral sprains of the ankle more than 2 weeks after acute injury; 38 were considered as positive. Twenty-five patients had operative evaluation, with four false negative and one false positive results. Small recesses adjacent to the lateral malleolus or opacification of the peroneal tendon sheaths are sequelae of an acute sprain with tear of the anterior talofibular and/or the calcaneofibular ligaments. Although false negative results occur, arthrography is useful in the preoperative assessment of chronic ankle instability.

  11. Arthrography of the ankle joint in chronic instability

    International Nuclear Information System (INIS)

    Dory, M.A.

    1986-01-01

    Papers on arthrography of injuries of the lateral ligaments of the ankle relate mainly to recent distortion of the joint. Arthrography performed at a later stage after injury generally is considered useless. In fact, changes in chronic instability are observed; they are subtle and consist either of small recesses adjacent to the lateral malleolus or communication of the joint with the peroneal tendon sheaths. Arthrography was assessed in 61 cases of recurrent lateral sprains of the ankle more than 2 weeks after acute injury; 38 were considered as positive. Twenty-five patients had operative evaluation, with four false negative and one false positive results. Small recesses adjacent to the lateral malleolus or opacification of the peroneal tendon sheaths are sequelae of an acute sprain with tear of the anterior talofibular and/or the calcaneofibular ligaments. Although false negative results occur, arthrography is useful in the preoperative assessment of chronic ankle instability. (orig.)

  12. Severe erosive arthritis of large joints in chronic renal failure

    International Nuclear Information System (INIS)

    Griffin, C.N. Jr.

    1984-01-01

    Two cases of chronic renal failure are presented in which a large joint severe erosive arthritis was the prominent radiologic feature of their renal osteodystrophy. In one both knees were involved, and in the other both knees and one wrist. Distal clavicular erosions were present in both, but hands were not radiographically involved. The literature is reviewed in regards other reports of erosive arthritis complicating renal failure. (orig.)

  13. Quantifying the impact of transient joint symptoms, chronic joint symptoms, and arthritis: a population-based approach.

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    Busija, Lucy; Buchbinder, Rachelle; Osborne, Richard H

    2009-10-15

    To estimate the prevalence and co-occurrence of self-reported doctor-diagnosed arthritis, chronic joint symptoms (pain, aching, stiffness, or swelling on most days for a month), and transient joint symptoms (pain, aching, stiffness, or swelling but not on most days for a month), and to compare the sociodemographic characteristics, activity limitations, and health-related quality of life (HRQOL) of people with joint conditions with those who have no self-reported doctor-diagnosed arthritis and no joint symptoms. Data from the 2004 population-based South Australian Health Omnibus Survey (n = 2,840, ages 18-96 years) were used in the study. Activity limitations were assessed using 10 activity limitations questions from the Short Form 36 health survey. HRQOL was assessed using the Assessment of Quality of Life scale. Half of all respondents reported having joint problems, with 26%, 11%, and 13% reporting self-reported doctor-diagnosed arthritis, chronic joint symptoms, and transient joint symptoms, respectively. Chronic joint conditions (self-reported doctor-diagnosed arthritis and chronic joint symptoms) accounted for 74% of all joint problems and were associated with higher odds of activity limitations and poorer HRQOL. The frequency of transient and chronic joint symptoms was highest among middle-aged participants (ages 45-54 years for transient and 45-64 years for chronic joint symptoms) and those who had a body mass index in the obese range. Prevalence of self-reported doctor-diagnosed arthritis increased with age and was higher among women and those who were overweight or obese. This study documented the high prevalence and impact of joint conditions in the community. Chronic joint conditions affect daily life and are substantial barriers for effective public health interventions aimed at reducing obesity and inactivity.

  14. Blood-induced joint damage: novel targets for therapy

    NARCIS (Netherlands)

    van Meegeren, M.E.R.

    2012-01-01

    -induced joint damage can occur due to a trauma but also during surgery when blood leaks into the joint cavity. Besides that, it is one of the major causes of morbidity amongst haemophilia patients. The aims of this thesis were to further unravel the pathogenesis of blood-induced joint damage and to

  15. Minimally invasive arthrodesis for chronic sacroiliac joint dysfunction using the SImmetry SI Joint Fusion system

    OpenAIRE

    Block, Jon; Miller,Larry

    2014-01-01

    Larry E Miller,1,2 Jon E Block21Miller Scientific Consulting, Inc., Asheville, NC, USA; 2The Jon Block Group, San Francisco, CA, USA Abstract: Chronic sacroiliac (SI) joint-related low back pain (LBP) is a common, yet under-diagnosed and undertreated condition due to difficulties in accurate diagnosis and highly variable treatment practices. In patients with debilitating SI-related LBP for at least 6 months duration who have failed conservative management, arthrodesis is a viable option. The...

  16. Obesity and worsening of chronic venous disease and joint mobility.

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    Belczak, Cleusa Ema Quilici; de Godoy, José Maria Pereira; Belzack, Sergio Quilici; Ramos, Rubiana Neves; Caffaro, Roberto Augusto

    2014-09-01

    The aim of this study was to investigate a possible relationship between obesity and decreased mobility of the talocrural joint and in turn chronic venous disease. One hundred obese patients recruited at Hospital Santa Casa de Maringa, Parana were enrolled by order of arrival at the hospital in a randomized quantitative cross-sectional study. Inclusion criteria were patients with a body mass index above 30 kg/m(2) and the exclusion criteria were infectious conditions that would interfere with the assessment. Patients were graded according to the clinical, etiological, anatomical and pathophysiological classification. Talocrural goniometry was performed to assess the degree of mobility of the legs. The Kolmogorov-Smirnov normality test, Kruskal-Wallis test, Dunn's Multiple comparison test and analysis of variance were used for statistical analysis tests with an alpha error of 5% being considered acceptable. The increase in body mass index is correlated to the reduction in joint mobility (Kruskal-Wallis test: p-value Kruskal-Wallis test: p-value <0.0001). Obesity is associated with deterioration in joint mobility and worsening of chronic venous disease. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. Minimally invasive arthrodesis for chronic sacroiliac joint dysfunction using the SImmetry SI Joint Fusion system

    Directory of Open Access Journals (Sweden)

    Miller LE

    2014-05-01

    Full Text Available Larry E Miller,1,2 Jon E Block21Miller Scientific Consulting, Inc., Asheville, NC, USA; 2The Jon Block Group, San Francisco, CA, USA Abstract: Chronic sacroiliac (SI joint-related low back pain (LBP is a common, yet under-diagnosed and undertreated condition due to difficulties in accurate diagnosis and highly variable treatment practices. In patients with debilitating SI-related LBP for at least 6 months duration who have failed conservative management, arthrodesis is a viable option. The SImmetry® SI Joint Fusion System is a novel therapy for SI joint fusion, not just fixation, which utilizes a minimally invasive surgical approach, instrumented fixation for immediate stability, and joint preparation with bone grafting for a secure construct in the long term. The purpose of this report is to describe the minimally invasive SI Joint Fusion System, including patient selection criteria, implant characteristics, surgical technique, postoperative recovery, and biomechanical testing results. Advantages and limitations of this system will be discussed. Keywords: arthrodesis, fusion, minimally invasive, sacroiliac, SImmetry

  18. [Bilateral chronic dislocation of the temporomandibular joints and Meige syndrome].

    Science.gov (United States)

    Arzul, L; Henoux, M; Marion, F; Corre, P

    2015-04-01

    Chronic dislocation of the temporo-mandibular joint (TMJ) is rare. It occurs when an acute dislocation is left untreated, in certain situations, including severe illness, neurologic or psychiatric diseases or prolonged oral intubation. A 79 years old woman, with Meige syndrome, suffered from bilateral dislocation of the TMJ for over 1 year. Surgical repositioning of the mandibular condyles and temporal bone eminectomy were performed. At the 18 postoperative months control, no recurrence has been noted. Treatment of chronic TMJ dislocations often requires a surgical procedure. Manual reduction, even under general anaesthesia, often fails because of severe muscular spasm and periarticular fibrotic changes. The management of this disorder is still controversial. We review available surgical procedures. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Neuromuscular adaptations induced by adjacent joint training.

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    Ema, R; Saito, I; Akagi, R

    2018-03-01

    Effects of resistance training are well known to be specific to tasks that are involved during training. However, it remains unclear whether neuromuscular adaptations are induced after adjacent joint training. This study examined the effects of hip flexion training on maximal and explosive knee extension strength and neuromuscular performance of the rectus femoris (RF, hip flexor, and knee extensor) compared with the effects of knee extension training. Thirty-seven untrained young men were randomly assigned to hip flexion training, knee extension training, or a control group. Participants in the training groups completed 4 weeks of isometric hip flexion or knee extension training. Standardized differences in the mean change between the training groups and control group were interpreted as an effect size, and the substantial effect was assumed to be ≥0.20 of the between-participant standard deviation at baseline. Both types of training resulted in substantial increases in maximal (hip flexion training group: 6.2% ± 10.1%, effect size = 0.25; knee extension training group: 20.8% ± 9.9%, effect size = 1.11) and explosive isometric knee extension torques and muscle thickness of the RF in the proximal and distal regions. Improvements in strength were accompanied by substantial enhancements in voluntary activation, which was determined using the twitch interpolation technique and RF activation. Differences in training effects on explosive torques and neural variables between the two training groups were trivial. Our findings indicate that hip flexion training results in substantial neuromuscular adaptations during knee extensions similar to those induced by knee extension training. © 2017 The Authors. Scandinavian Journal of Medicine & Science In Sports Published by John Wiley & Sons Ltd.

  20. Raptor Acupuncture for Treating Chronic Degenerative Joint Disease.

    Science.gov (United States)

    Choi, Keum Hwa; Buhl, Gail; Ponder, Julia

    2016-12-01

    A permanently captive 21-year-old male bald eagle was diagnosed with chronic degenerative joint disease in the right stifle with severe lameness (Grade 5) based on radiography. Clinical signs included decreased movement, vocalization, non weight-bearing on the affected limb, inappetence, depression, and pododermatitis on the left foot (bumblefoot, Grade 3). The eagle was treated with anti-inflammatory or analgesic drugs including carprofen and celecoxib. As there was no observed clinical improvement with any of the treatments, acupuncture treatment was provided. The eagle was treated with dry needle acupuncture once per week for 2 months and biweekly for another 2 months. The Traditional Eastern Medicine diagnosis of this eagle was Bony Bi syndrome. The selected acupuncture points were ST 36, LI 4, BL 40, BL 60, GB 34, and Ba Feng (Table 3). The lameness score improved from Grade 5 to Grade 1 after 4 months of acupuncture treatment. The observed pododermatitis improved from Grade 3 to Grade 0. Symptoms including inappetence and vocalizations were significantly reduced over the 4 month period. There was no significant improvement in the radiographic signs. In conclusion, acupuncture may be a potential medical option for permanently captive raptors having musculoskeletal conditions, such as degenerative joint disease. Copyright © 2016. Published by Elsevier B.V.

  1. Reconstruction of chronic acromioclavicular joint disruption with artificial ligament prosthesis

    Directory of Open Access Journals (Sweden)

    Chouhan Devendra Kumar

    2013-08-01

    Full Text Available 【Abstract】Objective: Management of Rockwood type 3 acromioclavicular disruptions is a matter of debate. Should we adopt conservative or operative measures at first presentation? It is not clear but most of the evidences are in favour of conservative management. We present our expe-rience in managing these patients surgically. Methods: We present a prospective series of eight cases of chronic Rockwood type 3 acromioclavicular joint disruptions treated surgically. Anatomical reconstruction of the coracoclavicular ligament was done by artificial braided polyester ligament prosthesis. Results: All the patients were able to perform daily activities from an average of the 14th postoperative day. All patients felt an improvement in pain, with decrease in ave-rage visual analogue scale from preoperative 6.5 points (range 3-9 points to 2.0 points (range 0-5 points, Constant score from 59% to 91% and American Shoulder and Elbow Surgeons shoulder score from 65 to 93 points postoperatively. These results improved or at least remained stationary on midterm follow-up, and no deterioration was recorded at an average follow-up of 46 months. Conclusion: This midterm outcome analysis of the artificial ligament prosthesis is the first such follow-up study with prosthesis. Our results are encouraging and justify the further use and evaluation of this relatively new and easily reproducible technique. Key words: Acromioclavicular joint; Prostheses and implants; Reconstructive surgical procedures; Ligaments

  2. Raptor Acupuncture for Treating Chronic Degenerative Joint Disease

    Directory of Open Access Journals (Sweden)

    Keum Hwa Choi

    2016-12-01

    Full Text Available A permanently captive 21-year-old male bald eagle was diagnosed with chronic degenerative joint disease in the right stifle with severe lameness (Grade 5 based on radiography. Clinical signs included decreased movement, vocalization, non weight-bearing on the affected limb, inappetence, depression, and pododermatitis on the left foot (bumblefoot, Grade 3. The eagle was treated with anti-inflammatory or analgesic drugs including carprofen and celecoxib. As there was no observed clinical improvement with any of the treatments, acupuncture treatment was provided. The eagle was treated with dry needle acupuncture once per week for 2 months and biweekly for another 2 months. The Traditional Eastern Medicine diagnosis of this eagle was Bony Bi syndrome. The selected acupuncture points were ST 36, LI 4, BL 40, BL 60, GB 34, and Ba Feng (Table 3. The lameness score improved from Grade 5 to Grade 1 after 4 months of acupuncture treatment. The observed pododermatitis improved from Grade 3 to Grade 0. Symptoms including inappetence and vocalizations were significantly reduced over the 4 month period. There was no significant improvement in the radiographic signs. In conclusion, acupuncture may be a potential medical option for permanently captive raptors having musculoskeletal conditions, such as degenerative joint disease.

  3. Chronic Intermittent Hypoxia Induces Atherosclerosis

    OpenAIRE

    Savransky, Vladimir; Nanayakkara, Ashika; Li, Jianguo; Bevans, Shannon; Smith, Philip L.; Rodriguez, Annabelle; Polotsky, Vsevolod Y.

    2007-01-01

    Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.

  4. Isolated Facet Joint Fracture as a Cause of Chronic Low Back Pain and Sciatica

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    Robert W Teasell

    1996-01-01

    Full Text Available A case of facet joint fracture following a rear-end motor vehicle accident who presented with chronic low back pain and sciatica is outlined. Diagnosis was made with 99Tc nuclear bone scan and was confirmed on computed tomographic scan after diagnosis with regular radiographs had failed. Facetectomy relieved pain but led to symptoms related to asymmetric load on the opposite facet joint. Symptoms were substantially relieved with a facet joint deinnervation procedure. Facet joint fracture was felt to occur as a consequence of compression forces on the facet joint at the time of impact.

  5. Knee joint mobilization reduces secondary mechanical hyperalgesia induced by capsaicin injection into the ankle joint.

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    Sluka, K A; Wright, A

    2001-01-01

    Joint mobilization is a treatment approach commonly used by physical therapists for the management of a variety of painful conditions. However, the clinical effectiveness when compared to placebo and the neurophysiological mechanism of action are not known. The purpose of this study was to establish that application of a manual therapy technique will produce antihyperalgesia in an animal model of joint inflammation and that the antihyperalgesia produced by joint mobilization depends on the time of treatment application. Capsaicin (0.2%, 50 microl) was injected into the lateral aspect of the left ankle joint and mechanical withdrawal threshold assessed before and after capsaicin injection in Sprague-Dawley rats. Joint mobilization of the ipsilateral knee joint was performed 2 h after capsaicin injection for a total of 3 min, 9 min or 15 min under halothane anaesthesia. Control groups included animals that received halothane for the same time as the group that received joint mobilization and those whose limbs were held for the same duration as the mobilization (no halothane). Capsaicin resulted in a decreased mechanical withdrawal threshold by 2 h after injection that was maintained through 4 h. Both 9 and 15 min of mobilization, but not 3 min of mobilization, increased the withdrawal threshold to mechanical stimuli to baseline values when compared with control groups. The antihyperalgesic effect of joint mobilization lasted 30 min. Thus, joint mobilization (9 or 15 min duration) produces a significant reversal of secondary mechanical hyperalgesia induced by intra-articular injection of capsaicin. Copyright 2001 European Federation of Chapters of the International Association for the Study of Pain.

  6. TOO MANY MOULDY JOINTS – MARIJUANA AND CHRONIC PULMONARY ASPERGILLOSIS

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    Youssef Gargani

    2011-01-01

    Full Text Available Chronic pulmonary aspergillosis is a progressive debilitating disease with multiple underlying pulmonary diseases described. Here we report the association of chronic pulmonary aspergillosis and long term marijuana smoking in 2 patients and review the literature related to invasive and allergic aspergillosis

  7. TOO MANY MOULDY JOINTS – MARIJUANA AND CHRONIC PULMONARY ASPERGILLOSIS

    Directory of Open Access Journals (Sweden)

    Youssef Gargani

    2011-01-01

    Full Text Available Chronic pulmonary aspergillosis is a progressive debilitating disease with multiple underlying pulmonary diseases described. Here we report the association of chronic pulmonary aspergillosis and long term marijuana smoking in 2 patients and review the literature related to invasive and allergic aspergillosis

  8. Differences in kinematic control of ankle joint motions in people with chronic ankle instability.

    Science.gov (United States)

    Kipp, Kristof; Palmieri-Smith, Riann M

    2013-06-01

    People with chronic ankle instability display different ankle joint motions compared to healthy people. The purpose of this study was to investigate the strategies used to control ankle joint motions between a group of people with chronic ankle instability and a group of healthy, matched controls. Kinematic data were collected from 11 people with chronic ankle instability and 11 matched control subjects as they performed a single-leg land-and-cut maneuver. Three-dimensional ankle joint angles were calculated from 100 ms before, to 200 ms after landing. Kinematic control of the three rotational ankle joint degrees of freedom was investigated by simultaneously examining the three-dimensional co-variation of plantarflexion/dorsiflexion, toe-in/toe-out rotation, and inversion/eversion motions with principal component analysis. Group differences in the variance proportions of the first two principal components indicated that the angular co-variation between ankle joint motions was more linear in the control group, but more planar in the chronic ankle instability group. Frontal and transverse plane motions, in particular, contributed to the group differences in the linearity and planarity of angular co-variation. People with chronic ankle instability use a different kinematic control strategy to coordinate ankle joint motions during a single-leg landing task. Compared to the healthy group, the chronic ankle instability group's control strategy appeared to be more complex and involved joint-specific contributions that would tend to predispose this group to recurring episodes of instability. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Management of chronic ankle pain using joint mobilization and ASTYM® treatment: a case report

    OpenAIRE

    Slaven, Emily J; Mathers, Jessie

    2011-01-01

    Treatment of ankle sprains predominately focuses on the acute management of this condition; less emphasis is placed on the treatment of ankle sprains in the chronic phase of recovery. Manual therapy, in the form of joint mobilization and manipulation, has been shown to be effective in the management of this condition, but the combination of joint mobilization and manipulation in tandem with ASTYM® treatment has not been explored. The purpose of this case report is to chronicle the management ...

  10. Temporal gene expression profiling of the rat knee joint capsule during immobilization-induced joint contractures.

    Science.gov (United States)

    Wong, Kayleigh; Sun, Fangui; Trudel, Guy; Sebastiani, Paola; Laneuville, Odette

    2015-05-26

    Contractures of the knee joint cause disability and handicap. Recovering range of motion is recognized by arthritic patients as their preference for improved health outcome secondary only to pain management. Clinical and experimental studies provide evidence that the posterior knee capsule prevents the knee from achieving full extension. This study was undertaken to investigate the dynamic changes of the joint capsule transcriptome during the progression of knee joint contractures induced by immobilization. We performed a microarray analysis of genes expressed in the posterior knee joint capsule following induction of a flexion contracture by rigidly immobilizing the rat knee joint over a time-course of 16 weeks. Fold changes of expression values were measured and co-expressed genes were identified by clustering based on time-series analysis. Genes associated with immobilization were further analyzed to reveal pathways and biological significance and validated by immunohistochemistry on sagittal sections of knee joints. Changes in expression with a minimum of 1.5 fold changes were dominated by a decrease in expression for 7732 probe sets occurring at week 8 while the expression of 2251 probe sets increased. Clusters of genes with similar profiles of expression included a total of 162 genes displaying at least a 2 fold change compared to week 1. Functional analysis revealed ontology categories corresponding to triglyceride metabolism, extracellular matrix and muscle contraction. The altered expression of selected genes involved in the triglyceride biosynthesis pathway; AGPAT-9, and of the genes P4HB and HSP47, both involved in collagen synthesis, was confirmed by immunohistochemistry. Gene expression in the knee joint capsule was sensitive to joint immobility and provided insights into molecular mechanisms relevant to the pathophysiology of knee flexion contractures. Capsule responses to immobilization was dynamic and characterized by modulation of at least three

  11. Ankylosing spondylitis in an athlete with chronic sacroiliac joint pain.

    Science.gov (United States)

    Miller, Timothy L; Cass, Nathan; Siegel, Courtney

    2014-02-01

    Ankylosing spondylitis is a disease in which inflammation of joints, most often in the axial skeleton, can lead to reactive fibrosis and eventual joint fusion with associated immobility and kyphosis. The disease often involves extra-articular features, such as uveitis and aortic regurgitation, as well as associated inflammatory conditions of the intestines. Its etiology is unknown. Ankylosing spondylitis most commonly presents in young males (15-30 years old) as persistent low back pain and stiffness that is worse in the morning and at night and improves with activity. The authors report the case of a young male athlete whose symptoms were initially incorrectly diagnosed as sacroiliac joint instability and dysfunction and later as a sacroiliac stress fracture before further workup revealed a seronegative spondyloarthropathy and the diagnosis of ankylosing spondylitis. The patient was prescribed oral indomethacin daily by the attending rheumatologist and started on a slow progression of return to running, jumping, and weight lifting. Within 4 weeks of beginning this treatment, the patient had complete cessation of pain with the medication. At follow-up 1 year after graduation from his university, the patient was nearly symptom free and working in a non-heavy labor job. The purpose of this case report is to remind sports medicine physicians of the prevalence of rheumatologic diseases in general and ankylosing spondylitis in particular and of the various ways in which spondyloarthropathies may present in athletes. Increased suspicion may lead to earlier diagnosis and treatment, potentially reducing illness severity and duration and improving the performance of athletes with this condition. Copyright 2014, SLACK Incorporated.

  12. The efficacy of negative pressure wound therapy in treating sacroiliac joint tuberculosis with a chronic sinus tract: a case series.

    Science.gov (United States)

    Luo, Xiaobo; Tang, Xiangyu; Ma, Yuanzheng; Zhang, Yonggang; Fang, Shuzhi

    2015-08-06

    Tuberculous sacroiliitis with abscess accounts for approximately 50 % of all sacroiliac joint tuberculosis cases. Tuberculous abscesses spread into the sacroiliac joint capsule, subcutaneous tissue, and the skin, and finally becomes a skin sinus. As there are no previous reports about sacroiliac joint tuberculosis with a chronic sinus, we evaluated its clinical characteristics and management by negative pressure wound therapy. A retrospective analysis of 12 patients with sacroiliac joint tuberculosis with chronic sinuses treated between January 2005 and January 2010 was conducted. Patients were treated with negative pressure wound therapy (NPWT). Treatment was divided into three phases: control phase, standard dressing changes daily for 4 weeks; interphase washout period, dressing changes every 3 days for 1 week; and intervention phase, no dressing changes until minimal sinus tract drainage (sacroiliac joint tuberculosis with a chronic sinus can be difficult. NPWT provides better healing of sacroiliac joint tuberculosis with a chronic sinus than standard dressing changes.

  13. Changes of the hip joints associated with chronic subluxation and dislocation: CT and plain radiography analysis

    International Nuclear Information System (INIS)

    Yang, Ik; Ryu, Kyung Nam; Lee, Sun Wha; Choi, Woo Suk; Lee, Eil Seong

    1993-01-01

    Secondary osteoarthritis of the hip joint is a common disease and is frequently followed by chronic subluxation and dislocation. Twenty four cases of the secondary osteoarthritis associated with chronic subluxation and dislocation of the hip joints were evaluated with plain radiography and computed tomography. We retrospectively analyzed 1) the osteoarthritis and calcification of the acetabular labrum, 2) the thickness of the quadrilateral plate of the ilium, and 3) anteroposterior diameter of the acetabulum. The changes of the hip joints in subluxation (n=14) revealed ossification of the acetabular labrum in 12 cases (86%), thickening of the quadrilateral plate of the ilium in 11 cases (78%) but anteroposterior diameter of the acetabulum was not changed. The changes of the hip joints in dislocation (n=10) revealed no evidence of the ossification of the acetabular labrum, thickening of the quadrilateral plate of the ilium in 10 cases (100%) and decreased anteroposterior diameter of the acetabulum. We conclude that CT findings of subluxation and dislocation of the hip joints can be helpful in the evaluation of the secondary osteoarthritis of the hip joints

  14. Radiology of chronic diseases of the ankle joint; Chronische Krankheitsbilder am Sprunggelenk

    Energy Technology Data Exchange (ETDEWEB)

    Rand, T. [Vienna Univ. (Austria). Einrichtung fuer Magnetresonanztomographie]|[Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria); Trattnig, S.; Breitenseher, M.; Imhof, H. [Vienna Univ. (Austria). Einrichtung fuer Magnetresonanztomographie; Kreuzer, S. [Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria); Wagesreither, S. [Vienna Univ. (Austria). Klinik fuer Zahn-, Mund- und Kieferheilkunde

    1999-01-01

    The etiology of chronic diseases of the ankle joint comprises a wide spectrum including chronic inflammatory processes and chronic degenerative, tumorous and neuropathic processes, as well as some specific syndromes based on chronic changes of the ankle joint. Of the inflammatory processes, chronic juvenile arthritis (JVC) is the most common disease. However, also Reiter disease, psoriasis or chronic monoarthritid diseases such as gout, as well as granulomatous diseases (tuberculosis, sarcoidosis) and fungal infections, may affect the ankle joint in a chronic course. Chronic degenerative changes are usually secondary due to abnormal positioning of the joint constituents or repetitive trauma. Neuropathic changes, as frequently seen in the course of diabetes, present with massive osseous destruction and malposition of the articular constituents. Chronic osseous as well as cartilaginous and synovial changes are seen in hemoplici patients. Chronic traumatic changes are represented by pigmented villonodular synovitis (PVNS), and chondromatosis, both with a predilection for the ankle joint. Due to the possibilities of magnetic resonance imaging (MRI), diagnosis of chronic ankle changes includes chronic ligamentous, tendinous and soft tissue changes. With the use MRI, specific syndromes can be defined which particularly affect the ankle joint in a chronic way, such as the os trigonum syndrome, the anterolateral impingement syndrome and the sinus tarsi syndrome. Nevertheless, plain film radiographs are still the basic element of any investigation. MRI, however, can be potentially used as a second investigation, saving an unnecessary cascade of investigations with ultrasound and CT. The latter investigations are used only with very specific indications, for instance CT for subtle bone structures and sonography for a limited investigation of tendons or evaluation of fluid. Particularly due to the possibilities of MRI and the development of special gradient-echo imaging or

  15. ASSESSMENT AND COMPARISION OF CERVICAL JOINT POSITION SENSE IN SUBJECTS WITH CHRONIC NECK PAIN vs NORMALS

    Directory of Open Access Journals (Sweden)

    Oberoi Mugdha

    2015-06-01

    Full Text Available Background: The abundance of mechanoreceptors in the cervical spine and their central and reflex afferent connections to the vestibular, visual and postural control system suggests that the cervical proprioceptive information provides important somatosensory information influencing postural stability, head orientation and eye movement control. Disturbances to the afferent input from the cervical region is thought to underlie symptoms of dizziness, unsteadiness, visual disturbances and signs of altered postural stability, cervical proprioception and head and eye movement control in people with chronic neck pain. This study aimed to assess and compare cervical joint position sense in subjects with chronic neck pain vs normals. Methods: Total 60 subjects, divided into two groups chronic neck pain group (n=30 (12 males and 18 females with mean age of 40.7 years and control group (n=30 with age and gender matched normal individuals were assessed for baseline data and demographic variables. Head repositioning accuracy test was used to assess cervical joint position sense in degrees. Results: The difference in the head repositioning error values were found to be extremely significant (p<0.0001 for all the neck movements for subjects with chronic neck pain as compared to normals. Conclusion: Cervical joint position sense in subjects with chronic neck pain is found to be altered as compared to age and gender matched normals.

  16. Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats.

    Science.gov (United States)

    Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A; Hernández-Reyes, Ana Gabriela; Martínez-Galero, Elizdath

    2015-08-01

    One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity.

  17. Ignoring the sacroiliac joint in chronic low back pain is costly

    Directory of Open Access Journals (Sweden)

    Polly DW

    2016-01-01

    Full Text Available David W Polly,1,2 Daniel Cher3 1Department of Orthopedic Surgery, 2Department of Neurosurgery, University of Minnesota, Minneapolis, MN, 3SI-BONE, Inc., San Jose, CA, USA Background: Increasing evidence supports minimally invasive sacroiliac joint (SIJ fusion as a safe and effective treatment for SIJ dysfunction. Failure to include the SIJ in the diagnostic evaluation of low back pain could result in unnecessary health care expenses. Design: Decision analytic cost model. Methods: A decision analytic model calculating 2-year direct health care costs in patients with chronic low back pain considering lumbar fusion surgery was used. Results: The strategy of including the SIJ in the preoperative diagnostic workup of chronic low back pain saves an expected US$3,100 per patient over 2 years. Cost savings were robust to reasonable ranges for costs and probabilities, such as the probability of diagnosis and the probability of successful surgical treatment. Conclusion: Including the SIJ as part of the diagnostic strategy in preoperative patients with chronic low back pain is likely to be cost saving in the short term. Keywords: chronic low back pain, lumbar fusion, sacroiliac joint pain, sacroiliac joint fusion, healthcare costs, decision modeling

  18. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

    NARCIS (Netherlands)

    Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas

    Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced

  19. Concomitant glenohumeral pathologies associated with acute and chronic grade III and grade V acromioclavicular joint injuries.

    Science.gov (United States)

    Jensen, Gunnar; Millett, Peter J; Tahal, Dimitri S; Al Ibadi, Mireille; Lill, Helmut; Katthagen, Jan Christoph

    2017-08-01

    The purpose of this study was to identify the risk of concomitant glenohumeral pathologies with acromioclavicular joint injuries grade III and V. Patients who underwent arthroscopically-assisted stabilization of acromioclavicular joint injuries grade III or grade V between 01/2007 and 12/2015 were identified in the patient databases of two surgical centres. Gender, age at index surgery, grade of acromioclavicular joint injury (Rockwood III or Rockwood V), and duration between injury and index surgery (classified as acute or chronic) were of interest. Concomitant glenohumeral pathologies were noted and their treatment was classified as debridement or reconstructive procedure. A total of 376 patients (336 male, 40 female) were included. Mean age at time of arthroscopic acromioclavicular joint reconstruction surgery was 42.1 ± 14.0 years. Overall, 201 patients (53%) had one or more concomitant glenohumeral pathologies. Lesions of the biceps tendon complex and rotator cuff were the most common. Forty-five patients (12.0%) had concomitant glenohumeral pathologies that required an additional repair. The remaining 156 patients (41.5%) received a debridement of their concomitant pathologies. Rockwood grade V compared to Rockwood grade III (p = 0.013; odds ratio 1.7), and chronic compared to acute injury were significantly associated with having a concomitant glenohumeral pathology (p = 0.019; odds ratio 1.7). The probability of having a concomitant glenohumeral pathology was also significantly associated with increasing age (p acromioclavicular joint injury of either grade III or V. Twenty-two percent of these patients with concomitant glenohumeral pathologies received an additional dedicated repair procedure. Although a significant difference in occurrence of concomitant glenohumeral pathologies was seen between Rockwood grades III and V, and between acute and chronic lesions, increasing age was identified as the most dominant predictor. Level IV, case series.

  20. Diagnosis and control for treatment of chronic arthritis and arthrosis of temporomandibular joint

    International Nuclear Information System (INIS)

    Ukrainskij, S.A.; Mirza, V.I.; Romanova, L.R.

    1991-01-01

    A study was made of anatomy and functions of temperomandibular joint in age aspect in patients with chronic arthritis and arthrosis using comprehensive clinicoroentgenological investigations. Such methods as X-ray examination, electromyography and diplography were important. The verification of results of treatment was also conducted on the base of clinicoroentgenological methods. It was shown that it was expedient to individual approach to treatment of petints with arthritis and arthrosis taking into account age-associated features

  1. Effects of joint mobilization on chronic ankle instability: a randomized controlled trial.

    Science.gov (United States)

    Cruz-Díaz, David; Lomas Vega, Rafael; Osuna-Pérez, Maria Catalina; Hita-Contreras, Fidel; Martínez-Amat, Antonio

    2015-01-01

    To evaluate the effects of joint mobilization, in which movement is applied to the ankle's dorsiflexion range of motion, on dynamic postural control and on the self-reported instability of patients with chronic ankle instability (CAI). A double-blind, placebo-controlled, randomized trial with repeated measures and a follow-up period. Ninety patients with a history of recurrent ankle sprain, self-reported instability, and a limited dorsiflexion range of motion, were randomly assigned to either the intervention group (Joint Mobilizations, 3 weeks, two sessions per week) the placebo group (Sham Mobilizations, same duration as joint mobilization) or the control group, with a 6 months follow-up. Dorsiflexion Range of Motion (DFROM), Star Excursion Balance Test (SEBT) and CAI Tool (CAIT) were outcome measures. A separate 3 × 4 mixed model analysis of variance was performed to examine the effect of treatment conditions and time, and intention-to-treat (ITT) analysis was applied to evaluate the effect of the independent variable. The application of joint mobilization resulted in better scores of DFROM, CAIT, and SEBTs in the intervention group when compared with the placebo or the control groups (p ankle DFROM, postural control, and self-reported instability. These results suggest that joint mobilization could be applied to patients with recurrent ankle sprain to help restore their functional stability. Implications for Rehabilitation Functional instability is a very common sequela in patients with CAI, resulting in reduced quality of living due to the limitations it imposes on daily life activities. The mobilization with movement technique presented by Mulligan, and based on the joint mobilization accompanied by active movement, appears as a valuable tool to be employed by physical therapists to restore ankle function after a recurrent ankle sprain history. ROM restriction, subjective feeling of instability and dynamic postural control are benefiting from the joint

  2. EFFICACY OF MULLIGAN MOBILIZATION VERSUS MUSCLE ENERGY TECHNIQUE IN CHRONIC SACROILIAC JOINT DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    Sabah Mohammed Easa Alkady

    2017-10-01

    Full Text Available Background: Sacroiliac joint dysfunction represents 15% of low back pain conditions. Normal sacroiliac joint works as a safeguard and transmits upper body weight into the pelvis and lower extremities. If the SIJ is hypomobile, it cannot effectively absorb forces and other body parts may be overstressed causing musculoskeletal dysfunction. The study conducted by comparing the effectiveness of Mulligan mobilization versus muscle energy technique in chronic SIJ dysfunction. Methods: 45 patients with chronic sacroiliac joint dysfunction from both genders joined the study. They were divided into three groups 15 in each group. Group A: received Mulligan mobilization with movement using posterior and anterior innominate methods plus conventional treatment program. Group B: received muscle energy technique using a post-isometric relaxation technique to erector spinae, hamstrings, iliopsoas and quadratus lumborum plus conventional treatment program. Group C: control group obtained conventional treatment program only. Doppler imaging of vibration, palpation meter, and the visual analogue scale was utilized for evaluating patients (pre and post-treatment. Results: The study findings revealed a statistical remarkable improvement in post-intervention values for sacroiliac mobility in Mulligan mobilization group (p > 0.0001 and a statistically significant decrease of anterior pelvic tilting angle in Mulligan mobilization and muscle energy technique groups (p > 0.0001, also a significant decrease of pain in the 3 groups compared with pre-intervention values (p > 0.0001, additionally, Mulligan mobilization group showed a statistical high detectable difference in right and left sacroiliac mobility more than muscle energy technique and control groups (p > 0.0001. Conclusion: Mulligan mobilization is more effective than muscle energy technique in the treatment of chronic sacroiliac joint dysfunction.

  3. Management of chronic ankle pain using joint mobilization and ASTYM® treatment: a case report.

    Science.gov (United States)

    Slaven, Emily J; Mathers, Jessie

    2011-05-01

    Treatment of ankle sprains predominately focuses on the acute management of this condition; less emphasis is placed on the treatment of ankle sprains in the chronic phase of recovery. Manual therapy, in the form of joint mobilization and manipulation, has been shown to be effective in the management of this condition, but the combination of joint mobilization and manipulation in tandem with ASTYM® treatment has not been explored. The purpose of this case report is to chronicle the management of a patient with chronic ankle pain who was treated with manual therapy including manipulation and ASTYM treatment. As a result of a fall down stairs 6 months previously, the patient sustained a severe ankle sprain. The soft tissue damage was accompanied by bony disruptions which warranted the patient spending 3 weeks in a walking boot. At the initial evaluation, the patient reported difficulty with descending stairs reciprocally and not being able to run more than 4 minutes on the treadmill before the pain escalated to the level that she had to stop running. After five sessions of therapy consisting of joint mobilization, manipulation and ASTYM, the patient was able to descend stairs and run 40 minutes without pain.

  4. Productivity benefits of minimally invasive surgery in patients with chronic sacroiliac joint dysfunction

    Directory of Open Access Journals (Sweden)

    Saavoss JD

    2016-04-01

    Full Text Available Josh D Saavoss,1 Lane Koenig,1 Daniel J Cher2 1KNG Health Consulting, LLC, Rockville, MD, 2SI-BONE, Inc., San Jose, CA, USA Introduction: Sacroiliac joint (SIJ dysfunction is associated with a marked decrease in quality of life. Increasing evidence supports minimally invasive SIJ fusion as a safe and effective procedure for the treatment of chronic SIJ dysfunction. The impact of SIJ fusion on worker productivity is not known. Methods: Regression modeling using data from the National Health Interview Survey was applied to determine the relationship between responses to selected interview questions related to function and economic outcomes. Regression coefficients were then applied to prospectively collected, individual patient data in a randomized trial of SIJ fusion (INSITE, NCT01681004 to estimate expected differences in economic outcomes across treatments. Results: Patients who receive SIJ fusion using iFuse Implant System® have an expected increase in the probability of working of 16% (95% confidence interval [CI] 11%–21% relative to nonsurgical patients. The expected change in earnings across groups was US $3,128 (not statistically significant. Combining the two metrics, the annual increase in worker productivity given surgical vs nonsurgical care was $6,924 (95% CI $1,890–$11,945. Conclusion: For employees with chronic, severe SIJ dysfunction, minimally invasive SIJ fusion may improve worker productivity compared to nonsurgical treatment. Keywords: sacroiliac joint fusion, low back pain, sacroiliac joint pain, clinical trial, health care costs, indirect costs

  5. Chronic vitamin C administration induces thermal hyperalgesia in ...

    African Journals Online (AJOL)

    Against a backdrop of neurological effects, the effects of acute and chronic administration of vitamin C (600mg/kg) on pain processing were investigated in male rats. Chronic administration of vitamin C induced significant thermal hyperalgesia while acute administration had no effect. In addition, the intraperitoneal ...

  6. Lower extremity joint coupling variability during gait in young adults with and without chronic ankle instability.

    Science.gov (United States)

    Lilley, Thomas; Herb, Christopher C; Hart, Joseph; Hertel, Jay

    2018-06-01

    Chronic ankle instability (CAI) is a condition resulting from a lateral ankle sprain. Shank-rearfoot joint-coupling variability differences have been found in CAI patients; however, joint-coupling variability (VCV) of the ankle and proximal joints has not been explored. Our purpose was to analyse VCV in adults with and without CAI during gait. Four joint-coupling pairs were analysed: knee sagittal-ankle sagittal, knee sagittal-ankle frontal, hip frontal-ankle sagittal and hip frontal-ankle frontal. Twenty-seven adults participated (CAI:n = 13, Control:n = 14). Lower extremity kinematics were collected during walking (4.83 km/h) and jogging (9.66 km/h). Vector-coding was used to assess the stride-to-stride variability of four coupling pairs. During walking, CAI patients exhibited higher VCV than healthy controls for knee sagittal-ankle frontal in latter parts of stance thru mid-swing. When jogging, CAI patients demonstrated lower VCV with specific differences occurring across various intervals of gait. The increased knee sagittal-ankle frontal VCV in CAI patients during walking may indicate an adaptation to deal with the previously identified decrease in variability in transverse plane shank and frontal plane rearfoot coupling during walking; while the decreased ankle-knee and ankle-hip VCV identified in CAI patients during jogging may represent a more rigid, less adaptable sensorimotor system ambulating at a faster speed.

  7. Chronic arthritis of the hip joint: an unusual complication of an inadequately treated fistula-in-ano

    Science.gov (United States)

    Raghunath, Rajat; Varghese, Gigi; Simon, Betty

    2014-01-01

    We report a case of chronic arthritis of the right hip joint in an otherwise healthy young male athlete as a complication of inadequately treated anal fistula. A young male athlete presented with symptoms of right hip pain and difficulty in walking and intermittent fever for 2 months. He had a history of perianal abscess drainage. On examination he was found to have a tender right hip joint with severe restriction of movements. He was also found to have a partially drained right ischiorectal abscess. X-ray and MRI of the hip joint revealed chronic arthritis of the right hip joint, which was communicating with a complex fistula-in-ano. He underwent a diversion sigmoid colostomy and right ischiorectal abscess drainage along with appropriate antibiotics with a plan for definitive hip joint procedure later. He was lost to follow-up and succumbed to severe perianal sepsis within a few months. PMID:25414226

  8. Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

    International Nuclear Information System (INIS)

    Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang; Huang, Changjiang; Yang, Dongren

    2016-01-01

    Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

  9. Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Yang, Dongren, E-mail: yangdongren@yahoo.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China)

    2016-07-15

    Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

  10. Management of Chronic Recurrent Dislocation of Temporomandibular Joint Using 'U' Shaped Graft: A New Restrictive Technique.

    Science.gov (United States)

    Gadre, Kiran; Singh, Divya; Gadre, Pushkar; Halli, Rajshekhar

    2017-06-01

    Numerous procedures have been described for the treatment of chronic recurrent dislocation of the temporo-mandibular joint (TMJ), either in the form of enhancement or restriction of the condylar movement, with their obvious merits and demerits. We present a new technique of using U shaped iliac bone graft to restrict the condylar movement and its advantages over the conventional techniques.We have used this technique successfully in 8 cases where Dautrey's procedure had failed with follow up period of 2 years. No patient complained of recurrent dislocation postoperatively. This a very simple and effective technique where other procedures have failed.

  11. Assessment of Relationships Between Joint Motion Quality and Postural Control in Patients With Chronic Ankle Joint Instability.

    Science.gov (United States)

    Bączkowicz, Dawid; Falkowski, Krzysztof; Majorczyk, Edyta

    2017-08-01

    Study Design Controlled laboratory study, cross-sectional. Background Lateral ankle sprains are among the most common injuries encountered during athletic participation. Following the initial injury, there is an alarmingly high risk of reinjury and development of chronic ankle instability (CAI), which is dependent on a combination of factors, including sensorimotor deficits and changes in the biomechanical environment of the ankle joint. Objective To evaluate CAI-related disturbances in arthrokinematic motion quality and postural control and the relationships between them. Methods Sixty-three male subjects (31 with CAI and 32 healthy controls) were enrolled in the study. For arthrokinematic motion quality analysis, the vibroarthrographic signals were collected during ankle flexion/extension motion using an acceleration sensor and described by variability (variance of mean squares [VMS]), amplitude (mean of 4 maximal and 4 minimal values [R4]), and frequency (vibroarthrographic signal bands of 50 to 250 Hz [P1] and 250 to 450 Hz [P2]) parameters. Using the Biodex Balance System, single-leg dynamic balance was measured by overall, anteroposterior, and mediolateral stability indices. Results Values of vibroarthrographic parameters (VMS, R4, P1 and P2) were significantly higher in the CAI group than those in the control group (Pankle arthrokinematic motion and postural control were present. Therefore, physical therapy interventions focused on improving ankle neuromuscular control and arthrokinematic function are necessary in CAI patient care. J Orthop Sports Phys Ther 2017;47(8):570-577. Epub 4 Nov 2016. doi:10.2519/jospt.2017.6836.

  12. Synovial Calprotectin: An Inexpensive Biomarker to Exclude a Chronic Prosthetic Joint Infection.

    Science.gov (United States)

    Wouthuyzen-Bakker, Marjan; Ploegmakers, Joris J W; Ottink, Karsten; Kampinga, Greetje A; Wagenmakers-Huizenga, Lucie; Jutte, Paul C; Kobold, Anneke C M

    2018-04-01

    To diagnose or exclude a chronic prosthetic joint infection (PJI) can be a clinical challenge. Therefore, sensitive and specific biomarkers are needed in the diagnostic work-up. Calprotectin is a protein with antimicrobial properties and is released by activated neutrophils, making it a specific marker for infection. Because of its low costs and ability to obtain a quantitative value as a point of care test, it is an attractive marker to use in clinical practice. In addition, the test is already used in routine care in most hospitals for other indications and therefore easy to implement. Between June 2015 and June 2017 we collected synovial fluid of all consecutive patients who underwent revision surgery of a prosthetic joint because of chronic pain with or without prosthetic loosening. Synovial calprotectin was measured using a lateral flow immunoassay. A PJI was defined by the diagnostic criteria described by the Musculoskeletal Infection Society. Fifty-two patients with chronic pain were included. A PJI was diagnosed in 15 of 52 (29%) patients. The median calprotectin in the PJI group was 859 mg/L (interquartile range 86-1707) vs 7 mg/L (interquartile range 3-25) in the control group (P < .001). With a cut-off value of 50 mg/L, synovial calprotectin showed a sensitivity, specificity, positive predictive value, and negative predictive value of 86.7%, 91.7%, 81.3%, and 94.4%, respectively. Synovial calprotectin is a useful and cheap biomarker to use in the diagnostic work-up of patients with chronic pain, especially to exclude a PJI prior to revision surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Audit of conservative management of chronic low back pain in a secondary care setting--part I: facet joint and sacroiliac joint interventions.

    Science.gov (United States)

    Chakraverty, Robin; Dias, Richard

    2004-12-01

    The work of a chronic back pain service in secondary care in the West Midlands is reported. The service offers acupuncture, spinal injection procedures, osteopathy and a range of other interventions for patients whose back pain has not responded to conservative management. This section of the report focuses on injection procedures for lumbar facet joint and sacroiliac joint pain, which have been shown to be the cause of chronic low back pain in 16-40% and 13-19% of patients respectively. Diagnosis relies on the use of intra-articular or sensory nerve block injections with local anaesthetic. Possible treatments following diagnosis include intra-articular corticosteroid, radiofrequency denervation (for facet joint pain) or ligament prolotherapy injections (for sacroiliac joint pain). The results of several hospital audits are reported. At six month follow up, 50% of 38 patients undergoing radiofrequency denervation following diagnostic blocks for facet joint pain had improved by more than 50%, compared to 29% of 34 patients treated with intra-articular corticosteroid injection. Sixty three per cent of 19 patients undergoing prolotherapy following diagnostic block injection for sacroiliac joint pain had improved at six months, compared to 33% of 33 who had intra-articular corticosteroid. Both radiofrequency denervation and sacroiliac prolotherapy showed good long-term outcomes at one year.

  14. Incidence of Infection and Inhospital Mortality in Patients With Chronic Renal Failure After Total Joint Arthroplasty.

    Science.gov (United States)

    Erkocak, Omer F; Yoo, Joanne Y; Restrepo, Camilo; Maltenfort, Mitchell G; Parvizi, Javad

    2016-11-01

    Patients with chronic renal failure (CRF) may require total joint arthroplasty (TJA) to treat degenerative joint disease, fractures, osteonecrosis, or amyloid arthropathy. There have been conflicting results, however, regarding outcomes of TJA in patients with chronic renal disease. The aim of this case-controlled study was to determine the outcome of TJA in patients with CRF, with particular interest in the incidence of infections and inhospital mortality. We queried our electronic database to determine which patients among the 29,389 TJAs performed at our institution between January 2000 and June 2012 had a diagnosis of CRF. A total of 359 CRF patients were identified and matched for procedure, gender, age (±4 years), date of surgery (±2 years), and body mass index (±5 kg/m 2 ) in a 2:1 ratio to 718 control patients. The incidence of infection and inhospital mortality was not significantly different between the nondialysis CRF patients and controls, whereas it was significantly higher in dialysis-dependent end-stage renal failure patients compared to controls. Of the 50 CRF patients receiving hemodialysis, 10 (20%) developed surgical site infection, of which 4 (8%) were periprosthetic joint infection, and 4 (8%) died during hospital stay. The odds ratio for infection in the dialysis group was 7.54 (95% confidence interval: 2.83-20.12) and 10.46 (95% confidence interval: 1.67-65.34) for the inhospital mortality. We conclude that end-stage renal failure patients receiving hemodialysis have higher postoperative infection and inhospital mortality rates after an elective TJA procedure, whereas nondialysis CRF patients have similar outcomes compared with the general TJA population. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Influence of chronic neck pain on cervical joint position error (JPE): Comparison between young and elderly subjects.

    Science.gov (United States)

    Alahmari, Khalid A; Reddy, Ravi Shankar; Silvian, Paul; Ahmad, Irshad; Nagaraj, Venkat; Mahtab, Mohammad

    2017-11-06

    Evaluation of cervical joint position sense in subjects with chronic neck pain has gained importance in recent times. Different authors have established increased joint position error (JPE) in subjects with acute neck pain. However, there is a paucity of studies to establish the influence of chronic neck pain on cervical JPE. The objective of the study was to understand the influence of chronic neck pain on cervical JPE, and to examine the differences in cervical JPE between young and elderly subjects with chronic neck pain. Forty-two chronic neck pain patients (mean age 47.4) were compared for cervical JPE with 42 age-matched healthy subjects (mean age 47.8), using a digital inclinometer. The cervical JPE were measured in flexion, extension, and rotation in right and left movement directions. The comparison of JPE showed significantly larger errors in subjects with chronic neck pain when compared to healthy subjects (ppain revealed no significant differences (P> 0.05) in cervical JPE. Cervical joint position sense is impaired in subjects with chronic neck pain.

  16. Chronic suppurative joint effusion due to burkholderia pseudomallei: A case report

    Directory of Open Access Journals (Sweden)

    Madhavi Deshmukh

    2013-01-01

    Full Text Available Burkholderia pseudomallei, a Gram-negative bacillus is the causative agent of Melioidosis, a glanders-like disease, primarily a disease of animals. Melioidosis has been only a rare and sporadic disease in humans outside its endemic region. Currently, diagnosis of B. pseudomallei in the clinical laboratory is very difficult, owing to low awareness of physicians to the nonspecific clinical manifestations, lack of responsiveness among microbiologists outside endemic areas, identification systems in the average sentinel laboratory, and the biosafety conditions necessary to process these organisms. We report a case of chronic left hip joint effusion in a known case of diabetes mellitus. Gram stain of computed tomography (CT-guided aspirate from the joint revealed Gram-negative bacilli along with pus cells. Culture was confirmed as Burkholderia pseudomallei on Vitek2C, which was sensitive to ceftazidime and trimethoprim/sulfmethoxazole. Unfortunately, patient could not be started on appropriate antibiotics due to delay in detection and patient succumbed to severe septicemia. This case is reported to highlight importance of automated identification and sensitivity especially in nonendemic areas and unusual antibiogram of this organism for which disc diffusion method is not standardized.

  17. CT evaluation of chronic hip joint diseases: avascular necrosis vs. osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Myeong Jin; Suh, Jin Seok; Lee, Jong Doo; Park, Chang Yoon [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1988-12-15

    Computed tomography (CT) of the hip was done on 37 patients those who have been suffered from chronic hip joint pain. There were 18 patients of avascular necrosis of hip (AVN), 67% of whom were affected bilaterally, 15 patients of degenerative arthritis (DA), 33% bilaterally; one patient of tuberculous arthritis, rheumatoid arthritis and traumatic arthritis respectively. Comparison of the staging by means of the CT and plain film showed good correlation between the two methods. The CT findings of the AVN and OA were also compared; crescent sign or fissure, loss of congruity, and loss or change of normal asterisk sign were more commonly seen in AVN. Acetabular change especially associated cystic appearance, osteophytes formation and joint narrowing were more frequent in OA. CT showed primary and secondary change of AVN and OA more clearly without confusion than plain film. We think that CT can be helpful in evaluation and understanding of each disease process and differentiation of the two lesions in difficult case000.

  18. CT evaluation of chronic hip joint diseases: avascular necrosis vs. osteoarthritis

    International Nuclear Information System (INIS)

    Kim, Myeong Jin; Suh, Jin Seok; Lee, Jong Doo; Park, Chang Yoon

    1988-01-01

    Computed tomography (CT) of the hip was done on 37 patients those who have been suffered from chronic hip joint pain. There were 18 patients of avascular necrosis of hip (AVN), 67% of whom were affected bilaterally, 15 patients of degenerative arthritis (DA), 33% bilaterally; one patient of tuberculous arthritis, rheumatoid arthritis and traumatic arthritis respectively. Comparison of the staging by means of the CT and plain film showed good correlation between the two methods. The CT findings of the AVN and OA were also compared; crescent sign or fissure, loss of congruity, and loss or change of normal asterisk sign were more commonly seen in AVN. Acetabular change especially associated cystic appearance, osteophytes formation and joint narrowing were more frequent in OA. CT showed primary and secondary change of AVN and OA more clearly without confusion than plain film. We think that CT can be helpful in evaluation and understanding of each disease process and differentiation of the two lesions in difficult cases.

  19. Passive accessory joint mobilization in the multimodal management of chronic dysesthesia following thalamic stroke.

    Science.gov (United States)

    Griffin, Kristina; O'Hearn, Michael; Franck, Carla C; Courtney, Carol A

    2018-03-20

    Case Report. Stroke is the most common cause of long-term disability. Dysesthesia, an unpleasant sensory disturbance, is common following thalamic stroke and evidence-based interventions for this impairment are limited. The purpose of this case report was to describe a decrease in dysesthesia following manual therapy intervention in a patient with history of right lacunar thalamic stroke. A 66-year-old female presented with tingling and dysesthesia in left hemisensory distribution including left trunk and upper/lower extremities, limiting function. Decreased left shoulder active range of motion, positive sensory symptoms but no sensory loss in light touch was found. She denied pain and moderate shoulder muscular weakness was demonstrated. Laterality testing revealed right/left limb discrimination deficits and neglect-like symptoms were reported. Passive accessory joint motion assessment of glenohumeral and thoracic spine revealed hypomobility and provoked dysesthesia. Interventions included passive oscillatory joint mobilization of glenohumeral joint, thoracic spine, ribs and shoulder strengthening. After six sessions, shoulder function, active range of motion, strength improved and dysesthesia decreased. Global Rating of Change Scale was +5 and QuickDASH score decreased from 45% to 22% disability. Laterality testing was unchanged. Manual therapy may be a beneficial intervention in management of thalamic stroke-related dysesthesia. Implications for Rehabilitation While pain is common following thalamic stroke, patients may present with chronic paresthesia or dysesthesia, often in a hemisensory distribution. Passive movement may promote inhibition of hyperexcitable cortical pathways, which may diminish aberrant sensations. Passive oscillatory manual therapy may be an effective way to treat sensory disturbances such as paresthesias or dysesthesia.

  20. Protection of Chinese herbs against Adenine-induced chronic renal ...

    African Journals Online (AJOL)

    The aim of the study is to evaluate the efficacy of Chinese herbs (Angelica sinensis, Ligusticum wallichii, Salvia miltiorrhiza, Rhizoma dioscoreae, Rhodiola crenilata, Astragalus membranaceus and Angelica sinensis) on adenine-induced chronic renal failure in rats. 30 age-matched male Wistar rats were divided into three ...

  1. Narcolepsy induced by chronic heavy alcohol consumption: a case report

    Science.gov (United States)

    Wang, Xinyuan

    2012-01-01

    Summary Narcolepsy is a chronic neurological disorder, characterized by uncontrollable excessive daytime sleepiness, cataplectic episodes, sleep paralysis, hypnagogic hallucinations, and night time sleep disruption. The paper reviewed the related literature and reported a case of long-term drinking induced narcolepsy which was significantly improved after treatment with paroxetine and dexzopiclone. PMID:25328357

  2. Efficacy of Radiation Synovectomy with Y-90 in chronic knee joint synovitis

    International Nuclear Information System (INIS)

    Roiz, C.; Raigoso, P.; Suarez, J.P.; Llana, B.; Zeidan, N.; Dominguez, M.L.; Bernardo, L.; Fernandez, J.A.; Nunez, R.

    2002-01-01

    Aim: To evaluate the efficiency of Radiation Synovectomy (RSO) with Y-90 in knee joints of patients with chronic synovitis (CS) resistant to classical conventional therapy, and assess its long-term prognosis. Material and Methods: 22 patients (7 males,15 females, mean age 50, range 12-81) with CS of the knees, of a duration ranging from 2 to 48 years, were included in the study. All patients had suffered from CS for more than 6 months, and were resistant to anti-inflammatory drugs, immunosuppressants and intraarticular (IA) steroid therapy. The cases included:10 patients with rheumatoid arthritis (RA), 5 psoriatic arthritis (PA), 3 pigmented villonodular synovitis, 2 seronegative oligo-polyarthritis and 2 chronic mono arthritis. We used an IA dose of 3 to 5 mCi (37-185 MBq)of Y-90. The effect of the therapy with Y-90 on 22 knees was evaluated from 3 to 12 months after the RSO. Patients' response was assess and classified according to the results of plain radiology and following conventional rheumatological criteria as: A) Excellent (E) with a visual improvement (VI) of 80-100mm, no pain in motion, little or no palpable swelling, no inflammation; B) Good (G) VI of 60-90mm, minimal pain in motion, little palpable swelling; C) Mild (M) VI of 20-59mm, moderate reduction of pain, obvious swelling; D) Bad (B) VI of only 0-19 mm, no changes or an increase of pain in the swollen joints. Results: The response observed was classified as: E in 5 patients (23%); G in 10 patients (45%); M in 3 patients (14%); and B in 4(18%). The 4 patients with a response B, had all of them joint erosion on plain radiology. Furthermore, one of the patients was a failure from prior surgical synovectomy (SS). The other 3 patients subsequently had SS. In contrast, all the responses E and G were obtained exclusively in patients with RA or PA. No short or long-term adverse side effects were noted. Conclusion: RSO is an effective treatment for patients with persistent CS, specially in RA and PA. The

  3. THERAPEUTIC EFFECTS OF ELECTROACUPUNCTURE PLUS POINT-PENETRATION FOR CHRONIC ANKLE JOINT SPRAIN

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yi-zao

    2005-01-01

    Objective: To observe clinical therapeutic effects of electroacupuncture plus point-penetration for chronic ankle joint sprain. Methods: 76 patients were randomly divided into treatment group (n=43) and control group (n=33).In teatment group, penetration needling from Qiuxu (丘墟 GB 40) to Zhaohai (照海 KI 6) was performed, combined with electrical stimulation for 30 min. Patients of control group were ordered to take Antinfan (50 mg,b.I.d.),supplemented with local external application of Votalin cream (b.I.d.).After 14 treatments (two courses), the therapeutic effect was assessed. Results: Following two courses of treatment, of the 43 cases and 33 cases in treatment and control groups,33 (76.7%) and 15 (45.5%) were cured, 4 (9.3%) and 7 (21.2%) had marked improvement in their symptoms, 3 (7.0%) and 2 (6.1%) had improvement, and 3 (7.0%) and 9(27.3%) failed, with the effective rates being 93.0% and 72.7% respectively. The therapeutic effect of treatment group was significantly superior to that of control group (P<0.05). Conclusion: Penetrative needling plus EA is significantly superior to medication in relieving chronic ankle spain patient's clinical symptoms and signs.

  4. Productivity benefits of minimally invasive surgery in patients with chronic sacroiliac joint dysfunction.

    Science.gov (United States)

    Saavoss, Josh D; Koenig, Lane; Cher, Daniel J

    2016-01-01

    Sacroiliac joint (SIJ) dysfunction is associated with a marked decrease in quality of life. Increasing evidence supports minimally invasive SIJ fusion as a safe and effective procedure for the treatment of chronic SIJ dysfunction. The impact of SIJ fusion on worker productivity is not known. Regression modeling using data from the National Health Interview Survey was applied to determine the relationship between responses to selected interview questions related to function and economic outcomes. Regression coefficients were then applied to prospectively collected, individual patient data in a randomized trial of SIJ fusion (INSITE, NCT01681004) to estimate expected differences in economic outcomes across treatments. Patients who receive SIJ fusion using iFuse Implant System(®) have an expected increase in the probability of working of 16% (95% confidence interval [CI] 11%-21%) relative to nonsurgical patients. The expected change in earnings across groups was US $3,128 (not statistically significant). Combining the two metrics, the annual increase in worker productivity given surgical vs nonsurgical care was $6,924 (95% CI $1,890-$11,945). For employees with chronic, severe SIJ dysfunction, minimally invasive SIJ fusion may improve worker productivity compared to nonsurgical treatment.

  5. Separate and joint effects of physical and mental health on participation of people with somatic chronic illness.

    NARCIS (Netherlands)

    Jansen, D.L.; Rijken, M.

    2011-01-01

    Aim: To examine the extent to which people with a somatic chronic illness participate in paid jobs, volunteer work, informal care and social activities, and to investigate the separate and joint effects of physical and mental health on participation. Background. Compared with healthy people, people

  6. Chronic inorganic mercury induced peripheral neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Chu, C.-C.; Huang, C.-C.; Ryu, S.-J. [Chang Gung Memorial Hospital and Chang Gung University, Dept. of Neurology, Tapei (Taiwan, Province of China); Wu, T.-N. [Executive Yuan, Dept. of Health, Surveillance and Quarantine Service, Taipei (Taiwan, Province of China)

    1998-12-01

    We report the clinical features, electrophysiological studies, and morphometric analysis of sural nerve pathology in a patient with polyneuropathy due to inorganic mercury intoxication. He developed slowly progressive generalized paralysis of all limbs after 3 months ingestion of herb drugs which contained mercuric sulfate. Electrophysiologic studies revealed axonal polyneuropathy involving both motor and sensory fibers. Sural nerve biopsy demonstrated axonal degeneration with demyelination and a predominant loss of large myelinated fibers. His muscle strength showed only mild improvement after 2 years` follow-up. We concluded that inorganic mercury exposure may induce severe axonal sensorimotor polyneuropathy in humans and that neurological deficits may persist in severe cases. (au) 21 refs.

  7. Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

    Directory of Open Access Journals (Sweden)

    Beverley Greenwood-Van Meerveld

    2017-11-01

    Full Text Available Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS. Early life stress (ELS is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for

  8. Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

    Science.gov (United States)

    Greenwood-Van Meerveld, Beverley; Johnson, Anthony C.

    2017-01-01

    Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress-induced

  9. A 5-year Evaluation and Results of Treatment of Chronic Llocked Dislocations of the Shoulder Joint

    Directory of Open Access Journals (Sweden)

    Syawash Mirsaid Ghazi

    2008-11-01

    Full Text Available Background:Chronic neglected dislocation of the shoulder joint can be defined as a neglected dislocation for more than a 3 week period.However, it has been shown that the negligence could range from a 24 hour period to 6 months1. Depending on age,signs, symptoms,etiology and types of dislocation, conservative treatment or surgical intervention could be considered.Methods: In this study, 16 patients (13 were male and 3 were female were treated with chronic shoulder dislocations, 3 of which had bilateral dislocations. The age of this group ranged from 13-65 years with a mean age of 34 years. These patients were treated by closed or open reduction, either anterior, posterior or both approaches. Of 19 dislocations, 6 were anterior unilateral, 7 posterior unilateral, 1 anterior bilateral and 2 posterior bilateral dislocations. The mean period between dislocations and treatments was 3 months (from 4 weeks to 11 months,And the mean follow up period was 40 months (from 21 months to 5 years.Results: This study has shown that treatment varies according to pathology. In  this study the mean size of head defects was 35% and the extent of severity determined the approach. Findings at the last follow up were assessed according to Rowe and Zarins score and of the 19 shoulders assessed, 9 showed good and 10 showed excellent results. There was no recurrence of the dislocation in any patient.Conclusion:In some selected instances, open reduction of a chronic locked neglected shoulder dislocation of a 6 months period or more in young patients is recommended.This method is, however, contraindicated in elderly patients; in such cases a shoulder prosthesis is indicated.  

  10. Surgical versus injection treatment for injection-confirmed chronic sacroiliac joint pain

    Science.gov (United States)

    Spiker, William Ryan; Lawrence, Brandon D.; Raich, Annie L.; Skelly, Andrea C.; Brodke, Darrel S.

    2012-01-01

    Study design: Systematic review. Study rationale: Chronic sacroiliac joint pain (CSJP) is a common clinical entity with highly controversial treatment options. A recent systematic review compared surgery with denervation, but the current systematic review compares outcomes of surgical intervention with therapeutic injection for the treatment of CSJP and serves as the next step for evaluating current evidence on the comparative effectiveness of treatments for non-traumatic sacroiliac joint pain. Objective or clinical question: In adult patients with injection-confirmed CSJP, does surgical treatment lead to better outcomes and fewer complications than injection therapy? Methods: A systematic review of the English-language literature was undertaken for articles published between 1970 and June 2012. Electronic databases and reference lists of key articles were searched to identify studies evaluating surgery or injection treatment for injection-confirmed CSJP. Studies involving traumatic onset or non-injection–confirmed CSJP were excluded. Two independent reviewers assessed the level of evidence quality using the grading of recommendations assessment, development and evaluation (GRADE) system, and disagreements were resolved by consensus. Results: We identified twelve articles (seven surgical and five injection treatment) meeting our inclusion criteria. Regardless of the type of treatment, most studies reported over 40% improvement in pain as measured by Visual Analog Scale or Numeric rating Scale score. Regardless of the type of treatment, most studies reported over 20% improvement in functionality. Most complications were reported in the surgical studies. Conclusion: Surgical fusion and therapeutic injections can likely provide pain relief, improve quality of life, and improve work status. The comparative effectiveness of these interventions cannot be evaluated with the current literature. PMID:23526911

  11. Acute versus chronic alcohol consumption in acetaminophen-induced hepatotoxicity

    DEFF Research Database (Denmark)

    Schmidt, L.E.; Dalhoff, K.P.; Poulsen, Henrik E.

    2002-01-01

    . With a time to NAC less than 12 hours, the mortality rate was 0.42% (95% CI, 0.05-2.7). When time to NAC exceeded 12, 24, and 48 hours, the mortality rate increased to 6.1%, 13%, and 19%, respectively. Chronic alcohol abuse was an independent risk factor of mortality (odds ratio [OR], 3.52; 95% CI, 1...... was confirmed as the major risk factor in acetaminophen-induced hepatotoxicity and mortality. Chronic alcohol abuse was an independent risk factor that could be counteracted by concomitant acute alcohol ingestion. We suggest that patients with chronic alcoholism and suspected acetaminophen poisoning due......The aim of this study was to determine by multivariate analysis how alcohol and other factors affect the clinical course and outcome in patients with acetaminophen (paracetamol) poisoning. A total of 645 consecutive patients admitted from 1994 to 2000 with single-dose acetaminophen poisoning were...

  12. Clinical forms of chronic dust-induced bronchitis

    Energy Technology Data Exchange (ETDEWEB)

    Levin, A.I.; Blokhina, L.M.

    1984-08-01

    Clinical study of 837 coal miners with chronic dust-induced bronchitis reveals three different forms of the disease: emphysematous, asthmatic and infectious. From development of clinical manifestations different etiologies of the disease are apparent. In early stages, three different types of chronic dust-induced bronchitis (CDB) are clearly distinguishable. With progression of condition differences are obliterated. Formulation of a diagnosis must reflect the form of illness, stage of respiratory insufficiency and status of blood exchange. Discrimination of different varieties of CDB has significant practical value in determining tactics for treating patients. Emphysematous CDB is treated by improvement of draining function of bronchi and elimination of respiratory insufficiency by prescribing respiratory gymnastics, broncholytic preparations and oxygen therapy. Treatment of asthmatic form of CDB is directed at restoring disturbances of bronchial passability by use of broncholytics and expectorants. In inflammatory form of CDB in addition to restoring the draining function of the lungs, active antibacterial therapy is introduced. 5 references.

  13. Exercise-induced metacarpophalangeal joint adaptation in the Thoroughbred racehorse

    Science.gov (United States)

    Muir, P; Peterson, A L; Sample, S J; Scollay, M C; Markel, M D; Kalscheur, V L

    2008-01-01

    Repetitive bone injury and development of stress fracture is a common problem in humans and animals. The Thoroughbred racehorse is a model in which adaptive failure and associated development of stress fracture is common. We performed a histologic study of the distal end of the third metacarpal bone in two groups of horses: young Thoroughbreds that were actively racing (n = 10) and a group of non-athletic horses (n = 8). The purpose of this study was to determine whether development of articular microcracks was associated with specific alterations to subchondral plate osteocytes. Morphometric measurements were made in five regions of the joint surface: lateral condyle, lateral condylar groove, sagittal ridge, medial condylar groove, and medial condyle. The following variables were quantified: hyaline cartilage width; calcified cartilage width; the number of tidemarks; microcrack density at the articular surface; blood vessel density entering articular cartilage; the presence of atypical bone matrix in the subchondral plate; bone volume fraction; and osteocyte density. Adaptation of articular cartilage was similar in both groups of horses. Vascularization of articular cartilage was increased in the group of non-athletic horses. Microcracks, which typically had an oblique orientation to the joint surface, were co-localized with blood vessels, and resorption spaces. Microcracking was increased in the condylar grooves of athletic horses compared with the other joint regions and was also increased compared with the condylar groove regions of non-athletic horses. Coalescence of microcracks also led to development of an intracortical articular condylar stress fracture in some joints and targeted remodeling of affected subchondral plate. The subchondral plate of the condyles in athletic horses was sclerotic, and contained atypically stained bone matrix with increased numbers of osteocytes with atypical morphology. However, osteocyte numbers were not significantly different

  14. Prevalence of Chronic Periodontitis, Bruxism and Temporomandibular Joint Disorders in Patients with Fibromyalgia Syndrome

    Directory of Open Access Journals (Sweden)

    Hatice Balcı Yüce

    2017-04-01

    Full Text Available Objective: Chronic periodontitis is a world-wide infectious and inflammatory disease and may have a relationship with other inflammatory diseases such as fibromyalgia syndrome (FMS. The aim of this study was to determine whether the prevalence of periodontitis is increased in individuals with FMS or not. Materials and Methods: Sixty-four patients with FMS and 70 systemically healthy individuals were included in the present study. Fibromyalgia patients did not have any other systemically disease. All subjects had at least 20 functioning teeth and underwent detailed oral and radiographic examination, in addition, bruxism and temporomandibular joint (TMJ examinations were performed. All clinical attachment levels, plaque and gingival indices were recorded. Results: Fibromyalgia patients tend to have higher gingival index scores than healthy individuals. There was a significant difference in the presence of bruxism between the study groups (p0.05. Conclusion: We found that the prevalence of periodontitis was not changed in FMS patients but was increased in healthy subjects above age 45.

  15. The Effect of Joint Mobilization on Dynamic Postural Control in Patients With Chronic Ankle Instability: A Critically Appraised Topic.

    Science.gov (United States)

    Kosik, Kyle B; Gribble, Phillip A

    2018-01-01

    Clinical Scenario: Dorsiflexion range of motion is an important factor in the performance of the Star Excursion Balance Test (SEBT). While patients with chronic ankle instability (CAI) commonly experience decreased reach distances on the SEBT, ankle joint mobilization has been suggested to be an effective therapeutic intervention for targeting dorsiflexion range of motion. What is the evidence to support ankle joint mobilization for improving performance on the SEBT in patients with CAI? Summary of Key Findings: The literature was searched for articles examining the effects of ankle joint mobilization on scores of the SEBT. A total of 3 peer-reviewed articles were retrieved, 2 prospective individual cohort studies and 1 randomized controlled trial. Only 2 articles demonstrated favorable results following 6 sessions of ankle joint mobilization. Clinical Bottom Line: Despite the mixed results, the majority of the available evidence suggests that ankle joint mobilization improves dynamic postural control. Strength of Recommendation: In accordance with the Centre of Evidence Based Medicine, the inconsistent results and the limited high-quality studies indicate that there is level C evidence to support the use of ankle joint mobilization to improve performance on the SEBT in patients with CAI.

  16. Genetic susceptibility factors for alcohol-induced chronic pancreatitis.

    Science.gov (United States)

    Aghdassi, Ali A; Weiss, F Ulrich; Mayerle, Julia; Lerch, Markus M; Simon, Peter

    2015-07-01

    Chronic pancreatitis is a progressive inflammatory disease of the pancreas and frequently associated with immoderate alcohol consumption. Since only a small proportion of alcoholics eventually develop chronic pancreatitis genetic susceptibility factors have long been suspected to contribute to the pathogenesis of the disease. Smaller studies in ethnically defined populations have found that not only polymorphism in proteins involved in the metabolism of ethanol, such as Alcohol Dehydrogenase and Aldehyde Dehydrogenase, can confer a risk for developing chronic pancreatitis but also mutations that had previously been reported in association with idiopathic pancreatitis, such as SPINK1 mutations. In a much broader approach employing genome wide search strategies the NAPS study found that polymorphisms in the Trypsin locus (PRSS1 rs10273639), and the Claudin 2 locus (CLDN2-RIPPLY1-MORC4 locus rs7057398 and rs12688220) confer an increased risk of developing alcohol-induced pancreatitis. These results from North America have now been confirmed by a European consortium. In another genome wide approach polymorphisms in the genes encoding Fucosyltransferase 2 (FUT2) non-secretor status and blood group B were not only found in association with higher serum lipase levels in healthy volunteers but also to more than double the risk for developing alcohol-associated chronic pancreatitis. These novel genetic associations will allow to investigate the pathophysiological and biochemical basis of alcohol-induced chronic pancreatitis on a cellular level and in much more detail than previously possible. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  17. Chronic Pain in Children and Adolescents: Diagnosis and Treatment of Primary Pain Disorders in Head, Abdomen, Muscles and Joints

    Directory of Open Access Journals (Sweden)

    Stefan J. Friedrichsdorf

    2016-12-01

    Full Text Available Primary pain disorders (formerly “functional pain syndromes” are common, under-diagnosed and under-treated in children and teenagers. This manuscript reviews key aspects which support understanding the development of pediatric chronic pain, points to the current pediatric chronic pain terminology, addresses effective treatment strategies, and discusses the evidence-based use of pharmacology. Common symptoms of an underlying pain vulnerability present in the three most common chronic pain disorders in pediatrics: primary headaches, centrally mediated abdominal pain syndromes, and/or chronic/recurrent musculoskeletal and joint pain. A significant number of children with repeated acute nociceptive pain episodes develop chronic pain in addition to or as a result of their underlying medical condition “chronic-on-acute pain.” We provide description of the structure and process of our interdisciplinary, rehabilitative pain clinic in Minneapolis, Minnesota, USA with accompanying data in the treatment of chronic pain symptoms that persist beyond the expected time of healing. An interdisciplinary approach combining (1 rehabilitation; (2 integrative medicine/active mind-body techniques; (3 psychology; and (4 normalizing daily school attendance, sports, social life and sleep will be presented. As a result of restored function, pain improves and commonly resolves. Opioids are not indicated for primary pain disorders, and other medications, with few exceptions, are usually not first-line therapy.

  18. Chronic Pain in Children and Adolescents: Diagnosis and Treatment of Primary Pain Disorders in Head, Abdomen, Muscles and Joints

    Science.gov (United States)

    Friedrichsdorf, Stefan J.; Giordano, James; Desai Dakoji, Kavita; Warmuth, Andrew; Daughtry, Cyndee; Schulz, Craig A.

    2016-01-01

    Primary pain disorders (formerly “functional pain syndromes”) are common, under-diagnosed and under-treated in children and teenagers. This manuscript reviews key aspects which support understanding the development of pediatric chronic pain, points to the current pediatric chronic pain terminology, addresses effective treatment strategies, and discusses the evidence-based use of pharmacology. Common symptoms of an underlying pain vulnerability present in the three most common chronic pain disorders in pediatrics: primary headaches, centrally mediated abdominal pain syndromes, and/or chronic/recurrent musculoskeletal and joint pain. A significant number of children with repeated acute nociceptive pain episodes develop chronic pain in addition to or as a result of their underlying medical condition “chronic-on-acute pain.” We provide description of the structure and process of our interdisciplinary, rehabilitative pain clinic in Minneapolis, Minnesota, USA with accompanying data in the treatment of chronic pain symptoms that persist beyond the expected time of healing. An interdisciplinary approach combining (1) rehabilitation; (2) integrative medicine/active mind-body techniques; (3) psychology; and (4) normalizing daily school attendance, sports, social life and sleep will be presented. As a result of restored function, pain improves and commonly resolves. Opioids are not indicated for primary pain disorders, and other medications, with few exceptions, are usually not first-line therapy. PMID:27973405

  19. Chronic Pain in Children and Adolescents: Diagnosis and Treatment of Primary Pain Disorders in Head, Abdomen, Muscles and Joints.

    Science.gov (United States)

    Friedrichsdorf, Stefan J; Giordano, James; Desai Dakoji, Kavita; Warmuth, Andrew; Daughtry, Cyndee; Schulz, Craig A

    2016-12-10

    Primary pain disorders (formerly "functional pain syndromes") are common, under-diagnosed and under-treated in children and teenagers. This manuscript reviews key aspects which support understanding the development of pediatric chronic pain, points to the current pediatric chronic pain terminology, addresses effective treatment strategies, and discusses the evidence-based use of pharmacology. Common symptoms of an underlying pain vulnerability present in the three most common chronic pain disorders in pediatrics: primary headaches, centrally mediated abdominal pain syndromes, and/or chronic/recurrent musculoskeletal and joint pain. A significant number of children with repeated acute nociceptive pain episodes develop chronic pain in addition to or as a result of their underlying medical condition "chronic-on-acute pain." We provide description of the structure and process of our interdisciplinary, rehabilitative pain clinic in Minneapolis, Minnesota, USA with accompanying data in the treatment of chronic pain symptoms that persist beyond the expected time of healing. An interdisciplinary approach combining (1) rehabilitation; (2) integrative medicine/active mind-body techniques; (3) psychology; and (4) normalizing daily school attendance, sports, social life and sleep will be presented. As a result of restored function, pain improves and commonly resolves. Opioids are not indicated for primary pain disorders, and other medications, with few exceptions, are usually not first-line therapy.

  20. Tyrosine kinase inhibitors induced immune thrombocytopenia in chronic myeloid leukemia?

    Directory of Open Access Journals (Sweden)

    Avital F. Barak

    2011-12-01

    Full Text Available The outcome and quality of life of chronic myeloid leukemia (CML patients has remarkably changed with the treatment of tyrosine kinase inhibitors (TKIs. Currently, hematopoietic stem cell transplantation (HSCT is considered mainly as a third line salvage therapy in cases of TKIs resistance or intolerance. Here we describe a patient with chronic phase CML who developed both resistance and late occurrence of s severe thrombocytopenia on first and second generation TKIs and eventually underwent HSCT. Although the mechanism of the myelosuppression is not fully understood, we showed for the first time the development of dose dependent platelet antibodies in the presence of TKIs, suggesting the possibility of TKIs induced thrombocytopenia. Our case emphasizes that late development of severe myelosuppression during imatinib treatment is probably an important indication for consideration of early HSCT.

  1. Effects of chronic sleep deprivation on the extracellular signal-regulated kinase pathway in the temporomandibular joint of rats.

    Directory of Open Access Journals (Sweden)

    Chuan Ma

    Full Text Available OBJECTIVES: To examine the possible involvement and regulatory mechanisms of extracellular signal-regulated kinase (ERK pathway in the temporomandibular joint (TMJ of rats subjected to chronic sleep deprivation (CSD. METHODS: Rats were subjected to CSD using the modified multiple platform method (MMPM. The serum levels of corticosterone (CORT and adrenocorticotropic hormone (ACTH were tested and histomorphology and ultrastructure of the TMJ were observed. The ERK and phospho-ERK (p-ERK expression levels were detected by Western blot analysis, and the MMP-1, MMP-3, and MMP-13 expression levels were detected by real-time quantitative polymerase chain reaction (PCR and Western blotting. RESULTS: The elevated serum CORT and ACTH levels confirmed that the rats were under CSD stress. Hematoxylin and eosin (HE staining and scanning electron microscopy (SEM showed pathological alterations in the TMJ following CSD; furthermore, the p-ERK was activated and the mRNA and protein expression levels of MMP-1, MMP-3, and MMP-13 were upregulated after CSD. In the rats administered with the selective ERK inhibitor U0126, decreased tissue destruction was observed. Phospho-ERK activation was visibly blocked and the MMP-1, MMP-3, and MMP-13 mRNA and protein levels were lower than the corresponding levels in the CSD without U0126 group. CONCLUSION: These findings indicate that CSD activates the ERK pathway and upregulates the MMP-1, MMP-3, and MMP-13 mRNA and protein levels in the TMJ of rats. Thus, CSD induces ERK pathway activation and causes pathological alterations in the TMJ. ERK may be associated with TMJ destruction by promoting the expression of MMPs.

  2. [Effect of tumour necrosis factor α blockade on bone metabolism in chronic inflammatory joint diseases].

    Science.gov (United States)

    Aguilar Del Rey, Francisco Javier; García Portales, Rosa; Haro Liger, Manuel; Rodríguez Andreu, José; Casals Sánchez, José Luis; Pérez González, Rita

    2016-07-15

    To evaluate the effect of anti-TNF treatments on bone mineral density (BMD), bone remodelling markers (BRM) and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) in patients with chronic inflammatory joint diseases. A longitudinal prospective study was performed under clinical practice conditions on 31 patients diagnosed of rheumatoid arthritis, psoriatic arthropathy and ankylosing spondylitis who had received treatment with anti-TNF alpha drugs for one year. BMD, OPG and RANKL soluble form (sRANKL) were studied at the onset and end of the study. During the study (0, 3, 6, 9 and 12 month), disease activity (SDAI, BASDAI and CRP), functional capacity (HAQ, BASFI), BRM and vitamin D were studied. BMD was not modified after one year of treatment. The patients who took corticosteroids had a mean bone mass loss of 3% in the lumbar spine (±1.6, P=.02). In regards to the BRM, did not experience significant changes over the course of the study. Disease activity, both SDAI (P=.002) and BASDAI (P=.002), decreased. OPG was maintained without changes during the year of treatment while both the sRANKL (0.28±0.22, P=.013) and sRANKL/OPG ratio significantly decreased (0.04±0.03, P=.031). The patients being treated with anti-TNF did not present with a significant loss of DMO during the study (one year), at the same time experiencing an improvement in disease activity. This protection has been clearer in the responding patients. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  3. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Herman, S E M; Niemann, C U; Farooqui, M

    2014-01-01

    Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further...... investigation. Here we report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes (LNs), spleen and bone marrow, assessed phenotypic changes of circulating cells and measured whole-blood viscosity. With just one dose of ibrutinib, the average...

  4. Psychometric properties including reliability, validity and responsiveness of the Majeed pelvic score in patients with chronic sacroiliac joint pain.

    Science.gov (United States)

    Bajada, Stefan; Mohanty, Khitish

    2016-06-01

    The Majeed scoring system is a disease-specific outcome measure that was originally designed to assess pelvic injuries. The aim of this study was to determine the psychometric properties of the Majeed scoring system for chronic sacroiliac joint pain. Internal consistency, content validity, criterion validity, construct validity and responsiveness to change was assessed prospectively for the Majeed scoring system in a cohort of 60 patients diagnosed with sacroiliac joint pain. This diagnosis was confirmed with CT-guided sacroiliac joint anaesthetic block. The overall Majeed score showed acceptable internal consistency (Cronbach alpha = 0.63). Similarly, it showed acceptable floor (0 %) and ceiling (0 %) effects. On the other hand, the domains of pain, work, sitting and sexual intercourse had high (>30 %) floor effects. Significant correlation with the physical component of the Short Form-36 (p = 0.005) and Oswestry disability index (p ≤ 0.001) was found indicating acceptable criterion validity. The overall Majeed score showed acceptable construct validity with all five developed hypotheses showing significance (p ≤ 0.05). The overall Majeed score showed acceptable responsiveness to change with a large (≥0.80) effect size and standardized response mean. Overall the Majeed scoring system demonstrated acceptable psychometric properties for outcome assessment in chronic sacroiliac joint pain. Thus, its use in this condition is adequate. However, some domains demonstrated suboptimal performance indicating that improvement might be achieved with the development of an outcome measure specific for sacroiliac joint dysfunction and degeneration.

  5. Inducing Assertive Behavior in Chronic Schizophrenics: A Comparison of Socioenvironmental Desensitization, and Relaxation Therapies

    Science.gov (United States)

    Weinman, Bernard; And Others

    1972-01-01

    It is concluded that systematic desensitization or relaxation therapy is not effective in inducing assertive behavior in the male chronic schizophrenic. The treatment of choice for the older chronic male schizophrenic remains socioenvironmental therapy. (Author)

  6. Chronic Intermittent Hypoxia Induces Chronic Low-Grade Neuroinflammation in the Dorsal Hippocampus of Mice.

    Science.gov (United States)

    Sapin, Emilie; Peyron, Christelle; Roche, Frédéric; Gay, Nadine; Carcenac, Carole; Savasta, Marc; Levy, Patrick; Dematteis, Maurice

    2015-10-01

    Obstructive sleep apnea (OSA) induces cognitive impairment that involves intermittent hypoxia (IH). Because OSA is recognized as a low-grade systemic inflammatory disease and only some patients develop cognitive deficits, we investigated whether IH-related brain consequences shared similar pathophysiology and required additional factors such as systemic inflammation to develop. Nine-week-old male C57BL/6J mice were exposed to 1 day, 6 or 24 w of IH (alternating 21-5% FiO2 every 30 sec, 8 h/day) or normoxia. Microglial changes were assessed in the functionally distinct dorsal (dH) and ventral (vH) regions of the hippocampus using Iba1 immunolabeling. Then the study concerned dH, as vH only tended to be lately affected. Seven proinflammatory and anti-inflammatory cytokine messenger RNA (mRNA) were assessed at all time points using semiquantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Similar mRNA analysis was performed after 6 w IH or normoxia associated for the past 3 w with repeated intraperitoneal low-dose lipopolysaccharide or saline. Chronic (6, 24 w) but not acute IH induced significant microglial changes in dH only, including increased density and morphological features of microglia priming. In dH, acute but not chronic IH increased IL-1β and RANTES/CCL5 mRNA, whereas the other cytokines remained unchanged. In contrast, chronic IH plus lipopolysaccharide increased interleukin (IL)-6 and IL10 mRNA whereas lipopolysaccharide alone did not affect these cytokines. The obstructive sleep apnea component intermittent hypoxia (IH) causes low-grade neuroinflammation in the dorsal hippocampus of mice, including early but transient cytokine elevations, delayed but long-term microglial changes, and cytokine response alterations to lipopolysaccharide inflammatory challenge. These changes may contribute to IH-induced cognitive impairment and pathological brain aging. © 2015 Associated Professional Sleep Societies, LLC.

  7. Joint immobilization inhibits spontaneous hyaline cartilage regeneration induced by a novel double-network gel implantation.

    Science.gov (United States)

    Arakaki, Kazunobu; Kitamura, Nobuto; Kurokawa, Takayuki; Onodera, Shin; Kanaya, Fuminori; Gong, Jian-Ping; Yasuda, Kazunori

    2011-02-01

    We have recently discovered that spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect in the rabbit, when we implant a novel double-network (DN) gel plug at the bottom of the defect. To clarify whether joint immobilization inhibits the spontaneous hyaline cartilage regeneration, we conducted this study with 20 rabbits. At 4 or 12 weeks after surgery, the defect in the mobile knees was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen, while no cartilage tissues were observed in the defect in the immobilized knees. Type-2 collagen, Aggrecan, and SOX9 mRNAs were expressed only in the mobile knees at each period. This study demonstrated that joint immobilization significantly inhibits the spontaneous hyaline cartilage regeneration induced by the DN gel implantation. This fact suggested that the mechanical environment is one of the significant factors to induce this phenomenon.

  8. Leakage flow-induced vibrations for variations of a tube-in-tube slip joint

    International Nuclear Information System (INIS)

    Mulcahy, T.M.

    1986-01-01

    Variations in the design of a specific slip joint separating two cantilevered, telescoping tubes conveying water were studied to determine their effect upon the leakage flow-induced vibration self-excitation mechanism known to exist for the original slip joint geometry. The important parameters controlling the self-excitation mechanism were identified, which, along with previous results, allowed the determination of a comprehensive set of design rules to avoid unstable vibrations. This was possible even though a new self-excitation mechanism was found when the engagement of the two tubes was small. 9 refs

  9. Chronic Inflammation and Neutrophil Activation as Possible Causes of Joint Diseases in Ballet Dancers

    Directory of Open Access Journals (Sweden)

    Leandro da Silva Borges

    2014-01-01

    Full Text Available Herein, we investigated the effects of a ballet class on the kinetic profiles of creatine kinase (CK and lactate dehydrogenase (LDH activities, cytokines, complement component 3 (C3, and the concentrations of immunoglobulin (Ig, IgA and IgM, in ballerinas. We also verified neutrophil death and ROS release. Blood samples were taken from 13 dancers before, immediately after, and 18 hours after a ballet class. The ballet class increased the plasma activities of CK-total (2.0-fold immediately after class, while the activities of CK-cardiac muscle (1.0-fold and LDH (3.0-fold were observed to increase 18 hours after the class. Levels of the TNF-α, IL-1β, IgG, and IgA were not affected under the study conditions. The exercise was found to induce neutrophil apoptosis (6.0-fold 18 hours after the ballet class. Additionally, immediately after the ballet class, the neutrophils from the ballerinas were found to be less responsive to PMA stimulus. Conclusion. Ballet class was found to result in inflammation in dancers. The inflammation caused by the ballet class remained for 18 hours after the exercise. These findings are important in preventing the development of chronic lesions that are commonly observed in dancers, such as those with arthritis and synovitis.

  10. Chronic inflammation and neutrophil activation as possible causes of joint diseases in ballet dancers.

    Science.gov (United States)

    Borges, Leandro da Silva; Bortolon, José Ricardo; Santos, Vinicius Coneglian; de Moura, Nivaldo Ribeiro; Dermargos, Alexandre; Cury-Boaventura, Maria Fernanda; Gorjão, Renata; Pithon-Curi, Tania Cristina; Hatanaka, Elaine

    2014-01-01

    Herein, we investigated the effects of a ballet class on the kinetic profiles of creatine kinase (CK) and lactate dehydrogenase (LDH) activities, cytokines, complement component 3 (C3), and the concentrations of immunoglobulin (Ig), IgA and IgM, in ballerinas. We also verified neutrophil death and ROS release. Blood samples were taken from 13 dancers before, immediately after, and 18 hours after a ballet class. The ballet class increased the plasma activities of CK-total (2.0-fold) immediately after class, while the activities of CK-cardiac muscle (1.0-fold) and LDH (3.0-fold) were observed to increase 18 hours after the class. Levels of the TNF-α , IL-1β, IgG, and IgA were not affected under the study conditions. The exercise was found to induce neutrophil apoptosis (6.0-fold) 18 hours after the ballet class. Additionally, immediately after the ballet class, the neutrophils from the ballerinas were found to be less responsive to PMA stimulus. Ballet class was found to result in inflammation in dancers. The inflammation caused by the ballet class remained for 18 hours after the exercise. These findings are important in preventing the development of chronic lesions that are commonly observed in dancers, such as those with arthritis and synovitis.

  11. Suprascapular block in the therapy of chronic pain in the shoulder and the shoulder joint: Suprascapular block

    Directory of Open Access Journals (Sweden)

    Palibrk Ivan

    2016-01-01

    Full Text Available Introduction: Chronic pain in the shoulder and the shoulder joint is a very common pathology in modern human population. The etiology of chronic pain is often unknown, although the trauma, degenerative diseases, inflammation, tumors and neurological disease appear as common etiologic factors. Patients with this pain had a significantly reduced quality of life.1,2 Method: During the two years, twelve patients diagnosed painful shoulder syndrome. Eleven of the twelve patients involved in the study had started physical therapy. Under the physical treatment pain intensity decreased, but not completely. Hand had reduced mobility. We applied a suprascapular block. We used 1 ml (7 mg betamethasone. Results: Suprascapular block was applied to the eleven patients in physical therapy. After three days of application, the pain was significantly reduced, by 50% in seven patients. Mobility of the hand was greatly improved. In three of the remaining four patients the block was repeated after one month. The pain was significantly smaller after that. Physical therapy is done all the time. Conclusion: The treatment of chronic pain in the shoulder and the shoulder joint is multidisciplinary. In some cases, the use of corticosteroids suprascapular block is very useful.

  12. A New Sacroiliac Joint Injection Technique and Its Short-Term Effect on Chronic Sacroiliac Region Pain.

    Science.gov (United States)

    Do, Kyung Hee; Ahn, Sang Ho; Jones, Rodney; Jang, Sung Ho; Son, Su Min; Lee, Dong Gyu; Cho, Hee Kyung; Choi, Gyu Sik; Cho, Yun-Woo

    2016-10-01

    Sacroiliac joint (SIJ) injections have been used to provide short-term relief of SIJ pain. In this study, the authors investigated a new technique using a superior approach. Twenty four patients with chronic SI joint paint were recruited. Each patient was treated with a single SIJ intra-articular injection plus a periarticular injection of local anesthetic and corticosteroid in one procedure. Technical accuracy of the intra-articular procedure was determined by having 2 independent observers review and rate the quality of arthrograms obtained. Treatment effects were evaluated using a numerical rating scale, the Oswestry disability index (ODI) and global perceived effect (GPE). Both independent observers agreed that satisfactory arthrograms were obtained in all patients. Pain scores and disability were significantly reduced at 2 weeks and 4 weeks after treatment. Nineteen patients (79%) reported satisfaction with treatment. No serious adverse effects were encountered. The superior approach consistently achieves good access to the SI joint, and achieves outcomes that are compatible with those of other techniques. The superior approach constitutes an alternative to other techniques for injections into the SI joint. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. A Mathematical Model for Temperature Induced Loosening due to Radial Expansion of Rectangle Thread Bolted Joints

    Directory of Open Access Journals (Sweden)

    Shiyuan Hou

    2015-01-01

    Full Text Available This paper proposed a mathematical model to investigate the radial expansion induced loosening of rectangle thread bolted joints that were subjected to cyclic temperature variation, which could cause slippage between contact pairs of engaged threads and bolt bearing. Firstly, integral equations were derived for the shear stress components caused by expansion difference, as well as the bearing and thread friction torque components, which depended on the temperature variation. Secondly, the relationship of displacement components was developed based on quasi-static hypotheses. Then, treating the rotation of bolt as plastic elongation, the bolt tension's evolution was obtained by using a one-dimensional bolted joint model. Numerical results showed that the temperature variation decreased the bearing and thread friction torque components, which could lead bolted joint to loosen. Finally, the effects of some associated factors on the progress were discussed.

  14. Hypoxia Induced Factor in Chronic Kidney Disease: Friend or Foe?

    Science.gov (United States)

    Li, Weiying; Zhao, Yuliang; Fu, Ping

    2017-01-01

    Many studies have shown evidence that erythropoiesis-stimulating agents (ESAs), as a classic treatment for chronic kidney disease (CKD)-related anemia, have several disadvantages and may trigger various adverse events with long-term use. The hypoxia-induced factor (HIF) pathway has been intensively investigated in kidney disease, especially in CKD, as research has shown that HIF-mediated erythropoiesis might work as a potential therapeutic strategy for managing CKD-related anemia. Development of prolyl hydroxylase domain inhibitors (PHIs), as an effective HIF activator, is a valuable step toward finding a replacement for ESAs, which showed an effective erythropoiesis through a comprehensive and physiological approach by promoting erythropoietin production, increasing iron bioavailability and improving chronic inflammatory status. Heretofore no adverse events or obvious off-target effects have been reported in clinical trials of PHIs. Nevertheless, a cautious inspection with extended follow-up period is warranted to validate the safety of prolonged HIF elevation, especially considering its ambiguous role in fibrogenesis and inflammation responses and possible risks in accelerating vascular calcification and tumorigenesis. A weighed dosing strategy might be the key to circumvent the unexpected side-effect brought by pleotropic effects of HIF elevation and achieve a selective augmentation of HIF-mediated signaling pathway. New studies with longer follow-up period and adequate analysis about the risks for proinflammation, vascular calcification and tumorigenesis are needed to ensure the drugs are safe for long-term use before being widely accepted in daily clinical practice.

  15. Intrahemispheric Perfusion in Chronic Stroke-Induced Aphasia

    Directory of Open Access Journals (Sweden)

    Cynthia K. Thompson

    2017-01-01

    Full Text Available Stroke-induced alterations in cerebral blood flow (perfusion may contribute to functional language impairments and recovery in chronic aphasia. Using MRI, we examined perfusion in the right and left hemispheres of 35 aphasic and 16 healthy control participants. Across 76 regions (38 per hemisphere, no significant between-subjects differences were found in the left, whereas blood flow in the right was increased in the aphasic compared to the control participants. Region-of-interest (ROI analyses showed a varied pattern of hypo- and hyperperfused regions across hemispheres in the aphasic participants; however, there were no significant correlations between perfusion values and language abilities in these regions. These patterns may reflect autoregulatory changes in blood flow following stroke and/or increases in general cognitive effort, rather than maladaptive language processing. We also examined blood flow in perilesional tissue, finding the greatest hypoperfusion close to the lesion (within 0–6 mm, with greater hypoperfusion in this region compared to more distal regions. In addition, hypoperfusion in this region was significantly correlated with language impairment. These findings underscore the need to consider cerebral perfusion as a factor contributing to language deficits in chronic aphasia as well as recovery of language function.

  16. Systematic review of patient history and physical examination to diagnose chronic low back pain originating from the facet joints.

    Science.gov (United States)

    Maas, E T; Juch, J N S; Ostelo, R W J G; Groeneweg, J G; Kallewaard, J W; Koes, B W; Verhagen, A P; Huygen, F J P M; van Tulder, M W

    2017-03-01

    Patient history and physical examination are frequently used procedures to diagnose chronic low back pain (CLBP) originating from the facet joints, although the diagnostic accuracy is controversial. The aim of this systematic review is to determine the diagnostic accuracy of patient history and/or physical examination to identify CLBP originating from the facet joints using diagnostic blocks as reference standard. We searched MEDLINE, EMBASE, CINAHL, Web of Science and the Cochrane Collaboration database from inception until June 2016. Two review authors independently selected studies for inclusion, extracted data and assessed the risk of bias. We calculated sensitivity and specificity values, with 95% confidence intervals (95% CI). Twelve studies were included, in which 129 combinations of index tests and reference standards were presented. Most of these index tests have only been evaluated in single studies with a high risk of bias. Four studies evaluated the diagnostic accuracy of the Revel's criteria combination. Because of the clinical heterogeneity, results were not pooled. The published sensitivities ranged from 0.11 (95% CI 0.02-0.29) to 1.00 (95% CI 0.75-1.00), and the specificities ranged from 0.66 (95% CI 0.46-0.82) to 0.91 (95% CI 0.83-0.96). Due to clinical heterogeneity, the evidence for the diagnostic accuracy of patient history and/or physical examination to identify facet joint pain is inconclusive. Patient history and physical examination cannot be used to limit the need of a diagnostic block. The validity of the diagnostic facet joint block should be studied, and high quality studies are required to confirm the results of single studies. Patient history and physical examination cannot be used to limit the need of a diagnostic block. The validity of the diagnostic facet joint block should be studied, and high quality studies are required to confirm the results of single studies. © 2016 European Pain Federation - EFIC®.

  17. Docosahexaenoic acid induces apoptosis in primary chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Romain Guièze

    2015-12-01

    Full Text Available Chronic lymphocytic leukemia is an indolent disorder with an increased infectious risk remaining one of the main causes of death. Development of therapies with higher safety profile is thus a challenging issue. Docosahexaenoic acid (DHA, 22:6 is an omega-3 fatty acid, a natural compound of normal cells, and has been shown to display antitumor potency in cancer. We evaluated the potential in vitro effect of DHA in primary CLL cells. DHA induces high level of in vitro apoptosis compared to oleic acid in a dose-dependent and time-dependent manner. Estimation of IC50 was only of 4.813 μM, which appears lower than those reported in solid cancers. DHA is highly active on CLL cells in vitro. This observation provides a rationale for further studies aiming to understand its mechanisms of action and its potent in vivo activity.

  18. A stress MRI of the shoulder for evaluation of ligamentous stabilizers in acute and chronic acromioclavicular joint instabilities.

    Science.gov (United States)

    Izadpanah, Kaywan; Winterer, Jan; Vicari, Marco; Jaeger, Martin; Maier, Dirk; Eisebraun, Leonie; Ute Will, Jutta; Kotter, Elmar; Langer, Mathias; Südkamp, Norbert P; Hennig, Jürgen; Weigel, Mathias

    2013-06-01

    To show the feasibility of a stress magnetic resonance imaging (MRI) as a new method for simultaneous evaluation of the morphology and the functional integrity of the acromioclavicular joint (ACJ) ligamentous stabilizers. MRI of four volunteers, 10 patients with acute, and six with chronic ACJ injuries was performed using a 0.25 T open MRI scanner. A 2D-proton-density and a 3D-gradient-echo sequence at rest and under 6.5 kg shoulder traction were performed. Comparative measurements of the coracoclavicular and the acromioclavicular distance were performed. Additionally, the conoid and trapezoid ligament lengths were measured with multiplanar reconstructions. MRI at rest correctly identified tears of the coracoclavicular and the acromioclavicular ligaments in eight patients suffering acute ACJ injuries. Stress application helped to distinguish between partial and complete coracoclavicular ligament tears in two cases. Insufficiency of the ACJ ligaments was present in all acute and chronic ACJ injuries. Stress application in chronic ACJ ligaments revealed isolated insufficiency of the conoid ligament in three cases and of the trapezoid ligament in one case. Combined insufficiency was present in two cases. Stress MRI facilitates simultaneous acquisition of morphologic and functional information of the ACJ stabilizers. In acute ACJ injuries it helps to distinguish between partial and complete ligament tears. In chronic ACJ injuries it provides functional information of the ligament regrinds. Copyright © 2012 Wiley Periodicals, Inc.

  19. Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage.

    Science.gov (United States)

    Siebelt, Michiel; Groen, Harald C; Koelewijn, Stuart J; de Blois, Erik; Sandker, Marjan; Waarsing, Jan H; Müller, Cristina; van Osch, Gerjo J V M; de Jong, Marion; Weinans, Harrie

    2014-01-29

    Articular cartilage needs sulfated-glycosaminoglycans (sGAGs) to withstand high pressures while mechanically loaded. Chondrocyte sGAG synthesis is regulated by exposure to compressive forces. Moderate physical exercise is known to improve cartilage sGAG content and might protect against osteoarthritis (OA). This study investigated whether rat knee joints with sGAG depleted articular cartilage through papain injections might benefit from moderate exercise, or whether this increases the susceptibility for cartilage degeneration. sGAGs were depleted from cartilage through intraarticular papain injections in the left knee joints of 40 Wistar rats; their contralateral joints served as healthy controls. Of the 40 rats included in the study, 20 rats remained sedentary, and the other 20 were subjected to a moderately intense running protocol. Animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes and single-photon emission computed tomography (SPECT)/CT to determine synovial macrophage activation. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology to measure sGAG content and cartilage thickness. All outcome measures were unaffected by moderate exercise in healthy control joints of running animals compared with healthy control joints of sedentary animals. Papain injections in sedentary animals resulted in severe sGAG-depleted cartilage, slight loss of subchondral cortical bone, increased macrophage activation, and osteophyte formation. In running animals, papain-induced sGAG-depleted cartilage showed increased cartilage matrix degradation, sclerotic bone formation, increased macrophage activation, and more osteophyte formation. Moderate exercise enhanced OA progression in papain-injected joints and did not protect against development of the disease. This was not restricted to more-extensive cartilage damage, but also resulted in pronounced

  20. Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage

    Science.gov (United States)

    2014-01-01

    Introduction Articular cartilage needs sulfated-glycosaminoglycans (sGAGs) to withstand high pressures while mechanically loaded. Chondrocyte sGAG synthesis is regulated by exposure to compressive forces. Moderate physical exercise is known to improve cartilage sGAG content and might protect against osteoarthritis (OA). This study investigated whether rat knee joints with sGAG depleted articular cartilage through papain injections might benefit from moderate exercise, or whether this increases the susceptibility for cartilage degeneration. Methods sGAGs were depleted from cartilage through intraarticular papain injections in the left knee joints of 40 Wistar rats; their contralateral joints served as healthy controls. Of the 40 rats included in the study, 20 rats remained sedentary, and the other 20 were subjected to a moderately intense running protocol. Animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes and single-photon emission computed tomography (SPECT)/CT to determine synovial macrophage activation. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology to measure sGAG content and cartilage thickness. Results All outcome measures were unaffected by moderate exercise in healthy control joints of running animals compared with healthy control joints of sedentary animals. Papain injections in sedentary animals resulted in severe sGAG-depleted cartilage, slight loss of subchondral cortical bone, increased macrophage activation, and osteophyte formation. In running animals, papain-induced sGAG-depleted cartilage showed increased cartilage matrix degradation, sclerotic bone formation, increased macrophage activation, and more osteophyte formation. Conclusions Moderate exercise enhanced OA progression in papain-injected joints and did not protect against development of the disease. This was not restricted to more-extensive cartilage

  1. Rotatory Subluxation and Facet Deformity in the Atlanto-occipital Joint in Patients with Chronic Atlantoaxial Rotatory Fixation: Two Case Reports.

    Science.gov (United States)

    Kashii, Masafumi; Masuhara, Kenta; Kaito, Takashi; Iwasaki, Motoki

    2017-01-01

    The relationship between the morphometry of atlantoaxial joint and chronic atlantoaxial rotatory fixation (AARF) is well known, but disorders in the atlanto-occipital joint in chronic AARF are not fully elucidated. The authors report two rare cases of secondary deformities in the atlanto-occipital joint in chronic AARF. Two patients with chronic AARF were treated with closed manipulation, skull traction and halo-vest immobilization. Clinical outcomes and radiographs were reviewed retrospectively, focusing on pathological changes in the atlanto-occipital joint using multiplanar reconstruction computed tomography and three-dimensional computed tomography images. Case 1 (12-year-old girl) had rotatory subluxation with a superior facet deformity of the atlas in the atlanto-occipital joint before the initiation of treatment. After a series of conservative treatments, both atlantoaxial and atlanto-occipital rotatory fixation could not be reduced, and both the superior facet deformity of the atlas and osteoarthritic changes in the atlanto-occipital developed. She was monitored without surgery because the disorder progressed to the spontaneous fusion of the occipital bone to the axis. Case 2 (13-year-old boy) had rotatory subluxation without facet deformity of the atlas in the atlanto-occipital joint before the initiation of treatment. However, both the superior facet deformity of the atlas and osteoarthritic changes in the atlanto-occipital developed over time, and both atlantoaxial and atlanto-occipital rotatory fixation could not be reduced after a series of conservative treatments. He still had severe neck pain and severely restricted neck mobility and underwent spinal fusion. Atlanto-occipital rotatory subluxation and facet deformity in the atlanto-occipital joint may occur after prolonged AARF. It is necessary to pay attention to pathological changes not only in the atlantoaxial joint but also in the atlanto-occipital joint, when orthopedic surgeons treat patients

  2. Lower limb joint motion during a cross cutting movement differs in individuals with and without chronic ankle instability.

    Science.gov (United States)

    Koshino, Yuta; Yamanaka, Masanori; Ezawa, Yuya; Ishida, Tomoya; Kobayashi, Takumi; Samukawa, Mina; Saito, Hiroshi; Takeda, Naoki

    2014-11-01

    To compare the kinematics of lower limb joints between individuals with and without chronic ankle instability (CAI) during cross-turn and -cutting movements. Cross-sectional study. Motion analysis laboratory. Twelve subjects with CAI and twelve healthy controls. Hip flexion, adduction, and internal rotation, knee flexion, and ankle dorsiflexion and inversion angles were calculated in the 200 ms before initial ground contact and from initial ground contact to toe-off (stance phase) in a cross-turn movement during gait and a cross-cutting movement from a forward jump, and compared across the two groups. In the cross-cutting movement, the CAI group exhibited greater hip and knee flexion than the control group during the stance phase, and more hip abduction during the period before initial contact and the stance phase. In the cross-turn movement the joint kinematics were similar in the two groups. CAI subjects exhibited an altered pattern of the proximal joint kinematics during a cross-cutting movement. It is important for clinicians to assess the function of the hip and knee as well as the ankle, and to incorporate coordination training for the entire lower limb into rehabilitation after lateral ankle sprains. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Chronic pelvic pain arising from dysfunctional stabilizing muscles of the hip joint and pelvis

    OpenAIRE

    Lee, Dae Wook; Lim, Chang Hun; Han, Jae Young; Kim, Woong Mo

    2016-01-01

    Chronic pelvic pain in women is a very annoying condition that is responsible for substantial suffering and medical expense. But dealing with this pain can be tough, because there are numerous possible causes for the pelvic pain such as urologic, gynecologic, gastrointestinal, neurologic, or musculoskeletal problems. Of these, musculoskeletal problem may be a primary cause of chronic pelvic pain in patients with a preceding trauma to the low back, pelvis, or lower extremities. Here, we report...

  4. Computed tomography and treatment of chronic temporomandibular joint arthritis in a sheep

    International Nuclear Information System (INIS)

    Warmerdam, E.P.L.; Weeren, P.R. van

    1996-01-01

    Diagnostic imaging and treatment of destructive right temporomandibular joint (TMJ) arthritis in a sheep are discussed. Computed tomography (CT) appears to be an attractive technique for imaging TMJ lesions in sheep. Surgical curettage of a deformed TMJ can result in functional recovery

  5. Effects of focal ankle joint cooling on unipedal static balance in individuals with and without chronic ankle instability.

    Science.gov (United States)

    Kim, Kyung-Min; Hart, Joseph M; Saliba, Susan A; Hertel, Jay

    2015-01-01

    Application of cryotherapy over an injured joint has been shown to improve muscle function, yet it is unknown how ankle cryotherapy affects postural control. Our purpose was to determine the effects of a 20-min focal ankle joint cooling on unipedal static stance in individuals with and without chronic ankle instability (CAI). Fifteen young subjects with CAI (9 males, 6 females) and 15 healthy gender-matched controls participated. All subjects underwent two intervention sessions on different days in which they had a 1.5L plastic bag filled with either crushed ice (active treatment) or candy corn (sham) applied to the ankle. Unipedal stance with eyes closed for 10s were assessed with a forceplate before and after each intervention. Center of pressure (COP) data were used to compute 10 specific dependent measures including velocity, area, standard deviation (SD), and percent range of COP excursions, and mean and SD of time-to-boundary (TTB) minima in the anterior-posterior (AP) and mediolateral directions. For each measure a three-way (Group-Intervention-Time) repeated ANOVAs found no significant interactions and main effects involving intervention (all Ps > 0.05). There were group main effects found for mean velocity (F(1,28) = 6.46, P = .017), area (F(1,28) = 12.83, P = .001), and mean of TTB minima in the AP direction (F(1,28) = 5.19, P = .031) indicating that the CAI group demonstrated greater postural instability compared to the healthy group. Postural control of unipedal stance was not significantly altered following focal ankle joint cooling in groups both with and without CAI. Ankle joint cryotherapy was neither beneficial nor harmful to single leg balance. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Development of porcine model of chronic tachycardia-induced cardiomyopathy.

    Science.gov (United States)

    Paslawska, Urszula; Gajek, Jacek; Kiczak, Liliana; Noszczyk-Nowak, Agnieszka; Skrzypczak, Piotr; Bania, Jacek; Tomaszek, Alicja; Zacharski, Maciej; Sambor, Izabela; Dziegiel, Piotr; Zysko, Dorota; Banasiak, Waldemar; Jankowska, Ewa A; Ponikowski, Piotr

    2011-11-17

    There are few experimental models of heart failure (HF) in large animals, despite structural and functional similarities to human myocardium. We have developed a porcine model of chronic tachycardia-induced cardiomyopathy. Homogenous siblings of White Large breed swine (n=6) underwent continuous right ventricular (RV) pacing at 170 bpm; 2 subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were presented for euthanasia at subsequent stages: mild, moderate and end-stage HF. Left ventricle (LV) sections were analyzed histologically and relative ANP, BNP, phospholamban and sarcoplasmic reticulum calcium ATPase 2a transcript levels in LV were quantified by real time RT-PCR. In the course of RV pacing, animals demonstrated reduced exercise capacity (time of running until being dyspnoeic: 6.6 ± 0.5 vs. 2.4 ± 1.4 min), LV dilatation (LVEDD: 4.9 ± 0.4 vs. 6.7 ± 0.4 cm), impaired LV systolic function (LVEF: 69 ± 8 vs. 32 ± 7 %), (all baseline vs. before euthanasia, all p<0.001). LV tissues from animals with moderate and end-stage HF demonstrated local foci of interstitial fibrosis, congestion, cardiomyocyte hypertrophy and atrophy, which was not detected in controls and mild HF animals. The up-regulation of ANP and BNP and a reduction in a ratio of sarcoplasmic reticulum calcium ATPase 2a and phospholamban in failing myocardium were observed as compared to controls. In pigs, chronic RV pacing at relatively low rate can be used as an experimental model of HF, as it results in a gradual deterioration of exercise tolerance accompanied by myocardial remodeling confirmed at subcellular level. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Candida-induced prosthetic joint infection. A literature review including 72 cases and a case report.

    Science.gov (United States)

    Cobo, Fernando; Rodríguez-Granger, Javier; López, Enrique M; Jiménez, Gemma; Sampedro, Antonio; Aliaga-Martínez, Luis; Navarro-Marí, José María

    2017-02-01

    The clinical and microbiological characteristics of prosthetic joint infection (PJI) caused by Candida species is described, including 72 cases in the literature and a case of Candida glabrata infection handled at the present centre. We describe one patient and using the key words 'fungal prosthetic joint infection' and 'candida prosthetic joint infection' we searched MEDLINE (National Library of Medicine, Bethesda, MD), Web of Science, CINAHL and Cochrane systematic review databases for case reports of this condition. Out of the 73 patients, 38 were female; mean age at diagnosis was 65.7 (± SD 18) yrs; 50 had risk factors for candidal infection such as systemic disease (e.g. rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus) and/or immunosuppressive therapy in 18 (24.6%) cases, diabetes mellitus in 14 (19.1%), immunosuppression due to malignant or chronic disease in 24 (32.8%) and long-term antibiotic use in four (5.4%) patients. Infection site was the knee in 36 patients and hip in 35; pain was present in 43 patients and swelling in 23 and the mean surgery-diagnosis interval was 32 months. The most frequent species was C. albicans, followed by C. parapsilosis. The diagnosis was obtained from joint fluid aspirate in 33 cases and intra-operative samples in 16. Susceptibility to antifungals was tested in only 21 isolates. The most frequently used antifungals were fluconazole and amphotericin B. Two-stage exchange arthroplasty was performed in 30 patients and resection arthroplasty in 31; 56 patients were cured with a combination of medical and surgical treatment; one patient died from the infection. PJI caused by Candida requires a high index of suspicion; surgery with long-term antifungal therapy is recommended.

  8. Motivational and behavioural models of change: A longitudinal analysis of change among men with chronic haemophilia-related joint pain.

    Science.gov (United States)

    Elander, J; Richardson, C; Morris, J; Robinson, G; Schofield, M B

    2017-09-01

    Motivational and behavioural models of adjustment to chronic pain make different predictions about change processes, which can be tested in longitudinal analyses. We examined changes in motivation, coping and acceptance among 78 men with chronic haemophilia-related joint pain. Using cross-lagged regression analyses of changes from baseline to 6 months as predictors of changes from 6 to 12 months, with supplementary structural equation modelling, we tested two models in which motivational changes influence behavioural changes, and one in which behavioural changes influence motivational changes. Changes in motivation to self-manage pain influenced later changes in pain coping, consistent with the motivational model of pain self-management, and also influenced later changes in activity engagement, the behavioural component of pain acceptance. Changes in activity engagement influenced later changes in pain willingness, consistent with the behavioural model of pain acceptance. Based on the findings, a combined model of changes in pain self-management and acceptance is proposed, which could guide combined interventions based on theories of motivation, coping and acceptance in chronic pain. This study adds longitudinal evidence about sequential change processes; a test of the motivational model of pain self-management; and tests of behavioural versus motivational models of pain acceptance. © 2017 European Pain Federation - EFIC®.

  9. Complications and Mortality in Chronic Renal Failure Patients Undergoing Total Joint Arthroplasty: A Comparison Between Dialysis and Renal Transplant Patients.

    Science.gov (United States)

    Cavanaugh, Priscilla K; Chen, Antonia F; Rasouli, Mohammad R; Post, Zachary D; Orozco, Fabio R; Ong, Alvin C

    2016-02-01

    In total joint arthroplasty (TJA) literature, there is a paucity of large cohort studies comparing chronic kidney disease (CKD) and end-stage renal disease (ESRD) vs non-CKD/ESRD patients. Thus, the purposes of this study were (1) to identify inhospital complications and mortality in CKD/ESRD and non-CKD/ESRD patients and (2) compare inhospital complications and mortality between dialysis and renal transplantation patients undergoing TJA. We queried the Nationwide Inpatient Sample database for patients with and without diagnosis of CKD/ESRD and those with a renal transplant or on dialysis undergoing primary or revision total knee or hip arthroplasty from 2007 to 2011. Patient comorbidities were identified using the Elixhauser comorbidity index. International Classification of Diseases, Ninth Revision, codes were used to identify postoperative surgical site infections (SSIs), wound complications, deep vein thrombosis, and transfusions. Chronic kidney disease/ESRD was associated with greater risk of SSIs (odds ratio [OR], 1.4; Prenal transplant patients. Chronic kidney disease/ESRD patients had a greater risk of SSIs and wound complications compared to those without renal disease, and the risk of these complications was even greater in CKD/ESRD patients receiving dialysis. These findings emphasize the importance of counseling CKD patients about higher potential complications after TJA, and dialysis patients may be encouraged to undergo renal transplantation before TJA. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Chronic lead exposure induces cochlear oxidative stress and potentiates noise-induced hearing loss.

    Science.gov (United States)

    Jamesdaniel, Samson; Rosati, Rita; Westrick, Judy; Ruden, Douglas M

    2018-08-01

    Acquired hearing loss is caused by complex interactions of multiple environmental risk factors, such as elevated levels of lead and noise, which are prevalent in urban communities. This study delineates the mechanism underlying lead-induced auditory dysfunction and its potential interaction with noise exposure. Young-adult C57BL/6 mice were exposed to: 1) control conditions; 2) 2 mM lead acetate in drinking water for 28 days; 3) 90 dB broadband noise 2 h/day for two weeks; and 4) both lead and noise. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS) lead-induced cochlear oxidative stress signaling was assessed using targeted gene arrays, and the hearing thresholds were assessed by recording auditory brainstem responses. Chronic lead exposure downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. Isolated exposure to lead or noise induced 8-12 dB and 11-25 dB shifts in hearing thresholds, respectively. Combined exposure induced 18-30 dB shifts, which was significantly higher than that observed with isolated exposures. This study suggests that chronic exposure to lead induces cochlear oxidative stress and potentiates noise-induced hearing impairment, possibly through parallel pathways. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  11. The relationship between chronic type III acromioclavicular joint dislocation and cervical spine pain

    Directory of Open Access Journals (Sweden)

    Vestri Anna R

    2009-12-01

    Full Text Available Abstract Background This study was aimed at evaluating whether or not patients with chronic type III acromioclavicular dislocation develop cervical spine pain and degenerative changes more frequently than normal subjects. Methods The cervical spine of 34 patients with chronic type III AC dislocation was radiographically evaluated. Osteophytosis presence was registered and the narrowing of the intervertebral disc and cervical lordosis were evaluated. Subjective cervical symptoms were investigated using the Northwick Park Neck Pain Questionnaire (NPQ. One-hundred healthy volunteers were recruited as a control group. Results The rate and distribution of osteophytosis and narrowed intervertebral disc were similar in both of the groups. Patients with chronic AC dislocation had a lower value of cervical lordosis. NPQ score was 17.3% in patients with AC separation (100% = the worst result and 2.2% in the control group (p Conclusions Our study shows that chronic type III AC dislocation does not interfere with osteophytes formation or intervertebral disc narrowing, but that it may predispose cervical hypolordosis. The higher average NPQ values were observed in patients with chronic AC dislocation, especially in those that developed cervical hypolordosis.

  12. Enhancing the smoothness of joint motion induced by functional electrical stimulation using co-activation strategies

    Directory of Open Access Journals (Sweden)

    Ruppel Mirjana

    2017-09-01

    Full Text Available The motor precision of today’s neuroprosthetic devices that use artificial generation of limb motion using Functional Electrical Stimulation (FES is generally low. We investigate the adoption of natural co-activation strategies as present in antagonistic muscle pairs aiming to improve motor precision produced by FES. In a test in which artificial knee-joint movements were generated, we could improve the smoothness of FES-induced motion by 513% when applying co-activation during the phases in which torque production is switched between muscles – compared to no co-activation. We further demonstrated how the co-activation level influences the joint stiffness in a pendulum test.

  13. Does chronic smoking affect induced-exercise catecholamine release?

    Directory of Open Access Journals (Sweden)

    Gökhan İpekoğlu

    2017-04-01

    Full Text Available This study was performed to investigate the acute effect of the submaximal aerobic exercise upon epinephrine and nor-epinephrine levels in chronic smokers and non-smoker.  The study was carried out upon 10 regular (15> cigarettes/day smoker untrained male along five years and 10 never smoker untrained male. Subjects performed an endurance exercise that continues 40 minutes at 70% maximal heart rate. There were 15cc venous blood samples extracted from the forearm pre-exercise (PRE, post-exercise (POST, post-exercise 2 hours (2h, post-exercise 24 hours (24h to measure of epinephrine and nor-epinephrine levels. The plasma level of each hormone increased after exercise and the tendency of rise was similar between groups as it seen in which 55,6% and 54,68% for epinephrine and 27,1% and 35,7% for norepinephrine. In this respect no group-time relationship has been found (p>0,05.  But in between-group analyses, basal and after exercise levels were different (p<0,05. The study revealed the fact that, smokers have higher plasma levels of epinephrine and norepinephrine before and after exercise. The results demonstrate that long-term smoking induces elevate baseline and post-aerobic submaximal exercise plasma epinephrine and nor-epinephrine levels.  The sympatho-adrenal activity appears to be disrupt with long-term smoking which effect the glycolytic and fat metabolism during exercise.

  14. Sulforaphane Modulates Joint Inflammation in a Murine Model of Complete Freund’s Adjuvant-Induced Mono-Arthritis

    Directory of Open Access Journals (Sweden)

    João Francisco Silva Rodrigues

    2018-04-01

    Full Text Available Rheumatoid arthritis (RA is characterized by inflammation of one or more joints, and affects ~1% of the adult population worldwide. Sulforaphane (SFN is a natural compound that has been suggested as an antioxidant. Here, SFN’s effects were evaluated in a murine mono-arthritis model. Mono-arthritis was induced in mice by a single intra-articular injection of Complete Freund’s Adjuvant (CFA-10 µg/joint, in 10 µL into the ipsilateral joint. The contralateral joint received an equal volume of PBS. On the 4th day post-joint inflammation induction, animals received either SFN (10 mg/kg or vehicle (3% DMSO in saline, intraperitoneally (i.p., twice a day for 3 days. Joint swelling and secondary mechanical allodynia and hyperalgesia were evaluated over 7 days post-CFA. After this period, animals were culled and their blood and synovial fluid samples were collected for analysis of cell populations, cytokine release and thioredoxin reductase (TrxR activity. Knee joint samples were also collected for histology. SFN reduced joint swelling and damage whilst increasing the recruitment of Ly6C+ and Ly6G+ cells to CFA-injected joints. SFN-treated animals presented down-regulation of CD11b and CD62L on synovial fluid Ly6G+ cells. Synovial fluid samples obtained from CFA-injected joints and plasma samples of SFN-treated mice presented higher levels of IL-6 and increased activity of TrxR, in comparison with controls. These results indicate that SFN reduces knee joint damage by modulating cell activation/migration to the joints, cytokine production and increasing the activity of TrxR, and therefore, may represent an alternative treatment to joint inflammation.

  15. The value of emission computer tomography (ECT) for chronic abnormalities of the knee joint

    International Nuclear Information System (INIS)

    Koenig, H.; Geiger, A.; Feine, U.; Tuebingen Univ.

    1987-01-01

    Twenty-eight patients with chronic abnormalities of the knee were examined by 3-phase scintigraphy and ECT. The unobscured images produced by ECT provide additional information for evaluating the localisation, extent and activity of the lesions. The diagnosis of meniscus abnormalities in particular revealed pathognomonic patterns. The indications and value of ECT was compared with other diagnostic measures and particularly with invasive techniques (arthroscopy and arthrotomy). (orig.) [de

  16. POSITION-SPECIFIC DEFICIT OF JOINT POSITION SENSE IN ANKLES WITH CHRONIC FUNCTIONAL INSTABILITY

    Directory of Open Access Journals (Sweden)

    Shigeki Yokoyama

    2008-12-01

    Full Text Available The present study was aimed to test a hypothesis that individuals with functional ankle instability (FAI underestimate the joint angle at greater plantarflexion and inversion. Seventeen males with unilateral FAI and 17 controls (males without FAI consented for participation in this IRB-approved, case-control study. Using a passive reproduction test, we assessed ankle joint position sense (JPS for test positions between 30 and -10 degrees plantarflexion with an inclement of 10 degrees with or without 20° inversion at each plantarflexion angle. The constant error (CE was defined as the value obtained by subtracting the true angle of a test position from the corresponding perceived angle. At plantarflexed and inverted test positions, the CE values were smaller in negative with greater in the FAI group than in the control group. That is, in the FAI group, the FAI group underestimated the true plantarflexion angle at combined 30° plantarflexion and 20° inversion. We conclude that the ankle with FAI underestimate the amount of plantarflexion, which increases the chance of reaching greater planterflexion and inversion than patients' intention at high risk situations of spraining such as landing

  17. Measurement-induced nonlocality in arbitrary dimensions in terms of the inverse approximate joint diagonalization

    Science.gov (United States)

    Zhang, Li-qiang; Ma, Ting-ting; Yu, Chang-shui

    2018-03-01

    The computability of the quantifier of a given quantum resource is the essential challenge in the resource theory and the inevitable bottleneck for its application. Here we focus on the measurement-induced nonlocality and present a redefinition in terms of the skew information subject to a broken observable. It is shown that the obtained quantity possesses an obvious operational meaning, can tackle the noncontractivity of the measurement-induced nonlocality and has analytic expressions for pure states, (2 ⊗d )-dimensional quantum states, and some particular high-dimensional quantum states. Most importantly, an inverse approximate joint diagonalization algorithm, due to its simplicity, high efficiency, stability, and state independence, is presented to provide almost-analytic expressions for any quantum state, which can also shed light on other aspects in physics. To illustrate applications as well as demonstrate the validity of the algorithm, we compare the analytic and numerical expressions of various examples and show their perfect consistency.

  18. Bilateral Dislocation of Temporomandibular Joint Induced by Haloperidol Following Suicide Attempt: A Case Report

    Directory of Open Access Journals (Sweden)

    Mosa Arghand Dargahi

    2012-03-01

    Full Text Available Drug induced dystonic reactions are among common presentations of patients in emergency departments, and typically occur with antidopaminergic agents as their extra-pyramidal side effects. Dystonic reactions usually occur within the first few hours or days after commencing a drug or dose increase. Unlike other extra-pyramidal side effects, a patient may experience acute dystonic reactions (ADRs with the administration of just a single dose. Oromandibular dystonia is a subtype of dystonia which can present with perioral manifestations. In extreme cases, it can lead to temporomandibular dislocation. Haloperidol, as a high potent typical antipsychotic drug, can induce dystonia with blocking D2 dopamine receptors. The present paper reports a case of bilateral dislocation of temporomandibular joint following ingestion of haloperidol in a suicidal attempt in a 17 years old girl.

  19. Chronic stress-induced effects of corticosterone on brain: direct and indirect

    NARCIS (Netherlands)

    Dallman, M. F.; Akana, S. F.; Strack, A. M.; Scribner, K. S.; Pecoraro, N.; La Fleur, S. E.; Houshyar, H.; Gomez, F.

    2004-01-01

    Acutely, glucocorticoids act to inhibit stress-induced corticotrophin-releasing factor (CRF) and adrenocorticotrophic hormone (ACTH) secretion through their actions in brain and anterior pituitary (canonical feedback). With chronic stress, glucocorticoid feedback inhibition of ACTH secretion changes

  20. [Resection of a carpal bone row in a Pustertaler Sprinze cow with chronic purulent arthritis of the carpal joint and osteomyelitis].

    Science.gov (United States)

    Kofler, J; Peterbauer, C

    2014-01-01

    This case report describes the clinical and radiographic findings and the surgical treatment of a serofibrinous arthritis of the antebrachiocarpal joint and of a chronic purulent arthritis of the intercarpal and carpometacarpal joints with osteomyelitis of the distal carpal bones and subchondral osteomyelitis of the proximal metacarpal bones in a cow of the breed "Pustertaler Sprinze". The therapy comprised an arthrotomy of both joint spaces and the resection of the distal row of the carpal bones. The right forelimb had been immobilised for 70 days by a full limb cast. After this period, radiographs revealed an ob- vious ankylosis of the carpal joint, and the cow showed only a slight lameness. Six years postoperatively this cow was still in the herd and had produced six calves.

  1. Effect of irradiation on the temporomandibular joint in streptozotocin-induced diabetic rat

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Ki Dong; Hwang, Eui Hwan; Lee, Sang Rae [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

    2004-06-15

    To investigate the histopathological changes in the temporomandibular joint in streptozotocin-induced diabetic rat following irradiation. Sprague-Dawley rats weighing about 250 gm were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control group were injected with citrate buffer only. After 5 days, the head and neck region of the rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy. The rats were killed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimen including the temporomandibular joint were sectioned and observed using a histopathological method. In the diabetic group, severe bone resorption in the mandibular condyle was observed throughout the period of experiment. Necrosis of bone marrow and trabeculae was observed at 28 days after diabetic state. Atrophy and fibrosis in the retrodiscal tissue was gradually progressed during the time of the experiment. In the diabetic-irradiated group, severe bone resorption in the mandibular condyle was observed during the early experimental phases, but regeneration of bone marrow was initiated at 14 days after diabetic state and irradiation. Also, calcification of abnormal trabeculae was observed at 28 days after diabetic state and irradiation. The retrodiscal tissue was degenerated in the early experimental phases, but it had been gradually regenerated during the experimental time. This experiment suggests that bone resorption and degeneration in the mandibular condyle are caused by the induction of diabetes, and abnormal bone formation is induced after irradiation in diabetic state.

  2. Effect of irradiation on the temporomandibular joint in streptozotocin-induced diabetic rat

    International Nuclear Information System (INIS)

    Ahn, Ki Dong; Hwang, Eui Hwan; Lee, Sang Rae

    2004-01-01

    To investigate the histopathological changes in the temporomandibular joint in streptozotocin-induced diabetic rat following irradiation. Sprague-Dawley rats weighing about 250 gm were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control group were injected with citrate buffer only. After 5 days, the head and neck region of the rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy. The rats were killed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimen including the temporomandibular joint were sectioned and observed using a histopathological method. In the diabetic group, severe bone resorption in the mandibular condyle was observed throughout the period of experiment. Necrosis of bone marrow and trabeculae was observed at 28 days after diabetic state. Atrophy and fibrosis in the retrodiscal tissue was gradually progressed during the time of the experiment. In the diabetic-irradiated group, severe bone resorption in the mandibular condyle was observed during the early experimental phases, but regeneration of bone marrow was initiated at 14 days after diabetic state and irradiation. Also, calcification of abnormal trabeculae was observed at 28 days after diabetic state and irradiation. The retrodiscal tissue was degenerated in the early experimental phases, but it had been gradually regenerated during the experimental time. This experiment suggests that bone resorption and degeneration in the mandibular condyle are caused by the induction of diabetes, and abnormal bone formation is induced after irradiation in diabetic state.

  3. Amlodipine-induced gingival hyperplasia in chronic renal

    African Journals Online (AJOL)

    Administrator

    Keywords: Amlodipine, gingival hyperplasia, chronic renal failure. African Health ... for the treatment of hypertension and angina. Pharmacokinetic ... patient appealed to the dentist at first. ... Am Heart J. 1989 Nov; 118(5 Pt 2):. 1100-1103. 2.

  4. Effects of the application of ankle functional rehabilitation exercise on the ankle joint functional movement screen and isokinetic muscular function in patients with chronic ankle sprain.

    Science.gov (United States)

    Ju, Sung-Bum; Park, Gi Duck

    2017-02-01

    [Purpose] This study was conducted to investigate the effects of ankle functional rehabilitation exercise on ankle joint functional movement screen results and isokinetic muscular function in patients with chronic ankle sprain patients. [Subjects and Methods] In this study, 16 patients with chronic ankle sprain were randomized to an ankle functional rehabilitation exercise group (n=8) and a control group (n=8). The ankle functional rehabilitation exercise centered on a proprioceptive sense exercise program, which was applied 12 times for 2 weeks. To verify changes after the application, ankle joint functional movement screen scores and isokinetic muscular function were measured and analyzed. [Results] The ankle functional rehabilitation exercise group showed significant improvements in all items of the ankle joint functional movement screen and in isokinetic muscular function after the exercise, whereas the control group showed no difference after the application. [Conclusion] The ankle functional rehabilitation exercise program can be effectively applied in patients with chronic ankle sprain for the improvement of ankle joint functional movement screen score and isokinetic muscular function.

  5. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

    Science.gov (United States)

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

  6. Proceedings of the 2nd joint seminar on atomic collisions and heavy ion induced nuclear reactions

    International Nuclear Information System (INIS)

    Harada, Kichinosuke; Ozawa, Kunio; Kamitsubo, H.; Nomura, T.; Awaya, Y.; Watanabe, T.

    1982-11-01

    The meeting of the 2nd joint seminar on atomic collisions and heavy ion induced nuclear reactions was held at the University of Tokyo, May 13 and 14, 1982. The aim of this seminar has been not only to recognize the common problems lying between above two research fields, but also to obtain an overview of the theoretical and experimental approaches to clear the current problems. In the seminar, more than 50 participants gathered and presented 16 papers. These are two general reviews and fourteen comprehensive surveys on topical subjects which have been developed very intensively in recent years. The editors would like to thank all participants for their assistance and cooperation in making possible a publication of these proceedings. (author)

  7. Comparison of welding induced residual stresses austenitic and ferritic steel weld joints

    International Nuclear Information System (INIS)

    Rajkumar, K.V.; Arun Kumar, S.; Mahadevan, S.; Manojkumar, R.; Rao, B. Purna Chandra; Albert, Shaju K.; Murugan, S.

    2015-01-01

    X-ray diffraction (XRD) is a well established technique for measurement of residual stresses in components and is being widely used. In XRD technique, the distance between the crystallographic planes (d spacing) is measured from peak position (2è) at various ø angles, where ø is the angle between the normal to the sample and the bisector of the incident and diffracted beam. From the slope of sin2ø vs. d spacing plot, the residual stresses are arrived by assuming a plane stress model. Welding induced residual stresses is of high importance as it is a major cause of failure in components. Surface compressive stresses improve the fatigue strength, whereas tensile residual stresses tend to decrease the fatigue strength. The present study compares the residual stresses that develop in 3 mm thick SS 316 and P91 TIG weld joints using the XRD technique. This study is aimed at understanding the influence of shrinkage during cooling and the effect of phase transformation induced volume changes on residual stress development in these two steels. While the first effect is predominant in the SS 316 weld, both the effects are present in the P91 welds. Stress measurements on SS 316 and P91 were carried out using Cr Kâ (λ-2.0840 Å) and Cr Ká (λ-2.2896 Å) radiations respectively. Typical 'M' type stress profile was observed across the weld centre line in both the welds. The variation and similarities between the longitudinal stress profiles observed in these two weld joints would be discussed. (author)

  8. A Best-Evidence Systematic Appraisal of the Diagnostic Accuracy and Utility of Facet (Zygapophysial) Joint Injections in Chronic Spinal Pain.

    Science.gov (United States)

    Boswell, Mark V; Manchikanti, Laxmaiah; Kaye, Alan D; Bakshi, Sanjay; Gharibo, Christopher G; Gupta, Sanjeeva; Jha, Sachin Sunny; Nampiaparampil, Devi E; Simopoulos, Thomas T; Hirsch, Joshua A

    2015-01-01

    Spinal zygapophysial, or facet, joints are a source of axial spinal pain and referred pain in the extremities. Conventional clinical features and other noninvasive diagnostic modalities are unreliable in diagnosing zygapophysial joint pain. A systematic review of the diagnostic accuracy of spinal facet joint nerve blocks. To determine the diagnostic accuracy of spinal facet joint nerve blocks in chronic spinal pain. A methodological quality assessment of included studies was performed using Quality Appraisal of Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. The level of evidence was classified as Level I to V based on the grading of evidence utilizing best evidence synthesis. Data sources included relevant literature identified through searches of PubMed and other electronic searches published from 1966 through March 2015, Cochrane reviews, and manual searches of the bibliographies of known primary and review articles. Studies must have been performed utilizing controlled local anesthetic blocks. The criterion standard must have been at least 50% pain relief from baseline scores and the ability to perform previously painful movements. The available evidence is Level I for lumbar facet joint nerve blocks with the inclusion of a total of 17 studies with dual diagnostic blocks, with at least 75% pain relief with an average prevalence of 16% to 41% and false-positive rates of 25% to 44%. The evidence for diagnosis of cervical facet joint pain with cervical facet joint nerve blocks is Level II based on a total of 11 controlled diagnostic accuracy studies, with significant variability among the prevalence in a heterogenous population with internal inconsistency. The prevalence rates ranged from 36% to 67% with at least 80% pain relief as the criterion standard and a false-positive rate of 27% to 63%. The level of evidence for the diagnostic accuracy of thoracic facet

  9. In-situ study of electromigration-induced grain rotation in Pb-free solder joint by synchrotron microdiffraction

    International Nuclear Information System (INIS)

    Chen, Kai; Tamura, Nobumichi; Tu, King-Ning

    2008-01-01

    The rotation of Sn grains in Pb-free flip chip solder joints hasn't been reported in literature so far although it has been observed in Sn strips. In this letter, we report the detailed study of the grain orientation evolution induced by electromigration by synchrotron based white beam X-ray microdiffraction. It is found that the grains in solder joint rotate more slowly than in Sn strip even under higher current density. On the other hand, based on our estimation, the reorientation of the grains in solder joints also results in the reduction of electric resistivity, similar to the case of Sn strip. We will also discuss the reason why the electric resistance decreases much more in strips than in the Sn-based solders, and the different driving force for the grain growth in solder joint and in thin film interconnect lines

  10. In-situ study of electromigration-induced grain rotation in Pb-free solder joint by synchrotron microdiffraction

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Kai; Tamura, Nobumichi; Tu, King-Ning

    2008-10-31

    The rotation of Sn grains in Pb-free flip chip solder joints hasn't been reported in literature so far although it has been observed in Sn strips. In this letter, we report the detailed study of the grain orientation evolution induced by electromigration by synchrotron based white beam X-ray microdiffraction. It is found that the grains in solder joint rotate more slowly than in Sn strip even under higher current density. On the other hand, based on our estimation, the reorientation of the grains in solder joints also results in the reduction of electric resistivity, similar to the case of Sn strip. We will also discuss the reason why the electric resistance decreases much more in strips than in the Sn-based solders, and the different driving force for the grain growth in solder joint and in thin film interconnect lines.

  11. Efficacy of indefinite chronic oral antimicrobial suppression for prosthetic joint infection in the elderly: a comparative study.

    Science.gov (United States)

    Prendki, V; Sergent, P; Barrelet, A; Oziol, E; Beretti, E; Berlioz-Thibal, M; Bouchand, F; Dauchy, F A; Forestier, E; Gavazzi, G; Ronde-Oustau, C; Stirnemann, J; Dinh, A

    2017-07-01

    During prosthetic joint infection (PJI), surgical management is sometimes impossible and indefinite chronic oral antimicrobial suppression (ICOAS) may be the only option. The outcomes of elderly patients who benefited from ICOAS with strictly palliative intent were evaluated. A national retrospective cohort study was performed in France, involving patients aged >75 years with a PJI who were managed with planned life-long ICOAS from 2009 to 2014. Patients who experienced an event were compared to those who did not. An event was defined as a composite outcome in patients undergoing ICOAS, including local or systemic progression of the infection, death, or discontinuation of antimicrobial therapy because of an adverse drug reaction. Twenty-one patients were included, with a median age of 85 years (interquartile range 81-88 years). Eight of the 21 patients experienced an event: one had an adverse drug reaction, three had systemic progression of sepsis, and two had local progression. Two of the 21 patients died. No death was related to ICOAS or infection. There was no significant difference between the population with an event and the population free of an event with regard to demographic, clinical, and microbiological characteristics (p>0.05). ICOAS appeared to be an effective and safe option in this cohort. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Measuring and Inducing Brain Plasticity in Chronic Aphasia

    Science.gov (United States)

    Fridriksson, Julius

    2011-01-01

    Brain plasticity associated with anomia recovery in aphasia is poorly understood. Here, I review four recent studies from my lab that focused on brain modulation associated with long-term anomia outcome, its behavioral treatment, and the use of transcranial brain stimulation to enhance anomia treatment success in individuals with chronic aphasia…

  13. Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

    Science.gov (United States)

    Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

    2014-01-01

    The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

  14. Lumbar Radiofrequency Rhizotomy in Patients with Chronic Low Back Pain Increases the Diagnosis of Sacroiliac Joint Dysfunction in Subsequent Follow-Up Visits

    Science.gov (United States)

    2017-01-01

    Chronic back pain is often a result of coexisting pathologies; secondary causes of pain can become more apparent sources of pain once the primary pathology has been addressed. The objective of our study was to determine if there is an increase in diagnosis of Sacroiliac joint pain following a Lumbar Rhizotomy. A list of patients who underwent Lumbar Radiofrequency during a 6-month period in our clinic was generated. Records from subsequent clinic visits were reviewed to determine if a new diagnosis of SI joint pathology was made. In patients who underwent a recent Lumbar Rhizotomy procedure to treat facetogenic pain, the prevalence of Sacroiliac joint pain increased to 70%. We infer that there is a significant increase in the diagnosis of Sacroiliac joint syndrome following a Lumbar Rhizotomy, potentially due to unmasking of a preexisting condition. In patients presenting with persistent back pain after Lumbar Rhizotomy, the clinician must have a high degree of suspicion for latent Sacroiliac joint pain prior to attributing the pain to block failure. It would be prudent to use >80% relief of pain after a diagnostic medial branch block as a diagnostic criterion for facetogenic pain rather than the currently accepted >50% in order to minimize unmasking of preexisting subclinical pain from the SI joint. PMID:28255260

  15. Lumbar Radiofrequency Rhizotomy in Patients with Chronic Low Back Pain Increases the Diagnosis of Sacroiliac Joint Dysfunction in Subsequent Follow-Up Visits

    Directory of Open Access Journals (Sweden)

    Varun Kumar Rimmalapudi

    2017-01-01

    Full Text Available Chronic back pain is often a result of coexisting pathologies; secondary causes of pain can become more apparent sources of pain once the primary pathology has been addressed. The objective of our study was to determine if there is an increase in diagnosis of Sacroiliac joint pain following a Lumbar Rhizotomy. A list of patients who underwent Lumbar Radiofrequency during a 6-month period in our clinic was generated. Records from subsequent clinic visits were reviewed to determine if a new diagnosis of SI joint pathology was made. In patients who underwent a recent Lumbar Rhizotomy procedure to treat facetogenic pain, the prevalence of Sacroiliac joint pain increased to 70%. We infer that there is a significant increase in the diagnosis of Sacroiliac joint syndrome following a Lumbar Rhizotomy, potentially due to unmasking of a preexisting condition. In patients presenting with persistent back pain after Lumbar Rhizotomy, the clinician must have a high degree of suspicion for latent Sacroiliac joint pain prior to attributing the pain to block failure. It would be prudent to use >80% relief of pain after a diagnostic medial branch block as a diagnostic criterion for facetogenic pain rather than the currently accepted >50% in order to minimize unmasking of preexisting subclinical pain from the SI joint.

  16. Lumbar Radiofrequency Rhizotomy in Patients with Chronic Low Back Pain Increases the Diagnosis of Sacroiliac Joint Dysfunction in Subsequent Follow-Up Visits.

    Science.gov (United States)

    Rimmalapudi, Varun Kumar; Kumar, Sanjeev

    2017-01-01

    Chronic back pain is often a result of coexisting pathologies; secondary causes of pain can become more apparent sources of pain once the primary pathology has been addressed. The objective of our study was to determine if there is an increase in diagnosis of Sacroiliac joint pain following a Lumbar Rhizotomy. A list of patients who underwent Lumbar Radiofrequency during a 6-month period in our clinic was generated. Records from subsequent clinic visits were reviewed to determine if a new diagnosis of SI joint pathology was made. In patients who underwent a recent Lumbar Rhizotomy procedure to treat facetogenic pain, the prevalence of Sacroiliac joint pain increased to 70%. We infer that there is a significant increase in the diagnosis of Sacroiliac joint syndrome following a Lumbar Rhizotomy, potentially due to unmasking of a preexisting condition. In patients presenting with persistent back pain after Lumbar Rhizotomy, the clinician must have a high degree of suspicion for latent Sacroiliac joint pain prior to attributing the pain to block failure. It would be prudent to use >80% relief of pain after a diagnostic medial branch block as a diagnostic criterion for facetogenic pain rather than the currently accepted >50% in order to minimize unmasking of preexisting subclinical pain from the SI joint.

  17. Radiosynovectomy of the knee joint in chronic arthritis; An easy and useful treatment. Radiosynoviectomie van de knie bij chronische artritis; Een eenvoudige en zinvolle behandeling

    Energy Technology Data Exchange (ETDEWEB)

    Boerbooms, A.M.T.; Putte, L.B.A. van de (Academisch Ziekenhuis St. Radboud, Nijmegen (Nteherlands). Afdeling Reumatologie); Corstens, F.H.M.; Buijs, W.C.A.M. (Academisch Ziekenhuis St. Radboud, Nijmegen (Netherlands). Afdeling Nucleaire Geneeskunde); Bruyn, G.A.W. (Medisch Centrum, Leeuwarden (Netherlands). Afdeling Reumatologie)

    1992-05-09

    185 MBq (5 mCi) colloidal 198-aurothioglucose ({sup 198}Au) or colloidal yttrium-90-silicate ({sup 90}Y) in 10 ml 0.9% NaCl was injected into knee joint cavity after aspiration of joint fluid. After that the patient stayed in bed for 3 days. Clinical examination, erythrocyte sedimentation rate, {sup 99m}Tc-pertechnetate uptake measurements and radiographs of the knee joints were performed at baseline and during follow-up. Main results, group 1. evaluation after 6 months and after 3 years showed significantly better results in the group of knee joints with no minimal pre-existing radiological abnormalities compared with the group of knee joints with moderate or severe radiological abnormalities (p<0.05). Group 2. 24 months (mean) after treatment with {sup 90}Y, 50% of the treated knees showed clinical improvement of the synovitis. Group 3. a significant reduction of haemarthrotic episodes of all 6 joints treated and a reduction of pain in 4 during a follow-up of 2.5 years.It is concluded that radiosynovectomy is a valuable and simple form of treatment for therapy-resistant chronic synovitis. (author). 20 refs.; 3 tabs.

  18. Chronic Periprosthetic Hip Joint Infection. A Retrospective, Observational Study on the Treatment Strategy and Prognosis in 130 Non-Selected Patients

    DEFF Research Database (Denmark)

    Lange, Jeppe; Troelsen, Anders; Søballe, Kjeld

    2016-01-01

    INTRODUCTION: Limited information is available regarding the treatment strategy and prognosis of non-selected patients treated for chronic periprosthetic hip joint infection. Such information is important as no head-to-head studies on treatment strategies are available. The purpose of this study...... is to report on the treatment strategy and prognosis of a non-selected, consecutive patient population. METHODS: We identified 130 patients in the National Patient Registry, consecutively treated for a chronic periprosthetic hip joint infection between 2003-2008 at 11 departments of orthopaedic surgery. We...... extracted information regarding patient demographics, treatment and outcome. 82 patients were re-implanted in a two-stage revision (national standard), the remaining 48 were not re-implanted in a two-stage revision. We were able to collect up-to-date information on all patients to date of death or medical...

  19. Chronic sleep restriction induces changes in the mandibular condylar cartilage of rats: roles of Akt, Bad and Caspase-3.

    Science.gov (United States)

    Zhu, Yong; Wu, Gaoyi; Zhu, Guoxiong; Ma, Chuan; Zhao, Huaqiang

    2014-01-01

    The aim of the present study was to observe changes in the temporomandibular joint (TMJ) of rats that had been subjected to chronic sleep restriction and to investigate whether Akt, Bad and Caspase3 play a role in the mechanism underlying the changes. One hundred and eighty male Wistar rats were randomly divided into three groups (n = 60 in each): cage control group, large-platform control group, and sleep restriction group. Each group was divided into three subgroups (n = 20 in each) of three different time points (7, 14 and 21 days), respectively. The modified multiple platform method was used to induce chronic sleep restriction. The TMJ tissue histology was studied by staining with haematoxylin and eosin. The expression of Akt, p-Aktser473, Bad, p-Badser136 and Caspase3 proteins was detected by immunohistochemistry and western blotting. The expression of Akt, Bad and Caspase3 mRNAs was measured by real-time quantitative polymerase chain reaction (RT-qPCR). Compared with the large-platform and cage control groups, condylar cartilage pathological alterations were found in the sleep restriction group. There were significantly decreased expression levels of Akt, p-Aktser473 and p-Badser136 and significantly increased expression levels of Bad and Caspase3 after sleep restriction. These data suggest that sleep restriction may induce pathological alterations in the condylar cartilage of rats. Alterations in Akt, Bad and Caspase3 may be associated with the potential mechanism by which chronic sleep restriction influences the condylar cartilage.

  20. Amlodipine-induced gingival hyperplasia in chronic renal failure: a ...

    African Journals Online (AJOL)

    Amlodipine is a dihydropyridine calcium channel blocker that is used in the management of both hypertension and angina. Amlodipine induced side effects are headache, dizziness, edema, flushing, palpitations, and rarely gingival hyperplasia. The exact reason of amlodipine-induced gingival hyperplasia is not known.

  1. Leakage flow-induced vibration of an eccentric tube-in-tube slip joint

    International Nuclear Information System (INIS)

    Mulcahy, T.M.

    1985-08-01

    Eccentricity of a specific slip-joint design separating two cantilevered, telescoping tubes did not create any self-excited lateral vibrations that had not been observed previously for a concentric slip joint. In fact, the eccentricity made instabilities less likely to occur, but only marginally. Most important, design rules previously established to avoid instabilities for the concentric slip joint remain valid for the eccentric slip joint. 6 refs., 9 figs., 2 tabs

  2. 3, 4-methylenedioximethamphetamin reverses anxiety induced by chronic mild stress

    Directory of Open Access Journals (Sweden)

    Laura Andrea León A

    2013-01-01

    Full Text Available Here we report the effects of subchronic 3, 4 methylenedioximethamphetamine (MDMA on the elevated plusmaze, a widely used animal model of anxiety. Rats exposed to a mild chronic stress (MCS protocol received intracerebroventricular microinjections of the selective serotonin reuptake inhibitor (SSRI – fluoxetine (2.0 ug/ul or MDMA, (2.0 ug/ul for seven days. On the eighth day rats were tested in the elevated plus-maze. Our results showed that sub chronic MDMA interacted with MCS leading to a decrease in anxiety related behaviors including: percentage of open arms entries (F [2, 26] = 4.00; p = 0.031, time spent in the open arms (F [2, 26] = 3.656; p = 0.040 and time spent in the open arms extremities (F [2, 26] = 5.842; p = 0.008. These results suggest a potential effect of MDMA in the reversion of the emotional significance of aversive stimuli.

  3. Balancing food and predator pressure induces chronic stress in songbirds.

    OpenAIRE

    Clinchy, Michael; Zanette, Liana; Boonstra, Rudy; Wingfield, John C.; Smith, James N. M.

    2004-01-01

    The never-ending tension between finding food and avoiding predators may be the most universal natural stressor wild animals experience. The 'chronic stress' hypothesis predicts: (i) an animal's stress profile will be a simultaneous function of food and predator pressures given the aforesaid tension; and (ii) these inseparable effects on physiology will produce inseparable effects on demography because of the resulting adverse health effects. This hypothesis was originally proposed to explain...

  4. Uncertainty in estimating probability of causation in a cross-sectional study: joint effects of radiation and hepatitis-C virus on chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Cologne, John B [Department of Statistics, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815 (Japan); Pawel, David J [Office of Radiation and Indoor Air, US Environmental Protection Agency, 1200 Pennsylvania Ave NW, Washington DC 20460 (United States); Sharp, Gerald B [Department of Epidemiology, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815 (Japan); Fujiwara, Saeko [Department of Clinical Studies, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima 732-0815 (Japan)

    2004-06-01

    Exposure to other risk factors is an important consideration in assessing the role played by radiation in producing disease. A cross-sectional study of atomic-bomb survivors suggested an interaction between whole-body radiation exposure and chronic hepatitis-C viral (HCV) infection in the etiology of chronic liver disease (chronic hepatitis and cirrhosis), but did not allow determination of the joint-effect mechanism. Different estimates of probability of causation (POC) conditional on HCV status resulted from additive and multiplicative models. We therefore estimated the risk for radiation conditional on HCV status using a more general, mixture model that does not require choosing between additivity or multiplicativity, or deciding whether there is interaction, in the face of the large uncertainty. The results support the conclusion that POC increases with radiation dose in persons without HCV infection, but are inconclusive regarding individuals with HCV infection, the lower confidence bound on estimated POC for radiation with HCV infection being zero over the entire dose range. Although the mixture model may not reflect the true joint-effect mechanism, it avoids restrictive model assumptions that cannot be validated using the available data yet have a profound influence on estimated POC. These considerations apply more generally, given that the additive and multiplicative models are often used in POC related work. We therefore consider that an empirical approach may be preferable to assuming a specific mechanistic model for estimating POC in epidemiological studies where the joint-effect mechanism is in doubt.

  5. Uncertainty in estimating probability of causation in a cross-sectional study: joint effects of radiation and hepatitis-C virus on chronic liver disease

    International Nuclear Information System (INIS)

    Cologne, John B; Pawel, David J; Sharp, Gerald B; Fujiwara, Saeko

    2004-01-01

    Exposure to other risk factors is an important consideration in assessing the role played by radiation in producing disease. A cross-sectional study of atomic-bomb survivors suggested an interaction between whole-body radiation exposure and chronic hepatitis-C viral (HCV) infection in the etiology of chronic liver disease (chronic hepatitis and cirrhosis), but did not allow determination of the joint-effect mechanism. Different estimates of probability of causation (POC) conditional on HCV status resulted from additive and multiplicative models. We therefore estimated the risk for radiation conditional on HCV status using a more general, mixture model that does not require choosing between additivity or multiplicativity, or deciding whether there is interaction, in the face of the large uncertainty. The results support the conclusion that POC increases with radiation dose in persons without HCV infection, but are inconclusive regarding individuals with HCV infection, the lower confidence bound on estimated POC for radiation with HCV infection being zero over the entire dose range. Although the mixture model may not reflect the true joint-effect mechanism, it avoids restrictive model assumptions that cannot be validated using the available data yet have a profound influence on estimated POC. These considerations apply more generally, given that the additive and multiplicative models are often used in POC related work. We therefore consider that an empirical approach may be preferable to assuming a specific mechanistic model for estimating POC in epidemiological studies where the joint-effect mechanism is in doubt

  6. Improved functional assessment of osteoarthritic knee joint after chondrogenically induced cell treatment.

    Science.gov (United States)

    Ude, C C; Ng, M H; Chen, C H; Htwe, O; Amaramalar, N S; Hassan, S; Djordjevic, I; Rani, R A; Ahmad, J; Yahya, N M; Saim, A B; Idrus, R B Hj

    2015-08-01

    Our previous studies on osteoarthritis (OA) revealed positive outcome after chondrogenically induced cells treatment. Presently, the functional improvements of these treated OA knee joints were quantified followed by evaluation of the mechanical properties of the engineered cartilages. Baseline electromyogram (EMGs) were conducted at week 0 (pre-OA), on the locomotory muscles of nine un-castrated male sheep (Siamese long tail cross) divided into controls, adipose-derived stem cells (ADSCs) and bone marrow stem cells (BMSCs), before OA inductions. Subsequent recordings were performed at week 7 and week 31 which were post-OA and post-treatments. Afterwards, the compression tests of the regenerated cartilage were performed. Post-treatment EMG analysis revealed that the control sheep retained significant reductions in amplitudes at the right medial gluteus, vastus lateralis and bicep femoris, whereas BMSCs and ADSCs samples had no further significant reductions (P < 0.05). Grossly and histologically, the treated knee joints demonstrated the presence of regenerated neo cartilages evidenced by the fluorescence of PKH26 tracker. Based on the International Cartilage Repair Society scores (ICRS), they had significantly lower grades than the controls (P < 0.05). The compression moduli of the native cartilages and the engineered cartilages differed significantly at the tibia plateau, patella femoral groove and the patella; whereas at the medial femoral condyle, they had similar moduli of 0.69 MPa and 0.40-0.64 MPa respectively. Their compression strengths at all four regions were within ±10 MPa. The tissue engineered cartilages provided evidence of functional recoveries associated to the structural regenerations, and their mechanical properties were comparable with the native cartilage. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  7. Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice.

    Science.gov (United States)

    Satoh, T; Murata, M; Iwabuchi, N; Odamaki, T; Wakabayashi, H; Yamauchi, K; Abe, F; Xiao, J Z

    2015-01-01

    Probiotics have been shown to have a preventative effect on skin photoaging induced by short term UV irradiation, however, the underlying mechanisms and the effect of probiotics on skin photoaging induced by chronic UV irradiation remain unclear. In this study, we investigated the effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in hairless mice. Mice were irradiated with UVB three times weekly and orally administered B. breve B-3 (2×10(9) cfu/mouse /day) for 7 weeks. Nonirradiated mice and UVB-irradiated mice without probiotic treatment were used as controls. B. breve B-3 significantly suppressed the changes of transepidermal water loss, skin hydration, epidermal thickening and attenuated the damage to the tight junction structure and basement membrane induced by chronic UVB irradiation. Administration of B. breve B-3 tended to suppress the UV-induced interleukin-1β production in skin (P=0.09). These results suggest that B. breve B-3 could potentially be used to prevent photoaging induced by chronic UV irradiation.

  8. Hip Abductor Muscle Volume and Strength Differences Between Women With Chronic Hip Joint Pain and Asymptomatic Controls.

    Science.gov (United States)

    Mastenbrook, Matthew J; Commean, Paul K; Hillen, Travis J; Salsich, Gretchen B; Meyer, Gretchen A; Mueller, Michael J; Clohisy, John C; Harris-Hayes, Marcie

    2017-12-01

    Study Design Secondary analysis, cross-sectional study. Background Chronic hip joint pain (CHJP) can lead to limitations in activity participation, but the musculoskeletal factors associated with the condition are relatively unknown. Understanding the factors associated with CHJP may help develop rehabilitation strategies to improve quality of life of individuals with long-term hip pain. Objectives To compare measures of hip abductor muscle volume and hip abductor muscle strength between women with CHJP and asymptomatic controls. Methods Thirty women, 15 with CHJP and 15 matched asymptomatic controls (age range, 18-40 years), participated in this study. Magnetic resonance imaging was used to determine the volume of the primary hip abductor muscles, consisting of the gluteus medius, gluteus minimus, a small portion of the gluteus maximus, and the tensor fascia latae, within a defined region of interest. Break tests were performed using a handheld dynamometer to assess hip abductor strength. During the strength test, the participant was positioned in sidelying with the involved hip in 15° of abduction. Independent-samples t tests were used to compare muscle volume and strength values between those with CHJP and asymptomatic controls. Results Compared to asymptomatic controls, women with CHJP demonstrated significantly increased gluteal muscle volume (228 ± 40 cm 3 versus 199 ± 29 cm 3 , P = .032), but decreased hip abductor strength (74.6 ± 16.8 Nm versus 93.6 ± 20.2 Nm, P = .009). There were no significant differences in tensor fascia lata muscle volume between the 2 groups (P = .640). Conclusion Women with CHJP appear to have larger gluteal muscle volume, but decreased hip abductor strength, compared to asymptomatic controls. J Orthop Sports Phys Ther 2017;47(12):923-930. Epub 9 Oct 2017. doi:10.2519/jospt.2017.7380.

  9. Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases.

    Science.gov (United States)

    Cameron, Robert B; Beeson, Craig C; Schnellmann, Rick G

    2016-12-08

    Mitochondria have various roles in cellular metabolism and homeostasis. Because mitochondrial dysfunction is associated with many acute and chronic degenerative diseases, mitochondrial biogenesis (MB) is a therapeutic target for treating such diseases. Here, we review the role of mitochondrial dysfunction in acute and chronic degenerative diseases and the cellular signaling pathways by which MB is induced. We then review existing work describing the development and application of drugs that induce MB in vitro and in vivo. In particular, we discuss natural products and modulators of transcription factors, kinases, cyclic nucleotides, and G protein-coupled receptors.

  10. Chronic sacroiliac joint and pelvic girdle dysfunction in a 35-year-old nulliparous woman successfully managed with multimodal and multidisciplinary approach.

    Science.gov (United States)

    Jonely, Holly; Brismée, Jean-Michel; Desai, Mehul J; Reoli, Rachel

    2015-02-01

    Sacroiliac joint pain and dysfunction affect 15-25% of patients reporting low back pain, including reports of spontaneous, idiopathic, traumatic, and non-traumatic onsets. The poor reliability and validity associated with diagnostic clinical and imaging techniques leads to challenges in diagnosing and managing sacroiliac joint dysfunction. A 35-year-old nulliparous female with a 14-year history of right sacroiliac joint dysfunction was managed using a multimodal and multidisciplinary approach when symptoms failed to resolve after 2 months of physical therapy. The plan of care included four prolotherapy injections, sacroiliac joint manipulation into nutation, pelvic girdle belting, and specific stabilization exercises. The patient completed 20 physical therapy sessions over a 12-month period. At 6 months, the patient's Oswestry Disability Questionnaire score was reduced from 34% to 14%. At 1-year follow-up, her score was 0%. The patient's rating of pain on a numeric rating scale decreased to an average of 4/10 at 6 months and 0/10 at 1-year follow-up. A multidisciplinary and multimodal approach for the management of chronic sacroiliac joint dysfunction appeared successful in a single-case design at 1-year follow-up.

  11. temporomandibular joint cartilage in rabbits affected by drug-induced osteoarthritis

    Directory of Open Access Journals (Sweden)

    Krzysztof Kałużyński

    2016-02-01

    Full Text Available Background: The aims of this study were to assess the anti-degenerative effects of pioglitazone and to compare these effects with those of methylprednisolone and hyaluronic acid on drug-induced osteoarthritis in rabbits’ temporomandibular joint cartilage.Material and Methods: The experiment was conducted on 40 Californian white rabbits. Degenerative changes were induced by intra-articular injections of papain. Subsequently, all of the animals were randomly assigned to one of four groups:1 a control group that received no medications;2 a group treated with 4 intra-articular injections of 2 mg (0.2 ml of hyaluronic acid at weekly intervals;3 a group treated with 4 intra-articular injections of 2 mg (0.1 ml of methylprednisolone at weekly intervals;4 a group administered pioglitazone orally in daily doses of 2 mg/kg of body weight. Four weeks after the beginning of drug administration, the rabbits were sacrificed. Sagittal sections of the intra-articular cartilage (discs and mandibular condyles were stained with hematoxylin and eosin by the PAS technique and with van Gieson’s solution. Histologic examinations, as well as cartilage thickness and number of cell layers measurements, were performed.Results: Histologic assessment in cases of arthritis-associated pathologies revealed that changes occurred most frequently in the control group and least frequently in the pioglitazone group. There were no differences in the histological structures of the intra-articular discs. Cartilage thickness measurements demonstrated the thinnest cartilage in group 2 and the thickest in group 3. Analysis of cell layer numbers showed the most numerous layers in the pioglitazone group and the least in the control group.Conclusion: Pioglitazone and hyaluronic acid showed anti-degenerative properties compared to methylprednisolone in an animal model.

  12. The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

    Science.gov (United States)

    Abd El Wahab, Manal Galal; Ali, Soad Shaker; Ayuob, Nasra Naeim

    2018-06-01

    This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

  13. MR imaging in solvent-induced chronic toxic encephalopathy

    International Nuclear Information System (INIS)

    Thuomas, K.AA.; Moeller, C.; Oedkvist, L.M.; Flodin, U.; Dige, N.

    1996-01-01

    To use MR to examine patients with CNS symptoms indicating chronic intoxication. Thirty-two subjects exposed to industrial solvents for 5 to 28 years and 40 age-matched, healthy controls were examined. All patients showed decreased signal in the basal ganglia on T2-weighted images. In 11 of the patients the white matter showed diffuse hyperintensity with loss of the grey-white matter discrimination and with distinct periventricular hyperintensities in 5 of the patients. The controls had no pathological changes in the brain. Although the relatively small number of patients may obscure the significance, findings observed on T2-weighted images were patchy periventricular hyperintensities and hypointensities in the basal ganglia. Fast spin-echo is a good technique with fast acquisition of images with true spin-echo contrast features. (orig.)

  14. Alterations in offspring behavior induced by chronic prenatal cocaine dosing.

    Science.gov (United States)

    Smith, R F; Mattran, K M; Kurkjian, M F; Kurtz, S L

    1989-01-01

    Sperm-positive female Long-Evans hooded rats were dosed subcutaneously with 10 mg/kg/day cocaine or an equal volume of vehicle (0.9% sterile saline) from gestation day 4 (GD4) through GD18. Offspring were assessed for development of negative geotaxis, righting reflex, spontaneous alternation, and open field activity, and for adult behaviors including DRL-20 acquisition, water maze, visual discrimination, barbiturate sleep time, shuttlebox avoidance, footshock sensitivity, and tail flick latency. Cocaine dosing produced no significant effects on dam weight gain, any measure of litter size and weight, or early postnatal behavioral tests, but there were significant drug effects on development of spontaneous alternation, development of open field activity, DRL-20 acquisition, water maze performance, tail flick, and footshock sensitivity. These data suggest that chronic administration of a modest dose of cocaine during gestation in the rat alters a number of behaviors in the offspring.

  15. Leakage flow-induced vibration of an unconstricted tube-in-tube slip joint

    International Nuclear Information System (INIS)

    Mulcahy, T.M.

    1986-12-01

    The conditions are given for which the more flexible of two cantilevered, telescoping tubes conveying fluid can be self-excited by flow leaking from an unconstricted slip joint. Also, a physical explanation of the excitation mechanism is discussed, and a design rule to avoid the mechanism is presented. In addition, the results for the unconstricted slip joint are shown to be similar to those for slip joints having annulus constrictions at very short engagement lengths

  16. Visually induced analgesia during massage treatment in chronic back pain patients.

    Science.gov (United States)

    Löffler, A; Trojan, J; Zieglgänsberger, W; Diers, M

    2017-11-01

    Previous findings suggest that watching sites of experimental and chronic pain can exert an analgesic effect. Our present study investigates whether watching one's back during massage increases the analgesic effect of this treatment in chronic back pain patients. Twenty patients with chronic back pain were treated with a conventional massage therapy. During this treatment, patients received a real-time video feedback of their own back. Watching a neutral object, a video of another person of the same sex being massaged, a picture of the own back, and keeping one's eyes closed were used as controls. These conditions were presented in randomized order on five separate days. All conditions yielded significant decreases in habitual pain intensity. The effect of real-time video feedback of the own back on massage treatment was the strongest and differed significantly from the effect of watching a neutral object, but not from the other control conditions, which may have induced slight effects of their own. Repeated real-time video feedback may be useful during massage treatment of chronic pain. This study shows that inducing visual induced analgesia during massage treatment can be helpful in alleviating chronic pain. © 2017 European Pain Federation - EFIC®.

  17. Effect of Xiaoyaosan Decoction on Learning and Memory Deficit in Rats Induced by Chronic Immobilization Stress

    OpenAIRE

    Meng, Zhen-Zhi; Chen, Jia-Xu; Jiang, You-Ming; Zhang, Han-Ting

    2013-01-01

    Xiaoyaosan (XYS) decoction is a famous prescription which can protect nervous system from stress and treat liver stagnation and spleen deficiency syndrome (LSSDS). In this experiment, we observed the effect of XYS decoction on chronic immobilization stress (CIS) induced learning and memory deficit in rats from behaviors and changes of proteins in hippocampus. We used XYS decoction to treat CIS induced learning and memory deficit in rats with rolipram as positive control, used change of body w...

  18. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Ignacio Negrón-Oyarzo

    2016-01-01

    Full Text Available Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.

  19. Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity.

    Science.gov (United States)

    Kras, J V; Kartha, S; Winkelstein, B A

    2015-11-01

    The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability. Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses. NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability. Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  20. Joint Instability and Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Darryl Blalock

    2015-01-01

    Full Text Available Joint instability creates a clinical and economic burden in the health care system. Injuries and disorders that directly damage the joint structure or lead to joint instability are highly associated with osteoarthritis (OA. Thus, understanding the physiology of joint stability and the mechanisms of joint instability-induced OA is of clinical significance. The first section of this review discusses the structure and function of major joint tissues, including periarticular muscles, which play a significant role in joint stability. Because the knee, ankle, and shoulder joints demonstrate a high incidence of ligament injury and joint instability, the second section summarizes the mechanisms of ligament injury-associated joint instability of these joints. The final section highlights the recent advances in the understanding of the mechanical and biological mechanisms of joint instability-induced OA. These advances may lead to new opportunities for clinical intervention in the prevention and early treatment of OA.

  1. Joint instability and osteoarthritis.

    Science.gov (United States)

    Blalock, Darryl; Miller, Andrew; Tilley, Michael; Wang, Jinxi

    2015-01-01

    Joint instability creates a clinical and economic burden in the health care system. Injuries and disorders that directly damage the joint structure or lead to joint instability are highly associated with osteoarthritis (OA). Thus, understanding the physiology of joint stability and the mechanisms of joint instability-induced OA is of clinical significance. The first section of this review discusses the structure and function of major joint tissues, including periarticular muscles, which play a significant role in joint stability. Because the knee, ankle, and shoulder joints demonstrate a high incidence of ligament injury and joint instability, the second section summarizes the mechanisms of ligament injury-associated joint instability of these joints. The final section highlights the recent advances in the understanding of the mechanical and biological mechanisms of joint instability-induced OA. These advances may lead to new opportunities for clinical intervention in the prevention and early treatment of OA.

  2. Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

    Directory of Open Access Journals (Sweden)

    Zhengxiu Su

    Full Text Available Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model or sham operation were treated for 2 weeks with a normal-(0.4% NaCl, or high-salt (4% NaCl diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54% phosphopeptides upregulated and 76 (46% phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49% phosphopeptides and downregulation of 88 (51% phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

  3. Criteria for solvent-induced chronic toxic encephalopathy: a systematic review

    NARCIS (Netherlands)

    van der Hoek, J. A.; Verberk, M. M.; Hageman, G.

    2000-01-01

    In 1985, a WHO Working Group presented diagnostic criteria and a classification for solvent-induced chronic toxic encephalopathy (CTE). In the same year, the "Workshop on neurobehavioral effects of solvents" in Raleigh, N.C., USA introduced a somewhat different classification for CTE. The objective

  4. Bone scintigraphy and tenofovir-induced osteomalacia in chronic hepatitis B

    Energy Technology Data Exchange (ETDEWEB)

    Hoe, Alex khoo cheen; Feng, Lee Yeong [Dept. of Nuclear Medicine, Penang Hospital, Georgetown (Malaysia)

    2017-06-15

    Tenofovir, used in the treatment of chronic hepatitis B and HIV, is known for its side effects on the kidneys and bones. We share interesting images of a patient with tenofovir-induced osteomalacia on Technetium-99 m hydroxymethyelene (Tc-99 m HDP) bone scintigraphy. Pattern recognition of this bone scintigraphy and correlation with the clinical history is essential to avoid misdiagnosis.

  5. Bone scintigraphy and tenofovir-induced osteomalacia in chronic hepatitis B

    International Nuclear Information System (INIS)

    Hoe, Alex khoo cheen; Feng, Lee Yeong

    2017-01-01

    Tenofovir, used in the treatment of chronic hepatitis B and HIV, is known for its side effects on the kidneys and bones. We share interesting images of a patient with tenofovir-induced osteomalacia on Technetium-99 m hydroxymethyelene (Tc-99 m HDP) bone scintigraphy. Pattern recognition of this bone scintigraphy and correlation with the clinical history is essential to avoid misdiagnosis

  6. Central role of T helper 17 cells in chronic hypoxia-induced pulmonary hypertension.

    Science.gov (United States)

    Maston, Levi D; Jones, David T; Giermakowska, Wieslawa; Howard, Tamara A; Cannon, Judy L; Wang, Wei; Wei, Yongyi; Xuan, Weimin; Resta, Thomas C; Gonzalez Bosc, Laura V

    2017-05-01

    Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4 + T cells are required for initiating and maintaining inflammation, suggesting that these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension. Our objective was to test the hypothesis that CD4 + T cells, specifically the T helper 17 subset, contribute to chronic hypoxia-induced pulmonary hypertension. We compared indices of pulmonary hypertension resulting from chronic hypoxia (3 wk) in wild-type mice and recombination-activating gene 1 knockout mice (RAG1 -/- , lacking mature T and B cells). Separate sets of mice were adoptively transferred with CD4 + , CD8 + , or T helper 17 cells before normoxic or chronic hypoxic exposure to evaluate the involvement of specific T cell subsets. RAG1 -/- mice had diminished right ventricular systolic pressure and arterial remodeling compared with wild-type mice exposed to chronic hypoxia. Adoptive transfer of CD4 + but not CD8 + T cells restored the hypertensive phenotype in RAG1 -/- mice. Interestingly, RAG1 -/- mice receiving T helper 17 cells displayed evidence of pulmonary hypertension independent of chronic hypoxia. Supporting our hypothesis, depletion of CD4 + cells or treatment with SR1001, an inhibitor of T helper 17 cell development, prevented increased pressure and remodeling responses to chronic hypoxia. We conclude that T helper 17 cells play a key role in the development of chronic hypoxia-induced pulmonary hypertension. Copyright © 2017 the American Physiological Society.

  7. Gadolinium-enhanced MRI features of acute gouty arthritis on top of chronic gouty involvement in different joints

    NARCIS (Netherlands)

    Emad, Yasser; Ragab, Yasser; El-Naggar, Ahmed; El Shaarawy, Nashwa; Abd-Allah, Mayada A.; Gamal, Rania M.; Fathy, Ahmed; Hawass, Mona; Rasker, Johannes J.

    2015-01-01

    The aims of the current study are to describe gadolinium-enhanced MRI features of an acute flare of established gouty arthritis in different joints and to examine a possible association between serum uric acid and MRI signs indicative of ongoing inflammation and/or structural joint damage as well as

  8. Epicutaneous immunization with type II collagen inhibits both onset and progression of chronic collagen-induced arthritis.

    Directory of Open Access Journals (Sweden)

    Jessica Strid

    Full Text Available Epicutaneous immunization is a potential non-invasive technique for antigen-specific immune-modulation. Topical application of protein antigens to barrier-disrupted skin induces potent antigen-specific immunity with a strong Th2-bias. In this study, we investigate whether the autoimmune inflammatory response of chronic collagen-induced arthritis (CCIA in DBA/1-TCR-beta Tg mice can be modified by epicutaneous immunization. We show that epicutaneous immunization with type II collagen (CII inhibited development and progression of CCIA and, importantly, also ameliorated ongoing disease as indicated by clinical scores of disease severity, paw swelling and joints histology. Treated mice show reduced CII-driven T cell proliferation and IFN-gamma production, as well as significantly lower levels of CII-specific IgG2a serum antibodies. In contrast, CII-driven IL-4 production and IgE antibody levels were increased consistent with skewing of the CII response from Th1 to Th2 in treated mice. IL-4 production in treated mice was inversely correlated with disease severity. Moreover, T cells from treated mice inhibited proliferation and IFN-gamma production by T cells from CCIA mice, suggesting induction of regulatory T cells that actively inhibit effector responses in arthritic mice. The levels of CD4(+CD25(+ T cells were however not increased following epicutaneous CII treatment. Together, these results suggest that epicutaneous immunization may be used as an immune-modulating procedure to actively re-programme pathogenic Th1 responses, and could have potential as a novel specific and simple treatment for chronic autoimmune inflammatory diseases such as rheumatoid arthritis.

  9. Prevalence of neuroleptic-induced movement disorders in chronic schizophrenia inpatients.

    Science.gov (United States)

    Janno, Sven; Holi, Matti; Tuisku, Katinka; Wahlbeck, Kristian

    2004-01-01

    Since most of the world's schizophrenia patients are treated with conventional antipsychotics, the authors evaluated various methods for establishing the prevalence of neuroleptic-induced movement disorders in these patients. DSM-IV criteria and established score thresholds on a movement disorder rating scale were used to identify cases of neuroleptic-induced movement disorder in a representative Estonian patient sample of 99 chronic institutionalized schizophrenia patients, 18-65 years old, treated with conventional neuroleptics (79.8%) or clozapine (20.2%). Neuroleptic-induced movement disorders according to DSM-IV criteria were found in 61.6% of the group: 31.3% had neuroleptic-induced akathisia, 23.2% had neuroleptic-induced parkinsonism, and 32.3% had neuroleptic-induced tardive dyskinesia. Prevalence rates for akathisia and tardive dyskinesia were similar when either DSM-IV criteria or rating scale scores were used, but the prevalence rate for parkinsonism was much lower per DSM-IV criteria than according to rating scale score. Nearly two-thirds of chronic schizophrenia patients suffered from a neuroleptic-induced movement disorder. Globally, extrapyramidal adverse effects still impose a huge burden on the majority of neuroleptic-treated individuals with schizophrenia. The discrepancy between the standard identification methods for neuroleptic-induced movement disorder indicate the need for further research.

  10. Protective effect of curcumin on experimentally induced arthritic rats: detailed histopathological study of the joints and white blood cell count

    OpenAIRE

    Kamarudin, Taty Anna; Othman, Faizah; Mohd Ramli, Elvy Suhana; Md Isa, Nurismah; Das, Srijit

    2012-01-01

    Curcuma longa (turmeric) rhizomes contains curcumin, an active compound which possesses anti-inflammatory effects. Collagen-induced arthritis (CIA) is an accepted experimental animal model of rheumatoid arthritis. The present study aimed to observe the histological changes in the joints of experimental arthritic rats treated with curcumin. Twenty four male Sprague-Dawley (approximately 7 weeks-old) rats were randomly divided into four groups. Three groups were immunized with 150 ?g collagen. ...

  11. Impairment induced by chronic occupational cadmium exposure during brazing process

    International Nuclear Information System (INIS)

    Anwar, S.M.; Aly, M.M.

    2002-01-01

    Cadmium (CD) is considered a metal of the 20 th century to which all inhabitants of develop societies are exposed. Long-term occupational and environmental exposure to CD often results in renal dysfunction as the kidney is considered the critical target organ. The aim of this work was to evalutate both resporatory and renal manifestations induced by occupational exposure to CD compounds during brazing process, and suggesting a protocol for prevention and control for CD- induced health effects. This study was conducted on 20 males occupationally exposed workers. They are divided into two groups: Group-1 included (10) exposed smokers and group-2 included (10) exposed non-smokers. Results of both groups were compared with those of 10 healthy age and sex matched non-smokers. All subjects were subjected to detailed history taking and laboratory investigations including blood and urinary CD, liver profile (SGOT, SGPT and alkline phosphates), kindey function tests (blood urea, creatinine and urinary beta 2 - microglobulin). The level of Cd in the atmosphere of the work plase air was also assessed to detect the degree of exposure as it was about 6 times greater than thesave level (1 mu /m 3 ). (1) This study demonstrated elevation levels of blood CD, urea, creatinine and urinary CD and beta 2 -microglobulin for both exposed worker groups than the controls. In additions no appreciable were noted for liver function tests, although the levels fell within normal range

  12. Six Sessions of Anterior-to-Posterior Ankle Joint Mobilizations Improve Patient-Reported Outcomes in Chronic Ankle Instability Patients: A Critically Appraised Topic.

    Science.gov (United States)

    Wikstrom, Erik A; Bagherian, Sajad; Cordero, Nicole B; Song, Kyeongtak

    2018-01-24

    Clinical Scenario: Chronic ankle instability (CAI) is a complex musculoskeletal condition that results in sensorimotor and mechanical alterations. Manual therapies, such as ankle joint mobilizations are known to improve clinician-oriented outcomes like dorsiflexion range of motion but their impact of patient-reported outcomes remains less clear. Focused Clinical Question: Do anterior-to-posterior ankle joint mobilizations improve patient reported outcomes in patients with CAI? Summary of Key Findings: Three studies (2 RCT, 1 Prospective cohort) quantified the effect of at least 2-weeks of anterior-to-posterior ankle joint mobilizations on improving patient reported outcomes immediately after the intervention and at a follow-up assessment. All three studies demonstrated significant improvements in at least one patient-reported outcome immediately after the intervention and at the follow-up assessment. Clinical Bottom Line: At least 2-weeks of ankle joint mobilization improves patient-reported outcomes in patients with CAI and these benefits are retained for at least a week following the termination of the intervention. Strength of Recommendation: Strength of recommendation is an A due to consistent good-quality patient-oriented evidence.

  13. Interferon alpha induced cytogenetic remissions of chronic myelocytic leukemia

    International Nuclear Information System (INIS)

    Oguma, Nobuo; Shigeta, Chiharu; Tanaka, Kimio; Kamada, Nanao; Kuramoto, Atsushi; Ito, Chikako.

    1994-01-01

    In two heavily exposed A-bomb survivors, Philadelphia (Ph 1 ) chromosomes completed disappeared by the treatment with interferon (IFN)-α for chronic myelocytic leukemia (CML). One is a 55-year-old man exposed at 2.0 km in Hiroshima at the age of 13. Periodic mass screening in 1987 showed the presence of Ph 1 chromosomes, in addition to an increased number of leukocytes and the presence of neocytes. Subcutaneous injection of IFN-α (6,000,000 units/day) was started with a diagnosis of CML, and 5 months later Ph 1 chromosomes disappeared. Then, because Ph 1 chromosomes were found in 2.8% of 143 cells one year and 6 months after the termination of IFN-α, re-injection of IFN-α was started. The other patient is a 53-year-old woman exposed at 2.0 km in Hiroshima at the age of 6. She was pointed out to have leukocytosis in 1992; bone marrow examination showed the presence of Ph 1 chromosomes in 88.1% of 88 cells analyzed, leading to a diagnosis of CML. Subcutaneous injection of IFN-α (6,000,000 units/day) was started and 5 months later Ph 1 chromosomes disappeared. As of 11 months after the start of injection, no Ph 1 chromosomes were observed, but the patient is still treated with IFN-α injection. Effects of IFN-α and problems of residual Ph 1 chromosomes are discussed in a review of the literature. (N.K.)

  14. Joint-position sense is altered by football pre-participation warm-up exercise and match induced fatigue.

    Science.gov (United States)

    Salgado, Eduardo; Ribeiro, Fernando; Oliveira, José

    2015-06-01

    The demands to which football players are exposed during the match may augment the risk of injury by decreasing the sense of joint position. This study aimed to assess the effect of pre-participation warm-up and fatigue induced by an official football match on the knee-joint-position sense of football players. Fourteen semi-professional male football players (mean age: 25.9±4.6 years old) volunteered in this study. The main outcome measures were rate of perceived exertion and knee-joint-position sense assessed at rest, immediately after a standard warm-up (duration 25 min), and immediately after a competitive football match (90 minutes duration). Perceived exertion increased significantly from rest to the other assessments (rest: 8.6±2.0; after warm-up: 12.1±2.1; after football match: 18.5±1.3; pfootball match compared to both rest (pfootball match-induced fatigue. Warm-up exercises could contribute to knee injury prevention, whereas the deleterious effect of match-induced fatigue on the sensorimotor system could ultimately contribute to knee instability and injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Expression of telomerase reverse transcriptase in radiation-induced chronic human skin ulcer

    International Nuclear Information System (INIS)

    Zhao Po; Li Zhijun; Lu Yali; Zhong Mei; Gu Qingyang; Wang Dewen

    2001-01-01

    Objective: To investigate the expression of the catalytic subunit of telomerase, telomerase reverse transcriptase (TRT) and the possible relationship between the TRT and cancer transformation or poor healing in radiation-induced chronic ulcer of human skin. Methods: Rabbit antibody against human TRT and SP immunohistochemical method were used to detect TRT expression in 24 cases of formalin-fixed, paraffin-embed human skin chronic ulcer tissues induced by radiation, 5 cases of normal skin, 2 of burned skin, and 8 of carcinoma. Results: The positive rate for TRT was 58.3%(14/24) in chronic radiation ulcers, of which the strongly positive rate was 41.7%(10/24) and the weakly positive 16.7%(4/24), 0% in normal (0/5) and burned skin (0/2), and 100% in carcinoma (8/8). The strongly positive expression of TRT was observed almost always in the cytoplasm and nucleus of squamous epithelial cells of proliferative epidermis but the negative and partly weakly positive expression in the smooth muscles, endothelia of small blood vessels and capillaries, and fibroblasts. Chronic inflammtory cells, plasmacytes and lymphocytes also showed weakly positive for TRT. Conclusion: TRT expression could be involved in the malignant transformation of chronic radiation ulcer into squamous carcinoma, and in the poor healing caused by sclerosis of small blood vessels and lack of granulation tissue consisting of capillaries and fibroblasts

  16. Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

    Science.gov (United States)

    Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

    2013-11-15

    Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

  17. Chronic Fluoxetine Induces Activity Changes in Recovery From Poststroke Anxiety, Depression, and Cognitive Impairment.

    Science.gov (United States)

    Vahid-Ansari, Faranak; Albert, Paul R

    2018-01-01

    Poststroke depression (PSD) is a common outcome of stroke that limits recovery and is only partially responsive to chronic antidepressant treatment. In order to elucidate changes in the cortical-limbic circuitry associated with PSD and its treatment, we examined a novel mouse model of persistent PSD. Focal endothelin-1-induced ischemia of the left medial prefrontal cortex (mPFC) in male C57BL6 mice resulted in a chronic anxiety and depression phenotype. Here, we show severe cognitive impairment in spatial learning and memory in the stroke mice. The behavioral and cognitive phenotypes were reversed by chronic (4-week) treatment with fluoxetine, alone or with voluntary exercise (free-running wheel), but not by exercise alone. To assess chronic cellular activation, FosB + cells were co-labeled for markers of glutamate/pyramidal (VGluT1-3/CaMKIIα), γ-aminobutyric acid (GAD67), and serotonin (TPH). At 6 weeks poststroke versus sham (or 4 days poststroke), left mPFC stroke induced widespread FosB activation, more on the right (contralesional) than on the left side. Stroke activated glutamate cells of the mPFC, nucleus accumbens, amygdala, hippocampus, and raphe serotonin neurons. Chronic fluoxetine balanced bilateral neuronal activity, reducing total FosB and FosB/CamKII + cells (mPFC, nucleus accumbens), and unlike exercise, increasing FosB/GAD67 + cells (septum, amygdala) or both (hippocampus, raphe). In summary, chronic antidepressant but not exercise mediates recovery in this unilateral ischemic PSD model that is associated with region-specific reversal of stroke-induced pyramidal cell hyperactivity and increase in γ-aminobutyric acidergic activity. Targeted brain stimulation to restore brain activity could provide a rational approach for treating clinical PSD.

  18. Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    GURPREET KAUR

    2015-03-01

    Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

  19. Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.

    Science.gov (United States)

    Zhang, Ning; Liang, Hanyu; Farese, Robert V; Li, Ji; Musi, Nicolas; Hussey, Sophie E

    2015-01-01

    To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats. For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp. Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP. Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo.

  20. Avoiding leakage flow-induced vibration by a tube-in-tube slip joint

    International Nuclear Information System (INIS)

    Mulcahy, T.M.

    1985-01-01

    Parameters and operating conditions (a stability map) were determined for which a specific slip-joint design did not cause self-excited lateral vibration of the two cantilevered, telescoping tubes forming the joint. The joint design featured a localized annular constriction. Flowrate, modal damping, tube engagement length, and eccentric positioning were among the parameters tested. Interestingly, all self-excited vibrations could be avoided by following a simple design rule: place constrictions only at the downstream end of the annular region between the tubes. Also, overall modal damping decreased with increased flowrate, at least initially, for upstream constrictions while the damping increased for downstream constrictions

  1. [The specificity and limitations of sacroiliac joint magnetic resonance imaging in the diagnosis of axial spondyloarthritis in patients with chronic low back pain].

    Science.gov (United States)

    Wang, Y Y; Zhao, Z; Luo, G; Li, Y; Zhang, J L; Huang, F

    2016-11-01

    Objective: To evaluate the specificity and limitations of sacroiliac joint magnetic resonance imaging (MRI) in the diagnosis of axial spondyloarthritis (SpA)in patients with chronic low back pain. Methods: We retrospectively analyzed clinical data of 390 patients with chronic low back pain in Department of Rheumatology, the PLA General Hospital from January 2013 to December 2015, including clinical manifestations, laboratory examinations and MRI data of sacroiliac joints. Results: There were 238 men and 152 women recruited. A total of 326 cases were diagnosed as axial SpA, including 216 men and 110 women with mean age (27.10±8.64) years and mean duration (7.64±3.50) months. Among these 326 patients, 243 (74.5%) were HLA-B 27 positive. The other 64 patients were considered as diagnoses rather than SpA (non-SpA), consisting of 22 men and 42 women with mean age (31.29±7.76) years and mean duration (5.75±2.90)months. Non-SpA group had 10 (15.6%) patients with HLA-B 27 positive. There were 68.1% and 65.0% SpA patients showing bone marrow edema and bone erosion of sacroiliac joint in MRI imaging respectively. Although there were 25.0% non-SpA patients with bone marrow edema and 7.8% with bone erosion in MRI of sacroiliac joint, the scores of bone marrow edema 0.00(0.00, 0.75) and bone erosion [0.00(0.00, 0.00)] were significantly lower compared with those in axial SpA group [bone marrow edema scores 2.00(0.00, 4.00), bone erosion scores 1.00(0.00, 3.00); P Sacroiliac joint MRI is a valuable method to diagnose axial SpA in patients with chronic low back pain. Yet it still has some limitations. Clinical presentations and spinal MRI would be helpful in some patients.

  2. 硫糖铝联合黄连素治疗慢性顽固性胃炎的临床疗效分析%Comprehensive Analysis Sucralfate Joint Berberine for the Treatment of Chronic Intractable Chronic Gastritis

    Institute of Scientific and Technical Information of China (English)

    董智常; 苏家新; 陈佩容

    2014-01-01

    Objective To analyze sucralfate joint berberine effect on the treatment of chronic stubborn gastritis. Methods Select 180 cases of patients who have confirmed with chronic stubborn gastritis, then all patients start taking sucralfate and berberine, and own symptoms before treatment and after treatment in patients with symptoms were compared, so we obtain the effective rate. Results Two drug combination treatment of chronic stubborn gastritis is very effective. Conclusions Sucralfate joint berberine treat chronic stubborn gastritis, making the patients symptoms improved after treatment, the total effective rate is higher, and severe side effects rarely only a handful of constipation, dry mouth, find out a way for clinical treatment of chronic stubborn gastritis.%目的:分析硫糖铝联合黄连素对慢性顽固性胃炎的治疗效果。方法选取已确诊的慢性顽固性胃炎患者180例,所有患者均开始服用硫糖铝和黄连素,将患者自身治疗前症状与治疗后症状进行对照,从而得出有效率。结果两药物联用治疗慢性顽固性胃炎极为有效。结论硫糖铝联合黄连素治疗慢性顽固性胃炎,使得患者治疗后症状大为改善,总有效率较高,且严重副作用极少仅少数出现便秘、口干,为临床上治疗慢性顽固性胃炎寻得出路。

  3. Cementless One-Stage Revision in Chronic Periprosthetic Hip Joint Infection. Ninety-One Percent Infection Free Survival in 56 Patients at Minimum 2-Year Follow-Up

    DEFF Research Database (Denmark)

    Lange, Jeppe; Troelsen, Anders; Solgaard, Søren

    2018-01-01

    was re-revision performed due to infection and was evaluated by competing risk analysis, with death and aseptic revision as competing events. All-cause mortality was evaluated by Kaplan-Meier survival analysis. Oxford Hip Score (OHS) was used as disease-specific patient-reported outcome measure. RESULTS......BACKGROUND: Cementless 1-stage revision in chronic periprosthetic hip joint infections is limited evaluated. The purpose of this study was to evaluate a specific treatment protocol in this patient group. METHODS: The study was performed as a multicenter, proof-of-concept, observational study...

  4. Mechanisms mediating vibration-induced chronic musculoskeletal pain analyzed in the rat.

    Science.gov (United States)

    Dina, Olayinka A; Joseph, Elizabeth K; Levine, Jon D; Green, Paul G

    2010-04-01

    While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and reexposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60-80Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a proinflammatory cytokine or reexposure to vibration. Exposure of a hind limb to vibration-produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for approximately 2 weeks. When nociceptive thresholds had returned to baseline, exposure to a proinflammatory cytokine or reexposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cepsilon, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-alpha (TNFalpha) receptor. Finally, in TNFalpha-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged. These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFalpha and the second messenger protein kinase Cepsilon as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome. Copyright 2010 American Pain Society. All rights reserved.

  5. Chronic caffeine exposure attenuates blast-induced memory deficit in mice.

    Science.gov (United States)

    Ning, Ya-Lei; Yang, Nan; Chen, Xing; Zhao, Zi-Ai; Zhang, Xiu-Zhu; Chen, Xing-Yun; Li, Ping; Zhao, Yan; Zhou, Yuan-Guo

    2015-01-01

    To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms. Adult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1, 4, and 8 weeks post-blast injury. Neurological deficit scoring, glutamate concentration, proinflammatory cytokines production, and neuropathological changes at 24 h, 1, 4, and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages. Adenosine A1 receptor expression was detected using qPCR. All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit, which is correlated with the neuroprotective effects against excitotoxicity, inflammation, astrogliosis and neuronal loss at different stages of injury. Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI; pre-bTBI and post-bTBI treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively. Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption. Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

  6. Maresin 1 Inhibits TRPV1 in Temporomandibular Joint-Related Trigeminal Nociceptive Neurons and TMJ Inflammation-Induced Synaptic Plasticity in the Trigeminal Nucleus

    Directory of Open Access Journals (Sweden)

    Chul-Kyu Park

    2015-01-01

    Full Text Available In the trigeminal system, disruption of acute resolution processing may lead to uncontrolled inflammation and chronic pain associated with the temporomandibular joint (TMJ. Currently, there are no effective treatments for TMJ pain. Recently, it has been recognized that maresin 1, a newly identified macrophage-derived mediator of inflammation resolution, is a potent analgesic for somatic inflammatory pain without noticeable side effects in mice and a potent endogenous inhibitor of transient receptor potential vanilloid 1 (TRPV1 in the somatic system. However, the molecular mechanisms underlying the analgesic actions of maresin 1 on TMJ pain are unclear in the trigeminal system. Here, by performing TMJ injection of a retrograde labeling tracer DiI (a fluorescent dye, I showed that maresin 1 potently inhibits capsaicin-induced TRPV1 currents and neuronal activity via Gαi-coupled G-protein coupled receptors in DiI-labeled trigeminal nociceptive neurons. Further, maresin 1 blocked TRPV1 agonist-evoked increases in spontaneous excitatory postsynaptic current frequency and abolished TMJ inflammation-induced synaptic plasticity in the trigeminal nucleus. These results demonstrate the potent actions of maresin 1 in regulating TRPV1 in the trigeminal system. Thus, maresin 1 may serve as a novel endogenous inhibitor for treating TMJ-inflammatory pain in the orofacial region.

  7. Development of a Method to Determine Abnormal Joint Torque Coupling Patterns During Walking In Chronic Hemiparetic Stroke

    NARCIS (Netherlands)

    Fricke, S.S.; Dragunas, Andrew C.; Gordon, Keith E.; van der Kooij, H.; van Asseldonk, E.H.F.; Dewald, Julius P. A.

    Motor impairments following stroke may lead to a reduced walking ability, however, no reliable assessments to quantify these impairments during walking are available [1]. For example, abnormal joint torque coupling between hip extension and hip adduction, previously reported under isometric

  8. Possible gasoline-induced chronic liver injury due to occupational malpractice in a motor mechanic: a case report

    OpenAIRE

    Gunathilaka, Mahesh Lakmal; Niriella, Madunil Anuk; Luke, Nathasha Vihangi; Piyarathna, Chathura Lakmal; Siriwardena, Rohan Chaminda; De Silva, Arjuna Priyadarshin; de Silva, Hithanadura Janaka

    2017-01-01

    Background Hydrocarbon-induced occupational liver injury is a well-known clinical entity among petroleum industry workers. There are many types of hydrocarbon exposure, with inhalation being the most common. Hydrocarbon-induced occupational liver injury is a rarely suspected and commonly missed etiological agent for liver injury. We report a case of a non-petroleum industry worker with chronic liver disease secondary to hydrocarbon-induced occupational liver injury caused by chronic low-grade...

  9. Effect of Bizhongxiao decoction and its dismantled formulae on IL-1 and TNF levels in collagen-induced arthritis in rat synovial joints

    Directory of Open Access Journals (Sweden)

    Guo Ya-jing

    2012-11-01

    Full Text Available Abstract Background Rheumatoid arthritis (RA, a chronic autoimmune disease, affects sufferers in many different ways. Treatment of this chronic condition is particularly challenging. Traditional Chinese Medicine (TCM provides alternatives. Bizhongxiao decoction (BZX is a TCM complex, which has been used clinically for many years to treat RA. The purpose of this study is to compare the effects of BZX decoction and its dismantled formulae on IL-1 and TNF-1 levels in rats with RA, and to elucidate its mechanism of action. Methods Ninety healthy normal female SD rats were randomly divided into six groups: normal (control, model, BZX decoction, and the three dismantled formulae (I: heat-clearing and detoxication, II: dissipating dampness, and III: blood circulation promotion. Apart from the normal (control group, the rats in each group were injected subcutaneously with bovine type II collagen and complete Freund adjuvant to establish a collagen-induced arthritis model, so that inhibition of foot swelling in the rats by BZX decoction and its dismantled formulae could be observed. Immunohistochemistry was used to assess the levels of the inflammatory cytokines IL-1 and TNF in synovial joints at various time points. Results Twenty-one days after the model was established, the levels of TNF and IL-1 were significantly higher in the model group, BZX decoction group and dismantled formula groups I, II and III than in the normal controls (P  Conclusions BZX decoction and the three dismantled formulae examined down-regulated the inflammatory factors IL-1 and TNF in collagen-induced arthritis rat models, but BZX exerted the strongest effect.

  10. Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.

    Science.gov (United States)

    Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza

    2017-02-05

    The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca 2+ ) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca 2+ and cause an increase in activity of calcium pumps, including Ca 2+ -ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Characterizing chronic and acute health risks of residues of veterinary drugs in food: latest methodological developments by the joint FAO/WHO expert committee on food additives.

    Science.gov (United States)

    Boobis, Alan; Cerniglia, Carl; Chicoine, Alan; Fattori, Vittorio; Lipp, Markus; Reuss, Rainer; Verger, Philippe; Tritscher, Angelika

    2017-11-01

    The risk assessment of residues of veterinary drugs in food is a field that continues to evolve. The toxicological end-points to be considered are becoming more nuanced and in light of growing concern about the development of antimicrobial resistance, detailed analysis of the antimicrobial activity of the residues of veterinary drugs in food is increasingly incorporated in the assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has refined its approaches to provide a more comprehensive and fit-for-purpose risk assessment. This publication describes in detail the consideration of acute and chronic effects, the estimation of acute and chronic dietary exposure, current approaches for including microbiological endpoints in the risk assessment, and JECFA's considerations for the potential effects of food processing on residues from veterinary drugs. JECFA now applies these approaches in the development of health-based guidance values (i.e. safe exposure levels) for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute and chronic risks by using corresponding estimates for acute and chronic exposure and suitable correction for the limited bioavailability of bound residues by the Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation products that occur from normal food processing of food containing veterinary drug residues. These approaches will continue to be refined to ensure the most scientifically sound basis for the establishment of health-based guidance values for veterinary drug residues.

  12. Overlapping mechanisms of stress-induced relapse to opioid use disorder and chronic pain: Clinical implications

    Directory of Open Access Journals (Sweden)

    Udi E Ghitza

    2016-05-01

    Full Text Available Over the past two decades, a steeply growing number of persons with chronic non-cancer pain have been using opioid analgesics chronically to treat it, accompanied by a markedly increased prevalence of individuals with opioid-related misuse, opioid use disorders, emergency department visits, hospitalizations, admissions to drug treatment programs, and drug overdose deaths. This opioid misuse and overdose epidemic calls for well-designed randomized-controlled clinical trials into more skillful and appropriate pain management and for developing effective analgesics which have lower abuse liability and are protective against stress induced by chronic non-cancer pain. However, incomplete knowledge regarding effective approaches to treat various types of pain has been worsened by an under-appreciation of overlapping neurobiological mechanisms of stress, stress-induced relapse to opioid use, and chronic non-cancer pain in patients presenting for care for these conditions. This insufficient knowledge base has unfortunately encouraged common prescription of conveniently-available opioid pain-relieving drugs with abuse liability, as opposed to treating underlying problems using team-based multidisciplinary, patient-centered, collaborative-care approaches for addressing pain and co-occurring stress and risk for opioid use disorder. This paper reviews recent neurobiological findings regarding overlapping mechanisms of stress-induced relapse to opioid misuse and chronic non-cancer pain, and then discusses these in the context of key outstanding evidence gaps and clinical-treatment research directions which may be pursued to fill these gaps. Such research directions, if conducted through well-designed randomized controlled trials, may substantively inform clinical practice in general medical settings on how to effectively care for patients presenting with pain-related distress and these common co-occurring conditions.

  13. Chronic alcohol feeding potentiates hormone-induced calcium signalling in hepatocytes.

    Science.gov (United States)

    Bartlett, Paula J; Antony, Anil Noronha; Agarwal, Amit; Hilly, Mauricette; Prince, Victoria L; Combettes, Laurent; Hoek, Jan B; Gaspers, Lawrence D

    2017-05-15

    Chronic alcohol consumption causes a spectrum of liver diseases, but the pathogenic mechanisms driving the onset and progression of disease are not clearly defined. We show that chronic alcohol feeding sensitizes rat hepatocytes to Ca 2+ -mobilizing hormones resulting in a leftward shift in the concentration-response relationship and the transition from oscillatory to more sustained and prolonged Ca 2+ increases. Our data demonstrate that alcohol-dependent adaptation in the Ca 2+ signalling pathway occurs at the level of hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) production and does not involve changes in the sensitivity of the IP 3 receptor or size of internal Ca 2+ stores. We suggest that prolonged and aberrant hormone-evoked Ca 2+ increases may stimulate the production of mitochondrial reactive oxygen species and contribute to alcohol-induced hepatocyte injury. ABSTRACT: 'Adaptive' responses of the liver to chronic alcohol consumption may underlie the development of cell and tissue injury. Alcohol administration can perturb multiple signalling pathways including phosphoinositide-dependent cytosolic calcium ([Ca 2+ ] i ) increases, which can adversely affect mitochondrial Ca 2+ levels, reactive oxygen species production and energy metabolism. Our data indicate that chronic alcohol feeding induces a leftward shift in the dose-response for Ca 2+ -mobilizing hormones resulting in more sustained and prolonged [Ca 2+ ] i increases in both cultured hepatocytes and hepatocytes within the intact perfused liver. Ca 2+ increases were initiated at lower hormone concentrations, and intercellular calcium wave propagation rates were faster in alcoholics compared to controls. Acute alcohol treatment (25 mm) completely inhibited hormone-induced calcium increases in control livers, but not after chronic alcohol-feeding, suggesting desensitization to the inhibitory actions of ethanol. Hormone-induced inositol 1,4,5 trisphosphate (IP 3 ) accumulation and phospholipase C

  14. Helicobacter pylori-Induced Chronic Gastritis and Assessing Risks for Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Gonzalo Carrasco

    2013-01-01

    Full Text Available Chronic gastritis is an inflammation of the gastric mucosa and has multiple etiologies. Here we discuss the pathological alterations induced by Helicobacter pylori (HP leading to chronic gastritis and the epigenetic bases underlying these changes. We review the histology of the normal gastric mucosa and overview the role of HP in the multistep cascade of GC. We attempt to define the role of the Operative Link for Gastritis Assessment (OLGA staging system in assessing the risk of GC. The epigenetic bases of chronic gastritis, mainly DNA methylation, are presented through examples such as (i the methylation of the promoter region of E-cadherin in HP-induced chronic gastritis and its reversion after HP eradication and (ii the association of methylation of the promoter region of Reprimo, a p53-mediated cell cycle arrest gene, with aggressive HP strains in high risk areas for GC. In addition, we discuss the finding of RPRM as a circulating cell-free DNA, offering the opportunity for noninvasive risk assessment of GC. Finally, the integration of OLGA and tissue biomarkers, by systems pathology approach, suggests that severe atrophy has a greater risk for GC development if, in addition, overexpressed p73. This trial is registered with ClinicalTrials.gov NCT01774266.

  15. Incoordination among Subcellular Compartments Is Associated with Depression-Like Behavior Induced by Chronic Mild Stress

    Science.gov (United States)

    Xu, Aiping; Cui, Shan

    2016-01-01

    Background: Major depressive disorder is characterized as persistent low mood. A chronically stressful life in genetically susceptible individuals is presumably the major etiology that leads to dysfunctions of monoamine and hypothalamus-pituitary-adrenal axis. These pathogenic factors cause neuron atrophy in the limbic system for major depressive disorder. Cell-specific pathophysiology is unclear, so we investigated prelimbic cortical GABAergic neurons and their interaction with glutamatergic neurons in depression-like mice. Methods: Mice were treated with chronic unpredictable mild stress for 3 weeks until they expressed depression-like behaviors confirmed by sucrose preference, Y-maze, and forced swimming tests. The structures and functions of GABAergic and glutamatergic units in prelimbic cortices were studied by cell imaging and electrophysiology in chronic unpredictable mild stress-induced depression mice vs controls. Results: In depression-like mice, prelimbic cortical GABAergic neurons show incoordination among the subcellular compartments, such as decreased excitability and synaptic outputs as well as increased reception from excitatory inputs. GABAergic synapses on glutamatergic cells demonstrate decreased presynaptic innervation and increased postsynaptic responsiveness. Conclusions: Chronic unpredictable mild stress-induced incoordination in prelimbic cortical GABAergic and glutamatergic neurons dysregulates their target neurons, which may be the pathological basis for depressive mood. The rebalance of compatibility among subcellular compartments would be an ideal strategy to treat neural disorders. PMID:26506857

  16. Oral Lesions Induced by Chronic Khat Use Consist Essentially of Thickened Hyperkeratinized Epithelium

    Directory of Open Access Journals (Sweden)

    Ochiba Mohammed Lukandu

    2015-01-01

    Full Text Available Objectives. The habit of khat chewing is prevalent in many Middle Eastern and African cultures and has been associated with various adverse conditions in humans. This study aimed to describe histological changes induced by chronic khat chewing on the buccal mucosa. Methods. Biopsies of the buccal mucosa from 14 chronic khat chewers, 20 chronic khat chewers who also smoked tobacco, and 8 nonchewers were compared for epithelial thickness, degree and type of keratinization, and connective tissue changes. Results. Tissues from khat chewers depicted abnormal keratinization of the superficial cell layer and showed increased epithelial thickness affecting all layers. Epithelial thickness in control samples was 205 ± 26 μm whereas thickness in khat chewers and khat chewers who smoked tobacco was significantly higher measuring 330 ± 35 μm and 335 ± 19 μm, respectively. Tissues from khat chewers also showed increased intracellular edema, increased melanin pigment deposits, and increased number of rete pegs most of which were thin and deep. Conclusions. These results show that oral lesions induced by chronic chewing of khat in the buccal mucosa present with white and brown discoloration due to increased epithelial thickness, increased keratinization, and melanin deposition.

  17. Chronic caffeine treatment prevents sleep deprivation-induced impairment of cognitive function and synaptic plasticity.

    Science.gov (United States)

    Alhaider, Ibrahim A; Aleisa, Abdulaziz M; Tran, Trinh T; Alzoubi, Karem H; Alkadhi, Karim A

    2010-04-01

    This study was undertaken to provide a detailed account of the effect of chronic treatment with a small dose of caffeine on the deleterious effects of sleep loss on brain function in rats. We investigated the effects of chronic (4 weeks) caffeine treatment (0.3 g/L in drinking water) on memory impairment in acutely (24 h) sleep-deprived adult male Wistar rats. Sleep deprivation was induced using the modified multiple platform model. The effects of caffeine on sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by 3 approaches: learning and memory performance in the radial arm water maze task, electrophysiological recording of early long-term potentiation (E-LTP) in area CA1 of the hippocampus, and levels of memory- and synaptic plasticity-related signaling molecules after E-LTP induction. The results showed that chronic caffeine treatment prevented impairment of hippocampus-dependent learning, shortterm memory and E-LTP of area CA1 in the sleep-deprived rats. In correlation, chronic caffeine treatment prevented sleep deprivation-associated decrease in the levels of phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) during expression of E-LTP. The results suggest that long-term use of a low dose of caffeine prevents impairment of short-term memory and E-LTP in acutely sleep-deprived rats.

  18. Numerical Modeling of Earthquake-Induced Landslide Using an Improved Discontinuous Deformation Analysis Considering Dynamic Friction Degradation of Joints

    Science.gov (United States)

    Huang, Da; Song, Yixiang; Cen, Duofeng; Fu, Guoyang

    2016-12-01

    Discontinuous deformation analysis (DDA) as an efficient technique has been extensively applied in the dynamic simulation of discontinuous rock mass. In the original DDA (ODDA), the Mohr-Coulomb failure criterion is employed as the judgment principle of failure between contact blocks, and the friction coefficient is assumed to be constant in the whole calculation process. However, it has been confirmed by a host of shear tests that the dynamic friction of rock joints degrades. Therefore, the friction coefficient should be gradually reduced during the numerical simulation of an earthquake-induced rockslide. In this paper, based on the experimental results of cyclic shear tests on limestone joints, exponential regression formulas are fitted for dynamic friction degradation, which is a function of the relative velocity, the amplitude of cyclic shear displacement and the number of its cycles between blocks with an edge-to-edge contact. Then, an improved DDA (IDDA) is developed by implementing the fitting regression formulas and a modified removing technique of joint cohesion, in which the cohesion is removed once the `sliding' or `open' state between blocks appears for the first time, into the ODDA. The IDDA is first validated by comparing with the theoretical solutions of the kinematic behaviors of a sliding block on an inclined plane under dynamic loading. Then, the program is applied to model the Donghekou landslide triggered by the 2008 Wenchuan earthquake in China. The simulation results demonstrate that the dynamic friction degradation of joints has great influences on the runout and velocity of sliding mass. Moreover, the friction coefficient possesses higher impact than the cohesion of joints on the kinematic behaviors of the sliding mass.

  19. Lithium modulates the chronic stress-induced effect on blood glucose level of male rats

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    Popović Nataša

    2010-01-01

    Full Text Available In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism.

  20. Chronic Enhancement of Serotonin Facilitates Excitatory Transcranial Direct Current Stimulation-Induced Neuroplasticity.

    Science.gov (United States)

    Kuo, Hsiao-I; Paulus, Walter; Batsikadze, Giorgi; Jamil, Asif; Kuo, Min-Fang; Nitsche, Michael A

    2016-04-01

    Serotonin affects memory formation via modulating long-term potentiation (LTP) and depression (LTD). Accordingly, acute selective serotonin reuptake inhibitor (SSRI) administration enhanced LTP-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. However, it usually takes some time for SSRI to reduce clinical symptoms such as anxiety, negative mood, and related symptoms of depression and anxiety disorders. This might be related to an at least partially different effect of chronic serotonergic enhancement on plasticity, as compared with single-dose medication. Here we explored the impact of chronic application of the SSRI citalopram (CIT) on plasticity induced by tDCS in healthy humans in a partially double-blinded, placebo (PLC)-controlled, randomized crossover study. Furthermore, we explored the dependency of plasticity induction from the glutamatergic system via N-methyl-D-aspartate receptor antagonism. Twelve healthy subjects received PLC medication, combined with anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took CIT (20 mg/day) consecutively for 35 days. During this period, four additional interventions were performed (CIT and PLC medication with anodal/cathodal tDCS, CIT and dextromethorphan (150 mg) with anodal/cathodal tDCS). Plasticity was monitored by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic application of CIT increased and prolonged the LTP-like plasticity induced by anodal tDCS for over 24 h, and converted cathodal tDCS-induced LTD-like plasticity into facilitation. These effects were abolished by dextromethorphan. Chronic serotonergic enhancement results in a strengthening of LTP-like glutamatergic plasticity, which might partially explain the therapeutic impact of SSRIs in depression and other neuropsychiatric diseases.

  1. Mechanisms Mediating Vibration-induced Chronic Musculoskeletal Pain Analyzed in the Rat

    OpenAIRE

    Dina, Olayinka A.; Joseph, Elizabeth K.; Levine, Jon D.; Green, Paul G.

    2009-01-01

    While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and re-exposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60–80 Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia t...

  2. Pegylated interferon de novo-induce autoimmune haemolytic anaemia in chronic hepatitis C patient

    OpenAIRE

    Said, Ashraf; Elbahrawy, Ashraf; Alfiomy, Mohamed; Abdellah, Mohamed; Shahat, Khaled; Salah, Mohamed; Mostafa, Sadek; Elwassief, Ahmed; Aboelfotoh, Attef; Abdelhafeez, Hafez; El-Sherif, Assem

    2011-01-01

    A 55-year-old Egyptian woman with chronic hepatitis C undergoing treatment with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin was referred to our hospital on November 2010 with prolonged easy fatigability and an attack of syncope; she had no prior history of autoimmune disorders or allergy. Laboratory investigations documented the presence of Peg-IFN induced autoimmune haemolytic anaemia and autoimmune thyroiditis. Intravenous γ globulin (IVGG) failed to correct the autoimmune process...

  3. Prevention of organophosphate-induced chronic epilepsy by early benzodiazepine treatment.

    Science.gov (United States)

    Shrot, Shai; Ramaty, Erez; Biala, Yoav; Bar-Klein, Guy; Daninos, Moshe; Kamintsky, Lyn; Makarovsky, Igor; Statlender, Liran; Rosman, Yossi; Krivoy, Amir; Lavon, Ophir; Kassirer, Michael; Friedman, Alon; Yaari, Yoel

    2014-09-02

    Poisoning with organophosphates (OPs) may induce status epilepticus (SE), leading to severe brain damage. Our objectives were to investigate whether OP-induced SE leads to the emergence of spontaneous recurrent seizures (SRSs), the hallmark of chronic epilepsy, and if so, to assess the efficacy of benzodiazepine therapy following SE onset in preventing the epileptogenesis. We also explored early changes in hippocampal pyramidal cells excitability in this model. Adult rats were poisoned with the paraoxon (450μg/kg) and immediately treated with atropine (3mg/kg) and obidoxime (20mg/kg) to reduce acute mortality due to peripheral acetylcholinesterase inhibition. Electrical brain activity was assessed for two weeks during weeks 4-6 after poisoning using telemetric electrocorticographic intracranial recordings. All OP-poisoned animals developed SE, which could be suppressed by midazolam. Most (88%) rats which were not treated with midazolam developed SRSs, indicating that they have become chronically epileptic. Application of midazolam 1min following SE onset had a significant antiepileptogenic effect (only 11% of the rats became epileptic; p=0.001 compared to non-midazolam-treated rats). Applying midazolam 30min after SE onset did not significantly prevent chronic epilepsy. The electrophysiological properties of CA1 pyramidal cells, assessed electrophysiologically in hippocampal slices, were not altered by OP-induced SE. Thus we show for the first time that a single episode of OP-induced SE in rats leads to the acquisition of chronic epilepsy, and that this epileptogenic outcome can be largely prevented by immediate, but not delayed, administration of midazolam. Extrapolating these results to humans would suggest that midazolam should be provided together with atropine and an oxime in the immediate pharmacological treatment of OP poisoning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. L-carnitine prevents memory impairment induced by chronic REM-sleep deprivation.

    Science.gov (United States)

    Alzoubi, Karem H; Rababa'h, Abeer M; Owaisi, Amani; Khabour, Omar F

    2017-05-01

    Sleep deprivation (SD) negatively impacts memory, which was related to oxidative stress induced damage. L-carnitine is a naturally occurring compound, synthesized endogenously in mammalian species and known to possess antioxidant properties. In this study, the effect of L-carnitine on learning and memory impairment induced by rapid eye movement sleep (REM-sleep) deprivation was investigated. REM-sleep deprivation was induced using modified multiple platform model (8h/day, for 6 weeks). Simultaneously, L-carnitine was administered (300mg/kg/day) intraperitoneally for 6 weeks. Thereafter, the radial arm water maze (RAWM) was used to assess spatial learning and memory. Additionally, the hippocampus levels of antioxidant biomarkers/enzymes: reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS) were assessed. The results showed that chronic REM-sleep deprivation impaired both short- and long-term memory (Psleep deprivation induced reduction in the hippocampus ratio of GSH/GSSG, activity of catalase, GPx, and SOD. No change was observed in TBARS among tested groups (P>0.05). In conclusion, chronic REM-sleep deprivation induced memory impairment, and treatment with L-carnitine prevented this impairment through normalizing antioxidant mechanisms in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  6. Environmental enrichment reduces chronic psychosocial stress-induced anxiety and ethanol-related behaviors in mice.

    Science.gov (United States)

    Bahi, Amine

    2017-07-03

    Previous research from our laboratory has shown that exposure to chronic psychosocial stress increased voluntary ethanol consumption and preference as well as acquisition of ethanol-induced conditioned place preference (CPP) in mice. This study was done to determine whether an enriched environment could have "curative" effects on chronic psychosocial stress-induced ethanol intake and CPP. For this purpose, experimental mice "intruders" were exposed to the chronic subordinate colony (CSC) housing for 19 consecutive days in the presence of an aggressive "resident" mouse. At the end of that period, mice were tested for their anxiety-like behavior using the elevated plus maze (EPM) test then housed in a standard or enriched environment (SE or EE respectively). Anxiety and ethanol-related behaviors were investigated using the open field (OF) test, a standard two-bottle choice drinking paradigm, and the CPP procedure. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to single housed colony (SHC) controls. In addition, CSC exposure increased voluntary ethanol intake and ethanol-CPP. Interestingly, we found that EE significantly and consistently reduced anxiety and ethanol consumption and preference. However, neither tastants' (saccharin and quinine) intake nor blood ethanol metabolism were affected by EE. Finally, and most importantly, EE reduced the acquisition of CPP induced by 1.5g/kg ethanol. Taken together, these results support the hypothesis that EE can reduce voluntary ethanol intake and ethanol-induced conditioned reward and seems to be one of the strategies to reduce the behavioral deficits and the risk of anxiety-induced alcohol abuse. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model.

    Science.gov (United States)

    Wei, Qin; Bian, Yeping; Yu, Fuchao; Zhang, Qiang; Zhang, Guanghao; Li, Yang; Song, Songsong; Ren, Xiaomei; Tong, Jiayi

    2016-11-01

    Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneous intermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5 weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis, and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), end-systolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fraction and fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normal arrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia induced factor (HIF)-1α, NF-kB, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of rats exposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronic intermittent hypoxia, which is associated with increased expression of HIF-1α and NF-kB signaling molecules and development of cardiac inflammation, apoptosis and fibrosis. © 2016 by the Journal of Biomedical Research. All rights reserved.

  8. Friction-Induced Mitochondrial Dysregulation Contributes to Joint Deterioration in Prg4 Knockout Mice

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    Kimberly A. Waller

    2017-06-01

    Full Text Available Deficiency of PRG4 (lubricin, the boundary lubricant in mammalian joints, contributes to increased joint friction accompanied by superficial and upper intermediate zone chondrocyte caspase-3 activation, as shown in lubricin-null (Prg4−/− mice. Caspase-3 activity appears to be reversible upon the restitution of Prg4 either endogenously in vivo, in a gene trap mouse, or as an applied lubricant in vitro. In this study we show that intra-articular injection of human PRG4 in vivo in Prg4−/− mice prevented caspase-3 activation in superficial zone chondrocytes and was associated with a modest decrease in whole joint friction measured ex vivo using a joint pendulum method. Non-lubricated Prg4−/− mouse cartilage shows caspase cascade activation caused by mitochondrial dysregulation, and significantly higher levels of peroxynitrite (ONOO− and −OH and superoxide (O−2 compared to Prg4+/+ and Prg4+/− cartilage. Enzymatic activity levels of caspase 8 across Prg4 mutant mice were not significantly different, indicating no extrinsic apoptosis pathway activation. Western blots showed caspase-3 and 9 activation in Prg4−/− tissue extracts, and the appearance of nitrosylated Cys163 in the active cleft of caspase-3 which inhibits its enzymatic activity. These findings are relevant to patients at risk for arthrosis, from camptodactyl-arthropathy-coxa vara-pericarditis (CACP syndrome and transient lubricin insufficiency due to trauma and inflammation.

  9. Chronic plus binge ethanol feeding induces myocardial oxidative stress, mitochondrial and cardiovascular dysfunction, and steatosis.

    Science.gov (United States)

    Matyas, Csaba; Varga, Zoltan V; Mukhopadhyay, Partha; Paloczi, Janos; Lajtos, Tamas; Erdelyi, Katalin; Nemeth, Balazs T; Nan, Mintong; Hasko, Gyorgy; Gao, Bin; Pacher, Pal

    2016-06-01

    Alcoholic cardiomyopathy in humans develops in response to chronic excessive alcohol consumption; however, good models of alcohol-induced cardiomyopathy in mice are lacking. Herein we describe mouse models of alcoholic cardiomyopathies induced by chronic and binge ethanol (EtOH) feeding and characterize detailed hemodynamic alterations, mitochondrial function, and redox signaling in these models. Mice were fed a liquid diet containing 5% EtOH for 10, 20, and 40 days (d) combined with single or multiple EtOH binges (5 g/kg body wt). Isocalorically pair-fed mice served as controls. Left ventricular (LV) function and morphology were assessed by invasive pressure-volume conductance approach and by echocardiography. Mitochondrial complex (I, II, IV) activities, 3-nitrotyrosine (3-NT) levels, gene expression of markers of oxidative stress (gp91phox, p47phox), mitochondrial biogenesis (PGC1α, peroxisome proliferator-activated receptor α), and fibrosis were examined. Cardiac steatosis and fibrosis were investigated by histological/immunohistochemical methods. Chronic and binge EtOH feeding (already in 10 days EtOH plus single binge group) was characterized by contractile dysfunction (decreased slope of end-systolic pressure-volume relationship and preload recruitable stroke work), impaired relaxation (decreased time constant of LV pressure decay and maximal slope of systolic pressure decrement), and vascular dysfunction (impaired arterial elastance and lower total peripheral resistance). This was accompanied by enhanced myocardial oxidative/nitrative stress (3-NT; gp91phox; p47phox; angiotensin II receptor, type 1a) and deterioration of mitochondrial complex I, II, IV activities and mitochondrial biogenesis, excessive cardiac steatosis, and higher mortality. Collectively, chronic plus binge EtOH feeding in mice leads to alcohol-induced cardiomyopathies (National Institute on Alcohol Abuse and Alcoholism models) characterized by increased myocardial oxidative

  10. Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats.

    Science.gov (United States)

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Borji, Abasalt; Samini, Mohammad; Farkhondeh, Tahereh

    2017-05-04

    Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research focused the protective effect of carnosol against the brain injury induced by the restraint stress. The restraint stress induced by keeping animals in restrainers for 21 consecutive days. Thereafter, the rats were injected carnosol or vehicle for 21 consecutive days. At the end of experiment, all the rats were subjected to his open field test and forced swimming test. Afterwards, the rats were sacrificed for measuring their oxidative stress parameters. To measure the modifications in the biochemical aspects after the experiment, the activities of malondialdehyde (MDA), reduced glutathione (GSH), as well as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) were evaluated in the whole brain. Our data showed that the animals received chronic stress had a raised immobility time versus the non-stressed animals (p < 0.01). Furthermore, chronic stress diminished the number of crossing in the animals that were subjected to the chronic stress versus the non-stressed rats (p < 0.01). Carnosol ameliorated this alteration versus the non-treated rats (p < 0.05). In the vehicle treated rats that submitted to the stress, the level of MDA levels was significantly increased (P < 0.001), and the levels of GSH and antioxidant enzymes were significantly decreased versus the non-stressed animals (P < 0.001). Carnosol treatment reduced the modifications in the stressed animals as compared with the control groups (P < 0.001). All of these carnosol effects were nearly similar to those observed with fluoxetine. The current research shows that the protective effects of carnosol may be accompanied with enhanced antioxidant defenses and decreased oxidative injury.

  11. Open dislocation of the proximal interphalangeal joint of the little finger subsequent to chronic radial collateral ligament injury: a case report of primary ligament reconstruction with a half-slip of the flexor digitorum superficialis: Case Report.

    Science.gov (United States)

    Wada, Kazuma; Hibino, Naohito; Kondo, Kenji; Yoshioka, Shinji; Terai, Tomoya; Henmi, Tatsuhiko; Sairyo, Koichi

    2015-01-01

    Open dislocation of the proximal interphalangeal (PIP) joint is relatively rare. We report a case of a 32-year-old man who had open dislocation of the PIP joint of the little finger while playing American football. He had a history of chronic radial collateral ligament injury. We reconstructed the radial collateral ligament with a half-slip of the flexor digitorum superficialis tendon.

  12. Resveratrol Ameliorates the Depressive-Like Behaviors and Metabolic Abnormalities Induced by Chronic Corticosterone Injection

    Directory of Open Access Journals (Sweden)

    Yu-Cheng Li

    2016-10-01

    Full Text Available Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors and metabolic abnormalities induced by chronic corticosterone injection. Male ICR mice were administrated corticosterone (40 mg/kg by subcutaneous injection for three weeks. Resveratrol (50 and 100 mg/kg, fluoxetine (20 mg/kg and pioglitazone (10 mg/kg were given by oral gavage 30 min prior to corticosterone administration. The behavioral tests showed that resveratrol significantly reversed the depressive-like behaviors induced by corticosterone, including the reduced sucrose preference and increased immobility time in the forced swimming test. Moreover, resveratrol also increased the secretion of insulin, reduced serum level of glucose and improved blood lipid profiles in corticosterone-treated mice without affecting normal mice. However, fluoxetine only reverse depressive-like behaviors, and pioglitazone only prevent the dyslipidemia induced by corticosterone. Furthermore, resveratrol and pioglitazone decreased serum level of glucagon and corticosterone. The present results indicated that resveratrol can ameliorate depressive-like behaviors and metabolic abnormalities induced by corticosterone, which suggested that the multiple effects of resveratrol could be beneficial for patients with depression and/or metabolic syndrome associated with long-term glucocorticoid therapy.

  13. Clinical features of Japanese patients with chronic cough induced by gastroesophageal reflux

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    Katsuya Fujimori

    1997-01-01

    Full Text Available Gastroesophageal reflux (GER has been reported as a cause of chronic cough (CC in the United States. It has been reported that 5–21% of CC cases are induced by GER. In Japan, however, detailed clinical features of CC induced by GER have not been described. The present study reports on six Japanese patients with GER-induced CC. The subjects were all females, with a mean age of 72 years. The average body mass index was 37 kg/m2, indicating obesity. No abnormalities were found with regard to concentrations of C-reactive protein, peripheral eosinophil counts, serum IgE concentrations, serum titers of cold agglutinins or antibodies to Mycoplasma pneumoniae, chest radiograph findings, respiratory function tests or blood gas analyses. Bronchial biopsy was performed in three patients and showed chronic inflammation characterized by lymphocytic infiltration, squamous metaplasia and mucosal basement membrane thickening. In the study population (Japanese patients, GER-induced CC tended to occur in elderly obese women and may be attributable to airway inflammation.

  14. Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

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    Amie L. Holmes

    2013-11-01

    Full Text Available Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration- and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D. Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent manner. Thus, chronic exposure to particulate nickel induces genotoxicity and cellular transformation in human lung epithelial cells.

  15. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

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    Xue-ying Chang

    2017-01-01

    Full Text Available Background. This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d, 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS/p38 mitogen activated protein kinase (p38MAPK pathway was determined to explore the potential mechanism. Results. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA and creatinine levels, malonaldehyde (MDA content, and superoxide dismutase (SOD activity in serum and the increases of calcium and alkaline phosphatase (ALP activity in the aorta (P<0.05 and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

  16. Protective effect of curcumin on experimentally induced arthritic rats: detailed histopathological study of the joints and white blood cell count

    Science.gov (United States)

    Kamarudin, Taty Anna; Othman, Faizah; Mohd Ramli, Elvy Suhana; Md Isa, Nurismah; Das, Srijit

    2012-01-01

    Curcuma longa (turmeric) rhizomes contains curcumin, an active compound which possesses anti-inflammatory effects. Collagen-induced arthritis (CIA) is an accepted experimental animal model of rheumatoid arthritis. The present study aimed to observe the histological changes in the joints of experimental arthritic rats treated with curcumin. Twenty four male Sprague-Dawley (approximately 7 weeks-old) rats were randomly divided into four groups. Three groups were immunized with 150 µg collagen. All rats with established CIA, with arthritis scores exceeding 1, were orally treated with betamethasone (0.5 mg/ml/kg body weight), curcumin (110 mg/ml/kg body weight) or olive oil (1.0 ml/kg body weight) daily, for two weeks. One remaining group was kept as normal control. Treatment with 110 mg/ml/kg curcumin showed significant mean differences in the average white blood cell (WBC) count (pPannus formation scores showed that curcumin supplementation successfully suppressed the pannus formation process that occurred in the articular cartilage of the CIA joints. The mean difference for histological scores for the curcumin group was insignificant compared to the betamethasone treated group. It is concluded that supplementation of curcumin has protective effect on the histopathological and degenerative changes in the joints of CIA rats which was at par with betamethasone. PMID:27366139

  17. Protective effect of curcumin on experimentally induced arthritic rats: detailed histopathological study of the joints and white blood cell count.

    Science.gov (United States)

    Kamarudin, Taty Anna; Othman, Faizah; Mohd Ramli, Elvy Suhana; Md Isa, Nurismah; Das, Srijit

    2012-01-01

    Curcuma longa (turmeric) rhizomes contains curcumin, an active compound which possesses anti-inflammatory effects. Collagen-induced arthritis (CIA) is an accepted experimental animal model of rheumatoid arthritis. The present study aimed to observe the histological changes in the joints of experimental arthritic rats treated with curcumin. Twenty four male Sprague-Dawley (approximately 7 weeks-old) rats were randomly divided into four groups. Three groups were immunized with 150 µg collagen. All rats with established CIA, with arthritis scores exceeding 1, were orally treated with betamethasone (0.5 mg/ml/kg body weight), curcumin (110 mg/ml/kg body weight) or olive oil (1.0 ml/kg body weight) daily, for two weeks. One remaining group was kept as normal control. Treatment with 110 mg/ml/kg curcumin showed significant mean differences in the average white blood cell (WBC) count (pcurcumin supplementation successfully suppressed the pannus formation process that occurred in the articular cartilage of the CIA joints. The mean difference for histological scores for the curcumin group was insignificant compared to the betamethasone treated group. It is concluded that supplementation of curcumin has protective effect on the histopathological and degenerative changes in the joints of CIA rats which was at par with betamethasone.

  18. Gain modulation of the middle latency cutaneous reflex in patients with chronic joint instability after ankle sprain.

    Science.gov (United States)

    Futatsubashi, Genki; Sasada, Shusaku; Tazoe, Toshiki; Komiyama, Tomoyoshi

    2013-07-01

    To investigate the neural alteration of reflex pathways arising from cutaneous afferents in patients with chronic ankle instability. Cutaneous reflexes were elicited by applying non-noxious electrical stimulation to the sural nerve of subjects with chronic ankle instability (n=17) and control subjects (n=17) while sitting. Electromyographic (EMG) signals were recorded from each ankle and thigh muscle. The middle latency response (MLR; latency: 70-120 ms) component was analyzed. In the peroneus longus (PL) and vastus lateralis (VL) muscles, linear regression analyses between the magnitude of the inhibitory MLR and background EMG activity showed that, compared to the uninjured side and the control subjects, the gain of the suppressive MLR was increased in the injured side. This was also confirmed by the pooled data for both groups. The degree of MLR alteration was significantly correlated to that of chronic ankle instability in the PL. The excitability of middle latency cutaneous reflexes in the PL and VL is modulated in subjects with chronic ankle instability. Cutaneous reflexes may be potential tools to investigate the pathological state of the neural system that controls the lower limbs in subjects with chronic ankle instability. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Three-dimensional analysis of morphological changes of rat mandibular head induced by administration of adjuvant in mandibular joint cavity

    International Nuclear Information System (INIS)

    Kuroki, Yosuke

    2008-01-01

    Temporal morphological changes of human osteoarthritis (OA) related to temporomandibular joint dysfunction (TMJ) are unknown because of lack of the animal model. The author made the model as in the title. Complete Freud's adjuvant (CFA) was injected in the mandibular joint cavity of male standard deviation (SD) rats with monitoring by X-ray. The site of injection was determined previously with the machine RmCT (in vivo 3D micro-X-ray CT for laboratory animals, Rigaku Corp.), which consisted of rotatable X-ray tube and facing flat panel detector, at whose center anesthetized rat was placed. The machine was also used for observation of the mandible just and 1-14 days after CFA injection and images were processed to 2D and 3D with the software I-view-R (Rigaku Corp.). Morphological changes were seen at 7-14 days on the CT images, and pathologically at 14 days, erosion or osteophytosis in 9/12 animals and enlargement of mandibular head. The cavity treated became larger for 1-14 days persistently. These results indicated that morphological changes accompanying the chronic inflammation had occurred, which was thought useful as a model of TMJ-OA. (R.T.)

  20. Preventive effects of chronic exogenous growth hormone levels on diet-induced hepatic steatosis in rats

    Directory of Open Access Journals (Sweden)

    Tian Ya-ping

    2010-07-01

    Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD, which is characterized by hepatic steatosis, can be reversed by early treatment. Several case reports have indicated that the administration of recombinant growth hormone (GH could improve fatty liver in GH-deficient patients. Here, we investigated whether chronic exogenous GH levels could improve hepatic steatosis induced by a high-fat diet in rats, and explored the underlying mechanisms. Results High-fat diet-fed rats developed abdominal obesity, fatty liver and insulin resistance. Chronic exogenous GH improved fatty liver, by reversing dyslipidaemia, fat accumulation and insulin resistance. Exogenous GH also reduced serum tumour necrosis factor-alpha (TNF-alpha levels, and ameliorated hepatic lipid peroxidation and oxidative stress. Hepatic fat deposition was also reduced by exogenous GH levels, as was the expression of adipocyte-derived adipokines (adiponectin, leptin and resistin, which might improve lipid metabolism and hepatic steatosis. Exogenous GH seems to improve fatty liver by reducing fat weight, improving insulin sensitivity and correcting oxidative stress, which may be achieved through phosphorylation or dephosphorylation of a group of signal transducers and activators of hepatic signal transduction pathways. Conclusions Chronic exogenous GH has positive effects on fatty liver and may be a potential clinical application in the prevention or reversal of fatty liver. However, chronic secretion of exogenous GH, even at a low level, may increase serum glucose and insulin levels in rats fed a standard diet, and thus increase the risk of insulin resistance.

  1. Chronic lead intoxication affects glial and neural systems and induces hypoactivity in adult rat.

    Science.gov (United States)

    Sansar, Wafa; Ahboucha, Samir; Gamrani, Halima

    2011-10-01

    Lead is an environmental toxin and its effects are principally manifested in the brain. Glial and neuronal changes have been described during development following chronic or acute lead intoxication, however, little is known about the effects of chronic lead intoxication in adults. In this study we evaluated immunohistochemically the glial and dopaminergic systems in adult male Wistar rats. 0.5% (v/v) lead acetate in drinking water was administrated chronically over a 3-month period. Hypertrophic immunoreactive astrocytes were observed in the frontal cortex and other brain structures of the treated animals. Analysis of the astroglial features showed increased number of astrocyte cell bodies and processes in treated rats, an increase confirmed by Western blot. Particular distribution of glial fibrillary acidic protein immunoreactivity was observed within the blood vessel walls in which dense immunoreactive glial processes emanate from astrocytes. Glial changes in the frontal cortex were concomitant with reduced tyrosine hydroxylase immunoreactive neuronal processes, which seem to occur as a consequence of significantly reduced dopaminergic neurons within the nucleus of origin in the substantia nigra. These glial and neuronal changes following lead intoxication may affect animal behavior as evidenced by reduced locomotor activity in an open field test. These findings demonstrate that chronic lead exposure induces astroglial changes, which may compromise neuronal function and consequently animal behavior. Copyright © 2010 Elsevier GmbH. All rights reserved.

  2. Effect of atracylodes rhizome polysaccharide in rats with adenine-induced chronic renal failure.

    Science.gov (United States)

    Yang, C; Liu, C; Zhou, Q; Xie, Y C; Qiu, X M; Feng, X

    2015-01-01

    The aim of the study was to elucidate the therapeutic effects of Atracylodes rhizome polysaccharide on adenine-induced chronic renal failure in rats. Fifty male Sprague Dawley rats were selected and randomly divided in to 5 groups (n=10 rats per group): The normal control group, the chronic renal failure pathological control group, the dexamethasone treatment group and two Atracylodes rhizome polysaccharide treatment groups, treated with two different concentrations of the polysaccharide, the Atracylodes rhizome polysaccharide high group and the Atracylodes rhizome polysaccharide low group. All the rats, except those in the normal control group were fed adenine-enriched diets, containing 10 g adenine per kg food for 3 weeks. After being fed with adenine, the dexamethasone treatment group, Atracylodes rhizome polysaccharide high group and Atracylodes rhizome polysaccharide low group rats were administered the drug orally for 2 weeks. On day 35, the kidney coefficient of the rats and the serum levels of creatinine, blood urea nitrogen, total protein and hemalbumin were determined. Subsequent to experimentation on a model of chronic renal failure in rats, the preparation was proven to be able to reduce serum levels of creatinine, blood urea nitrogen and hemalbumin levels (Prenal function. Atracylodes rhizome polysaccharide had reversed the majority of the indices of chronic renal failure in rats.

  3. Silica-induced Chronic Inflammation Promotes Lung Carcinogenesis in the Context of an Immunosuppressive Microenvironment

    Directory of Open Access Journals (Sweden)

    Javier Freire

    2013-08-01

    Full Text Available The association between inflammation and lung tumor development has been clearly demonstrated. However, little is known concerning the molecular events preceding the development of lung cancer. In this study, we characterize a chemically induced lung cancer mouse model in which lung cancer developed in the presence of silicotic chronic inflammation. Silica-induced lung inflammation increased the incidence and multiplicity of lung cancer in mice treated with N-nitrosodimethylamine, a carcinogen found in tobacco smoke. Histologic and molecular analysis revealed that concomitant chronic inflammation contributed to lung tumorigenesis through induction of preneoplastic changes in lung epithelial cells. In addition, silica-mediated inflammation generated an immunosuppressive microenvironment in which we observed increased expression of programmed cell death protein 1 (PD-1, transforming growth factor-β1, monocyte chemotactic protein 1 (MCP-1, lymphocyte-activation gene 3 (LAG3, and forkhead box P3 (FOXP3, as well as the presence of regulatory T cells. Finally, the K-RAS mutational profile of the tumors changed from Q61R to G12D mutations in the inflammatory milieu. In summary, we describe some of the early molecular changes associated to lung carcinogenesis in a chronic inflammatory microenvironment and provide novel information concerning the mechanisms underlying the formation and the fate of preneoplastic lesions in the silicotic lung.

  4. Helicobacter pylori-induced premature senescence of extragastric cells may contribute to chronic skin diseases.

    Science.gov (United States)

    Lewinska, Anna; Wnuk, Maciej

    2017-04-01

    Helicobacter pylori, one of the most frequently observed bacterium in the human intestinal flora, has been widely studied since Marshall and Warren documented a link between the presence of H. pylori in the gastrointestinal tract and gastritis and gastric ulcers. Interestingly, H. pylori has also been found in several other epithelial tissues, including the eyes, ears, nose and skin that may have direct or indirect effects on host physiology and may contribute to extragastric diseases, e.g. chronic skin diseases. More recently, it has been shown that H. pylori cytotoxin CagA expression induces cellular senescence of human gastric nonpolarized epithelial cells that may lead to gastrointestinal disorders and systemic inflammation. Here, we hypothesize that also chronic skin diseases may be promoted by stress-induced premature senescence (SIPS) of skin cells, namely fibroblasts and keratinocytes, stimulated with H. pylori cytotoxins. Future studies involving cell culture models and clinical specimens are needed to verify the involvement of H. pylori in SIPS-based chronic skin diseases.

  5. Effectiveness of Physical Therapy as an Adjunctive Treatment for Trauma-induced Chronic Torticollis in Raptors.

    Science.gov (United States)

    Nevitt, Benjamin N; Robinson, Narda; Kratz, Gail; Johnston, Matthew S

    2015-03-01

    Management of trauma-induced chronic torticollis in raptors has historically been challenging. Euthanasia is common in affected birds because of their inability to maintain normal cervical position, although they may be able to function normally. To assess effectiveness of physical therapy of the neck and head as an adjunct treatment for this condition, a case-control study was done in raptors admitted to the Rocky Mountain Raptor Program from 2003 to 2010. Eleven cases were identified with a diagnosis of chronic torticollis resulting from traumatic brain injury. Five cases were treated with physical therapy of the head and neck, and 6 control cases did not receive any physical therapy for the torticollis. Of the control cases, 0 of 6 had resolution of the torticollis, 0 of 6 were released, and 5 of 6 were euthanatized. Of the treated cases, 4 of 5 had complete resolution of the torticollis and 5 of 5 were released. Resolution of torticollis differed significantly between cases receiving physical therapy and controls. These results indicate that physical therapy should be used as an adjunctive therapy in cases of chronic torticollis induced by trauma in raptors because it results in better resolution of the torticollis and increased likelihood of release.

  6. Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice.

    Science.gov (United States)

    Zhang, Hui-yu; Zhao, Yu-nan; Wang, Zhong-li; Huang, Yu-fang

    2015-01-01

    Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice.

  7. [Therapeutic effect observation of chronic knee joint pain assisted with the central-square needling technique of the thumb-tack needles].

    Science.gov (United States)

    Yang, Yang; Qi, Si; Liu, Mengyue; Zhao, Yu; Li, Ning

    2017-10-12

    To compare the differences in the clinical therapeutic effects on chronic knee joint pain between the combination of the central-square needling technique of thumb-tack needles with the routine therapy of acupuncture, moxibustion and tuina and the routine therapy of acupuncture, moxibustion and tuina . One hundred and twenty patients of chronic knee joint pain were randomized into an observation group and a control group, 60 cases in each one. In the control group, the routine therapy of acupuncture, moxibustion and tuina was adopted. In the observation group, at the end of treatment with the routine therapy of acupuncture, moxibustion and tuina , the subcutaneous embedding therapy was followed with four thumb-tack needles at the sites 1 to 1.5 cm above, below and bilateral to the main point ( ashi point) separately, and the needles were retained for 24 h to 48 h. The treatment was given once every two days, three times a week, totally 6 times in two weeks; and the follow-up visit was done for 3 months in patients of the two groups. The visual analogue scale (VAS) score before and after each treatment, Lequesne index score before treatment and at the end of follow-up and the case numbers of proactive use of painkillers or receiving acupuncture treatment in the follow-up stage were compared and observed in the patients of the two groups. The VAS score was reduced gradually after treatment in the patients of the two groups. The differences were significant statistically after the second treatment as compared with those before the treatment in the two groups (all P 0.05). In the follow-up stage, there were 0 case in the observation group and 9 cases in the control group in terms of proactive use of painkillers ( P 0.05). The acupuncture scheme in assistance with the central-square needling technique of thumb-tack needles obviously relieves chronic knee joint pain, much better sustains the analgesic effects of acupuncture and improves patient compliance.

  8. The Effect of Chronic Administration of Buspirone on 6-Hydroxydopamine-Induced Catalepsy in Rats

    Directory of Open Access Journals (Sweden)

    Hamdolah Sharifi

    2012-06-01

    Full Text Available Purpose: Several evidences show that serotonergic neurons play a role in the regulation of movements executed by the basal ganglia. Recently we have reported that single dose of buspirone improved 6-hydroxydopamine (6-OHDA and haloperidol-induced catalepsy. This study is aimed to investigate effect of chronic intraperitoneal (i.p. administration of buspirone on 6-OHDA-induced catalepsy in male Wistar rats. Methods: Catalepsy was induced by unilateral infusion of 6-OHDA (8 μg/2 μl/rat into the central region of the SNc and was assayed by the bar-test method 5, 60, 120 and 180 min after drugs administration in 10th day. The effect of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days was assessed in 6-OHDA-lesioned rats. Results: The results showed that chronic injection of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days decreased catalepsy when compared with the control group. The best anticataleptic effect was observed at the dose of 1 mg/kg. The catalepsy-improving effect of buspirone was reversed by 1-(2-methoxyphenyl- 4-[4-(2-phthalimido butyl]piperazine hydrobromide (NAN-190, 0.5 mg/kg, i.p.,as a 5-HT1A receptor antagonist. Conclusion: Our study indicates that chronic administration of buspirone improves catalepsy in a 6-OHDA-induced animal model of parkinson's disease (PD. We also suggest that buspirone may be used as an adjuvant therapy to increase effectiveness of antiparkinsonian drugs. In order to prove this hypothesis, further clinical studies should be done.

  9. Electromyographic analyses of muscle pre-activation induced by single joint exercise.

    Science.gov (United States)

    Júnior, Valdinar A R; Bottaro, Martim; Pereira, Maria C C; Andrade, Marcelino M; P Júnior, Paulo R W; Carmo, Jake C

    2010-01-01

    To investigate whether performing a low-intensity, single-joint exercises for knee extensors was an efficient strategy for increasing the number of motor units recruited in the vastus lateralis muscle during a subsequent multi-joint exercises. Nine healthy male participants (23.33+/-3.46 yrs) underwent bouts of exercise in which knee extension and 45 degrees , and leg press exercises were performed in sequence. In the low-intensity bout (R30), 15 unilateral knee extensions were performed, followed by 15 repetitions of the leg presses at 30% and 60% of one maximum repetition load (1-MR), respectively. In the high-intensity bout (R60), the same sequence was performed, but the applied load was 60% of 1-MR for both exercises. A single set of 15 repetitions of the leg press at 60% of 1-MR was performed as a control exercise (CR). The surface electromyographic signals of the vastus lateralis muscle were recorded by means of a linear electrode array. The root mean square (RMS) values were determined for each repetition of the leg press, and linear regressions were calculated from these results. The slopes of the straight lines obtained were then normalized using the linear coefficients of the regression equations and compared using one-way ANOVAs for repeated measures. The slopes observed in the CR were significantly lower than those in the R30 and R60 (precruitment of motor units was more effective when a single-joint exercise preceded the multi-joint exercise. Article registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) under the number ACTRN12609000413224.

  10. Rosuvastatin-Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study.

    Science.gov (United States)

    Rollefstad, S; Ikdahl, E; Hisdal, J; Olsen, I C; Holme, I; Hammer, H B; Smerud, K T; Kitas, G D; Pedersen, T R; Kvien, T K; Semb, A G

    2015-07-01

    mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction. Intensive lipid-lowering treatment with rosuvastatin induced atherosclerotic regression and reduced the LDL cholesterol level significantly in patients with inflammatory joint disease. © 2015, American College of Rheumatology.

  11. Diet, nutrition and the prevention of chronic diseases: report of a Joint WHO/FAO Expert Consultation

    National Research Council Canada - National Science Library

    2003-01-01

    ..., nutrition and the prevention of chronic diseases through the life course 4.2.1 Fetal development and the maternal environment 4.2.2 Infancy 4.2.3 Childhood and adolescence 4.2.4 Adulthood 4.2....

  12. High-intensity laser therapy during chronic degenerative tenosynovitis experimentally induced in broiler chickens

    Science.gov (United States)

    Fortuna, Damiano; Rossi, Giacomo; Bilotta, Teresa W.; Zati, Allesandro; Gazzotti, Valeria; Venturini, Antonio; Pinna, Stefania; Serra, Christian; Masotti, Leonardo

    2002-10-01

    The aims of this study was the safety and the efficacy of High Intensity Laser Therapy (HILT) on chronic degenerative tenosynovitis. We have effectuated the histological evaluation and seroassay (C reactive protein) on 18 chickens affect by chronic degenerative tenosynovitis experimentally induced. We have been employed a Nd:YAG laser pulsed wave; all irradiated subjects received the same total energy (270 Joule) with a fluence of 7,7 J/cm2 and intensity of 10,7 W/cm2. The histological findings revealed a distinct reduction of the mineralization of the choral matrix, the anti-inflammatory effect of the laser, the hyperplasia of the synoviocytes and ectasia of the lymphatic vessels.

  13. Ghrelin alleviates anxiety- and depression-like behaviors induced by chronic unpredictable mild stress in rodents.

    Science.gov (United States)

    Huang, Hui-Jie; Zhu, Xiao-Cang; Han, Qiu-Qin; Wang, Ya-Lin; Yue, Na; Wang, Jing; Yu, Rui; Li, Bing; Wu, Gen-Cheng; Liu, Qiong; Yu, Jin

    2017-05-30

    As a regulator of food intake, ghrelin also plays a key role in mood disorders. Previous studies reported that acute ghrelin administration defends against depressive symptoms of chronic stress. However, the effects of long-term ghrelin on rodents under chronic stress hasn't been revealed. In this study, we found chronic peripheral administration of ghrelin (5nmol/kg/day for 2 weeks, i.p.) could alleviate anxiety- and depression-like behaviors induced by chronic unpredictable mild stress (CUMS). The depression-like behaviors were assessed by the forced swimming test (FST), and anxiety-like behaviors were assessed by the open field test (OFT) and the elevated plus maze test (EPM). Meanwhile, we observed that peripheral acylated ghrelin, together with gastral and hippocampal ghrelin prepropeptide mRNA level, were significantly up-regulated in CUMS mice. Besides, the increased protein level of growth hormone secretagogue receptor (GHSR) in hippocampus were also detected. These results suggested that the endogenous ghrelin/GHSR pathway activated by CUMS plays a role in homeostasis. Further results showed that central treatment of ghrelin (10μg/rat/day for 2 weeks, i.c.v.) or GHRP-6 (the agonist of GHSR, 10μg/rat/day for 2 weeks, i.c.v.) significantly alleviated the depression-like behaviors induced by CUMS in FST and sucrose preference test (SPT). Based on these results, we concluded that central GHSR is involved in the antidepressant-like effect of exogenous ghrelin treatment, and ghrelin/GHSR may have the inherent neuromodulatory properties against depressive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain

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    Su Lin

    2011-11-01

    Full Text Available Abstract Background Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8 ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI to the sciatic nerve. Results Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia. Conclusions TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.

  15. Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory.

    Science.gov (United States)

    Abush, Hila; Akirav, Irit

    2013-07-01

    Repeated stress is one of the environmental factors that precipitates and exacerbates mental illnesses like depression and anxiety as well as cognitive impairments. We have previously shown that cannabinoids can prevent the effects of acute stress on learning and memory. Here we aimed to find whether chronic cannabinoid treatment would alleviate the long-term effects of exposure to chronic restraint stress on memory and plasticity as well as on behavioral and neuroendocrine measures of anxiety and depression. Late adolescent rats were exposed to chronic restraint stress for 2 weeks followed each day by systemic treatment with vehicle or with the CB1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). Thirty days after the last exposure to stress, rats demonstrated impaired long-term potentiation (LTP) in the ventral subiculum-nucleus accumbens (NAc) pathway, impaired performance in the prefrontal cortex (PFC)-dependent object-recognition task and the hippocampal-dependent spatial version of this task, increased anxiety levels, and significantly reduced expression of glucocorticoid receptors (GRs) in the amygdala, hippocampus, PFC, and NAc. Chronic WIN55,212-2 administration prevented the stress-induced impairment in LTP levels and in the spatial task, with no effect on stress-induced alterations in unconditioned anxiety levels or GR levels. The CB1 antagonist AM251 (0.3 mg/kg) prevented the ameliorating effects of WIN55,212-2 on LTP and short-term memory. Hence, the beneficial effects of WIN55,212-2 on memory and plasticity are mediated by CB1 receptors and are not mediated by alterations in GR levels in the brain areas tested. Our findings suggest that cannabinoid receptor activation could represent a novel approach to the treatment of cognitive deficits that accompany a variety of stress-related neuropsychiatric disorders.

  16. Mitochondrial ROS induced by chronic ethanol exposure promote hyper-activation of the NLRP3 inflammasome

    Directory of Open Access Journals (Sweden)

    Laura R. Hoyt

    2017-08-01

    Full Text Available Alcohol use disorders are common both in the United States and globally, and are associated with a variety of co-morbid, inflammation-linked diseases. The pathogenesis of many of these ailments are driven by the activation of the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1β and IL-18. We hypothesized that protracted exposure of leukocytes to ethanol would amplify inflammasome activation, which would help to implicate mechanisms involved in diseases associated with both alcoholism and aberrant NLRP3 inflammasome activation. Here we show that long-term ethanol exposure of human peripheral blood mononuclear cells and a mouse macrophage cell line (J774 amplifies IL-1β secretion following stimulation with NLRP3 agonists, but not with AIM2 or NLRP1b agonists. The augmented NRLP3 activation was mediated by increases in iNOS expression and NO production, in conjunction with increases in mitochondrial membrane depolarization, oxygen consumption rate, and ROS generation in J774 cells chronically exposed to ethanol (CE cells, effects that could be inhibited by the iNOS inhibitor SEITU, the NO scavenger carboxy-PTIO, and the mitochondrial ROS scavenger MitoQ. Chronic ethanol exposure did not alter K+ efflux or Zn2+ homeostasis in CE cells, although it did result in a lower intracellular concentration of NAD+. Prolonged administration of acetaldehyde, the product of alcohol dehydrogenase (ADH mediated metabolism of ethanol, mimicked chronic ethanol exposure, whereas ADH inhibition prevented ethanol-induced IL-1β hypersecretion. Together, these results indicate that increases in iNOS and mitochondrial ROS production are critical for chronic ethanol-induced IL-1β hypersecretion, and that protracted exposure to the products of ethanol metabolism are probable mediators of NLRP3 inflammasome hyperactivation. Keywords: Inflammasome, IL

  17. The efficacy of conventional radiofrequency denervation in patients with chronic low back pain originating from the facet joints: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Lee, Chang-Hyun; Chung, Chun Kee; Kim, Chi Heon

    2017-11-01

    Radiofrequency denervation is commonly used for the treatment of chronic facet joint pain that has been refractory to more conservative treatments, although the evidence supporting this treatment has been controversial. We aimed to elucidate the precise effects of radiofrequency denervation in patients with low back pain originating from the facet joints relative to those obtained using control treatments, with particular attention to consistency in the denervation protocol. A meta-analysis of randomized controlled trials was carried out. Adult patients undergoing radiofrequency denervation or control treatments (sham or epidural block) for facet joint disease of the lumbar spine comprised the patient sample. Visual analog scale (VAS) pain scores were measured and stratified by response of diagnostic block procedures. We searched PubMed, Embase, Web of Science, and the Cochrane Database for randomized controlled trials regarding radiofrequency denervation and control treatments for back pain. Changes in VAS pain scores of the radiofrequency group were compared with those of the control group as well as the minimal clinically important difference (MCID) for back pain VAS. Meta-regression model was developed to evaluate the effect of radiofrequency treatment according to responses of diagnostic block while controlling for other variables. We then calculated mean differences and 95% confidence intervals (CIs) using random-effects models. We included data from seven trials involving 454 patients who had undergone radiofrequency denervation (231 patients) and control treatments such as sham or epidural block procedures (223 patients). The radiofrequency group exhibited significantly greater improvements in back pain score when compared with the control group for 1-year follow-up. Although the average improvement in VAS scores exceeded the MCID, the lower limit of the 95% CI encompassed the MCID. A subgroup of patients who responded very well to diagnostic block

  18. Effect of chronic alcohol ingestion on the progression of periodontitis induced in Fisher-344 rats

    Directory of Open Access Journals (Sweden)

    Éder Ricardo Biasoli

    2009-01-01

    Full Text Available Objective: Understand the effect of chronic alcohol on the progression of periodontitis induced in Fischer-344 rats.Methods: For the study, 22 Fischer-344 rats, two months old were used, divided into groups: alcohol (n=8, ligature (n=7 and control (n=7. On the first day, the animals in the alcohol group were exposed to ingestion of a water solution containing 20% alcohol (size/size, up to day 90. After thirty days from the beginning of the experiment, the animals in the alcohol group and the ligature group were submitted to the placement of a silk thread around the right maxillary second molar. Nothing was performed on the left side, serving as control. All the groups were submitted to euthanasia 60 days after ligature placement. To assess the destruction of periodontitis, a radiographic exam was used to measure the destruction of bone height. Results: The results of the study showed that on the side in which periodontitis was induced, the group that ingested alcohol suffered an increase in destruction, with statistical differences when compared with the ligature and control groups and increased bone destruction in the ligature group when compared to control. Conclusion: Within the limitations of the study, it was concluded that chronic alcohol consumption by Fischer-344 rats led to greater progression of induced periodontitis.

  19. Ocimum basilicum improve chronic stress-induced neurodegenerative changes in mice hippocampus.

    Science.gov (United States)

    Ayuob, Nasra Naeim; El Wahab, Manal Galal Abd; Ali, Soad Shaker; Abdel-Tawab, Hanem Saad

    2018-01-22

    Alzheimer's disease (AD), one of the progressive neurodegenerative diseases might be associated with exposure to stress and altered living conditions. This study aimed to evaluate the effectiveness of Ocimum basilicum (OB) essential oils in improving the neurodegenerative-like changes induced in mice after exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice divided into four groups (n = 10); the control, CUMS, CUMS + Fluoxetine, CUMS + OB were used. Behavioral tests, serum corticosterone level, hippocampus protein level of the glucocorticoid receptors (GRs) and brain-dreived neurotropic factor (BDNF) were determined after exposure to CUMS. Hippocampus was histopathologically examined. Data were analyzed using statistical package for the social sciences (SPSS) and P value of less than 0.05 was considered significant. OB diminished the depression manifestation as well as impaired short term memory observed in the mice after exposure to the CUMS as evidenced by the forced swimming and elevated plus maze test. OB also up-regulated the serum corticosterone level, hippocampal protein level of the glucocorticoid receptor and the brain-derived neurotropic factor and reduced the neurodegenerative and atrophic changes induced in the hippocampus after exposure to CUMS. Essential oils of OB alleviated the memory impairment and hippocampal neurodegenerative changes induced by exposure to the chronic unpredictable stress indicating that it is the time to test its effectiveness on patients suffering from Alzheimer disease.

  20. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

    Science.gov (United States)

    Chang, Xue-Ying; Cui, Lei; Wang, Xing-Zhi; Zhang, Lei; Zhu, Dan; Zhou, Xiao-Rong; Hao, Li-Rong

    2017-01-01

    This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta ( P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

  1. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

    Science.gov (United States)

    Chang, Xue-ying; Cui, Lei; Wang, Xing-zhi; Zhang, Lei; Zhu, Dan

    2017-01-01

    Background This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Results Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway. PMID:28691026

  2. [The method and result analyses of pathogenic bacteria culture on chronic periprosthetic joint infection after total knee arthroplasty and total hip arthroplasty].

    Science.gov (United States)

    Ji, Baochao; Xu, Enjie; Cao, Li; Yang, Desheng; Xu, Boyong; Guo, Wentao; Aili, Rehei

    2015-02-01

    To analyze the results of pathogenic bacteria culture on chronic periprosthetic joint infection after total knee arthroplasty (TKA) and total hip arthroplasty (THA). The medical data of 23 patients with chronic periprosthetic joint infection after TKA or THA from September 2010 to March 2014 were reviewed. Fifteen cases of TKA and 8 cases of THA were included in this study. There were 12 male and 11 female patients with the mean age of 62 years (range from 32 to 79 years), and among them 9 patients with sinus. All patients discontinued antibiotic therapy for a minimum of 2 weeks before arthrocentesis, taking pathogenic bacteria culture and antimicrobial susceptibility test by using synovial fluid taken preoperatively and intraoperatively of revision. Common pathogenic bacteria culture and pathological biopsy were taken on tissues intraoperatively of revision. Culture-negative specimens were prolonged the period of incubation for 2 weeks. The overall culture-positive rate of all 23 patients for 1 week before revision was 30.4% (7/23), and the positive rate of culture-negative samples which prolonged for 2 weeks was 39.1% (9/23). The overall culture-positive rate of patients for 1 week intraoperatively of revision was 60.9% (14/23), and the positive rate of culture-negative samples which prolonged for 2 weeks was 82.6% (19/23). The incubation results of 7 cases (30.4%) preoperatively conformed to that of intraoperation. The culture-positive rate of pathogenic bacteria culture can be increased evidently by discontinuing antimicrobial therapy for a minimum of 2 weeks prior to the definite diagnosis.

  3. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats

    Science.gov (United States)

    Deep, Satayanarayan; Prasad, Dipti; Singh, Shashi Bala; Khan, Nilofar

    2016-01-01

    Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH) in Unpredictable Chronic Mild Stress (UCMS) induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM), open field test (OFT), force swim test (FST), as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks) these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF) in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state. PMID:26901349

  4. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats.

    Directory of Open Access Journals (Sweden)

    Neetu Kushwah

    Full Text Available Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH in Unpredictable Chronic Mild Stress (UCMS induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM, open field test (OFT, force swim test (FST, as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state.

  5. Pacing-induced chronic atrial fibrillation impairs sinus node function in dogs. Electrophysiological remodeling.

    Science.gov (United States)

    Elvan, A; Wylie, K; Zipes, D P

    1996-12-01

    We assessed the effects of pacing-induced chronic atrial fibrillation (AF) on sinus node function, intra-atrial conduction, and atrial refractoriness. In 15 mongrel dogs (20 to 30 kg), AV nodal block was produced by radiofrequency catheter ablation, and a ventricular-inhibited (VVI) pacemaker (Minix 8330, Medtronic) was implanted and programmed to pace at 80 pulses per minute. In 11 of these dogs, right atrial endocardial pacing leads were connected to a pulse generator (Itrel 7432, Medtronic) and set at a rate of 20 Hz to induce AF. Corrected sinus node recovery time, P-wave duration, 24-hour Holter ECG to assess AF duration, maximal heart rate in response to isoproterenol (10 micrograms/min), intrinsic heart rate after administration of atropine (0.04 mg/kg) and propranolol (0.1 mg/kg), and atrial effective refractory periods (ERPs) were obtained at baseline (EPS-1) and after 2 to 6 weeks (EPS-2) of VVI pacing alone (n = 4) or VVI pacing and rapid atrial pacing (n = 11). At EPS-2, corrected sinus node recovery time and P-wave duration were prolonged, maximal heart rate and intrinsic heart rate were decreased, atrial ERPs were shortened, and the duration of AF was increased significantly compared with EPS-1. These changes partially reversed toward baseline 1 week after conversion to sinus rhythm. Sinus node function and AF inducibility observed in the control dogs that underwent ventricular pacing alone (n = 4) did not change. Pacing-induced chronic AF induces sinus node dysfunction, prolongs intra-atrial conduction time, shortens atrial refractoriness, and perpetuates AF, changes that reverse gradually after termination of AF.

  6. Music-Induced Analgesia in Chronic Pain Conditions: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Garza-Villarreal, Eduardo A; Pando, Victor; Vuust, Peter; Parsons, Christine

    2017-11-01

    , analgesia, music-induced analgesia, chronic pain, meta-analysis, systematic review, therapy.

  7. Masked rat: an x-ray-induced mutant with chronic blepharitis, alopecia, and pasteurellosis

    International Nuclear Information System (INIS)

    Kent, R.L.; Lutzner, M.A.; Hansen, C.T.

    1976-01-01

    An autosomal recessive mutation had been previously x-ray-induced in the rat and named the masked rat (genotype mk/mk). This study describes the mutant's appearance, histology, and microflora. The rat's eyelids were swollen, often to the point of closure, and its face was partially covered by a brownish crust, giving the mutant a mask-like appearance. The chronic blepharitis was also accompanied by alopecia that appeared as bare patches across the mutant's back. Pasteurella pneumotropica was found in eyelids and on skin from all masked rats. The normal rat demonstrated a resistance to Pasteurella pneumotropica infection, or, conversely, the masked rat appeared to be genetically predisposed to pasteurellosis

  8. Homogeneous (Cu, Ni)6Sn5 intermetallic compound joints rapidly formed in asymmetrical Ni/Sn/Cu system using ultrasound-induced transient liquid phase soldering process.

    Science.gov (United States)

    Li, Z L; Dong, H J; Song, X G; Zhao, H Y; Tian, H; Liu, J H; Feng, J C; Yan, J C

    2018-04-01

    Homogeneous (Cu, Ni) 6 Sn 5 intermetallic compound (IMC) joints were rapidly formed in asymmetrical Ni/Sn/Cu system by an ultrasound-induced transient liquid phase (TLP) soldering process. In the traditional TLP soldering process, the intermetallic joints formed in Ni/Sn/Cu system consisted of major (Cu, Ni) 6 Sn 5 and minor Cu 3 Sn IMCs, and the grain morphology of (Cu, Ni) 6 Sn 5 IMCs subsequently exhibited fine rounded, needlelike and coarse rounded shapes from the Ni side to the Cu side, which was highly in accordance with the Ni concentration gradient across the joints. However, in the ultrasound-induced TLP soldering process, the intermetallic joints formed in Ni/Sn/Cu system only consisted of the (Cu, Ni) 6 Sn 5 IMCs which exhibited an uniform grain morphology of rounded shape with a remarkably narrowed Ni concentration gradient. The ultrasound-induced homogeneous intermetallic joints exhibited higher shear strength (61.6 MPa) than the traditional heterogeneous intermetallic joints (49.8 MPa). Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Modulation of Cervical Facet Joint Nociception and Pain Attenuates Physical and Psychological Features of Chronic Whiplash: A Prospective Study.

    Science.gov (United States)

    Smith, Ashley Dean; Jull, Gwendolen; Schneider, Geoff M; Frizzell, Bevan; Hooper, Robert A; Sterling, Michele

    2015-09-01

    To investigate changes in clinical (physical and psychological) features of individuals with chronic whiplash-associated disorder who had previously undergone cervical radiofrequency neurotomy at the time point when the effects of radiofrequency neurotomy had dissipated and pain returned. Prospective cohort observational trial of consecutive patients. Tertiary spinal intervention centre in Calgary, Alberta, Canada. A total of 53 consecutive individuals with chronic whiplash-associated disorder. Individuals underwent radiofrequency neurotomy and were assessed before radiofrequency neurotomy, at 1 and 3 months postprocedure, and then after the return of pain (approximately 10 months postprocedure). Quantitative sensory tests (pressure; thermal pain thresholds; brachial plexus provocation test), nociceptive flexion reflex, and motor function (cervical range of movement; craniocervical flexion test) were measured. Self-reported disability, psychological distress, pain catastrophization, and posttraumatic stress disorder symptoms also were measured. Upon the return of pain after radiofrequency neurotomy, levels of disability increased (P .22). There were no significant changes in pressure hyperalgesia (P > .054) or craniocervical flexion test performance (P > .07) after the return of pain. Psychological distress and pain catastrophizing increased significantly after the return of pain (P .13). However, there was no difference in number or severity of posttraumatic stress symptoms after the return of pain (P > .30). Physical and psychological features of chronic whiplash-associated disorder are modulated dynamically with cervical radiofrequency neurotomy. These findings indicate that peripheral nociception is involved in the manifestations of chronic whiplash-associated disorder in this cohort of individuals. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  10. Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human

    DEFF Research Database (Denmark)

    Pouzet, B; Mow, T; Kreilgaard, Mads

    2003-01-01

    compounds in an animal model of weight gain. With the aim of evaluating whether the rat can be used as a model for antipsychotic-induced weight gain, we have investigated the effect of chronic treatment (3 weeks) with one antipsychotic drug inducing weight gain in clinic (olanzapine) and one antipsychotic...

  11. Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells.

    Science.gov (United States)

    Haruta, Nami; Kubota, Yoshino; Hishida, Takashi

    2012-09-01

    UV radiation induces two major types of DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidine photoproducts, which are both primarily repaired by nucleotide excision repair (NER). Here, we investigated how chronic low-dose UV (CLUV)-induced mutagenesis occurs in rad14Δ NER-deficient yeast cells, which lack the yeast orthologue of human xeroderma pigmentosum A (XPA). The results show that rad14Δ cells have a marked increase in CLUV-induced mutations, most of which are C→T transitions in the template strand for transcription. Unexpectedly, many of the CLUV-induced C→T mutations in rad14Δ cells are dependent on translesion synthesis (TLS) DNA polymerase η, encoded by RAD30, despite its previously established role in error-free TLS. Furthermore, we demonstrate that deamination of cytosine-containing CPDs contributes to CLUV-induced mutagenesis. Taken together, these results uncover a novel role for Polη in the induction of C→T transitions through deamination of cytosine-containing CPDs in CLUV-exposed NER deficient cells. More generally, our data suggest that Polη can act as both an error-free and a mutagenic DNA polymerase, depending on whether the NER pathway is available to efficiently repair damaged templates.

  12. Pegylated interferon de novo-induce autoimmune haemolytic anaemia in chronic hepatitis C patient.

    Science.gov (United States)

    Said, Ashraf; Elbahrawy, Ashraf; Alfiomy, Mohamed; Abdellah, Mohamed; Shahat, Khaled; Salah, Mohamed; Mostafa, Sadek; Elwassief, Ahmed; Aboelfotoh, Attef; Abdelhafeez, Hafez; El-Sherif, Assem

    2011-08-11

    A 55-year-old Egyptian woman with chronic hepatitis C undergoing treatment with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin was referred to our hospital on November 2010 with prolonged easy fatigability and an attack of syncope; she had no prior history of autoimmune disorders or allergy. Laboratory investigations documented the presence of Peg-IFN induced autoimmune haemolytic anaemia and autoimmune thyroiditis. Intravenous γ globulin (IVGG) failed to correct the autoimmune process; on the other hand steroid therapy dramatically corrected both haematological and thyroid values, and step down the immune process. Our report indicated that Peg-IFN de novo-induce autoimmune haemolysis, documenting a previous report. IVGG failed to step down the immune process in our case.

  13. Nocardia brasiliensis induces an immunosuppressive microenvironment that favors chronic infection in BALB/c mice.

    Science.gov (United States)

    Rosas-Taraco, Adrian G; Perez-Liñan, Amira R; Bocanegra-Ibarias, Paola; Perez-Rivera, Luz I; Salinas-Carmona, Mario C

    2012-07-01

    Nocardia brasiliensis is an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4+ Foxp3+ regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whether N. brasiliensis modulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship between N. brasiliensis immunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (P 1 log) was also observed (P brasiliensis modulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.

  14. Sodium valproate induced gingival enlargement with pre-existing chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Vaibhavi Joshipura

    2012-01-01

    Full Text Available Gingival enlargement is a common clinical feature of gingival and periodontal diseases. Currently, more than 20 prescription medications are associated with gingival enlargement. Although the mechanisms of action may be different, the clinical and microscopic appearance of drug-induced gingival enlargement is similar with any drug. Gingival enlargement produces esthetic changes, and clinical symptoms including pain, tenderness, bleeding, speech disturbances, abnormal tooth movement, dental occlusion problems, enhancement of caries development and periodontal disorders. Sodium valproate is considered to produce gingival enlargement, but very rarely. This case report features sodium valproate induced gingival enlargement in a patient with pre-existing chronic periodontitis, who came to the Dental Department, Chinmaya Mission Hospital, Bangalore. The case is special as the patient did not develop the enlargement in spite of taking phenytoin for 1 year and developed enlargement with sodium valproate within 6 months.

  15. Sodium valproate induced gingival enlargement with pre-existing chronic periodontitis.

    Science.gov (United States)

    Joshipura, Vaibhavi

    2012-04-01

    Gingival enlargement is a common clinical feature of gingival and periodontal diseases. Currently, more than 20 prescription medications are associated with gingival enlargement. Although the mechanisms of action may be different, the clinical and microscopic appearance of drug-induced gingival enlargement is similar with any drug. Gingival enlargement produces esthetic changes, and clinical symptoms including pain, tenderness, bleeding, speech disturbances, abnormal tooth movement, dental occlusion problems, enhancement of caries development and periodontal disorders. Sodium valproate is considered to produce gingival enlargement, but very rarely. This case report features sodium valproate induced gingival enlargement in a patient with pre-existing chronic periodontitis, who came to the Dental Department, Chinmaya Mission Hospital, Bangalore. The case is special as the patient did not develop the enlargement in spite of taking phenytoin for 1 year and developed enlargement with sodium valproate within 6 months.

  16. Investigation of redox status in chronic cerebral hypoperfusion-induced neurodegeneration in rats

    Directory of Open Access Journals (Sweden)

    Anil Kumar Saxena

    2015-06-01

    Full Text Available Aging related reduction in cerebral blood flow (CBF has been linked with neurodegenerative disorders including Alzheimer's disease and dementia. Experimentally, a condition of chronic cerebral hypoperfusion due to reduced CBF can be induced by permanent bilateral occlusion of common carotid arteries (2-vessel occlusion, 2VO in rats. Since oxidative stress, leading to neuronal apoptosis and death, is one of the mechanisms, which is thought to play a significant role in chronic degenerative neurological disorders, the present study was planned to assess the ROS status by measuring the levels of anti-oxidant enzymes that might occur during chronic cerebral hypoperfusion. Antioxidant enzymes namely glutathione peroxidase (GPx, superoxide dismutase (SOD, and catalase were measured in the brain tissue at eight weeks of 2VO induction in rats. Results show significantly elevated levels of GPx, SOD, and catalase enzymes as compared with the control group. It is possible that compensatory rise in antioxidant enzymes occurs in response to increased oxidative stress following ischemic insult.

  17. Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure.

    Science.gov (United States)

    Rouas, Caroline; Souidi, Maâmar; Grandcolas, Line; Grison, Stephane; Baudelin, Cedric; Gourmelon, Patrick; Pallardy, Marc; Gueguen, Yann

    2009-11-01

    The extensive use of uranium in civilian and military applications increases the risk of human chronic exposure. Uranium is a slightly radioactive heavy metal with a predominantly chemical toxicity, especially in kidney but also in liver. Few studies have previously shown some effects of uranium on xenobiotic-metabolizing enzymes (XME) that might disturb drug pharmacokinetic. The aim of this study was to determine whether a chronic (9 months) non-nephrotoxic low dose exposure to depleted uranium (DU, 1mg/rat/day) could modify the liver XME, using a single non-hepatotoxic acetaminophen (APAP) treatment (50mg/kg). Most of XME analysed were induced by APAP treatment at the gene expression level but at the protein level only CYP3A2 was significantly increased 3h after APAP treatment in DU-exposed rats whereas it remained at a basal level in unexposed rats. In conclusion, these results showed that a chronic non-nephrotoxic DU exposure specially modify CYP3A2 after a single therapeutic APAP treatment. Copyright © 2009 Elsevier B.V. All rights reserved.

  18. Chronological changes in astrocytes induced by chronic electrical sensorimotor cortex stimulation in rats.

    Science.gov (United States)

    Morishita, Takashi; Yamashita, Akiko; Katayama, Yoichi; Oshima, Hideki; Nishizaki, Yuji; Shijo, Katsunori; Fukaya, Chikashi; Yamamoto, Takamitsu

    2011-01-01

    Motor cortex stimulation (MCS) is a treatment option for various disorders such as medically refractory pain, poststroke hemiplegia, and movement disorders. However, the exact mechanisms underlying its effects remain unknown. In this study, the effects of long-term chronic MCS were investigated by observing changes in astrocytes. A quadripolar stimulation electrode was implanted on the dura over the sensorimotor cortex of adult rats, and the cortex was continuously stimulated for 3 hours, 1 week, 4 weeks, and 8 weeks. Immunohistochemical staining of microglia (ionized calcium-binding adaptor molecule 1 [Iba1] staining) and astrocytes (glial fibrillary acidic protein [GFAP] staining), and neuronal degeneration histochemistry (Fluoro-Jade B staining) were carried out to investigate the morphological changes following long-term chronic MCS. Iba1 staining and Fluoro-Jade B staining showed no evidence of Iba1-positive microglial changes or neurodegeneration. Following continuous MCS, GFAP-positive astrocytes were enlarged and their number increased in the cortex and the thalamus of the stimulated hemisphere. These findings indicate that chronic electrical stimulation can continuously activate astrocytes and result in morphological and quantitative changes. These changes may be involved in the mechanisms underlying the neuroplasticity effect induced by MCS.

  19. Diagnosis and treatment of patients with nonacid gastroesophageal reflux-induced chronic cough

    Directory of Open Access Journals (Sweden)

    Xianghuai Xu

    2015-01-01

    Full Text Available Gastroesophageal reflux (GER is one of the most common causes of chronic cough, and chronic cough due to GER represents a subtype of GER-related diseases. Gastroesophageal reflux-induced chronic cough (GERC can be divided into two subgroups based on the pH of the GER. Nonacid GERC is less common than acid GERC, and its diagnosis and treatment strategy have not been standardized. However, nonacid GERC usually presents with its unique set of characteristics and features upon diagnosis and treatment in the clinic. Although the underlying molecular mechanism of nonacid GERC is not fully understood, it is considered to be associated with reflux theory, reflex theory and airway hypersensitivity. Multi-channel intraluminal impedance combined with pH monitoring is a promising new technique that can detect both acid and nonacid reflux, and our findings as well as those of others have shown its usefulness in diagnosing nonacid GERC. Development of new diagnostic techniques has led to an increased rate of nonacid GERC diagnosis. We summarize our experience in the diagnosis and treatment of nonacid GERC and provide a guide for future therapeutic approaches.

  20. Chinese herbal medicine Shenqi Detoxification Granule inhibits fibrosis in adenine induced chronic renal failure rats.

    Science.gov (United States)

    Peng, Min; Cai, Pingping; Ma, Hongbo; Meng, Hongyan; Xu, Yuan; Zhang, Xiaoyi; Si, Guomin

    2014-01-01

    Progressive fibrosis accompanies all chronic renal disease, connective tissue growth factor (CTGF,) and platelet-derived growth factor-B, (PDGF-B,) play important roles in extra-cellular matrix abnormal accumulation, while endothelin-1 (ET-1) nitric oxide (NO,) are related to endothelial dysfunction, which mediates the progression of renal fibrosis. Shenqi Detoxification Granule (SDG), a traditional Chinese herbal formula, has been used for treatment of chronic renal failure in clinic for many years. In order to evaluate the efficacy, and explore the mechanism of SDG to inhibit the progression of renal fibrosis, study was carried out using the adenine-induced Wister rats as the CRF model, and losartan as postive control drug. Levels of serum creatinine [Scr], and blood urea nitrogen (BUN), albumin (ALB), 24hrs, urine protein (24hUP), triacylglycerol (TG), and cholesterol (CHO), together with ET-1, and NO were detected. Pathological changes of renal tissues were observed by HE, staining. In addition, CTGF and PDGF-B expression were analyzed by immuno-histo-chemistry. The results indicated that SDG can effectively reduce Scr, BUN, 24hUP, TG, and CHO levels, increase ALB levels, inhibit renal tissue damage in CRF rats, and the mechanism maybe reduce PDGF-B, CTGF expression and ET-1/NO. Shenqi Detoxification Granule is a beneficial treatment for chronic renal failure.

  1. 13. Sacroiliac joint pain

    NARCIS (Netherlands)

    Vanelderen, P.; Szadek, K.M.; Cohen, S.P.; Witte, J.; Lataster, A.; Patijn, J.; Mekhail, N.; van Kleef, M.; van Zundert, J.

    2010-01-01

    The sacroiliac joint accounts for approximately 16% to 30% of cases of chronic mechanical low back pain. Pain originating in the sacroiliac joint is predominantly perceived in the gluteal region, although pain is often referred into the lower and upper lumbar region, groin, abdomen, and/ or lower

  2. Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

    International Nuclear Information System (INIS)

    Tong, Ying; Smith, M.A.; Tucker, S.B.

    1997-01-01

    Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → G, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab

  3. Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P Rats.

    Directory of Open Access Journals (Sweden)

    Jessica Godfrey

    Full Text Available Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total or were given access only to water (control. Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4-desaturase (Degs2, an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels

  4. Chronic stress accelerates ligature-induced periodontitis by suppressing glucocorticoid receptor-α signaling.

    Science.gov (United States)

    Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan; Zhao, Lisheng

    2016-03-25

    Periodontitis is a common chronic inflammatory disease. Recent studies have shown that chronic stress (CS) might modulate periodontal disease, but there are few models of CS-induced periodontitis, and the underlying mechanisms are unclear. The present study established a rat model of periodontitis associated with CS induced by nylon thread ligatures. The severity of periodontitis was evaluated in this model by radiographic and pathological examination. The inflammatory reaction indicated by the elevated serum levels of interleukin (IL)-1β, IL-6 and IL-8 was assessed by enzyme-linked immunosorbent assay. Toll-like receptor-4 (TLR4) and glucocorticoid receptor-α (GR-α) expressions were detected by reverse transcriptase-PCR and western blotting. Open-field tests and serum corticosterone were used to evaluate CS. The results showed that CS induced behavioral changes and increased corticosterone levels of the animals with periodontitis. CS stimulation markedly increased alveolar bone loss, periodontal pocket depth and the number of plaques. It also enhanced the inflammatory reaction. These results suggest that CS accelerated the ligature-induced pathological changes associated with periodontitis. Further analysis of the mechanisms involved showed that GR-α expression was significantly downregulated in periodontal tissues of the animals undergoing CS. Blocking GR-α signaling in lipopolysaccharide and corticosteroid-treated human periodontal ligament fibroblast cells in vitro significantly upregulated the expression of p-Akt (protein kinase B) and TLR4, promoted nuclear factor-κB activity and increased levels of IL-1β, IL-6 and IL-8. This research suggests that CS might accelerate the pathological progression of periodontitis by a GR-α signaling-mediated inflammatory response and that this may be a potential therapeutic target for the treatment of periodontal disease, particularly in patients with CS.

  5. Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

    Science.gov (United States)

    Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

    2015-04-01

    Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Glucose administration attenuates spatial memory deficits induced by chronic low-power-density microwave exposure.

    Science.gov (United States)

    Lu, Yonghui; Xu, Shangcheng; He, Mindi; Chen, Chunhai; Zhang, Lei; Liu, Chuan; Chu, Fang; Yu, Zhengping; Zhou, Zhou; Zhong, Min

    2012-07-16

    Extensive evidence indicates that glucose administration attenuates memory deficits in rodents and humans, and cognitive impairment has been associated with reduced glucose metabolism and uptake in certain brain regions including the hippocampus. In the present study, we investigated whether glucose treatment attenuated memory deficits caused by chronic low-power-density microwave (MW) exposure, and the effect of MW exposure on hippocampal glucose uptake. We exposed Wistar rats to 2.45 GHz pulsed MW irradiation at a power density of 1 mW/cm(2) for 3 h/day, for up to 30 days. MW exposure induced spatial learning and memory impairments in rats. Hippocampal glucose uptake was also reduced by MW exposure in the absence or presence of insulin, but the levels of blood glucose and insulin were not affected. However, these spatial memory deficits were reversed by systemic glucose treatment. Our results indicate that glucose administration attenuates the spatial memory deficits induced by chronic low-power-density MW exposure, and reduced hippocampal glucose uptake may be associated with cognitive impairment caused by MW exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice.

    Science.gov (United States)

    Wang, Zhi; Li, Liaoliao; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi

    2015-08-01

    Obesity can cause pathological changes in organs. We determined the effects of chronic high fat diet (HFD) and intermittent fasting, a paradigm providing organ protection, on mouse heart. Seven-week old CD1 male mice were randomly assigned to control, HFD and intermittent fasting groups. Control mice had free access to regular diet (RD). RD was provided every other day to mice in the intermittent fasting group. Mice in HFD group had free access to HFD. Their left ventricles were harvested 11 months after they had been on these diet regimens. HFD increased cardiomyocyte cross-section area and fibrosis. HFD decreased active caspase 3, an apoptosis marker, and the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3I, an autophagy marker. HFD increased the phospho-glycogen synthase kinase-3β (GSK-3β) at Ser9, a sign of GSK-3β inhibition. Nuclear GATA binding protein 4 and yes-associated protein, two GSK-3β targeting transcription factors that can induce hypertrophy-related gene expression, were increased in HFD-fed mice. Mice on intermittent fasting did not have these changes except for the increased active caspase 3 and decreased ratio of LC3II/LC3I. These results suggest that chronic HFD induces myocardial hypertrophy and fibrosis, which may be mediated by GSK-3β inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition in the large airways.

    Directory of Open Access Journals (Sweden)

    Jill R Johnson

    Full Text Available Chronic allergic asthma is characterized by Th2-polarized inflammation and leads to airway remodeling and fibrosis but the mechanisms involved are not clear. To determine whether epithelial-mesenchymal transition contributes to airway remodeling in asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extract for up to 15 consecutive weeks. We report that respiratory exposure to HDM led to significant airway inflammation and thickening of the smooth muscle layer in the wall of the large airways. Transforming growth factor beta-1 (TGF-β1 levels increased in mouse airways while epithelial cells lost expression of E-cadherin and occludin and gained expression of the mesenchymal proteins vimentin, alpha-smooth muscle actin (α-SMA and pro-collagen I. We also observed increased expression and nuclear translocation of Snail1, a transcriptional repressor of E-cadherin and a potent inducer of EMT, in the airway epithelial cells of HDM-exposed mice. Furthermore, fate-mapping studies revealed migration of airway epithelial cells into the sub-epithelial regions of the airway wall. These results show the contribution of EMT to airway remodeling in chronic asthma-like inflammation and suggest that Th2-polarized airway inflammation can trigger invasion of epithelial cells into the subepithelial regions of the airway wall where they contribute to fibrosis, demonstrating a previously unknown plasticity of the airway epithelium in allergic airway disease.

  9. Hif1a inactivation rescues photoreceptor degeneration induced by a chronic hypoxia-like stress.

    Science.gov (United States)

    Barben, Maya; Ail, Divya; Storti, Federica; Klee, Katrin; Schori, Christian; Samardzija, Marijana; Michalakis, Stylianos; Biel, Martin; Meneau, Isabelle; Blaser, Frank; Barthelmes, Daniel; Grimm, Christian

    2018-04-17

    Reduced choroidal blood flow and tissue changes in the ageing human eye impair oxygen delivery to photoreceptors and the retinal pigment epithelium. As a consequence, mild but chronic hypoxia may develop and disturb cell metabolism, function and ultimately survival, potentially contributing to retinal pathologies such as age-related macular degeneration (AMD). Here, we show that several hypoxia-inducible genes were expressed at higher levels in the aged human retina suggesting increased activity of hypoxia-inducible transcription factors (HIFs) during the physiological ageing process. To model chronically elevated HIF activity and investigate ensuing consequences for photoreceptors, we generated mice lacking von Hippel Lindau (VHL) protein in rods. This activated HIF transcription factors and led to a slowly progressing retinal degeneration in the ageing mouse retina. Importantly, this process depended mainly on HIF1 with only a minor contribution of HIF2. A gene therapy approach using AAV-mediated RNA interference through an anti-Hif1a shRNA significantly mitigated the degeneration suggesting a potential intervention strategy that may be applicable to human patients.

  10. Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat.

    Science.gov (United States)

    Nurulain, Syed M; Petroianu, Georg; Shafiullah, Mohamed; Kalász, Huba; Oz, Murat; Saeed, Tariq; Adem, Abdu; Adeghate, Ernest

    2013-10-01

    There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Immune System Modifications Induced in a Mouse Model of Chronic Exposure to (90)Sr.

    Science.gov (United States)

    Synhaeve, Nicholas; Musilli, Stefania; Stefani, Johanna; Nicolas, Nour; Delissen, Olivia; Dublineau, Isabelle; Bertho, Jean-Marc

    2016-03-01

    Strontium 90 ((90)Sr) remains in the environment long after a major nuclear disaster occurs. As a result, populations living on contaminated land are potentially exposed to daily ingesting of low quantities of (90)Sr. The potential long-term health effects of such chronic contamination are unknown. In this study, we used a mouse model to evaluate the effects of (90)Sr ingestion on the immune system, the animals were chronically exposed to (90)Sr in drinking water at a concentration of 20 kBq/l, for a daily ingestion of 80-100 Bq/day. This resulted in a reduced number of CD19(+) B lymphocytes in the bone marrow and spleen in steady-state conditions. In contrast, the results from a vaccine experiment performed as a functional test of the immune system showed that in response to T-dependent antigens, there was a reduction in IgG specific to tetanus toxin (TT), a balanced Th1/Th2 response inducer antigen, but not to keyhole limpet hemocyanin (KLH), a strong Th2 response inducer antigen. This was accompanied by a reduction in Th1 cells in the spleen, consistent with the observed reduction in specific IgG concentration. The precise mechanisms by which (90)Sr acts on the immune system remain to be elucidated. However, our results suggest that (90)Sr ingestion may be responsible for some of the reported effects of internal contamination on the immune system in civilian populations exposed to the Chernobyl fallout.

  12. Desipramine rescues age-related phenotypes in depression-like rats induced by chronic mild stress.

    Science.gov (United States)

    Xie, Xiaoxian; Chen, Yangyang; Wang, Qi; Shen, Qichen; Ma, Lingyan; Huang, Liangfeng; Wu, Tao; Fu, Zhengwei

    2017-11-01

    Our previous finding demonstrates that major depressive disorder can mediate accelerated aging in rats. Desipramine is a typical tricyclic antidepressant, and can provide neuroprotection and counteract depression-like behaviors. However, whether desipramine can rescue age-related phenotypes in depressed individuals is not understood. In the present study, we investigated the physiological function of desipramine on rescuing the age-related phenotypes in these animals. The rats were induced by chronic mild stress paradigm, and the depression-like behaviors of rats were detected by sucrose intake test, open field test (OFT) and forced swimming test (FST). Then the depressed rats were treated by desipramine. Desipramine administration was effective in counteracting depression-like behaviors by increasing the sucrose solution intake, reducing the immobility time in the FST, and increasing total distance travelled and numbers of grid line crossed in the OFT. Moreover, desipramine treatment was able to reduce the oxidative damage to rat liver, and to increase the expression of telomerase reverse transcriptase (TERT), leading to correspondingly restored telomerase activity. Our findings identify that one function of desipramine may partly be to rescue age-related phenotypes in depressed individuals induced by chronic stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Hyperoside protects against chronic mild stress-induced learning and memory deficits.

    Science.gov (United States)

    Gong, Yeli; Yang, Youhua; Chen, Xiaoqing; Yang, Min; Huang, Dan; Yang, Rong; Zhou, Lianying; Li, Changlei; Xiong, Qiuju; Xiong, Zhe

    2017-07-01

    Hyperoside (quercetin-3-O-b-d-galactosidepyranose) is a plant-derived flavonoid mainly found in fruits, fruit juices (most notably flavanols, flavanones, and anthocyanins) and Chinese traditional medicines. It has been applied to relieve pain and improve cardiovascular functions in clinic. However, the effects of hyperoside on cognitive impairment induced by chronic stress and the underlying molecular mechanisms remain unclear. In the current study, we used chronic mild stress (CMS) rats to investigate the effects of hyperoside on learning and memory and further explore the possible mechanisms. Our results demonstrated that hyperoside reduced the escape latency and the swimming distance of CMS rats in Morris water maze test and reversed depressive symptoms in forced swim test (FST) and sucrose preference test. In addition, hyperoside increased the expression of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS rats without influencing the corticosterone (CORT) level in blood plasma. Furthermore, K252a, an inhibitor of the BDNF receptor TrkB, prevented the protective effects of hyperoside on learning and memory in CMS rats. Taken together, these results indicate that hyperoside reverses the cognitive impairment induced by CMS, which is associated with the regulation of BDNF signaling pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Complement C3 deficiency attenuates chronic hypoxia-induced pulmonary hypertension in mice.

    Directory of Open Access Journals (Sweden)

    Eileen M Bauer

    Full Text Available Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension.Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.

  15. Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds.

    Science.gov (United States)

    Stier, Antoine; Massemin, Sylvie; Criscuolo, François

    2014-12-01

    Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost.

  16. Aspartame-induced fibromyalgia, an unusual but curable cause of chronic pain.

    Science.gov (United States)

    Ciappuccini, R; Ansemant, T; Maillefert, J-F; Tavernier, C; Ornetti, P

    2010-01-01

    We report for the first time an unusual musculoskeletal adverse effect of aspartame in two patients. A 50-year-old woman had been suffering from widespread pain and fatigue for more than 10 years leading to the diagnosis of fibromyalgia. During a vacation in a foreign country, she did not suffer from painful symptoms since she had forgotten to take her aspartame. All of the symptoms reappeared in the days following her return when she reintroduced aspartame into her daily diet. Thus, aspartame was definitively excluded from her diet, resulting in a complete regression of the fibromyalgia symptoms. A 43-year-old man consulted for a 3-year history of bilateral forearm, wrist, and hand and cervical pain with various unsuccessful treatments. A detailed questioning allowed to find out that he had been taking aspartame for three years. The removal of aspartame was followed by a complete regression of pain, without recurrence. We believe that these patients' chronic pain was due to the ingestion of aspartame, a potent flavouring agent, widely used in food as a calorie-saver. The benefit/ risk ratio of considering the diagnosis of aspartame-induced chronic pain is obvious: the potential benefit is to cure a disabling chronic disease, to spare numerous laboratory and imaging investigations, and to avoid potentially harmful therapies; the potential risk is to temporarily change the patient's diet. Thus, practitioners should ask patients suffering from fibromyalgia about their intake of aspartame. In some cases, this simple question might lead to the resolution of a disabling chronic disease.

  17. Reproducibility of biomarkers in induced sputum and in serum from chronic smokers.

    Science.gov (United States)

    Zuiker, Rob G J A; Kamerling, Ingrid M C; Morelli, Nicoletta; Calderon, Cesar; Boot, J Diderik; de Kam, Marieke; Diamant, Zuzana; Burggraaf, Jacobus; Cohen, Adam F

    2015-08-01

    Soluble inflammatory markers obtained from non-invasive airway sampling such as induced sputum may be useful biomarkers for targeted pharmaceutical interventions. However, before these soluble markers can be used as potential targets, their variability and reproducibility need to be established in distinct study populations. This study aimed to assess the reproducibility of biomarkers obtained from induced sputum and serum in chronic smokers and non-smokers. Sputum and serum samples were obtained from 16 healthy non-smokers and 16 asymptomatic chronic smokers (for both groups: 8M/8F, 30-52 years, FEV1 ≥80% pred.; ≥10 pack years for the smokers) on 2 separate visits 4-10 days apart. Soluble markers in serum and sputum were analysed by ELISA. The differences between smokers vs non-smokers were analysed with a t-test and variability was assessed on log-transformed data by a mixed model ANOVA. Analysable sputum samples could be obtained from all 32 subjects. In both study populations neutrophils and macrophages were the predominant cell types. Serum Pulmonary Surfactant Associated Protein D had favourable reproducibility criteria for reliability ratio (0.99), intra-subject coefficient of variation (11.2%) and the Bland Altman limits of agreement. Furthermore, chronic smokers, compared to non-smokers, had significantly higher sputum concentrations of IL-8 (1094.6 pg/mL vs 460.8 pg/mL, p = 0.006)), and higher serum concentrations of Pulmonary Surfactant Associated Protein D (110.9 pg/mL vs 64.7 pg/mL, p = 0.019), and lower concentrations of Serum Amyloid A (1352.4 pg/mL vs 2297.5 pg/mL, p = 0.022). Serum Pulmonary Surfactant Associated Protein D proved to be a biomarker that fulfilled the criteria for reproducibility in both study groups. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Chronic exposure to graphene-based nanomaterials induces behavioral deficits and neural damage in Caenorhabditis elegans.

    Science.gov (United States)

    Li, Ping; Xu, Tiantian; Wu, Siyu; Lei, Lili; He, Defu

    2017-10-01

    Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the environment and health are still not well understood. In the present study, the potential adverse effects of graphite (G), graphite oxide nanoplatelets (GO) and graphene quantum dots (GQDs) on the motor nervous system were investigated using nematode Caenorhabditis elegans as the assay system. After being characterized using TEM, SEM, XPS and PLE, three nanomaterials were chronically exposed to C. elegans for 6 days. In total, 50-100 mg l -1 GO caused a significant reduction in the survival rate, but G and GDDs showed low lethality on nematodes. After chronic exposure of sub-lethal dosages, three nanomaterials were observed to distribute primarily in the pharynx and intestine; but GQDs were widespread in nematode body. Three graphene-based nanomaterials resulted in significant declines in locomotor frequency of body bending, head thrashing and pharynx pumping. In addition, mean speed, bending angle-frequency and wavelength of the crawling movement were significantly reduced after exposure. Using transgenic nematodes, we found high concentrations of graphene-based nanomaterials induced down-expression of dat-1::GFP and eat-4::GFP, but no significant changes in unc-47::GFP. This indicates that graphene-based nanomaterials can lead to damages in the dopaminergic and glutamatergic neurons. The present data suggest that chronic exposure of graphene-based nanomaterials may cause neurotoxicity risks of inducing behavioral deficits and neural damage. These findings provide useful information to understand the toxicity and safe application of graphene-based nanomaterials. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Trigeminal Inflammatory Compression (TIC) injury induces chronic facial pain and susceptibility to anxiety-related behaviors.

    Science.gov (United States)

    Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N

    2015-06-04

    Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Ganoderma Lucidum Pharmacopuncture for Teating Ethanol-induced Chronic Gastric Ulcers in Rats

    Directory of Open Access Journals (Sweden)

    Jae-Heung Park

    2015-03-01

    Full Text Available Objectives: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP on chronic gastric ulcers in rats. Methods: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 (中脘 and ST36 (足三里 were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. Results: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX, B-cell lymphoma 2 (Bcl-2 and Transforming growth factor-beta 1 (TGF-β1. Conclusion: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer.

  1. Effect of chronic forced swimming stress on whole brain radiation induced cognitive dysfunction and related mechanism

    International Nuclear Information System (INIS)

    Zhang Yuan; Sun Rui; Zhu Yaqun; Zhang Liyuan; Ji Jianfeng; Li Kun; Tian Ye

    2014-01-01

    Objective: To explore whether chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction and possible mechanism. Methods: Thirty-nine one month old male Sprague-Dawley rats were randomized into sham control group(C), swimming group(C-S), radiation group(R), and radiation plus swimming group(R-S). Radiation groups were given a single dose of 20 Gy on whole-brain. Rats in the swimming groups were trained with swimming of 15 min/d, 5 d/w. Rat behavior was performed 3 months after radiation in an order of free activity in an open field and the Morris water maze test including the place navigation and spatial probe tests. Then, the protein expressions of BDNF, P-ERK, T-ERK, P-CREB and T-CREB in the rat hippocampus tissue were assayed by Western blot. Results: On the day 2, in the place navigation test of Morris water maze, the latency of swimming group was significantly shorter than that of sham group, the latency of sham group was significantly shorter than that of radiation group, and the latency of radiation swimming group was significantly shorter than that of radiation group(P 0.05). Western blot assay showed that the expressions of BDNF and its downstream signals including P-ERK and P-CREB were markedly reduced by radiation (P < 0.05), but this reduction was attenuated by the chronic forced swimming stress. Conclusion: The chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction by up-regulating the expressions of BDNF and its downstream signal molecules of P-ERK and P-CREB in hippocampus. (authors)

  2. Sweet food improves chronic stress-induced irritable bowel syndrome-like symptoms in rats.

    Science.gov (United States)

    Rho, Sang-Gyun; Kim, Yong Sung; Choi, Suck Chei; Lee, Moon Young

    2014-03-07

    To investigate whether palatable sweet foods have a beneficial effect on chronic stress-induced colonic motility and inflammatory cytokines. Adult male rats were divided into 3 groups: control (CON, n = 5), chronic variable stress with chow (CVS-A, n = 6), and chronic variable stress with chow and sweet food (CVS-B, n = 6). The rats were fed standard rodent chow as the chow food and/or AIN-76A as the sweet food. A food preference test for AIN-76A was performed in another group of normal rats (n = 10) for twelve days. Fecal pellet output (FPO) was measured for 6 wk during water bedding stress in the CVS groups. The weight of the adrenal glands, adrenocorticotropic hormone (ACTH) and corticosterone levels in plasma were measured. The expression levels of transforming growth factor-β, interleukin (IL)-2, and interferon-gamma (IFN-γ) were measured in the distal part of colonic tissues and plasma using Western blot analysis. In sweet preference test, all rats initially preferred sweet food to chow food. However, the consumption rate of sweet food gradually decreased and reduced to below 50% of total intake eight days after sweet food feeding. Accumulated FPO was higher in the CVS-A group compared with the CVS-B group over time. All stress groups showed significant increases in the adrenal to body weight ratio (CVS-A, 0.14 ± 0.01; CVS-B, 0.14 ± 0.01) compared with the control group (0.12 ± 0.01, P food ingestion during CVS might have an effect on the reduction of stress-induced colonic hyper-motility and pro-inflammatory cytokine production in rats.

  3. Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2016-04-01

    Full Text Available This study investigates the in vivo functions of ginseng berry extract (GB as a therapy for dextran sodium sulfate (DSS-induced colitis. C57BL/6 mice were given drinking water containing DSS (3% for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103−CD11c+ dendritic cells (cDCs, and macrophages. In addition, GB treatment promoted the migration of CD103+CD11c+ cDCs and expansion of Foxp3+ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis.

  4. Establishment of a rat model of chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) induced by immunization with a novel peptide T2.

    Science.gov (United States)

    Ihsan, Awais Ullah; Khan, Farhan Ullah; Nawaz, Waqas; Khan, Muhammad Zahid; Yang, Mengqi; Zhou, Xiaohui

    2017-07-01

    The exact etiological mechanism of Chronic Prostatitis/chronic pelvic pain syndrome (CP/CPPS) is still unclear however autoimmunity is the most valid theory. We developed a rat model of Chronic Prostatitis/chronic pelvic pain syndrome by using a novel peptide (T2) isolated from TRPM8. This model might be beneficial in elucidating mechanisms involved in the pathogenesis of Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS). 40 male Sprague-Dawley rats with an average weight of 180-220g were equally distributed into five groups. The normal control group was injected with normal saline (.9% NACL), the CFA group with CFA, AL(OH)3 group was given AL(OH)3 injection, T2 group using a novel peptide T2 and T2+AL(OH)3+CFA group was injected with T2+AL(OH)3+CFA. Dosing to all rat groups were injected subcutaneously. Hematoxylin and eosin staining and Immunohistochemistry were used to investigate inflammatory cell infiltration and IL-1β in the prostate tissue respectively. ELISA technique was used to measure the serum level of CRP and TNF-α. T-test was used to analyze the results. Maximum infiltration of inflammatory cells and the highest level of IL-1β in the prostate tissue was observed in T2+AL(OH)3+CFA group as revealed by histopathology and Immunohistochemistry, respectively. Furthermore, T2+AL(OH)3+CFA group attained the peak value of serum TNF-α and CRP as determined by ELISA technique. Our results demonstrated that T2 in combination with AL(OH)3 and CFA induced severe Prostatitis in rats. We believe that our present model will be highly beneficial for investigation of the pathophysiology of Chronic Prostatitis/Chronic Pelvic Pain Syndrome. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Interstitial atoms enable joint twinning and transformation induced plasticity in strong and ductile high-entropy alloys.

    Science.gov (United States)

    Li, Zhiming; Tasan, Cemal Cem; Springer, Hauke; Gault, Baptiste; Raabe, Dierk

    2017-01-12

    High-entropy alloys (HEAs) consisting of multiple principle elements provide an avenue for realizing exceptional mechanical, physical and chemical properties. We report a novel strategy for designing a new class of HEAs incorporating the additional interstitial element carbon. This results in joint activation of twinning- and transformation-induced plasticity (TWIP and TRIP) by tuning the matrix phase's instability in a metastable TRIP-assisted dual-phase HEA. Besides TWIP and TRIP, such alloys benefit from massive substitutional and interstitial solid solution strengthening as well as from the composite effect associated with its dual-phase structure. Nanosize particle formation and grain size reduction are also utilized. The new interstitial TWIP-TRIP-HEA thus unifies all metallic strengthening mechanisms in one material, leading to twice the tensile strength compared to a single-phase HEA with similar composition, yet, at identical ductility.

  6. Ceftriaxone-induced immune hemolytic anemia as a life-threatening complication of antibiotic treatment of 'chronic Lyme disease'.

    Science.gov (United States)

    De Wilde, Maarten; Speeckaert, Marijn; Callens, Rutger; Van Biesen, Wim

    2017-04-01

    'Chronic Lyme disease' is a controversial condition. As any hard evidence is lacking that unresolved systemic symptoms, following an appropriately diagnosed and treated Lyme disease, are related to a chronic infection with the tick-borne spirochaetes of the Borrelia genus, the term 'chronic Lyme disease' should be avoided and replaced by the term 'post-treatment Lyme disease syndrome.' The improper prescription of prolonged antibiotic treatments for these patients can have an impact on the community antimicrobial resistance and on the consumption of health care resources. Moreover, these treatments can be accompanied by severe complications. In this case report, we describe a life-threatening ceftriaxone-induced immune hemolytic anemia with an acute kidney injury (RIFLE-stadium F) due to a pigment-induced nephropathy in a 76-year-old woman, who was diagnosed with a so-called 'chronic Lyme disease.'

  7. Autophagy Protects against CYP2E1/Chronic Ethanol-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Yongke Lu

    2015-10-01

    Full Text Available Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver injury in a chronic ethanol-fed mouse model. Wild type (WT, CYP2E1 knockout (KO or CYP2E1 humanized transgenic knockin (KI, mice were fed an ethanol liquid diet or control dextrose diet for four weeks. In the last week, some mice received either saline or 3-methyladenine (3-MA, an inhibitor of autophagy, or rapamycin, which stimulates autophagy. Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury. Treatment with 3-MA enhanced the ethanol-induced fat accumulation in WT mice and caused necrosis in the KI mice; little or no effect was found in the ethanol-fed KO mice or any of the dextrose-fed mice. 3-MA treatment further lowered the ethanol-decrease in hepatic GSH levels and further increased formation of TBARS in WT and KI mice, whereas rapamycin blunted these effects of ethanol. Neither 3-MA nor rapamycin treatment affected CYP2E1 catalytic activity or content or the induction CYP2E1 by ethanol. The 3-MA treatment decreased levels of Beclin-1 and Atg 7 but increased levels of p62 in the ethanol-fed WT and KI mice whereas rapamycin had the opposite effects, validating inhibition and stimulation of autophagy, respectively. These

  8. Chronic ciguatoxin treatment induces synaptic scaling through voltage gated sodium channels in cortical neurons.

    Science.gov (United States)

    Martín, Víctor; Vale, Carmen; Rubiolo, Juan A; Roel, Maria; Hirama, Masahiro; Yamashita, Shuji; Vieytes, Mercedes R; Botana, Luís M

    2015-06-15

    Ciguatoxins are sodium channels activators that cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents with long-term neurological alterations. In central neurons, chronic perturbations in activity induce homeostatic synaptic mechanisms that adjust the strength of excitatory synapses and modulate glutamate receptor expression in order to stabilize the overall activity. Immediate early genes, such as Arc and Egr1, are induced in response to activity changes and underlie the trafficking of glutamate receptors during neuronal homeostasis. To better understand the long lasting neurological consequences of ciguatera, it is important to establish the role that chronic changes in activity produced by ciguatoxins represent to central neurons. Here, the effect of a 30 min exposure of 10-13 days in vitro (DIV) cortical neurons to the synthetic ciguatoxin CTX 3C on Arc and Egr1 expression was evaluated using real-time polymerase chain reaction approaches. Since the toxin increased the mRNA levels of both Arc and Egr1, the effect of CTX 3C in NaV channels, membrane potential, firing activity, miniature excitatory postsynaptic currents (mEPSCs), and glutamate receptors expression in cortical neurons after a 24 h exposure was evaluated using electrophysiological and western blot approaches. The data presented here show that CTX 3C induced an upregulation of Arc and Egr1 that was prevented by previous coincubation of the neurons with the NaV channel blocker tetrodotoxin. In addition, chronic CTX 3C caused a concentration-dependent shift in the activation voltage of NaV channels to more negative potentials and produced membrane potential depolarization. Moreover, 24 h treatment of cortical neurons with 5 nM CTX 3C decreased neuronal firing and induced synaptic scaling mechanisms, as evidenced by a decrease in the amplitude of mEPSCs and downregulation in the protein level of glutamate receptors that was also prevented by tetrodotoxin

  9. Inactivation of basolateral amygdala prevents chronic immobilization stress-induced memory impairment and associated changes in corticosterone levels.

    Science.gov (United States)

    Tripathi, Sunil Jamuna; Chakraborty, Suwarna; Srikumar, B N; Raju, T R; Shankaranarayana Rao, B S

    2017-07-01

    Chronic stress causes detrimental effects on various forms of learning and memory. The basolateral amygdala (BLA) not only plays a crucial role in mediating certain forms of memory, but also in the modulation of the effects of stress. Chronic immobilization stress (CIS) results in hypertrophy of the BLA, which is believed to be one of the underlying causes for stress' effects on learning. Thus, it is plausible that preventing the effects of CIS on amygdala would preclude its deleterious cognitive effects. Accordingly, in the first part, we evaluated the effect of excitotoxic lesion of the BLA on chronic stress-induced hippocampal-dependent spatial learning using a partially baited radial arm maze task. The BLA was ablated bilaterally using ibotenic acid prior to CIS. Chronically stressed rats showed impairment in spatial learning with decreased percentage correct choice and increased reference memory errors. Excitotoxic lesion of the BLA prevented the impairment in spatial learning and reference memory. In the retention test, lesion of the BLA was able to rescue the chronic stress-induced impairment. Interestingly, stress-induced enhanced plasma corticosterone levels were partially prevented by the lesion of BLA. These results motivated us to evaluate if the same effects can be observed with temporary inactivation of BLA, only during stress. We found that chronic stress-induced spatial learning deficits were also prevented by temporary inactivation of the BLA. Additionally, temporary inactivation of BLA partially precluded the stress-induced increase in plasma corticosterone levels. Thus, inactivation of BLA precludes stress-induced spatial learning deficits, and enhanced plasma corticosterone levels. It is speculated that BLA inactivation-induced reduction in corticosterone levels during stress, might be crucial in restoring spatial learning impairments. Our study provides evidence that amygdalar modulation during stress might be beneficial for strategic

  10. Hypothalamic GPR40 Signaling Activated by Free Long Chain Fatty Acids Suppresses CFA-Induced Inflammatory Chronic Pain

    OpenAIRE

    Nakamoto, Kazuo; Nishinaka, Takashi; Sato, Naoya; Mankura, Mitsumasa; Koyama, Yutaka; Kasuya, Fumiyo; Tokuyama, Shogo

    2013-01-01

    GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently inc...

  11. Dorsoradial capsulodesis for trapeziometacarpal joint instability.

    Science.gov (United States)

    Rayan, Ghazi; Do, Viet

    2013-02-01

    We describe an alternative method for treating chronic trapeziometacarpal (TM) joint instability after acute injury or chronic repetitive use of the thumb by performing a dorsoradial capsulodesis procedure. The procedure is done by imbricating the redundant TM joint dorsoradial ligament and capsule after reducing the joint by pronating the thumb. The dorsoradial capsulodesis is a reasonable reconstructive option for chronic TM joint instability and subluxation. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  12. Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

    Directory of Open Access Journals (Sweden)

    María F Ferrer

    Full Text Available Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

  13. Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet.

    Science.gov (United States)

    Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

    2013-01-15

    Caffeine alleviates cognitive impairment associated with a variety of health conditions. In this study, we examined the effect of caffeine treatment on chronic stress- and/or high fat-high carbohydrate Western diet (WD)-induced impairment of learning and memory in rats. Chronic psychosocial stress, WD and caffeine (0.3 g/L in drinking water) were simultaneously administered for 3 months to adult male Wistar rats. At the conclusion of the 3 months, and while the previous treatments continued, rats were tested in the radial arm water maze (RAWM) for learning, short-term and long-term memory. This procedure was applied on a daily basis to all animals for 5 consecutive days or until the animal reaches days to criterion (DTC) in the 12th learning trial and memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Chronic stress and/or WD groups caused impaired learning, which was prevented by chronic caffeine administration. In the memory tests, chronic caffeine administration also prevented memory impairment during chronic stress conditions and/or WD. Furthermore, DTC value for caffeine treated stress, WD, and stress/WD groups indicated that caffeine normalizes memory impairment in these groups. These results showed that chronic caffeine administration prevented stress and/or WD-induced impairment of spatial learning and memory. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice.

    Science.gov (United States)

    Bahi, Amine; Dreyer, Jean-Luc

    2014-01-01

    We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

  15. The Effect of 2 Forms of Talocrural Joint Traction on Dorsiflexion Range of Motion and Postural Control in Those With Chronic Ankle Instability.

    Science.gov (United States)

    Powden, Cameron J; Hogan, Kathleen K; Wikstrom, Erik A; Hoch, Matthew C

    2017-05-01

    Talocrural joint mobilizations are commonly used to address deficits associated with chronic ankle instability (CAI). Examine the immediate effects of talocrural joint traction in those with CAI. Blinded, crossover. Laboratory. Twenty adults (14 females; age = 23.80 ± 4.02 y; height = 169.55 ± 12.38 cm; weight = 78.34 ± 16.32 kg) with self-reported CAI participated. Inclusion criteria consisted of a history of ≥1 ankle sprain, ≥2 episodes of giving way in the previous 3 mo, answering "yes" to ≥4 questions on the Ankle Instability Instrument, and ≤24 on the Cumberland Ankle Instability Tool. Subjects participated in 3 sessions in which they received a single treatment session of sustained traction (ST), oscillatory traction (OT), or a sham condition in a randomized order. Interventions consisted of four 30-s sets of traction with 1 min of rest between sets. During ST and OT, the talus was distracted distally from the ankle mortise to the end-range of accessory motion. ST consisted of continuous distraction and OT involved 1-s oscillations between the mid and end-range of accessory motion. The sham condition consisted of physical contact without force application. Preintervention and postintervention measurements of weight-bearing dorsiflexion, dynamic balance, and static single-limb balance were collected. The independent variable was treatment (ST, OT, sham). The dependent variables included pre-to-posttreatment change scores for the WBLT (cm), normalized SEBTAR (%), and time-to-boundary (TTB) variables(s). Separate 1-way ANOVAs examined differences between treatments for each dependent variable. Alpha was set a priori at P manual therapies.

  16. The diagnostic performance of radiography for detection of osteoarthritis-associated features compared with MRI in hip joints with chronic pain

    International Nuclear Information System (INIS)

    Xu, Li; Hayashi, Daichi; Guermazi, Ali; Hunter, David J.; Li, Ling; Winterstein, Anton; Bohndorf, Klaus; Roemer, Frank W.

    2013-01-01

    To evaluate the diagnostic performance of radiography for the detection of MRI-detected osteoarthritis-associated features in various articular subregions of the hip joint. Forty-four patients with chronic hip pain (mean age, 63.3 ± 9.5 years), who were part of the Hip Osteoarthritis MRI Scoring (HOAMS) cohort, underwent both weight-bearing anteroposterior pelvic radiography and 1.5 T MRI. The HOAMS study was a prospective observational study involving 52 subjects, conducted to develop a semiquantitative MRI scoring system for hip osteoarthritis features. In the present study, eight subjects were excluded because of a lack of radiographic assessment. On radiography, the presence of superior and medial joint space narrowing, superior and inferior acetabular/femoral osteophytes, acetabular subchondral cysts, and bone attrition of femoral head was noted. On MRI, cartilage, osteophytes, subchondral cysts, and bone attrition were evaluated in the corresponding locations. Diagnostic performance of radiography was compared with that of MRI, and the area under curve (AUC) was calculated for each pathological feature. Compared with MRI, radiography provided high specificity (0.76-0.90) but variable sensitivity (0.44-0.78) for diffuse cartilage damage (using JSN as an indirect marker), femoral osteophytes, acetabular subchondral cysts and bone attrition of the femoral head, and a low specificity (0.42 and 0.58) for acetabular osteophytes. The AUC of radiography for detecting overall diffuse cartilage damage, marginal osteophytes, subchondral cysts and bone attrition was 0.76, 0.78, 0.67, and 0.82, respectively. Diagnostic performance of radiography is good for bone attrition, fair for marginal osteophytes and cartilage damage, but poor for subchondral cysts. (orig.)

  17. Application of posterior pelvic tilt taping for the treatment of chronic low back pain with sacroiliac joint dysfunction and increased sacral horizontal angle.

    Science.gov (United States)

    Lee, Jung-hoon; Yoo, Won-gyu

    2012-11-01

    Kinesio Taping (KT) is a therapeutic method used by physical therapists and athletic trainers in combination with other treatment techniques for various musculoskeletal and neuromuscular problems. However, no research has evaluated the effect of KT in patients with low back pain (LBP). The purpose of this case was to describe the application of posterior pelvic tilt taping (PPTT) with Kinesio tape as a treatment for chronic LBP and to reduce the anterior pelvic tilt angle. Case report. The patien was a 20-year-old female amateur swimmer with a Cobb's angle (L1-S1) of 68°, a sacral horizontal angle of 45°, and pain in both medial buttock areas and sacroiliac joints. We performed PPTT with Kinesio tape for 2 weeks (six times per week for an average of 9 h each time). The patient’s radiographs showed that the Cobb's angle (L1-S1) had decreased from 68° to 47° and that the sacral horizontal angle had decreased from 45° to 31°. Reductions in hypomobility or motion asymmetry, as assessed by the motion palpation test, and in pain, as measured by the pain-provocation tests, were observed. On palpation for both medial buttock areas in the prone position, the patient felt no pain. The patient experienced no pain or stiffness in the low back area while performing forward flexion in the standing position with knees fully extended when washing dishes in the sink. The case study demonstrated that PPTT intervention favourably affected the pelvic inclination and sacral horizontal angle, leading to beneficial effects on sacroiliac joint dysfunction (SIJD) and medial buttock pain. Additional research on the clinical effects of this taping procedure requires greater numbers of athletes with SIJD or LBP who have inappropriate anterior pelvic tilt angles and hyperlordosis.

  18. The diagnostic performance of radiography for detection of osteoarthritis-associated features compared with MRI in hip joints with chronic pain

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Li [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States); Beijing Jishuitan Hospital, Department of Radiology, Beijing (China); Hayashi, Daichi; Guermazi, Ali [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States); Hunter, David J. [University of Sydney, Department of Medicine, Sydney (Australia); Li, Ling [New England Baptist Hospital, Division of Research, Boston, MA (United States); Winterstein, Anton; Bohndorf, Klaus [Klinikum Augsburg, Department of Radiology, Augsburg (Germany); Roemer, Frank W. [Boston University School of Medicine, Quantitative Imaging Center, Department of Radiology, Boston, MA (United States); Klinikum Augsburg, Department of Radiology, Augsburg (Germany); University of Erlangen, Department of Radiology, Erlangen (Germany)

    2013-10-15

    To evaluate the diagnostic performance of radiography for the detection of MRI-detected osteoarthritis-associated features in various articular subregions of the hip joint. Forty-four patients with chronic hip pain (mean age, 63.3 {+-} 9.5 years), who were part of the Hip Osteoarthritis MRI Scoring (HOAMS) cohort, underwent both weight-bearing anteroposterior pelvic radiography and 1.5 T MRI. The HOAMS study was a prospective observational study involving 52 subjects, conducted to develop a semiquantitative MRI scoring system for hip osteoarthritis features. In the present study, eight subjects were excluded because of a lack of radiographic assessment. On radiography, the presence of superior and medial joint space narrowing, superior and inferior acetabular/femoral osteophytes, acetabular subchondral cysts, and bone attrition of femoral head was noted. On MRI, cartilage, osteophytes, subchondral cysts, and bone attrition were evaluated in the corresponding locations. Diagnostic performance of radiography was compared with that of MRI, and the area under curve (AUC) was calculated for each pathological feature. Compared with MRI, radiography provided high specificity (0.76-0.90) but variable sensitivity (0.44-0.78) for diffuse cartilage damage (using JSN as an indirect marker), femoral osteophytes, acetabular subchondral cysts and bone attrition of the femoral head, and a low specificity (0.42 and 0.58) for acetabular osteophytes. The AUC of radiography for detecting overall diffuse cartilage damage, marginal osteophytes, subchondral cysts and bone attrition was 0.76, 0.78, 0.67, and 0.82, respectively. Diagnostic performance of radiography is good for bone attrition, fair for marginal osteophytes and cartilage damage, but poor for subchondral cysts. (orig.)

  19. Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1β-induced chronic inflammation.

    Science.gov (United States)

    Liang, Wen; Lindeman, Jan H; Menke, Aswin L; Koonen, Debby P; Morrison, Martine; Havekes, Louis M; van den Hoek, Anita M; Kleemann, Robert

    2014-05-01

    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β (IL-1β), administered by slow-release minipumps) and metabolic dietary triggers (carbohydrate, cholesterol) of inflammation on the progression of bland liver steatosis (BS) to NASH. Transgenic APOE3*Leiden.huCETP (APOE3L.CETP) mice fed a high-fat diet (HFD) developed BS after 10 weeks. Then, inflammatory triggers were superimposed or not (control) for six more weeks. Mouse livers were analyzed with particular emphasis on hallmarks of inflammation which were defined in human liver biopsies with and without NASH. Livers of HFD-treated control mice remained steatotic and did not progress to NASH. All four inflammatory triggers activated hepatic nuclear factor-κB (NF-κB) significantly and comparably (≥5-fold). However, HFD+LPS or HFD+IL-1β did not induce a NASH-like phenotype and caused intrahepatic accumulation of almost exclusively mononuclear cells. By contrast, mice treated with metabolic triggers developed NASH, characterized by enhanced steatosis, hepatocellular hypertrophy, and formation of mixed-type inflammatory foci containing myeloperoxidase-positive granulocytes (neutrophils) as well as mononuclear cells, essentially as observed in human NASH. Specific for the metabolic inducers was an activation of the proinflammatory transcription factor activator protein-1 (AP-1), neutrophil infiltration, and induction of risk factors associated with human NASH, that is, dyslipidemia (by cholesterol) and insulin resistance (by carbohydrate). In conclusion, HFD feeding followed by NF-κB activation per se (LPS, IL-1β) does not promote the transition from BS to NASH. HFD feeding followed by metabolically evoked inflammation induces additional inflammatory components

  20. A stepwise protocol for the treatment of refractory gastroesophageal reflux-induced chronic cough

    Science.gov (United States)

    Xu, Xianghuai; Lv, Hanjing; Yu, Li; Chen, Qiang; Liang, Siwei

    2016-01-01

    Background Refractory gastroesophageal reflux-induced chronic cough (GERC) is difficult to manage. The purpose of the study is to evaluate the efficacy of a novel stepwise protocol for treating this condition. Methods A total of 103 consecutive patients with suspected refractory reflux-induced chronic cough failing to a standard anti-reflux therapy were treated with a stepwise therapy. Treatment commences with high-dose omeprazole and, if necessary, is escalated to subsequent sequential treatment with ranitidine and finally baclofen. The primary end-point was overall cough resolution, and the secondary end-point was cough resolution after each treatment step. Results High-dose omeprazole eliminated or improved cough in 28.1% of patients (n=29). Further stepwise of treatment with the addition of ranitide yielded a favorable response in an additional 12.6% (n=13) of patients, and subsequent escalation to baclofen provoked response in another 36.9% (n=38) of patients. Overall, this stepwise protocol was successful in 77.6% (n=80) of patients. The diurnal cough symptom score fell from 3 [1] to 1 [0] (Z=6.316, P=0.000), and the nocturnal cough symptom score decreased from 1 [1] to 0 [1] (Z=–4.511, P=0.000), with a corresponding reduction in the Gastroesophageal Reflux Diagnostic Questionnaire score from 8.6±1.7 to 6.8±0.7 (t=3.612, P=0.000). Conversely, the cough threshold C2 to capsaicin was increased from 0.49 (0.49) µmol/L to 1.95 (2.92) µmol/L (Z=–5.892, P=0.000), and the cough threshold C5 was increased from 1.95 (2.92) µmol/L to 7.8 (5.85) µmol/L (Z=–5.171, P=0.000). Conclusions Sequential stepwise anti-reflux therapy is a useful therapeutic strategy for refractory reflux-induced chronic cough. PMID:26904227

  1. Egr-1 regulates autophagy in cigarette smoke-induced chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Zhi-Hua Chen

    2008-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7. Cigarette smoke extract (CSE is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1 and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1(-/- mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.

  2. Chronic restraint-induced stress has little modifying effect on radiation hematopoietic toxicity in mice

    International Nuclear Information System (INIS)

    Wang, Bing; Tanaka, Kaoru; Katsube, Takanori; Ninomiya, Yasuharu; Vares, Guillaume; Nakajima, Tetsuo; Nenoi, Mitsuru; Liu Qiang; Morita, Akinori

    2015-01-01

    Both radiation and stresses cause detrimental effects on humans. Besides possible health effects resulting directly from radiation exposure, the nuclear plant accident is a cause of social psychological stresses. A recent study showed that chronic restraint-induced stresses (CRIS) attenuated Trp53 functions and increased carcinogenesis susceptibility of Trp53-heterozygous mice to total-body X-irradiation (TBXI), having a big impact on the academic world and a sensational effect on the public, especially the residents living in radioactively contaminated areas. It is important to investigate the possible modification effects from CRIS on radiation-induced health consequences in Trp53 wild-type (Trp53wt) animals. Prior to a carcinogenesis study, effects of TBXI on the hematopoietic system under CRIS were investigated in terms of hematological abnormality in the peripheral blood and residual damage in the bone marrow erythrocytes using a mouse restraint model. Five-week-old male Trp53wt C57BL/6J mice were restrained 6 h per day for 28 consecutive days, and TBXI (4 Gy) was given on the 8th day. Results showed that CRIS alone induced a marked decrease in the red blood cell (RBC) and the white blood cell (WBC) count, while TBXI caused significantly lower counts of RBCs, WBCs and blood platelets, and a lower concentration of hemoglobin regardless of CRIS. CRIS alone did not show any significant effect on erythrocyte proliferation and on induction of micronucleated erythrocytes, whereas TBXI markedly inhibited erythrocyte proliferation and induced a significant increase in the incidences of micronucleated erythrocytes, regardless of CRIS. These findings suggest that CRIS does not have a significant impact on radiation-induced detrimental effects on the hematopoietic system in Trp53wt mice. (author)

  3. Osteoarthritis-like pathologic changes in the knee joint induced by environmental disruption of circadian rhythms is potentiated by a high-fat diet.

    Science.gov (United States)

    Kc, Ranjan; Li, Xin; Forsyth, Christopher B; Voigt, Robin M; Summa, Keith C; Vitaterna, Martha Hotz; Tryniszewska, Beata; Keshavarzian, Ali; Turek, Fred W; Meng, Qing-Jun; Im, Hee-Jeong

    2015-11-20

    A variety of environmental factors contribute to progressive development of osteoarthritis (OA). Environmental factors that upset circadian rhythms have been linked to various diseases. Our recent work establishes chronic environmental circadian disruption - analogous to rotating shiftwork-associated disruption of circadian rhythms in humans - as a novel risk factor for the development of OA. Evidence suggests shift workers are prone to obesity and also show altered eating habits (i.e., increased preference for high-fat containing food). In the present study, we investigated the impact of chronic circadian rhythm disruption in combination with a high-fat diet (HFD) on progression of OA in a mouse model. Our study demonstrates that when mice with chronically circadian rhythms were fed a HFD, there was a significant proteoglycan (PG) loss and fibrillation in knee joint as well as increased activation of the expression of the catabolic mediators involved in cartilage homeostasis. Our results, for the first time, provide the evidence that environmental disruption of circadian rhythms plus HFD potentiate OA-like pathological changes in the mouse joints. Thus, our findings may open new perspectives on the interactions of chronic circadian rhythms disruption with diet in the development of OA and may have potential clinical implications.

  4. The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Kanduri, M; Tobin, G [Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala (Sweden); Åleskog, A [Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala (Sweden); Nilsson, K; Rosenquist, R [Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala (Sweden)

    2011-03-01

    Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo.

  5. The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Kanduri, M; Tobin, G; Åleskog, A; Nilsson, K; Rosenquist, R

    2011-01-01

    Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo

  6. The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

    Science.gov (United States)

    Kanduri, M; Tobin, G; Åleskog, A; Nilsson, K; Rosenquist, R

    2011-01-01

    Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo. PMID:22829125

  7. Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy

    Science.gov (United States)

    Ismahil, Mohamed Ameen; Hamid, Tariq; Haberzettl, Petra; Gu, Yan; Chandrasekar, Bysani; Srivastava, Sanjay; Bhatnagar, Aruni

    2011-01-01

    Environmental triggers of dilated cardiomyopathy are poorly understood. Acute exposure to acrolein, a ubiquitous aldehyde pollutant, impairs cardiac function and cardioprotective responses in mice. Here, we tested the hypothesis that chronic oral exposure to acrolein induces inflammation and cardiomyopathy. C57BL/6 mice were gavage-fed acrolein (1 mg/kg) or water (vehicle) daily for 48 days. The dose was chosen based on estimates of human daily unsaturated aldehyde consumption. Compared with vehicle-fed mice, acrolein-fed mice exhibited significant (P acrolein adduct formation indicative of physical translocation of ingested acrolein to the heart. Acrolein also induced myocyte hypertrophy (∼2.2-fold increased myocyte area, P acrolein-exposed hearts, along with upregulated gene expression of proinflammatory cytokines tumor necrosis factor-α and interleukin-1β. Long-term oral exposure to acrolein, at an amount within the range of human unsaturated aldehyde intake, induces a phenotype of dilated cardiomyopathy in the mouse. Human exposure to acrolein may have analogous effects and raise consideration of an environmental, aldehyde-mediated basis for heart failure. PMID:21908791

  8. Morphological alterations in the elastic fibers of the rabbit craniomandibular joint following experimentally induced anterior disk displacement.

    Science.gov (United States)

    Ali, A M; Sharawy, M; O'Dell, N L; al-Behery, G

    1993-01-01

    Elastic fibers are important components of the connective tissue that attaches the articular disk of the craniomandibular joint (CMJ) to the skull and mandible. Biopsies of the articular disk proper and bilaminar zone (BZ) tissues from patients with anterior disk displacement (ADD) have shown previously that there is a marked loss of elastic fibers. In the present study, the effects of inducing ADD on the elastic fibers in the rabbit CMJ disk proper, BZ and condylar cartilage were investigated. The right CMJ was exposed surgically and the discal attachments were severed except for the BZ attachments. Then, the disk was displaced anteriorly and sutured to the zygomatic arch. The CMJs were removed after 1, 2 or 6 weeks and processed for histochemical demonstration of elastic fibers. The results showed osteoarthritic changes following ADD, and a significant decrease in the number of the elastic fibers in the disk proper and BZ. The remaining elastic fibers were abnormal in their appearance and orientation. In addition, ADD led to the appearance of fine elastic fibers among the chondrocytes in the hyaline cartilage of the condyle that were not present in the cartilage of the control condyle. We conclude that induced ADD can lead to a significant loss of elastic fibers in the articular disk, and result in the appearance of elastic fibers within the cartilage of the mandibular condyle.

  9. Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

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    P Padmini S J Khedoe

    Full Text Available COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD, and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L mice.Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study or in week 14, 16, 18 and 20 (chronic study. Inflammatory parameters were measured in bronchoalveolar lavage (BAL and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment.These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

  10. Enlargement of induced variations by combined method of chronic irradiations with callus culture in sugarcane

    International Nuclear Information System (INIS)

    Nagatomi, Shigeki

    1993-01-01

    The present study was conducted to elucidate the effects of gamma ray irradiation and callus culture upon induced variation of the regeneratives. The populations regenerated from young leaf tissue of chronic irradiated plnats grown under a gamma field receiving a total dose of 300 and 100 Gy, showed rather wider variation on quantitative characters than plants from populations of the non-irradiated. This variation extended in both negative and positive directions. Analysis of variance also revealed that variation and heritability in broad sense of most agronomic characters increased significantly among the subclones as the irradiation done rose. Principal component analysis also indicated that the subclones from the irradiated population were more variable than the non-irradiated. Such variation with higher heritability could be transmitted to the following generations by clonal propagation and utilized as genetic sources in mutation breeding. The combined method with chronic irradiation followed by tissue culture is evaluated as an effective method of widening mutation spectrum and increasing mutation frequency in regenerated plants. In addition, this method is valid to improve any crop species which can regenerate plants through callus culture. (author)

  11. Protective Effects of Tinospora cordifolia on Hepatic and Gastrointestinal Toxicity Induced by Chronic and Moderate Alcoholism.

    Science.gov (United States)

    Sharma, Bhawana; Dabur, Rajesh

    2016-01-01

    Heavy alcohol intake depletes the plasma vitamins due to hepatotoxicity and decreased intestinal absorption. However, moderate alcohol intake is often thought to be healthy. Therefore, effects of chronic moderate alcohol intake on liver and intestine were studied using urinary vitamin levels. Furthermore, effects of Tinospora cordifolia water extract (TCE) (hepatoprotective) on vitamin excretion and intestinal absorption were also studied. In the study, asymptomatic moderate alcoholics (n = 12) without chronic liver disease and healthy volunteers (n = 14) of mean age 39 ± 2.2 (mean ± SD) were selected and divided into three groups. TCE treatment was performed for 14 days. The blood and urine samples were collected on Day 0 and 14 after treatment with TCE and analyzed. In alcoholics samples, a significant increase in the levels of gamma-glutamyl transferase, aspartate transaminase, alanine transaminase, Triglyceride, Cholesterol, HDL and LDL (P alcoholic samples; however, TCE intervention restored the CA and biotin levels. Vitamin metabolism biomarkers, i.e. homocysteine and xanthurenic acid, were also normalized after TCE intervention. Overall data depict that moderate alcohol intake is also hepatotoxic and decreases intestinal absorption. However, TCE treatment effectively increased the intestinal absorption and retaining power of liver that regulated alcohol-induced multivitamin deficiency. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  12. Nilotinib-Induced Acute Pancreatitis in a Patient with Chronic Myeloid Leukemia

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    Vihang Patel

    2017-05-01

    Full Text Available Nilotinib, a second-generation tyrosine kinase inhibitor, is used for treatment of chronic myeloid leukemia (CML; it has been widely used especially for imatinib-resistant CML. Despite being a novel drug in this therapeutic class, it has the potential to be harmful. We present the case of an elderly woman who developed life-threatening acute pancreatitis as an adverse event after having started the drug. There is only one reported case in the literature of nilotinib-induced acute pancreatitis. The purpose of this case report is to educate physicians who prescribe this medication to be aware of potential life-threatening adverse events. As more and more therapies are available, physicians should be aware of potential effects of cancer treatment that could be life-threatening to patients.

  13. Increased FKBP51 in induced sputum cells of chronic obstructive pulmonary disease patients after therapy

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    Holownia A

    2009-12-01

    Full Text Available Abstract Objective Immunophilin FKBP51 assists polypeptide folding, participates in glucocorticoid actions and may play a role in glucocorticoid resistance. FKBP51 is altered in patients with asthma, but its role in chronic obstructive pulmonary disease (COPD characterized by dysregulation of several pro/antiinflammatory genes is less clear. Methods We assessed changes in nuclear/cytosolic FKBP51 protein using SDS-PAGE/WB and FKBP51 mRNA by qRT-PCR in cells isolated from induced sputum of stable COPD patients treated with formoterol/budesonide or formoterol/budesonide/theophylline for 4 wk. Results Expression of FKBP51 was higher in formoterol/budesonide/theophylline-treated patients, compared with formoterol/budesonide group in both cytosolic and nuclear fractions by about 57% and 31%, respectively (P Conclusions Increased FKBP51 in COPD patients treated with formoterol/budesonide/theophylline may be important in altering signaling from corticosteroid receptors.

  14. Pancreatitis induced by pegylated interferon alfa-2b in a patient affected by chronic hepatitis C.

    Science.gov (United States)

    Cecchi, Enrica; Forte, Paolo; Cini, Elisabetta; Banchelli, Grazia; Ferlito, Chiara; Mugelli, Alessandro

    2004-01-01

    A middle-aged man was admitted to the ED because of nausea and vomiting, abdominal distention and fainting. A blood analysis revealed high levels of serum amylase and lipase, confirming a diagnosis of acute pancreatitis. The history showed that the patient had self-administered a single dose of pegylated interferon alfa-2b and ribavirin daily for 7 days for chronic hepatitis C. The medications were stopped and his condition gradually improved. In agreement with the literature and the Naranjo algorythm result, pegylated interferon alfa-2b is associated with acute pancreatitis. Identification of a few signs and symptoms is the first 'signal' in preventing a serious drug-induced adverse event.

  15. Prevalence and prediction of exercise-induced oxygen desaturation in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    van Gestel, A J R; Clarenbach, C F; Stöwhas, A C; Teschler, S; Russi, E W; Teschler, H; Kohler, M

    2012-01-01

    Previous studies with small sample sizes reported contradicting findings as to whether pulmonary function tests can predict exercise-induced oxygen desaturation (EID). To evaluate whether forced expiratory volume in one second (FEV(1)), resting oxygen saturation (SpO(2)) and diffusion capacity for carbon monoxide (DLCO) are predictors of EID in chronic obstructive pulmonary disease (COPD). We measured FEV(1), DLCO, SpO(2) at rest and during a 6-min walking test as well as physical activity by an accelerometer. A drop in SpO(2) of >4 to daily physical activity (r = -0.31, p = 0.008). EID is highly prevalent among patients with COPD and can be predicted by FEV(1). EID seems to be associated with impaired daily physical activity which supports its clinical importance. Copyright © 2012 S. Karger AG, Basel.

  16. Behavioral Impairment and Oxidative Damage Induced by Chronic Application of Nonylphenol

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    Zhen Mao

    2010-12-01

    Full Text Available Nonylphenol (NP is a degradation product of nonylphenol polyethoxylates, which are widely used in the production of industrial and consumer surfactants. The aim of the present study was to evaluate the effect of NP on the antioxidant capacity and cognitive ability of mice. NP was given orally by gavages at doses of 0, 50, 100, and 200 mg kg−1 d−1 for 90 days. The results showed that NP significantly decreased the activity of superoxide dismutases (SOD, catalase (CAT, glutathione peroxidase (GPx, and glutathione reductase (GR and at the same time increased malondialdehyde (MDA levels in mice brains. Exploration, memory function and ability to learn a novel task were significantly decreased in NP fed mice. These results indicate that chronic high dose of NP exposure has the potential to generate oxidative stress and induce the cognitive impairment in male mice.

  17. HMGB1 mediates depressive behavior induced by chronic stress through activating the kynurenine pathway.

    Science.gov (United States)

    Wang, Bo; Lian, Yong-Jie; Su, Wen-Jun; Peng, Wei; Dong, Xin; Liu, Lin-Lin; Gong, Hong; Zhang, Ting; Jiang, Chun-Lei; Wang, Yun-Xia

    2017-11-28

    Our previous study has reported that the proactive secretion and role of central high mobility group box 1 (HMGB1) in lipopolysaccharide-induced depressive behavior. Here, the potential mechanism of HMGB1 mediating chronic-stress-induced depression through the kynurenine pathway (KP) was further explored both in vivo and in vitro. Depression model was established with the 4-week chronic unpredictable mild stress (CUMS). Sucrose preference and Barnes maze test were performed to reflect depressive behaviors. The ratio of kynurenine (KYN)/tryptophan (Trp) represented the enzyme activity of indoleamine-2,3-dioxygenase (IDO). Gene transcription and protein expression were assayed by real-time RT-PCR and western-blot or ELISA kit respectively. Along with depressive behaviors, HMGB1 concentrations in the hippocampus and serum substantially increased post 4-week CUMS exposure. Concurrent with the upregulated HMGB1 protein, the regulator of translocation of HMGB1, sirtuin 1 (SIRT1) concentration in the hippocampus remarkably increased. In addition to HMGB1 and SIRT1, IDO, the rate limiting enzyme of KP, was upregulated at the level of mRNA expression and enzyme activity in stressed hippocampi and LPS/HMGB1-treated hippocampal slices. The gene transcription of kynurenine monooxygenase (KMO) and kynureninase (KYNU) in the downstream of KP also increased both in vivo and in vitro. Mice treated with ethyl pyruvate (EP), the inhibitor of HMGB1 releasing, were observed with lower tendency of developing depressive behaviors and reduced activation of enzymes in KP. All of these experiments demonstrate that the role of HMGB1 on the induction of depressive behavior is mediated by KP activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice

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    Dorsey Susan G

    2011-04-01

    Full Text Available Abstract Background A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH wide dynamic range neurons in oxaliplatin-treated mice Results We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH. Conclusions Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds.

  19. IL-1 signal affects both protection and pathogenesis of virus-induced chronic CNS demyelinating disease

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    Kim Byung S

    2012-09-01

    Full Text Available Abstract Background Theiler’s virus infection induces chronic demyelinating disease in mice and has been investigated as an infectious model for multiple sclerosis (MS. IL-1 plays an important role in the pathogenesis of both the autoimmune disease model (EAE and this viral model for MS. However, IL-1 is known to play an important protective role against certain viral infections. Therefore, it is unclear whether IL-1-mediated signaling plays a protective or pathogenic role in the development of TMEV-induced demyelinating disease. Methods Female C57BL/6 mice and B6.129S7-Il1r1tm1Imx/J mice (IL-1R KO were infected with Theiler’s murine encephalomyelitis virus (1 x 106 PFU. Differences in the development of demyelinating disease and changes in the histopathology were compared. Viral persistence, cytokine production, and immune responses in the CNS of infected mice were analyzed using quantitative PCR, ELISA, and flow cytometry. Results Administration of IL-1β, thereby rending resistant B6 mice susceptible to TMEV-induced demyelinating disease, induced a high level of Th17 response. Interestingly, infection of TMEV into IL-1R-deficient resistant C57BL/6 (B6 mice also induced TMEV-induced demyelinating disease. High viral persistence was found in the late stage of viral infection in IL-1R-deficient mice, although there were few differences in the initial anti-viral immune responses and viral persistent levels between the WT B6 and IL-1R-deficiecent mice. The initial type I IFN responses and the expression of PDL-1 and Tim-3 were higher in the CNS of TMEV-infected IL-1R-deficient mice, leading to deficiencies in T cell function that permit viral persistence. Conclusions These results suggest that the presence of high IL-1 level exerts the pathogenic role by elevating pathogenic Th17 responses, whereas the lack of IL-1 signals promotes viral persistence in the spinal cord due to insufficient T cell activation by elevating the production of

  20. Effects and mechanisms of total glucosides of paeony on joint damage in rat collagen-induced arthritis.

    Science.gov (United States)

    Zhu, L; Wei, W; Zheng, Y-Q; Jia, X-Y

    2005-05-01

    To investigate the therapeutic effects and mechanisms of total glucosides of paeony (TGP), an effective compound of Chinese traditional herbal medicine (CTM), on collagen -induced arthritis (CIA) in rats. CIA was induced in male Sprague-Dawley rats immunized with chicken type II collagen in Freund's complete adjuvant. TGP (25, 50, 100 mg/kg/d) was orally administered to rats from day 14 to 28 after immunization. Arthritis was evaluated by hind paw swelling, polyarthritis index, and histological examination. Activities of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) were determined and the ultrastructure of synoviocytes was observed. The proliferation and the production of vascular epidermal growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase 1 (MMP-1) and MMP-3 in fibroblast-like synoviocytes (FLS) were detected. The administration of TGP (25, 50, 100 mg/kg, ig x 14 days) suppressed secondary inflammatory reactions and histological changes in CIA model. The ultrastructure of synoviocytes from CIA rats was changed, and the level of IL-1 and TNF alpha produced by macrophage-like synoviocytes (MLS) from CIA rats was elevated. TGP (50, 100 mg/kg, ig x 14 days) inhibited above changes significantly. The MLS supernatants of CIA rats induced more cell proliferation and more production of VEGF, bFGF, MMP-1 and MMP-3 in FLS of CIA than those supernatants from CIA rats treated with TGP (50, 100 mg/kg, ig x 14 days). These results indicate that TGP exerts a suppressive effect on joint destruction in rat CIA. The therapeutic effect of TGP could be associated with its ability to ameliorate the secretion and metabolism of synoviocytes and to inhibit the abnormal proliferation and VEGF, bFGF, MMP-1 and MMP-3 production by FLS.

  1. Progression of cartilage degradation, bone resorption and pain in rat temporomandibular joint osteoarthritis induced by injection of iodoacetate.

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    Xue-Dong Wang

    Full Text Available BACKGROUND: Osteoarthritis (OA is an important subtype of temporomandibular disorders. A simple and reproducible animal model that mimics the histopathologic changes, both in the cartilage and subchondral bone, and clinical symptoms of temporomandibular joint osteoarthritis (TMJOA would help in our understanding of its process and underlying mechanism. OBJECTIVE: To explore whether injection of monosodium iodoacetate (MIA into the upper compartment of rat TMJ could induce OA-like lesions. METHODS: Female rats were injected with varied doses of MIA into the upper compartment and observed for up to 12 weeks. Histologic, radiographic, behavioral, and molecular changes in the TMJ were evaluated by light and electron microscopy, MicroCT scanning, head withdrawal threshold test, real-time PCR, immunohistochemistry, and TUNEL assay. RESULTS: The intermediate zone of the disc loosened by 1 day post-MIA injection and thinned thereafter. Injection of an MIA dose of 0.5 mg or higher induced typical OA-like lesions in the TMJ within 4 weeks. Condylar destruction presented in a time-dependent manner, including chondrocyte apoptosis in the early stages, subsequent cartilage matrix disorganization and subchondral bone erosion, fibrosis, subchondral bone sclerosis, and osteophyte formation in the late stages. Nociceptive responses increased in the early stages, corresponding to severe synovitis. Furthermore, chondrocyte apoptosis and an imbalance between anabolism and catabolism of cartilage and subchondral bone might account for the condylar destruction. CONCLUSIONS: Multi-level data demonstrated a reliable and convenient rat model of TMJOA could be induced by MIA injection into the upper compartment. The model might facilitate TMJOA related researches.

  2. Sealing of rock joints by induced calcite precipitation. A case study from Bergeforsen hydro power plant

    International Nuclear Information System (INIS)

    Hakami, E.; Qvarfort, U.; Ekstav, A.

    1991-01-01

    The possibilities of sealing rock fractures by injecting water saturated with calcite solution, and hereby inducing a calcite precipitation inside the fracture, is investigated. The way of reaction and the amount of calcite precipitation will depend on the saturation of calcium carbonate in the water, the temperature, the pH and the CO 2 -pressure. There is experience of lime-saturated water injection in the rock foundation below the dam at Bergeforsens power plant (1955-1968). It was observed that the consumption of injected lime water decreased with time. A possible reason to the decrease in lime water consumption is that calcite has precipitated such that the permeability of the rock in general is lowered. Another explanation to this could be that calcite precipitation is concentrated to the fractures surrounding the injection holes, thus preventing the lime water from penetrating further into the rock. It is recommended that further studies of the fracture fillings in drill cores from Bergeforsen is performed. The aim of such study should be to determine the extent of induced calcite precipitation and to investigate its chemical and physical properties. (authors)

  3. The joint impact of habitual exercise and glycemic control on the incidence of chronic kidney disease (CKD) in middle-aged and older males.

    Science.gov (United States)

    Michishita, Ryoma; Matsuda, Takuro; Kawakami, Shotaro; Tanaka, Satoshi; Kiyonaga, Akira; Tanaka, Hiroaki; Morito, Natsumi; Higaki, Yasuki

    2017-11-06

    This retrospective study evaluated the influence of the joint impact of habitual exercise and glycemic control on the incidence of chronic kidney disease (CKD) during a 6-year follow-up period in middle-aged and older males. The study population included 303 males without a history of cardiovascular disease, stroke, renal dysfunction, or dialysis treatment. Their lifestyle behaviors regarding exercise and physical activity were evaluated using a standardized self-administered questionnaire. The participants were divided into four categories according to the performance or non-performance of habitual exercise and the presence or absence of hyperglycemia. After 6 years, 32 subjects (10.6%) developed CKD (estimated glomerular filtration rate exercise and hyperglycemic subjects (log-rank test: p exercise (HR = 2.82, 95% confidence of interval (CI) = 1.07-7.36, p = 0.034) and that in hyperglycemic subjects who did not perform habitual exercise (HR = 5.89, 95% CI = 1.87-16.63, p = 0.003) were significantly higher in comparison to the subjects with a NGT who performed habitual exercise. These results suggest that the habitual exercise and good glycemic control and their combination were associated with the incidence of CKD.

  4. Multimorbidity care model: Recommendations from the consensus meeting of the Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS).

    Science.gov (United States)

    Palmer, Katie; Marengoni, Alessandra; Forjaz, Maria João; Jureviciene, Elena; Laatikainen, Tiina; Mammarella, Federica; Muth, Christiane; Navickas, Rokas; Prados-Torres, Alexandra; Rijken, Mieke; Rothe, Ulrike; Souchet, Laurène; Valderas, Jose; Vontetsianos, Theodore; Zaletel, Jelka; Onder, Graziano

    2018-01-01

    Patients with multimorbidity have complex health needs but, due to the current traditional disease-oriented approach, they face a highly fragmented form of care that leads to inefficient, ineffective, and possibly harmful clinical interventions. There is limited evidence on available integrated and multidimensional care pathways for multimorbid patients. An expert consensus meeting was held to develop a framework for care of multimorbid patients that can be applied across Europe, within a project funded by the European Union; the Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS). The experts included a diverse group representing care providers and patients, and included general practitioners, family medicine physicians, neurologists, geriatricians, internists, cardiologists, endocrinologists, diabetologists, epidemiologists, psychologists, and representatives from patient organizations. Sixteen components across five domains were identified (Delivery of Care; Decision Support; Self Management Support; Information Systems and Technology; and Social and Community Resources). The description and aim of each component are described in these guidelines, along with a summary of key characteristics and relevance to multimorbid patients. Due to the lack of evidence-based recommendations specific to multimorbid patients, this care model needs to be assessed and validated in different European settings to examine specifically how multimorbid patients will benefit from this care model, and whether certain components have more importance than others. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Chronic whiplash-associated disorder and traumatic cerebrospinal fluid leak. Analysis of cases with radioisotope cisternography, epidural blood patch, and cervical facet joint blocks

    International Nuclear Information System (INIS)

    Ishikawa, Shinichi; Kobayashi, Hiroyuki; Takahara, Hiroshi; Kojo, Shigeru; Hashimoto, Hidenori; Moriyama, Eiji; Nishida, Ayumi

    2008-01-01

    This paper describes RI cisternographic (RIC) examinations of whiplash-associated disorder (WAD) and results of their treatment with nerve block and epidural blood patch (EBP) conducted in authors' facilities. Subjects were 40 chronic (av. symptomatic period of 3.1 y) WAD patients (av. age 34 y) with traffic (28 cases), sports (7) and falling (5) causes with complication of suspicious cerebrospinal fluid (CSF) leak. RIC was done 2.5-24 hr after injection of 37 MBq of 111 In-diethylenetriamine pentaacetic acid (DTPA) in the medullary space through epidural puncturing needle. Positive finding of clear leak or early accumulation of RI in the bladder was seen in 21 cases and negative, in 19. Positive patients had significantly higher rates of headache, abnormal vision and fatigue than negative ones. EBP was conducted through X-ray to all positive patients and to negative ones with strongly suspicious leak complication (7 cases), which resulted in improvement of symptoms like headache and vision in the former, but no improvement in the latter cases. Repeated RIC of the patients with poor improvement in the former was suggested effective for judgment of repetition of EBP treatment. Cervical facet joint blocks were found effective in cases with posterior cervical pain. Symptoms in WAD accompanying headache should be differentially diagnosed whether it is derived from posttraumatic CSF leak or from pain due to cervical facet arthritis. (R.T.)

  6. Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice.

    Science.gov (United States)

    Sena, Maria Clecia P; Nunes, Fabíola C; Salvadori, Mirian G S Stiebbe; Carvalho, Cleyton Charles D; Morais, Liana Clebia S L; Braga, Valdir A

    2011-01-01

    Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16) had access to sugarcane spirit + distilled water, the mice in Group B (n = 15) had access to ethanol + distilled water, and the mice in Group C (control, n = 14) had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 ± 8 vs. 7 ± 2 s, n = 9) or sugarcane spirit (36 ± 9 vs. 7 ± 2 s, n = 9) compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 ± 1 for the control group, 27 ± 2 for the ethanol group, and 31 ± 3 for the sugarcane-spirit group; n = 9 for each group). In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 ± 0.17 for the control group and 2.67 ± 0.17 for the sugarcane spirit group; n = 8 for each group). The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

  7. Chronic consumption of distilled sugarcane spirit induces anxiolytic-like effects in mice

    Directory of Open Access Journals (Sweden)

    Maria Clecia P. Sena

    2011-01-01

    Full Text Available OBJECTIVE: Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. METHOD: Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16 had access to sugarcane spirit + distilled water, the mice in Group B (n = 15 had access to ethanol + distilled water, and the mice in Group C (control, n = 14 had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. RESULTS: In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 + 8 vs. 7 + 2 s, n = 9 or sugarcane spirit (36 + 9 vs. 7 + 2 s, n = 9 compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 + 1 for the control group, 27 + 2 for the ethanol group, and 31 + 3 for the sugarcane-spirit group; n = 9 for each group. In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 + 0.17 for the control group and 2.67 + 0.17 for the sugarcane spirit group; n = 8 for each group. CONCLUSION: The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.

  8. Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

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    Godwin Sokpor

    2012-05-01

    animals that drank water.Conclusions: Ethanol-induced structural liver injury was qualitatively and quantitatively milder in rats which chronically imbibed alcohol then afterward drank NCP beverage in place of water. The antioxidant and anti-inflammatory properties of polyphenols in NCP are postulated in mitigating the damage of rat liver due to chronic ethanol consumption. Thus, it is suggested from these findings that regular drinking of NCP beverage may slow progression of alcoholic liver disease in dipsomaniacs.

  9. The impact of shift work induced chronic circadian disruption on IL-6 and TNF-α immune responses

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    Spallek Michael

    2010-07-01

    Full Text Available Abstract AIM Sleep disturbances induce proinflammatory immune responses, which might increase cardiovascular disease risk. So far the effects of acute sleep deprivation and chronic sleep illnesses on the immune system have been investigated. The particular impact of shift work induced chronic circadian disruption on specific immune responses has not been addressed so far. Methods Pittsburgh-Sleep-Quality-Index (PSQI questionnaire and blood sampling was performed by 225 shift workers and 137 daytime workers. As possible markers the proinflammatory cytokines IL-6 and TNF-α and lymphocyte cell count were investigated. A medical examination was performed and biometrical data including age, gender, height, weight, waist and hip circumference and smoking habits were collected by a structured interview. Results Shift workers had a significantly higher mean PSQI score than day workers (6.73 vs. 4.66; p Conclusion Shift work induces chronic sleep debt. Our data reveals that chronic sleep debt might not always lead to an activation of the immune system, as we did not observe differences in lymphocyte count or level of IL-6 or TNF-α serum concentration between shift workers and day workers. Therefore chronic sleep restriction might be eased by a long-term compensating immune regulation which (in healthy protects against an overstimulation of proinflammatory immune mechanisms and moderates metabolic changes, as they are known from short-term sleep deprivation or sleep related breathing disorders.

  10. Epicutaneous Immunization with Type II Collagen Inhibits both Onset and Progression of Chronic Collagen-Induced Arthritis

    OpenAIRE

    Strid, Jessica; Tan, Lee Aun; Strobel, Stephan; Londei, Marco; Callard, Robin

    2007-01-01

    Epicutaneous immunization is a potential non-invasive technique for antigen-specific immune-modulation. Topical application of protein antigens to barrier-disrupted skin induces potent antigen-specific immunity with a strong Th2-bias. In this study, we investigate whether the autoimmune inflammatory response of chronic collagen-induced arthritis (CCIA) in DBA/1-TCR-beta Tg mice can be modified by epicutaneous immunization. We show that epicutaneous immunization with type II collagen (CII) inh...

  11. Intrinsic and extrinsic apoptotic pathways are involved in rat testis by cold water immersion-induced acute and chronic stress.

    Science.gov (United States)

    Juárez-Rojas, Adriana Lizbeth; García-Lorenzana, Mario; Aragón-Martínez, Andrés; Gómez-Quiroz, Luis Enrique; Retana-Márquez, María del Socorro

    2015-01-01

    Testicular apoptosis is activated by stress, but it is not clear which signaling pathway is activated in response to stress. The aim of this study was to investigate whether intrinsic, extrinsic, or both apoptotic signaling pathways are activated by acute and chronic stress. Adult male rats were subjected to cold water immersion-induced stress for 1, 20, 40, and 50 consecutive days. The seminiferous tubules:apoptotic cell ratio was assayed on acute (1 day) and chronic (20, 40, 50 days) stress. Apoptotic markers, including cleaved-caspase 3 and 8, the pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were also determined after acute and chronic stress induction. Additionally, epididymal sperm quality was evaluated, as well as corticosterone and testosterone levels. An increase in tubule apoptotic cell count percentage after an hour of acute stress and during chronic stress induction was observed. The apoptotic cells rate per tubule increment was only detected one hour after acute stress, but not with chronic stress. Accordingly, there was an increase in Bax, cleaved caspase-8 and caspase-3 pro-apoptotic proteins with a decrease of anti-apoptotic Bcl-2 in both acutely and chronically stressed male testes. In addition, sperm count, viability, as well as total and progressive motility were low in chronically stressed males. Finally, the levels of corticosterone increased whereas testosterone levels decreased in chronically stressed males. Activation of the extrinsic apoptotic pathway was shown by cleaved caspase-8 increase whereas the intrinsic apoptotic pathway activation was determined by the increase of Bax, along with Bcl-2 decrease, making evident a cross-talk between these two pathways with the activation of caspase-3. These results suggest that both acute and chronic stress can potentially activate the intrinsic/extrinsic apoptosis pathways in testes. Chronic stress also reduces the quality of epididymal spermatozoa, possibly due to a decrease in testosterone.

  12. High-Performance Liquid Chromatography (HPLC) Quantification of Liposome-Delivered Doxorubicin in Arthritic Joints of Collagen-Induced Arthritis Rats.

    Science.gov (United States)

    Niu, Hongqing; Xu, Menghua; Li, Shuangtian; Chen, Junwei; Luo, Jing; Zhao, Xiangcong; Gao, Chong; Li, Xiaofeng

    2017-04-14

    BACKGROUND Neoangiogenesis occurring in inflamed articular synovium in early rheumatoid arthritis (RA) is characterized by enhanced vascular permeability that allows nanoparticle agents, including liposomes, to deliver encapsulated drugs to arthritic joints and subsequently improve therapeutic efficacy and reduce adverse effects. However, the targeting distribution of liposomes in arthritic joints during RA has not been quantitatively demonstrated. We performed this study to evaluate the targeting distribution of PEGylated doxorubicin liposomes in the arthritic joints of collagen-induced arthritis (CIA) rats by high-performance liquid chromatography (HPLC). MATERIAL AND METHODS Two doxorubicin formulations were administered to CIA rats via tail intravenous injection at a single dose (50 mg/m²). CIA rats were sacrificed and the tissues of the inflamed ankle joints were collected. The content of doxorubicin in the arthritic joints was analyzed by a validated and reproducible HPLC method. A two-way ANOVA for 2×5 factorial design was used for statistical analysis. RESULTS The developed HPLC method was sensitive, precise, and reproducible. The method was successfully applied to quantify doxorubicin content in arthritic tissues. At each time point (6, 12, 24, 48, and 72 h), doxorubicin content in the arthritic joints of the doxorubicin liposome group (DOX-LIP group) was higher than in the free doxorubicin group (DOX group) (P<0.05). In the DOX-LIP group, doxorubicin levels in the arthritic joints increased gradually and significantly in the interval of 6-72 h post-administration. CONCLUSIONS PEGylated doxorubicin liposomes were targeted to, accumulated, and retained in the arthritic joints of CIA rats. The present study indicates that liposome encapsulation increases the therapeutic efficacy of antirheumatic drugs, presenting a promising therapeutic strategy for RA.

  13. Data on IL-10R neutralization-induced chronic colitis in Lipocalin 2 deficient mice on BALB/c background

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    Vishal Singh

    2017-04-01

    Full Text Available The data herein is related to the research article entitled “Microbiota-inducible Innate Immune, Siderophore Binding Protein Lipocalin 2 is Critical for Intestinal Homeostasis” (Singh et al., 2016 [1] where we have demonstrated that C57BL/6 Lipocalin 2 deficient mice (Lcn2KO developed chronic colitis upon anti-interleukin-10 receptor (αIL-10R monoclonal antibody administration. In the present article, we evaluated the susceptibility of BALB/c Lcn2KO mice and their WT littermates to the αIL-10R neutralization-induced chronic colitis. Our data showed that αIL-10R mAb-treated BALB/c Lcn2KO mice exhibited severe chronic colitis (i.e., splenomegaly, colomegaly, colonic pathology, and incidence of rectal prolapse when compared to WT mice.

  14. Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem.

    Science.gov (United States)

    Shibasaki, Masahiro; Ishii, Kazunori; Masukawa, Daiki; Ando, Koji; Ikekubo, Yuiko; Ishikawa, Yutori; Shibasaki, Yumiko; Mori, Tomohisa; Suzuki, Tsutomu

    2014-09-05

    Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days. mGlu5 receptor protein levels were significantly increased after treatment with zolpidem for 7 days, and this change was accompanied by the up-regulation of phospholipase Cβ1 and calcium/calmodulin-dependent protein kinase IIα, which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that mGlu5 receptor is directly involved in dopamine-related behavior in mice following chronic treatment with zolpidem, we measured morphine-induced hyperlocomotion after chronic treatment with zolpidem in the presence or absence of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem significantly enhanced morphine-induced hyperlocomotion, this enhancement of morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5 receptor antagonist MPEP. These results suggest that chronic treatment with zolpidem caused neural plasticity in response to activation of the mesolimbic dopaminergic system accompanied by an increase in mGlu5 receptor. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Assessment of chronic spontaneous urticaria by serum-induced tumor necrosis factor alpha and matrix metalloproteinase-9 release

    DEFF Research Database (Denmark)

    Falkencrone, Sidsel; Bindslev-Jensen, Carsten; Skov, Per Stahl

    BACKGROUND Previous studies from our group have demonstrated that IgE-mediated basophil activation leads to release of TNFα that in turn can induce matrix metallo-proteinase-9 (MMP-9) release from monocytes. We wished to investigate if serum from chronic spontaneous urticaria-patients with auto-a...

  16. Interleukin-4 inhibits both paracrine and autocrine tumor necrosis factor-alpha-induced proliferation of B chronic lymphocytic leukemia cells

    NARCIS (Netherlands)

    van Kooten, C.; Rensink, I.; Aarden, L.; van Oers, R.

    1992-01-01

    The proliferative response of purified malignant B cells from 26 patients with chronic lymphocytic leukemia (CLL) was investigated in vitro. In the majority of these patients, a proliferative response could be induced by the combination of tumor necrosis factor (TNF)-alpha and PMA. The concentration

  17. Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

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    Amira M. Abo-youssef

    2016-06-01

    Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experimentally induced stress in rats. Briefly rats were subdivided into four groups. Three groups were subjected to chronic mild stress and the fourth group served as normal control group. One week before induction of stress drugs or saline was administered daily and continued for another nine weeks. At the end of the experimental period behavioral tests including sucrose preference test, forced swim test and elevated plus maze test were assessed. In addition, brain biochemical parameters including MDA, GSH, NO and serotonin were determined. Vanillin succeeded to restore the behavioral and biochemical changes associated with stress. It significantly increased sucrose consumption in sucrose preference test and time spent in open arm in elevated plus maze test as compared to stress control group. It also reduced immobility time in forced swim test and time spent in closed arm in elevated plus maze test. Additionally, it significantly decreased brain MDA and NO levels and significantly increased brain GSH and Serotonin levels compared to stress control group. It could be concluded that vanillin showed beneficial protective effects against experimentally induced stress in rats.

  18. Effects of ethanol on social avoidance induced by chronic social defeat stress in mice.

    Science.gov (United States)

    Favoretto, Cristiane A; Macedo, Giovana C; Quadros, Isabel M H

    2017-01-01

    In rodents, chronic social defeat stress promotes deficits in social interest and social interaction. We further explored these antisocial effects by comparing the consequences of two different defeat stress protocols (episodic vs. continuous stress) in a social investigation test. We expected that continuous, but not episodic, stress would induce social deficits in this model. Furthermore, we tested whether a potentially anxiolytic dose of ethanol reverses social deficits induced by defeat stress. Male Swiss mice were exposed to a 10-day social defeat protocol, using daily confrontations with an aggressive resident mouse. Episodic stress consisted of brief defeat episodes, after which the defeated mouse was returned to its home cage, until the next defeat 24 h later (n = 7-11/group). For continuous stress, similar defeat episodes were followed by cohabitation with the aggressive resident for 24 h, separated by a perforated divider, until the following defeat (n = 8-14/group). Eight days after stress termination, defeated and control mice were assessed in a social investigation test, after treatment with ethanol (1.0 g/kg, i.p.) or 0.9% saline. Considering the time spent investigating a social target, mice exposed to episodic or continuous social stress showed less social investigation than controls (p stress or ethanol. Thus, a history of social defeat stress, whether episodic or continuous, promotes deficits in social investigation that were not reversed by acute treatment with ethanol.

  19. Vitamin C-induced hyperoxaluria causing reversible tubulointerstitial nephritis and chronic renal failure: a case report

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    Rathi Shradha

    2007-11-01

    Full Text Available Abstract Vitamin C is a precursor of oxalate and promoter of its absorption, potentially causing hyperoxaluria. Malabsorption causes Calcium (Ca chelation with fatty acids, producing enteric hyperoxaluria. Case A 73-year-old man with both risk factors was hospitalized with serum creatinine of 8.4 mg/dL (versus 1.2 mg/dL four months earlier (normal 0.6–1.3 mg/dL. Given his oxalate-rich diet, chronic diarrhea, and daily 680 mg vitamin C and furosemide, we postulated Ca oxalate-induced nephropathy, a diagnosis confirmed by documenting hyperoxaluria, and finding of diffuse intraluminal crystals and extensive interstitial fibrosis on biopsy. He was hemodialysed 6 times to remove excess oxalate. Two weeks off vitamin C, his creatinine spontaneously fell to 3.1 mg/dL. Three months later, on low oxalate diet and 100 mg vitamin B6, urine oxalate to creatinine ratio decreased from 0.084 to 0.02 (normal Conclusion 1 High-dose vitamin C can induce hyperoxaluric nephropathy and progressive renal failure, especially if aggravated by diarrhea, oxalate-rich diet, metabolic acidosis, and dehydration. 2 The diagnosis should be suspected in unexplained renal insufficiency when associated with these risk factors. 3 Since prompt treatment could avert end-stage renal disease, we recommend monitoring urinary oxalate in patients on high-dose vitamin C and renal biopsy if necessary.

  20. Rutin (quercetin rutinoside) induced protein-energy malnutrition in chronic kidney disease, but quercetin acted beneficially.

    Science.gov (United States)

    Hsieh, Chiu-Lan; Peng, Chiung-Chi; Chen, Kuan-Chou; Peng, Robert Y

    2013-07-31

    Nutraceutically, much of the literature has indicated that an aglycon and its related glycoside would act similarly. However, controversial reports are accumulating. We hypothesize that rutin (RT) and quercetin (QT) pharmacodynamically could act differently. To confirm this, doxorubicin (DR) (8.5 mg/kg) was used to induce rat chronic kidney disease (CKD) and then treated with QT and RT (each 70 mg/kg body weight per day) for 13 weeks. QT exhibited better body weight gaining effect (420 ± 45) vs RT, 350 ± 57 g/rat (p protein-energy malnutrition". RT stimulated serum creatinine (sCr) production to reach 6.0 ± 0.9 mg/dL (p < 0.001). QT did not alter the sCr level. RT but not QT induced uremia and hypercreatininemia. DR significantly downregulated Bcl-2, but highly upregulated Bax, Bad, and cleaved caspase-3, implicating the intrinsic mitochondrial pathway. DR damaged DNA, but QT completely rescued such an effect and recovered renal amyloidosis and collagen deposition. Conclusively, RT and QT act differently, and RT is inferior to QT with respect to treating CKD.

  1. A novel adjustable automated system for inducing chronic intermittent hypoxia in mice.

    Science.gov (United States)

    Polšek, Dora; Bago, Marcel; Živaljić, Marija; Rosenzweig, Ivana; Lacza, Zsombor; Gajović, Srećko

    2017-01-01

    Sleep apnea is a chronic, widely underdiagnosed condition characterized by disruption of sleep architecture and intermittent hypoxia due to short cessations of breathing. It is a major independent risk factor for myocardial infarction, congestive heart failure and stroke as well as one of the rare modifiable risk factors for Alzheimer's Dementia. Reliable animal disease models are needed to understand the link between sleep apnea and the various clinically linked disorders. An automated system for inducing hypoxia was developed, in which the major improvement was the possibility to efficiently adjust the length and intensity of hypoxia in two different periods. The chamber used a small volume of gas allowing for fast exchanges of different oxygen levels. The mice were kept in their cages adapted with the system on the cage lid. As a proof of principle, they were exposed to a three week period of intermittent hypoxia for 8 hours a day, with 90 s intervals of 5, 7% and 21% oxygen to validate the model. Treated (n = 8) and control mice (no hypoxia, n = 7) were handled in the same manner and their hippocampal brain regions compared by histology. The chamber provided a fast, reliable and precise intermittent hypoxia, without inducing noticeable side effects to the animals. The validation experiment showed that apoptotic neurons in the hippocampus were more numerous in the mice exposed to intermittent hypoxia than in the control group, in all tested hippocampal regions (cornu ammonis 1 (CA1) P apnea, which was validated by apoptosis of hippocampal neurons.

  2. Chronic Intermittent Hypoxia Induces the Long-Term Facilitation of Genioglossus Corticomotor Activity

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    Ying Zou

    2018-01-01

    Full Text Available Obstructive sleep apnea (OSA is characterized by the repetitive collapse of the upper airway and chronic intermittent hypoxia (CIH during sleep. It has been reported that CIH can increase the EMG activity of genioglossus in rats, which may be related to the neuromuscular compensation of OSA patients. This study aimed to explore whether CIH could induce the long-term facilitation (LTF of genioglossus corticomotor activity. 16 rats were divided into the air group (n=8 and the CIH group (n=8. The CIH group was exposed to hypoxia for 4 weeks; the air group was subjected to air under identical experimental conditions in parallel. Transcranial magnetic stimulation (TMS was applied every ten minutes and lasted for 1 h/day on the 1st, 3rd, 7th, 14th, 21st, and 28th days of air/CIH exposure. Genioglossus EMG was also recorded at the same time. Compared with the air group, the CIH group showed decreased TMS latency from 10 to 60 minutes on the 7th, 14th, 21st, and 28th days. The increased TMS amplitude lasting for 60 minutes was only observed on the 21st day. Genioglossus EMG activity increased only on the 28th day of CIH. We concluded that CIH could induce LTF of genioglossus corticomotor activity in rats.

  3. Ameliorative effect of ethyl pyruvate in neuropathic pain induced by chronic constriction injury of sciatic nerve

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    Varsha J. Bansode

    2014-01-01

    Full Text Available Objective: The present study was designed to investigate the ameliorative effects of ethyl pyruvate (EP in chronic constriction injury (CCI-induced painful neuropathy in rats. Materials and Methods: EP 50 and 100 mg/kg was administered for 21 consecutive days starting from the day of surgery. The effects of EP in the paw pressure, acetone drop, and tail heat immersion tests were assessed, reflecting the degree of mechanical hyperalgesia, cold allodynia, and spinal thermal sensation, respectively. Axonal degeneration of the sciatic nerve was assessed histopathologically. The levels of thiobarbituric acid reactive species, reduced glutathione (GSH, catalase (CAT, and superoxide dismutase (SOD were determined to assess oxidative stress. Key Findings: Administration of 50 and 100 mg/kg EP attenuated the reduction of nociceptive threshold in the paw pressure, acetone drop, and tail heat immersion tests. EP 100 mg/kg significantly attenuated reactive changes in histopathology and increase in oxidative stress. Conclusion: EP 100 mg/kg showed beneficial activity against nerve trauma-induced neuropathy. Hence, it can be used as a better treatment option in neuropathic pain (NP. The observed antinociceptive effects of EP may possibly be attributed to its antioxidant and anti-inflammatory activity.

  4. Indagation of serum and salivary reactive oxygen metabolite and cortisol levels in chronic periodontitis and stress-induced chronic periodontitis patients

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    Uma Sudhakar

    2017-01-01

    Full Text Available Background: Periodontal disease is not a conventional bacterial infection but is an inflammatory disease initiated by immune response against a group of microorganisms in susceptible hosts. There are many intriguing researches that unfold the secrets of chronic periodontitis. The current researches in chronic periodontitis are directed toward an approach that respects the scientific relationship between the various risk factors, the genetic factors, and the progression of the disease. Aim: This study aims to evaluate the cortisol and reactive oxygen metabolites (ROM concentration in serum and to find out their association in periodontal health and disease. Materials and Methods: In this study, totally thirty patients have been taken and divided into two groups of chronic periodontitis (Group I and stress-induced chronic periodontitis (Group II and evaluated the correlation between the ROM and cortisol levels in them. This is the first study, where both the levels of ROM and cortisol are checked in the serum and saliva. The analysis is done to check the association between them. Statistical Analysis: The data were statistically analyzed using software program (SPSSV 16, Pearson correlation, and paired t-test. Results: Comparison of the mean ROM levels in Group I and Group II showed that mean ROM level in Group II is highly significant than Group I. Conclusion: Our study suggests that stress can have a role in the progression of periodontal disease by increasing the cortisol and ROM levels.

  5. Indagation of serum and salivary reactive oxygen metabolite and cortisol levels in chronic periodontitis and stress-induced chronic periodontitis patients.

    Science.gov (United States)

    Sudhakar, Uma; Thyagarajan, Ramakrishnan; Jeyapal, Bhagyameena; Jagadeesh, Sushuruthi; Jayakumar, Parvathee

    2017-01-01

    Periodontal disease is not a conventional bacterial infection but is an inflammatory disease initiated by immune response against a group of microorganisms in susceptible hosts. There are many intriguing researches that unfold the secrets of chronic periodontitis. The current researches in chronic periodontitis are directed toward an approach that respects the scientific relationship between the various risk factors, the genetic factors, and the progression of the disease. This study aims to evaluate the cortisol and reactive oxygen metabolites (ROM) concentration in serum and to find out their association in periodontal health and disease. In this study, totally thirty patients have been taken and divided into two groups of chronic periodontitis (Group I) and stress-induced chronic periodontitis (Group II) and evaluated the correlation between the ROM and cortisol levels in them. This is the first study, where both the levels of ROM and cortisol are checked in the serum and saliva. The analysis is done to check the association between them. The data were statistically analyzed using software program (SPSSV 16), Pearson correlation, and paired t -test. Comparison of the mean ROM levels in Group I and Group II showed that mean ROM level in Group II is highly significant than Group I. Our study suggests that stress can have a role in the progression of periodontal disease by increasing the cortisol and ROM levels.

  6. Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds.

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    Antonia Alcaraz

    Full Text Available Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary to provide the final sealing epidermis. Previously we have shown that Amniotic Membrane (AM induced a robust epithelialisation in deep traumatic wounds.To better understand this phenomenon, we used keratinocytes to investigate the effect of AM on chronic wounds. Using keratinocytes, we saw that AM treatment is able to exert an attenuating effect upon Smad2 and Smad3 TGFß-induced phosphorylation while triggering the activation of several MAPK signalling pathways, including ERK and JNK1, 2. This also has a consequence for TGFß-induced regulation on cell cycle control key players CDK1A (p21 and CDK2B (p15. The study of a wider set of TGFß regulated genes showed that the effect of AM was not wide but very concrete for some genes. TGFß exerted a powerful cell cycle arrest; the presence of AM however prevented TGFß-induced cell cycle arrest. Moreover, AM induced a powerful cell migration response that correlates well with the expression of c-Jun protein at the border of the healing assay. Consistently, the treatment with AM of human chronic wounds induced a robust expression of c-Jun at the wound border.The effect of AM on the modulation of TGFß responses in keratinocytes that favours proliferation together with AM-induced keratinocyte migration is the perfect match that allows chronic wounds to move on from their non-healing state and progress into epithelialization. Our results may explain why the application of AM on chronic wounds is able to promote epithelialisation.

  7. Gene expression in skin tumors induced in hairless mice by chronic exposure to ultraviolet B irradiation

    International Nuclear Information System (INIS)

    Sato, Hiromi; Tanaka, Misao; Kobayashi, Shizuko; Suzuki, Junko S.; Ogiso, Manabu; Tohyama, Chiharu

    1997-01-01

    We investigated the expressions of c-Ha-ras, c-jun, c-fos, c-myc genes and p53 protein in the development of skin tumours induced by chronic exposure to UVB without a photosensitizer using hairless mice. When mice were exposed to UVB at a dose of 2 kJ/m 2 three times a week, increased c-Ha-ras and c-myc transcripts were detected after only 5 weeks of exposure, while no tumour appeared on the exposed skin. The increase in gene expression continued until 25 weeks, when tumours, identified pathologically as mainly squamous cell carcinomas (SCC), developed in the dorsal skin. In these SCC, overexpression of c-fos mRNA was also observed along with the increases in c-Ha-ras and c-myc. A single dose of UVB (2 kJ/m 2 ) applied to the backs of hairless mice transiently induced overexpression of the early event genes c-fos, c-jun and c-myc, but not c-Ha-ras, in the exposed area of skin. Accumulation of p53 protein was determined by Western blotting analysis of immunohistochemistry using monoclonal antibodies PAb 240 or 246, which recognize mutant or wide type, respectively. In the SCC, a mutant p53 protein accumulated in the cytoplasm and nucleus. After single-dose irradiation, the increased wild-type p53 protein was observed in the nuclei of epidermal cells. The present results suggest that overexpression of the c-fos, c-myc and c-Ha-ras genes, and the mutational changes in p53 protein might be associated with skin photocarcinogenesis. Moreover, overexpression of the c-Ha-ras and c-myc genes might be an early event in the development of UVB-induced skin tumors in mice. (author)

  8. Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4.

    Science.gov (United States)

    Drager, Luciano F; Yao, Qiaoling; Hernandez, Karen L; Shin, Mi-Kyung; Bevans-Fonti, Shannon; Gay, Jason; Sussan, Thomas E; Jun, Jonathan C; Myers, Allen C; Olivecrona, Gunilla; Schwartz, Alan R; Halberg, Nils; Scherer, Philipp E; Semenza, Gregg L; Powell, David R; Polotsky, Vsevolod Y

    2013-07-15

    Obstructive sleep apnea is a risk factor for dyslipidemia and atherosclerosis, which have been attributed to chronic intermittent hypoxia (CIH). Intermittent hypoxia inhibits a key enzyme of lipoprotein clearance, lipoprotein lipase, and up-regulates a lipoprotein lipase inhibitor, angiopoietin-like 4 (Angptl4), in adipose tissue. The effects and mechanisms of Angptl4 up-regulation in sleep apnea are unknown. To examine whether CIH induces dyslipidemia and atherosclerosis by increasing adipose Angptl4 via hypoxia-inducible factor-1 (HIF-1). ApoE(-/-) mice were exposed to intermittent hypoxia or air for 4 weeks while being treated with Angptl4-neutralizing antibody or vehicle. In vehicle-treated mice, hypoxia increased adipose Angptl4 levels, inhibited adipose lipoprotein lipase, increased fasting levels of plasma triglycerides and very low density lipoprotein cholesterol, and increased the size of atherosclerotic plaques. The effects of CIH were abolished by the antibody. Hypoxia-induced increases in plasma fasting triglycerides and adipose Angptl4 were not observed in mice with germline heterozygosity for a HIF-1α knockout allele. Transgenic overexpression of HIF-1α in adipose tissue led to dyslipidemia and increased levels of adipose Angptl4. In cultured adipocytes, constitutive expression of HIF-1α increased Angptl4 levels, which was abolished by siRNA. Finally, in obese patients undergoing bariatric surgery, the severity of nocturnal hypoxemia predicted Angptl4 levels in subcutaneous adipose tissue. HIF-1-mediated increase in adipose Angptl4 and the ensuing lipoprotein lipase inactivation may contribute to atherosclerosis in patients with sleep apnea.

  9. A novel approach to adenine-induced chronic kidney disease associated anemia in rodents.

    Directory of Open Access Journals (Sweden)

    Asadur Rahman

    Full Text Available To date, good experimental animal models of renal anemia are not available. Therefore, the purpose of this study was to establish a novel approach to induce chronic kidney disease (CKD with severe anemia by oral administration of adenine in rodents. Adenine was administered to 6-week-old male C57BL/6 mice (25 and 50 mg/kg body weight by oral gavage daily for 28 days. Serum creatinine and BUN as well as hematocrit, hemoglobin (Hb and plasma erythropoietin (EPO levels were monitored to assess renal function and anemia, respectively. Adenine at 25 mg/kg for 28 days slightly increased plasma creatinine levels, but did not induce anemia. In contrast, 50 mg/kg of adenine daily for 28 days showed severe renal dysfunction (plasma creatinine 1.9 ± 0.10 mg/dL and anemia (hematocrit 36.5 ± 1.0% and EPO 28 ± 2.4 pg/mL as compared with vehicle-treated mice (0.4 ± 0.02 mg/dL, 49.6 ± 1.6% and 61 ± 4.0 pg/mL, respectively. At the end of experiment, level of Hb also significantly reduced in 50 mg/kg adenine administration group. Remarkable histological changes of kidney tissues characterized by interstitial fibrosis and cystic appearance in tubules were observed in 50 mg/kg of adenine treatment group. These results have demonstrated that oral dosing with adenine at 50 mg/kg for 28 days is suitable to induce a stable anemia associated with CKD in mice.

  10. Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

    Science.gov (United States)

    Ali, B H; Al Balushi, K; Al-Husseini, I; Mandel, P; Nemmar, A; Schupp, N; Ribeiro, D A

    2015-12-01

    Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

  11. Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint.

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    Hatch, R J; Jennings, E A; Ivanusic, J J

    2013-08-01

    Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih ) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system. © 2012 European Federation of International Association for the Study of Pain Chapters.

  12. Radiation-induced temporo-mandibular joint disorder in post-radiotherapy nasopharyngeal carcinoma patients: assessment and treatment.

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    Wu, Vincent W C; Lam, Ying-Na

    2016-06-01

    Nasopharyngeal carcinoma (NPC) is endemic in southern China, and its incidence in Hong Kong is relatively high. Radiotherapy is the mainstay treatment for NPC due to its relatively high radiosensitivity and deep-seated anatomical position, which is not readily accessible by surgery. Although the technique of radiotherapy in NPC has been advancing and offers promising treatment outcome, complications around the irradiation areas are inevitable and the quality of life of the post-radiotherapy patients is often compromised. Trismus, which is defined as the restricted mouth opening or jaw movement due to the disorder of temporo-mandibular joint (TMJ), is one of the possible late complications for radiotherapy of NPC and is found in 5-17% of the post-radiotherapy (post-RT) patients. Trismus at early stage may only affect the speech, but in severe cases nutritional intake and oral hygiene condition may deteriorate seriously. This article reviewed the possible causes of radiation-induced TMJ damage, the various assessments including imaging modalities and possible treatments. The conclusion is that the availability of simple, yet effective examinations for trismus is essential for delaying the progression and restoring TMJ functions. Although there is no absolutely effective treatment for trismus, many supportive, restorative and palliative management are possible under different clinical situations.

  13. Can Ocimum basilicum relieve chronic unpredictable mild stress-induced depression in mice?

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    Ayuob, Nasra Naeim; Firgany, Alaa El-Din L; El-Mansy, Ahmed A; Ali, Soad

    2017-10-01

    Depression is one of the important world-wide health problems. This study aimed to assess the ameliorative effect of Ocimum basilicum (OB) essential oil on the behavioral, biochemical and histopathological changes resulted from exposure to chronic unpredictable mild stress (CUMS). It also aimed to investigate the underlying mechanism in an animal model of depression. Forty male Swiss albino mice were divided into four groups (n=10): control, CUMS (exposed to CUMS for 4weeks), CUMS plus fluoxetine, and CUMS plus OB. At the end of the experiment, behavioral changes, serum corticosterone level, protein and gene expressions of brain derived neurotropic factor (BDNF) and glucocorticoid receptors (GR) in the hippocampus was all assessed. Immunoexpression of surface makers of glial fibrillary acidic protein (GFAP), Ki67, Caspase-3, BDNF and GR in the hippocampus were estimated. Data were analyzed by using the statistical package for the social sciences (SPSS). OB alleviated both behavioral and biochemical changes recorded in mice after exposure to CUMS. It also reduced neuronal atrophy observed in the hippocampal region III cornu ammonis (CA3) and dentate gyrus and restored back astrocyte number. OB decreased apoptosis in both neurons and glial cells and increased neurogenesis in the dentate gyrus in a pattern comparable to that of fluoxetine. Increased BDNF and GR gene and protein expressions seems to be behind the antidepressant-like effect of OB. Ocimum basilicum ameliorates the changes induced after exposure to the chronic stress. Assessing Ocimum basilicum efficacy on human as antidepressant is recommended in further studies. Copyright © 2017. Published by Elsevier Inc.

  14. Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice.

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    Shang, Xueliang; Shang, Yingchun; Fu, Jingxuan; Zhang, Tao

    2017-08-01

    The aim of this study was to examine if nicotine was able to improve cognition deficits in a mouse model of chronic mild stress. Twenty-four male C57BL/6 mice were divided into three groups: control, stress, and stress with nicotine treatment. The animal model was established by combining chronic unpredictable mild stress (CUMS) and isolated feeding. Mice were exposed to CUMS continued for 28 days, while nicotine (0.2 mg/kg) was also administrated for 28 days. Weight and sucrose consumption were measured during model establishing period. The anxiety and behavioral despair were analyzed using the forced swim test (FST) and open-field test (OFT). Spatial cognition was evaluated using Morris water maze (MWM) test. Following behavioral assessment, both long-term potentiation (LTP) and depotentiation (DEP) were recorded in the hippocampal dentate gyrus (DG) region. Both synaptic and Notch1 proteins were measured by Western. Nicotine increased stressed mouse's sucrose consumption. The MWM test showed that spatial learning and reversal learning in stressed animals were remarkably affected relative to controls, whereas nicotine partially rescued cognitive functions. Additionally, nicotine considerably alleviated the level of anxiety and the degree of behavioral despair in stressed mice. It effectively mitigated the depression-induced impairment of hippocampal synaptic plasticity, in which both the LTP and DEP were significantly inhibited in stressed mice. Moreover, nicotine enhanced the expression of synaptic and Notch1 proteins in stressed animals. The results suggest that nicotine ameliorates the depression-like symptoms and improves the hippocampal synaptic plasticity closely associated with activating transmembrane ion channel receptors and Notch signaling components. Graphical Abstract ᅟ.

  15. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice.

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    Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M

    2010-12-01

    Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc

  16. Three kinds of Ganoderma lucidum polysaccharides attenuate DDC-induced chronic pancreatitis in mice.

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    Li, Koukou; Yu, Min; Hu, Yang; Ren, Guangming; Zang, Tingting; Xu, Xiuhong; Qu, Juanjuan

    2016-03-05

    Chronic pancreatitis (CP) is a progressive inflammation of pancreas characterized by irreversible morphologic change and dysfunction. Patients with chronic pancreatitis often present with abdominal pain, diarrhoea, jaundice, weight loss and the development of diabetes. Polysaccharides of Ganoderma lucidum strain S3 (GLPS3) possess antioxidative and immunomodulatory activities. This study was to characterize chemical structures of GLPS3 and determine their effects on diethyldithiocarbamate (DDC)-induced CP in mice. The total sugar content of GLPS3 from fermentation broth (GLPS3-Ⅰ), cultured mycelia (GLPS3-Ⅱ) and fruiting body (GLPS3-Ⅲ) was 90.4%, 92.2% and 91.8% respectively. GLPS3-Ⅰ, GLPS3-Ⅱ and GLPS3-Ⅲ were composed of Glu:Gal:Ara:Xyl, Glu:Gal:Ara:Xyl:Man:Rha, and Glu:Gal:Xyl:Man:Rha:Fuc, with molar ratio of 2.82: 1.33: 1.26: 0.87, 5.84: 2.23: 0.72:1.38: 1.40: 0.51 and 5.34: 2.72: 1.14: 1.10: 0.33: 0.38, respectively. The antioxidative activity of GLPS3-Ⅱfrom cultured mycelia in vitro is higher than other two polysaccharides. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were increased while the malondialdehyde (MDA) levels were reversely decreased by GLPS3 treatment. Serum amylase (AMS) and lactic dehydrogenase (LDH) changes indicated the therapeutic effects of GLPS3. Moreover, interleukin-1beta (IL-1β) and interferon-gamma (INF-γ) contents were reduced most by GLPS3-Ⅱ. The results revealed that GLPS3 especially GLPS3-Ⅱfrom cultured mycelia were effective for CP therapy and bioactivity difference might be attributed to monosaccharide composition. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Possible gasoline-induced chronic liver injury due to occupational malpractice in a motor mechanic: a case report.

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    Gunathilaka, Mahesh Lakmal; Niriella, Madunil Anuk; Luke, Nathasha Vihangi; Piyarathna, Chathura Lakmal; Siriwardena, Rohan Chaminda; De Silva, Arjuna Priyadarshin; de Silva, Hithanadura Janaka

    2017-07-03

    Hydrocarbon-induced occupational liver injury is a well-known clinical entity among petroleum industry workers. There are many types of hydrocarbon exposure, with inhalation being the most common. Hydrocarbon-induced occupational liver injury is a rarely suspected and commonly missed etiological agent for liver injury. We report a case of a non-petroleum industry worker with chronic liver disease secondary to hydrocarbon-induced occupational liver injury caused by chronic low-grade hydrocarbon ingestion due to occupational malpractice. A 23-year-old Sri Lankan man who was a motor mechanic presented to our hospital with decompensated cirrhosis. He had been chronically exposed to gasoline via inadvertent ingestion due to occupational malpractice. He used to remove gasoline from carburetors by sucking and failed to practice mouth washing thereafter. On evaluation, he had histologically proven established cirrhosis. A comprehensive history and workup ruled out other nonoccupational etiologies for cirrhosis. The patient's long-term occupational gasoline exposure and clinical course led us to a diagnosis of hydrocarbon-induced occupational liver injury leading to decompensated cirrhosis. Hydrocarbon-induced occupational liver injury should be considered as a cause when evaluating a patient with liver injury with possible exposure in relevant occupations.

  18. Diffusion tensor and volumetric magnetic resonance imaging using an MR-compatible hand-induced robotic device suggests training-induced neuroplasticity in patients with chronic stroke.

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    Lazaridou, Asimina; Astrakas, Loukas; Mintzopoulos, Dionyssios; Khanicheh, Azadeh; Singhal, Aneesh B; Moskowitz, Michael A; Rosen, Bruce; Tzika, Aria A

    2013-11-01

    Stroke is the third leading cause of mortality and a frequent cause of long-term adult impairment. Improved strategies to enhance motor function in individuals with chronic disability from stroke are thus required. Post‑stroke therapy may improve rehabilitation and reduce long-term disability; however, objective methods for evaluating the specific impact of rehabilitation are rare. Brain imaging studies on patients with chronic stroke have shown evidence for reorganization of areas showing functional plasticity after a stroke. In this study, we hypothesized that brain mapping using a novel magnetic resonance (MR)-compatible hand device in conjunction with state‑of‑the‑art magnetic resonance imaging (MRI) can serve as a novel biomarker for brain plasticity induced by rehabilitative motor training in patients with chronic stroke. This hypothesis is based on the premises that robotic devices, by stimulating brain plasticity, can assist in restoring movement compromised by stroke-induced pathological changes in the brain and that these changes can then be monitored by advanced MRI. We serially examined 15 healthy controls and 4 patients with chronic stroke. We employed a combination of diffusion tensor imaging (DTI) and volumetric MRI using a 3-tesla (3T) MRI system using a 12-channel Siemens Tim coil and a novel MR-compatible hand‑induced robotic device. DTI data revealed that the number of fibers and the average tract length significantly increased after 8 weeks of hand training by 110% and 64%, respectively (probotics in the molecular medicine era.

  19. An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Susana eMonteiro

    2015-02-01

    Full Text Available Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight and an overactive hypothalamic-pituitary-adrenal (HPA axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen.The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to chronic unpredictable stress.

  20. Exercise training attenuated chronic cigarette smoking-induced up-regulation of FIZZ1/RELMα in lung of rats.

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    Ma, Wan-li; Cai, Peng-cheng; Xiong, Xian-zhi; Ye, Hong

    2013-02-01

    FIZZ/RELM is a new gene family named "found in inflammatory zone" (FIZZ) or "resistin-like molecule" (RELM). FIZZ1/RELMα is specifically expressed in lung tissue and associated with pulmonary inflammation. Chronic cigarette smoking up-regulates FIZZ1/RELMα expression in rat lung tissues, the mechanism of which is related to cigarette smoking-induced airway hyperresponsiveness. To investigate the effect of exercise training on chronic cigarette smoking-induced airway hyperresponsiveness and up-regulation of FIZZ1/RELMα, rat chronic cigarette smoking model was established. The rats were treated with regular exercise training and their airway responsiveness was measured. Hematoxylin and eosin (HE) staining, immunohistochemistry and in situ hybridization of lung tissues were performed to detect the expression of FIZZ1/RELMα. Results revealed that proper exercise training decreased airway hyperresponsiveness and pulmonary inflammation in rat chronic cigarette smoking model. Cigarette smoking increased the mRNA and protein levels of FIZZ1/RELMα, which were reversed by the proper exercise. It is concluded that proper exercise training prevents up-regulation of FIZZ1/RELMα induced by cigarette smoking, which may be involved in the mechanism of proper exercise training modulating airway hyperresponsiveness.

  1. Chronic Hypergravity Induces Changes in the Dopaminergic Neuronal System in Drosophila Melanogaster

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    Pelos, Andrew; Hosamani, Ravikumar; Bhattacharya, Sharmila

    2017-01-01

    Upon atmospheric exitre-entry and during training, astronauts are subjected to temporary periods of hypergravity, which has been implicated in the activation of oxidative stress pathways contributing to mitochondrial dysfunction and neuronal degeneration. The pathogenesis of Parkinsons disease and other neurodegenerative disorders is associated with oxidative damage to neurons involved in dopamine systems of the brain. Our study aims to examine the effects of a hypergravitational developmental environment on the degeneration of dopaminergic systems in Drosophila melanogaster. Male and female flies (Gal4-UAS transgenic line) were hatched and raised to adulthood in centrifugal hypergravity (97rpm, 3g). The nuclear expression of the reporter, Green Fluorescent Protein (GFP) is driven by the dopaminergic enzyme tyrosine hydroxylase (TH) promoter, allowing for the targeted visualization of dopamine producing neurons. After being raised to adulthood and kept in hypergravity until 18 days of age, flies were dissected and the expression of TH was measured by fluorescence confocal microscopy. TH expression in the fly brains was used to obtain counts of healthy dopaminergic neurons for flies raised in chronic hypergravity and control groups. Dopaminergic neuron expression data were compared with those of previous studies that limited hypergravity exposure to late life in order to determine the flies adaptability to the gravitational environment when raised from hatching through adulthood. Overall, we observed a significant effect of chronic hypergravity exposure contributing to deficits in dopaminergic neuron expression (p 0.003). Flies raised in 3g had on average lower dopaminergic neuron counts (mean 97.7) when compared with flies raised in 1g (mean 122.8). We suspect these lower levels of TH expression are a result of oxidative dopaminergic cell loss in flies raised in hypergravity. In future studies, we hope to further elucidate the mechanism by which hypergravity-induced

  2. Repetitive transcranial magnetic stimulation induces oscillatory power changes in chronic tinnitus

    Directory of Open Access Journals (Sweden)

    Martin eSchecklmann

    2015-10-01

    Full Text Available Chronic tinnitus is associated with neuroplastic changes in auditory and non-auditory cortical areas. About ten years ago, repetitive transcranial magnetic stimulation (rTMS of auditory and prefrontal cortex was introduced as potential treatment for tinnitus. The resulting changes in tinnitus loudness are interpreted in the context of rTMS induced activity changes (neuroplasticity. Here, we investigate the effect of single rTMS sessions on oscillatory power to probe the capacity of rTMS to interfere with tinnitus-specific cortical plasticity. We measured 20 patients with bilateral chronic tinnitus and 20 healthy controls comparable for age, sex, handedness, and hearing level with a 63-channel EEG system. Educational level, intelligence, depressivity and hyperacusis were controlled for by analysis of covariance. Different rTMS protocols were tested: Left and right temporal and left and right prefrontal cortices were each stimulated with 200 pulses at 1Hz and with an intensity of 60% stimulator output. Stimulation of central parietal cortex with 6-fold reduced intensity (inverted passive-cooled coil served as sham condition. Before and after each rTMS protocol five minutes of resting state EEG were recorded. The order of rTMS protocols was randomized over two sessions with one week interval in between.Analyses on electrode level showed that people with and without tinnitus differed in their response to left temporal and right frontal stimulation. In tinnitus patients left temporal rTMS decreased frontal theta and delta and increased beta2 power, whereas right frontal rTMS decreased right temporal beta3 and gamma power. No changes or increases were observed in the control group. Only non-systematic changes in tinnitus loudness were induced by single sessions of rTMS.This is the first study to show tinnitus-related alterations of neuroplasticity that were specific to stimulation site and oscillatory frequency. The observed effects can be interpreted

  3. Repetitive transcranial magnetic stimulation induces oscillatory power changes in chronic tinnitus

    Science.gov (United States)

    Schecklmann, Martin; Lehner, Astrid; Gollmitzer, Judith; Schmidt, Eldrid; Schlee, Winfried; Langguth, Berthold

    2015-01-01

    Chronic tinnitus is associated with neuroplastic changes in auditory and non-auditory cortical areas. About 10 years ago, repetitive transcranial magnetic stimulation (rTMS) of auditory and prefrontal cortex was introduced as potential treatment for tinnitus. The resulting changes in tinnitus loudness are interpreted in the context of rTMS induced activity changes (neuroplasticity). Here, we investigate the effect of single rTMS sessions on oscillatory power to probe the capacity of rTMS to interfere with tinnitus-specific cortical plasticity. We measured 20 patients with bilateral chronic tinnitus and 20 healthy controls comparable for age, sex, handedness, and hearing level with a 63-channel electroencephalography (EEG) system. Educational level, intelligence, depressivity and hyperacusis were controlled for by analysis of covariance. Different rTMS protocols were tested: Left and right temporal and left and right prefrontal cortices were each stimulated with 200 pulses at 1 Hz and with an intensity of 60% stimulator output. Stimulation of central parietal cortex with 6-fold reduced intensity (inverted passive-cooled coil) served as sham condition. Before and after each rTMS protocol 5 min of resting state EEG were recorded. The order of rTMS protocols was randomized over two sessions with 1 week interval in between. Analyses on electrode level showed that people with and without tinnitus differed in their response to left temporal and right frontal stimulation. In tinnitus patients left temporal rTMS decreased frontal theta and delta and increased beta2 power, whereas right frontal rTMS decreased right temporal beta3 and gamma power. No changes or increases were observed in the control group. Only non-systematic changes in tinnitus loudness were induced by single sessions of rTMS. This is the first study to show tinnitus-related alterations of neuroplasticity that were specific to stimulation site and oscillatory frequency. The observed effects can be

  4. Exacerbation of N-nitrosodiethylamine Induced Hepatotoxicity and DNA Damage in Mice Exposed to Chronic Unpredictable Stress

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    Nayeem Bilal

    2017-06-01

    Full Text Available Psychological stress contributes to increased susceptibility to a number of diseases including cancer. The present study was designed to assess the effect of chronic unpredictable stress on N-nitrosodiethylamine induced liver toxicity in terms of in vivo antioxidant status and DNA damage in Swiss albino mice. The animals used in this study were randomized into different groups based on the treatment with N-nitrosodiethylamine or chronic unpredictable stress alone and post-stress administration of N-nitrosodiethylamine. The mice were sacrificed after 12 weeks of treatment, and the status of major enzymatic and non-enzymatic antioxidants, liver function markers, lipid peroxidation and the extent of DNA damage were determined in circulation and liver tissues of all the groups. The N-nitrosodiethylamine treated group showed significantly compromised levels of the antioxidant enzymes, lipid peroxidation, and the liver function markers with enhanced DNA damage as compared to chronic unpredictable stress or control groups. A similar but less typical pattern observed in the chronic unpredictable stress treated mice. All the measured biochemical parameters were significantly altered in the group treated with the combination of chronic unpredictable stress and N-nitrosodiethylamine when compared to controls, or chronic unpredictable stress alone and/or N-nitrosodiethylamine alone treated groups. Thus, exposure to continuous, unpredictable stress conditions even in general life may significantly enhance the hepatotoxic potential of N-nitrosodiethylamine through an increase in the oxidative stress and DNA damage.

  5. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

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    Bahi, Amine

    2013-07-01

    Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

  6. Effect of WeiJia on carbon tetrachloride induced chronic liver injury

    Science.gov (United States)

    Cheung, Pik-Yuen; Zhang, Qi; Zhang, Ya-Ou; Bai, Gan-Rong; Lin, Marie Chia-Mi; Chan, Bernard; Fong, Chi-Chun; Shi, Lin; Shi, Yue-Feng; Chun, Jay; Kung, Hsiang-Fu; Yang, Mengsu

    2006-01-01

    AIM: To study the effect of WeiJia on chronic liver injury using carbon tetrachloride (CCl4) induced liver injury animal model. METHODS: Wistar rats weighing 180-220g were randomly divided into three groups: normal control group (Group A), CCl4 induced liver injury control group (Group B) and CCl4 induction with WeiJia treatment group (Group C). Each group consisted of 14 rats. Liver damage and fibrosis was induced by subcutaneous injection with 40% CCl4 in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and C rats whereas olive oil was used for Group A rats. Starting from the third week, Group C rats also received daily intraperitoneal injection of WeiJia at a dose of 1.25 μg/kg body weight. Animals were sacrificed at the fifth week (4 male, 3 female), and eighth week (4 male, 3 female) respectively. Degree of fibrosis were measured and serological markers for liver fibrosis and function including hyaluronic acid (HA), type IV collagen (CIV), γ-glutamyl transferase (γ-GT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Alpha smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) immunohistochemistry were also performed. RESULTS: CCl4 induction led to the damage of liver and development of fibrosis in Group B and Group C rats when compared to Group A rats. The treatment of WeiJia in Group C rats could reduce the fibrosis condition significantly compared to Group B rats. The effect could be observed after three weeks of treatment and was more obvious after eight weeks of treatment. Serum HA, CIV, ALT, AST and γ-GT levels after eight weeks of treatment for Group C rats were 58±22 µg/L (P0.05) respectively, similar to normal control group (Group A), but significantly different from CCl4 induced liver injury control group (Group B). An increase in PCNA and decrease in α-SMA expression level was also observed. CONCLUSION: WeiJia could improve liver function and reduce liver

  7. Chronic restraint stress exacerbates nociception and inflammatory response induced by bee venom in rats: the role of the P2X7 receptors.

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    Li, Xiao-Qiu; Li, Man; Zhou, Zhong-He; Liu, Bao-Jun; Chen, Hui-Sheng

    2016-02-01

    Chronic restraint stress exacerbates pain and inflammation. The present study was designed to evaluate the effect of chronic restraint stress on inflammatory pain induced by subcutaneous injection of bee venom (BV). First, we investigated: (1) the effect of two-week restraint stress with daily 2 or 8 h on the baseline paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL) and paw circumference (PC); (2) the effect of chronic stress on the spontaneous paw-flinching reflex (SPFR), decrease in PWM, PWTL and increase in PC of the injected paw induced by BV. The results showed that (1) chronic restraint decreased significantly the PWMT and inhibited significantly the increase in PC, but had no effect on PWTL, compared with control group; (2) chronic restraint enhanced significantly BV-induced SPFR and inflammatory swelling of the injected paw. In a second series of experiments, the role of P2X7 receptor (P2X7R) in the enhancement of BV-induced inflammatory pain produced by chronic restraint stress was determined. Systemic pretreatment with P2X7R antagonist completely reversed the decrease in PWMT produced by chronic restraint, inhibited significantly the enhancement of BV-induced inflammatory pain produced by chronic restraint stress. Taken together, our data indicate that chronic restraint stress-enhanced nociception and inflammation in the BV pain model, possibly involving the P2X7R.

  8. Exercise-induced muscle fatigue in the unaffected knee joint and its influence on postural control and lower limb kinematics in stroke patients

    Directory of Open Access Journals (Sweden)

    Sun Wook Park

    2017-01-01

    Full Text Available This study aimed to investigate the effects of exercise-induced muscle fatigue in the unaffected knee joint on postural control and kinematic changes in stroke patients. Forty participants (20 stroke patients, 20 age-matched healthy participants were recruited. To induce fatigue, maximum voluntary isometric contractions were performed in the unaffected knee joint in a Leg Extension Rehab exercise machine using the pneumatic resistance. We measured static and dynamic balance and lower-limb kinematics during gait. Changes in postural control parameters anteroposterior sway speed and total center of pressure distance differed significantly between the stroke and control groups. In addition, changes in gait kinematic parameters knee and ankle angles of initial contact differed significantly between stroke (paretic and non-paretic and control groups. Muscle fatigue in the unaffected knee and ankle impaired postural control and debilitates kinematic movement of ipsilateral and contralateral lower limbs, and may place the fatigued stroke patients at greater risk for falls.

  9. A novel adjustable automated system for inducing chronic intermittent hypoxia in mice.

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    Dora Polšek

    Full Text Available Sleep apnea is a chronic, widely underdiagnosed condition characterized by disruption of sleep architecture and intermittent hypoxia due to short cessations of breathing. It is a major independent risk factor for myocardial infarction, congestive heart failure and stroke as well as one of the rare modifiable risk factors for Alzheimer's Dementia. Reliable animal disease models are needed to understand the link between sleep apnea and the various clinically linked disorders.An automated system for inducing hypoxia was developed, in which the major improvement was the possibility to efficiently adjust the length and intensity of hypoxia in two different periods. The chamber used a small volume of gas allowing for fast exchanges of different oxygen levels. The mice were kept in their cages adapted with the system on the cage lid. As a proof of principle, they were exposed to a three week period of intermittent hypoxia for 8 hours a day, with 90 s intervals of 5, 7% and 21% oxygen to validate the model. Treated (n = 8 and control mice (no hypoxia, n = 7 were handled in the same manner and their hippocampal brain regions compared by histology.The chamber provided a fast, reliable and precise intermittent hypoxia, without inducing noticeable side effects to the animals. The validation experiment showed that apoptotic neurons in the hippocampus were more numerous in the mice exposed to intermittent hypoxia than in the control group, in all tested hippocampal regions (cornu ammonis 1 (CA1 P <0.001; cornu ammonis 3 (CA3 P <0.001; and dentate gyrus (DG P = 0.023. In both, control and hypoxic conditions, there was a significantly higher number of apoptotic neurons in the DG compared to the CA1 and CA3 subfields (P <0.001.The new design of a hypoxic chamber provides a fast, adjustable and reliable model of obstructive sleep apnea, which was validated by apoptosis of hippocampal neurons.

  10. Protection of dichlorvos induced oxidative stress and nigrostriatal neuronal death by chronic Coenzyme Q10 pretreatment

    International Nuclear Information System (INIS)

    Binukumar, BK; Gupta, Nidhi; Bal, Amanjit; Gill, Kiran Dip

    2011-01-01

    Numerous epidemiological studies have shown an association between pesticide exposure and increased risk of developing Parkinson's diseases. Oxidative stress generated as a result of mitochondrial dysfunction has been implicated as an important factor in the etiology of Parkinson's disease. Previously, we reported that chronic dichlorvos exposure causes mitochondrial impairments and nigrostriatal neuronal death in rats. The present study was designed to test whether Coenzyme Q 10 (CoQ 10 ) administration has any neuroprotective effect against dichlorvos mediated nigrostriatal neuronal death, α-synuclein aggregation, and motor dysfunction. Male albino rats were administered dichlorvos by subcutaneous injection at a dose of 2.5 mg/kg body weight over a period of 12 weeks. Results obtained there after showed that dichlorvos exposure leads to enhanced mitochondrial ROS production, α-synuclein aggregation, decreased dopamine and its metabolite levels resulting in nigrostriatal neurodegeneration. Pretreatment by Coenzyme Q 10 (4.5 mg/kg ip for 12 weeks) to dichlorvos treated animals significantly attenuated the extent of nigrostriatal neuronal damage, in terms of decreased ROS production, increased dopamine and its metabolite levels, and restoration of motor dysfunction when compared to dichlorvos treated animals. Thus, the present study shows that Coenzyme Q 10 administration may attenuate dichlorvos induced nigrostriatal neurodegeneration, α-synuclein aggregation and motor dysfunction by virtue of its antioxidant action. - Highlights: → CoQ 10 administration attenuates dichlorvos induced nigrostriatal neurodegenaration. → CoQ 10 pre treatment leads to preservation of TH-IR neurons. → CoQ 10 may decrease oxidative damage and α-synuclin aggregation. → CoQ 10 treatment enhances motor function and protects rats from catalepsy.

  11. Haemophilus influenzae from Patients with Chronic Obstructive Pulmonary Disease Exacerbation Induce More Inflammation than Colonizers

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    Chin, Cecilia L.; Manzel, Lori J.; Lehman, Erin E.; Humlicek, Alicia L.; Shi, Lei; Starner, Timothy D.; Denning, Gerene M.; Murphy, Timothy F.; Sethi, Sanjay; Look, Dwight C.

    2005-01-01

    Rationale: Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Objective: To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD. Methods: Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells. Results: H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-κB and p38 mitogen-activated protein kinase signaling pathways. Conclusions: The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function. PMID:15805181

  12. Hypoxia Inducible Factor 1α Promotes Endogenous Adaptive Response in Rat Model of Chronic Cerebral Hypoperfusion

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    Ying Yang

    2017-01-01

    Full Text Available Hypoxia inducible factor 1α (HIF-1α, a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH. Lentivirus expressing HIF-1α small hairpin RNA was injected into the bilateral hippocampus and bilateral ventricles to knock down HIF-1α gene expression in the hippocampus and other brain areas. Permanent bilateral common carotid artery occlusions, known as 2-vessel occlusions (2VOs, were used to induce CCH in rats. Angiogenesis, oxidative stress, histopathological changes of the brain, and cognitive function were tested. Knockdown of HIF-1α prior to 2VO significantly exacerbates the impairment of learning and memory after four weeks of CCH. Mechanically, reduced cerebral angiogenesis, increased oxidative damage, and increased density of astrocytes and microglia in the cortex and some subregions of hippocampus are also shown after four weeks of CCH. Furthermore, HIF-1α knockdown also disrupts upregulation of regulated downstream genes. Our findings suggest that HIF-1α-protects the brain from oxidative stress and inflammation response in the disease process of CCH. Accumulated HIF-1α during CCH mediates endogenous adaptive processes to defend against more severe hypoperfusion injury of the brain, which may provide a therapeutic benefit.

  13. Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites

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    Darin J. Knapp

    2016-07-01

    Full Text Available Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C–C motif ligand 2 (CCL2, interleukin-1-beta (IL-1β, tumor necrosis factor alpha (TNFα and toll-like receptor 4 (TLR4 mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally—based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1 receptor inhibition in blocking WCE-induced cytokine mRNAs—the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals

  14. Curcumin reverses the depressive-like behavior and insulin resistance induced by chronic mild stress.

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    Shen, Ji-Duo; Wei, Yu; Li, Yu-Jie; Qiao, Jing-Yi; Li, Yu-Cheng

    2017-08-01

    Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity. Serum parameters were detected using commercial kits. Real-time quantitative PCR was used to examine mRNA expression. CMS rats exhibited reduced sucrose consumption, increased serum glucose, insulin, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), non-esterified fatty acid (NEFA), glucagon, leptin, and corticosterone levels, as well as impaired insulin sensitivity. Curcumin upregulated the phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (Akt) in the liver, enhanced insulin sensitivity, and reversed the metabolic abnormalities and depressive-like behaviors mentioned above. Moreover, curcumin increased the hepatic glycogen content by inhibiting glycogen synthase kinase (GSK)-3β and prevented gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These results suggest that curcumin not only exerted antidepressant-like effects, but also reversed the insulin resistance and metabolic abnormalities induced by CMS. These data may provide evidence to support the potential use of curcumin against depression and/or metabolic disorders.

  15. Ultrastructural alterations of atrial myocardium induced by adriamycin in chronically treated animals.

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    Lambertenghi-Deliliers, G; Zanon, P L; Pozzoli, E F; Bellini, O; Praga, C

    1978-02-28

    The clinical use of adriamycin (AM) is limited by a possible dose-dependent myocardiopathy. Severe lesions of ventricular myocardium widely described by electron microscopy have been correlated to irreversible congestive heart failure. On the other hand, the atrial contractile elements which differ from the ventricular ones because of the presence of the so-called specific granules have rarely been considered. In the work described in this paper, adriamycin was injected into rabbits and mice according to schedules of chronic toxicity. At the end of the treatment the atrial myocells presented diffuse ultrastructural lesions of mitochondria, sarcoplasmic reticulum and myofibrillar bundles. These alterations might be caused by the ribonucleoprotein synthesis inhibition, by a direct drug toxicity or by an energetic crisis due to early mitochondrial lesions. Besides, adriamycin produces a decrease of the specific atrial granules that play a hypothetic role in the metabolism of myocardial cells. However, lack of information about the contents and the exact function of atrial granules does not allow us to conclude that their decrease in treated animals has a pathogenetic significance in myocardiopathy induced by adriamycin.

  16. Posaconazole-Induced Adrenal Insufficiency in a Case of Chronic Myelomonocytic Leukemia

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    Ann Miller

    2018-01-01

    Full Text Available Introduction. Posaconazole is an azole used in treatment and prophylaxis of a broad spectrum of fungal infections. Antifungals such as ketoconazole have been shown to cause primary adrenal insufficiency (AI as a result of direct inhibition on the steroidogenesis pathway. There is only one reported case of primary AI induced by posaconazole in a patient with mucormycosis. We report a case of posaconazole-related primary AI. Case. A 63-year-old man with chronic myelomonocytic leukemia was admitted for fatigue and intermittent nausea and vomiting. He had recently discontinued prophylactic posaconazole 300 mg daily. He was assessed for AI with a morning cortisol of 1.9 mcg/dL followed by a failed cosyntropin stimulation (CS test. Adrenocorticotropic hormone (ACTH level was 154.6 pg/mL with negative 21-hydroxylase antibodies. The patient’s symptoms improved with initiation of hydrocortisone and fludrocortisone. One year after discontinuation of posaconazole, he underwent a repeat CS test which showed normal adrenal function with normal ACTH at 34.1 pg/mL. Conclusion. In this case, we demonstrate that prolonged use of posaconazole is associated with primary AI. As use of posaconazole increases, knowledge of the potential risk of AI is important and must be included in the differential diagnosis when these patients present with hypotension, hypoglycemia, and failure to thrive.

  17. Impairment of the spatial learning and memory induced by learned helplessness and chronic mild stress.

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    Song, Li; Che, Wang; Min-Wei, Wang; Murakami, Yukihisa; Matsumoto, Kinzo

    2006-02-01

    Increasing evidences indicate the concurrence and interrelationship of depression and cognitive impairments. The present study was undertaken to investigate the effects of two depressive animal models, learned helplessness (LH) and chronic mild stress (CMS), on the cognitive functions of mice in the Morris water maze task. Our results demonstrated that both LH and CMS significantly decreased the cognitive performance of stressed mice in the water maze task. The escaping latency to the platform was prolonged and the probe test percentage in the platform quadrant was reduced. These two models also increased the plasma corticosterone concentration and decreased the brain derived neurotrophic factor (BDNF) and cAMP-response element-biding protein (CREB) messenger ribonucleic acid (mRNA) levels in hippocampus, which might cause the spatial cognition deficits. Repeated treatment with antidepressant drugs, imipramine (Imi) and fluoxetine (Flu), significantly reduced the plasma corticosterone concentration and enhanced the BDNF and CREB levels. Furthermore, antidepressant treated animals showed an ameliorated cognitive performance compared with the vehicle treated stressed animals. These data suggest that both LH and CMS impair the spatial cognitive function and repeated treatment with antidepressant drugs decreases the prevalence of cognitive impairments induced by these two animal models. Those might in part be attributed to the reduced plasma corticosterone and enhanced hippocampal BDNF and CREB expressions. This study provided a better understanding of molecular mechanisms underlying interactions of depression and cognitive impairments, although animal models used in this study can mimic only some aspects of depression or cognition of human.

  18. Hypoxia-Inducible Factor and Its Role in the Management of Anemia in Chronic Kidney Disease

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    Joshua M. Kaplan

    2018-01-01

    Full Text Available Hypoxia-inducible factor (HIF plays a crucial role in the response to hypoxia at the cellular, tissue, and organism level. New agents under development to pharmacologically manipulate HIF may provide new and exciting possibilities in the treatment of anemia of chronic kidney disease (CKD as well as in multiple other disease states involving ischemia–reperfusion injury. This article provides an overview of recent studies describing current standards of care for patients with anemia in CKD and associated clinical issues, and those supporting the clinical potential for targeting HIF stabilization with HIF prolyl-hydroxylase inhibitors (HIF-PHI in these patients. Additionally, articles reporting the clinical potential for HIF-PHIs in ‘other’ putative therapeutic areas, the tissue and intracellular distribution of HIF- and prolyl-hydroxylase domain (PHD isoforms, and HIF isoforms targeted by the different PHDs, were identified. There is increasing uncertainty regarding the optimal treatment for anemia of CKD with poorer outcomes associated with treatment to higher hemoglobin targets, and the increasing use of iron and consequent risk of iron imbalance. Attainment and maintenance of more physiologic erythropoietin levels associated with HIF stabilization may improve the management of patients resistant to treatment with erythropoiesis-stimulating agents and improve outcomes at higher hemoglobin targets.

  19. Decay-accelerating factor 1 deficiency exacerbates Trypanosoma cruzi-induced murine chronic myositis.

    Science.gov (United States)

    Solana, María E; Ferrer, María F; Novoa, María Mercedes; Song, Wen-Chao; Gómez, Ricardo M

    2012-10-01

    Murine infection with Trypanosoma cruzi (Tc) has been used to study the role of T-cells in the pathogenesis of human inflammatory idiopathic myositis. Absence of decay-accelerating factor 1 (Daf1) has been shown to enhance murine T-cell responses and autoimmunity. To determine whether Daf1 deficiency can exacerbate Tc-induced myositis, C57BL/6 DAF(+/+) and DAF(-/-) mice were inoculated with 5 × 10(4) trypomastigotes, and their morbidity, parasitemia, parasite burden, histopathology, and T-cell expansion were studied in the acute and chronic stages. DAF(-/-) mice had lower parasitemia and parasite burden but higher morbidity, muscle histopathology, and increased number of CD44(+) (activated/memory phenotype) splenic CD4(+) and CD8(+) T-cells. An enhanced CD8(+) T-cell immune-specific response may explain the lower parasitemia and parasite burden levels and the increase in histopathological lesions. We propose that Tc-inoculated DAF(-/-) mice are a useful model to study T-cell mediated immunity in skeletal muscle tissues. Copyright © 2012 Wiley Periodicals, Inc.

  20. Chronic nitrate enrichment decreases severity and induces protection against an infectious disease.

    Science.gov (United States)

    Smallbone, Willow; Cable, Jo; Maceda-Veiga, Alberto

    2016-05-01

    Excessive fertilisation is one of the most pernicious forms of global change resulting in eutrophication. It has major implications for disease control and the conservation of biodiversity. Yet, the direct link between nutrient enrichment and disease remains largely unexplored. Here, we present the first experimental evidence that chronic nitrate enrichment decreases severity and induces protection against an infectious disease. Specifically, this study shows that nitrate concentrations ranging between 50 and 250mgNO3(-)/l reduce Gyrodactylus turnbulli infection intensity in two populations of Trinidadian guppies Poecilia reticulata, and that the highest nitrate concentration can even clean the parasites from the fish. This added to the fact that host nitrate pre-exposure altered the fish epidermal structure and reduced parasite intensity, suggests that nitrate protected the host against the disease. Nitrate treatments also caused fish mortality. As we used ecologically-relevant nitrate concentrations, and guppies are top-consumers widely used for mosquito bio-control in tropical and often nutrient-enriched waters, our results can have major ecological and social implications. In conclusion, this study advocates reducing nitrate level including the legislative threshold to protect the aquatic biota, even though this may control an ectoparasitic disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Chronic Powder Diet After Weaning Induces Sleep, Behavioral, Neuroanatomical, and Neurophysiological Changes in Mice.

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    Emiko Anegawa

    Full Text Available The purpose of this study is to clarify the effects of chronic powder diet feeding on sleep patterns and other physiological/anatomical changes in mice. C57BL/6 male mice were divided into two groups from weaning: a group fed with solid food (SD and a group fed with powder food (PD, and sleep and physiological and anatomical changes were compared between the groups. PD exhibited less cranial bone structure development and a significant weight gain. Furthermore, these PD mice showed reduced number of neurogenesis in the hippocampus. Sleep analysis showed that PD induced attenuated diurnal sleep/wake rhythm, characterized by increased sleep during active period and decreased sleep during rest period. With food deprivation (FD, PD showed less enhancement of wake/locomotor activity compared to SD, indicating reduced food-seeking behavior during FD. These results suggest that powder feeding in mice results in a cluster of detrimental symptoms caused by abnormal energy metabolism and anatomical/neurological changes.

  2. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

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    Yihan Zhang

    2016-01-01

    Full Text Available Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R after high (25 mM or low (5.5 mM glucose culture. Cell viability, reactive oxygen species (ROS, and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2 and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

  3. Protective role of hydrogen sulfide against noise-induced cochlear damage: a chronic intracochlear infusion model.

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    Xu Li

    Full Text Available BACKGROUND: A reduction in cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL. The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2S has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H(2S in cochlear blood flow regulation and noise protection. METHODOLOGY/PRINCIPAL FINDINGS: The gene and protein expression of the H(2S synthetase cystathionine-γ-lyase (CSE in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP, NaHS or DL-propargylglycine (PPG were locally administered. Local sodium hydrosulfide (NaHS significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR, cochlear scanning electron microscope (SEM and outer hair cell (OHC count. The highest percentage of OHC loss occurred in the PPG group. CONCLUSIONS/SIGNIFICANCE: Our results suggest that H(2S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases.

  4. Dasatinib Induced Avascular Necrosis of Femoral Head in Adult Patient with Chronic Myeloid Leukemia

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    Mohamed A. Yassin

    2015-01-01

    Full Text Available Chronic myeloid leukemia (CML is a myeloproliferative neoplasm characterized by the presence of the Philadelphia (Ph chromosome resulting from the reciprocal translocation t(9;22(q34;q11. The molecular consequence of this translocation is the generation of the BCR-ABL fusion gene, which encodes a constitutively active protein tyrosine kinase. The oncogenic protein tyrosine kinase, which is located in the cytoplasm, is responsible for the leukemia phenotype through the constitutive activation of multiple signaling pathways involved in the cell cycle and in adhesion and apoptosis. Avascular necrosis of the femoral head (AVNFH is not a specific disease. It occurs as a complication or secondary to various causes. These conditions probably lead to impaired blood supply to the femoral head. The diagnosis of AVNFH is based on clinical findings and is supported by specific radiological manifestations. We reported a case of a 34-year-old Sudanese female with CML who developed AVNFH after receiving dasatinib as a second-line therapy. Though the mechanism by which dasatinib can cause avascular necrosis (AVN is not clear, it can be postulated because of microcirculatory obstruction of the femoral head. To the best of our knowledge and after extensive literature search, this is the first reported case of AVNFH induced by dasatinib in a patient with CML.

  5. Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner.

    Science.gov (United States)

    Fernandes, Elizabeth S; Russell, Fiona A; Alawi, Khadija M; Sand, Claire; Liang, Lihuan; Salamon, Robin; Bodkin, Jennifer V; Aubdool, Aisah A; Arno, Matthew; Gentry, Clive; Smillie, Sarah-Jane; Bevan, Stuart; Keeble, Julie E; Malcangio, Marzia; Brain, Susan D

    2016-01-11

    The effect of cold temperature on arthritis symptoms is unclear. The aim of this study was to investigate how environmental cold affects pain and blood flow in mono-arthritic mice, and examine a role for transient receptor potential ankyrin 1 (TRPA1), a ligand-gated cation channel that can act as a cold sensor. Mono-arthritis was induced by unilateral intra-articular injection of complete Freund's adjuvant (CFA) in CD1 mice, and in mice either lacking TRPA1 (TRPA1 KO) or respective wildtypes (WT). Two weeks later, nociception and joint blood flow were measured following exposure to 10 °C (1 h) or room temperature (RT). Primary mechanical hyperalgesia in the knee was measured by pressure application apparatus; secondary mechanical hyperalgesia by automated von Frey system; thermal hyperalgesia by Hargreaves technique, and weight bearing by the incapacitance test. Joint blood flow was recorded by full-field laser perfusion imager (FLPI) and using clearance of (99m)Technetium. Blood flow was assessed after pretreatment with antagonists of either TRPA1 (HC-030031), substance P neurokinin 1 (NK1) receptors (SR140333) or calcitonin gene-related peptide (CGRP) (CGRP8-37). TRPA1, TAC-1 and CGRP mRNA levels were examined in dorsal root ganglia, synovial membrane and patellar cartilage samples. Cold exposure caused bilateral primary mechanical hyperalgesia 2 weeks after CFA injection, in a TRPA1-dependent manner. In animals maintained at RT, clearance techniques and FLPI showed that CFA-treated joints exhibited lower blood flow than saline-treated joints. In cold-exposed animals, this reduction in blood flow disappears, and increased blood flow in the CFA-treated joint is observed using FLPI. Cold-induced increased blood flow in CFA-treated joints was blocked by HC-030031 and not observed in TRPA1 KOs. Cold exposure increased TRPA1 mRNA levels in patellar cartilage, whilst reducing it in synovial membranes from CFA-treated joints. We provide evidence that environmental

  6. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

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    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  7. Chronic Fluoxetine Induces the Enlargement of Perforant Path-Granule Cell Synapses in the Mouse Dentate Gyrus

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    Kitahara, Yosuke; Ohta, Keisuke; Hasuo, Hiroshi; Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Togo, Akinobu; Nakamura, Kei-ichiro; Nishi, Akinori

    2016-01-01

    A selective serotonin reuptake inhibitor is the most commonly prescribed antidepressant for the treatment of major depression. However, the mechanisms underlying the actions of selective serotonin reuptake inhibitors are not fully understood. In the dentate gyrus, chronic fluoxetine treatment induces increased excitability of mature granule cells (GCs) as well as neurogenesis. The major input to the dentate gyrus is the perforant path axons (boutons) from the entorhinal cortex (layer II). Through voltage-sensitive dye imaging, we found that the excitatory neurotransmission of the perforant path synapse onto the GCs in the middle molecular layer of the mouse dentate gyrus (perforant path-GC synapse) is enhanced after chronic fluoxetine treatment (15 mg/kg/day, 14 days). Therefore, we further examined whether chronic fluoxetine treatment affects the morphology of the perforant path-GC synapse, using FIB/SEM (focused ion beam/scanning electron microscopy). A three-dimensional reconstruction of dendritic spines revealed the appearance of extremely large-sized spines after chronic fluoxetine treatment. The large-sized spines had a postsynaptic density with a large volume. However, chronic fluoxetine treatment did not affect spine density. The presynaptic boutons that were in contact with the large-sized spines were large in volume, and the volumes of the mitochondria and synaptic vesicles inside the boutons were correlated with the size of the boutons. Thus, the large-sized perforant path-GC synapse induced by chronic fluoxetine treatment contains synaptic components that correlate with the synapse size and that may be involved in enhanced glutamatergic neurotransmission. PMID:26788851

  8. Aquaporin-1 and aquaporin-3 expressions in the temporo-mandibular joint condylar cartilage after an experimentally induced osteoarthritis.

    Science.gov (United States)

    Meng, Juan-hong; Ma, Xu-chen; Li, Zhi-min; Wu, Deng-cheng

    2007-12-20

    Over 70% of the total tissue weight in the cartilage matrix consists of water, and the early-stage osteoarthritic cartilage is characterized by swelling. Water transport in the cartilage matrix and across the membranes of chondrocytes may be important in normal and pathological conditions of cartilage. The purpose of this study was to identify aquaporin-1 (AQP1) and aquaporin-3 (AQP3) expressions in the mandibular condylar cartilage after experimentally induced osteoarthritis (OA) in rats. An experimental temporomandibular joint OA was induced by partial discectomy in rats. The pathological characteristics of the normal, early-stage, and late-stage osteoarthritic TMJ cartilages were verified by histological techniques. The AQP1 and AQP3 gene expressions in the normal and osteoarthritic cartilages were measured using quantitative real-time reverse-transcription PCR analysis. The cartilage sections were incubated in primary polyclonal antibodies to AQP3; immunofluorescent microscopy was used to examine the AQP3 expression shown by its protein level. The mRNA expression levels of AQP1 and AQP3, analyzed using quantitative PCR, revealed that AQP3 mRNA was highly up-regulated in the OA cartilage, which was considered significant. There was no notable difference in the expression of AQP1 mRNA between OA and normal controls. With the progressing of the OA, the localization of the AQP3 protein was quite different from that of the normal cartilage. Compared to the normal cartilage, the expressions of AQP3 protein were observed mainly in the proliferative zone and the upper mid-zone chondrocytes at the early-stage of OA, and were observed to appear frequently throughout the mid- and deep zone during the late-stage of OA. The high expression of AQP3 mRNA in the OA cartilage and the different localization of the AQP3 protein suggest that it may play a particular role in OA pathogenesis. Further study of AQP3 function may provide new insight into the understanding of the

  9. An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice.

    Science.gov (United States)

    Monteiro, Susana; Roque, Susana; de Sá-Calçada, Daniela; Sousa, Nuno; Correia-Neves, Margarida; Cerqueira, João José

    2015-01-01

    Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic-pituitary-adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS.

  10. Metabolic fingerprinting of joint tissue of collagen-induced arthritis (CIA) rat: In vitro, high resolution NMR (nuclear magnetic resonance) spectroscopy based analysis.

    Science.gov (United States)

    Srivastava, Niraj Kumar; Sharma, Shikha; Sharma, Rajkumar; Sinha, Neeraj; Mandal, Sudhir Kumar; Sharma, Deepak

    2018-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease whose major characteristics persistent joint inflammation that results in joint destruction and failure of the function. Collagen-induced arthritis (CIA) rat is an autoimmune disease model and in many ways shares features with RA. The CIA is associated with systemic manifestations, including alterations in the metabolism. Nuclear magnetic resonance (NMR) spectroscopy-based metabolomics has been successfully applied to the perchloric acid extract of the joint tissue of CIA rat and control rat for the analysis of aqueous metabolites. GPC (Glycerophosphocholine), carnitine, acetate, and creatinine were important discriminators of CIA rats as compared to control rats. Level of lactate (significance; p = 0.004), alanine (p = 0.025), BCA (Branched-chain amino acids) (p = 0.006) and creatinine (p = 0.023) was significantly higher in CIA rats as compared to control rats. Choline (p = 0.038) and GPC (p = 0.009) were significantly reduced in CIA rats as compared to control rats. Choline to GPC correlation was good and negative (Pearson correlation = -0.63) for CIA rats as well as for control rats (Pearson correlation = -0.79). All these analyses collectively considered as metabolic fingerprinting of the joint tissue of CIA rat as compared to control rat. The metabolic fingerprinting of joint tissue of CIA rats was different as compared to control rats. The metabolic fingerprinting reflects inflammatory disease activity in CIA rats with synovitis, demonstrating that underlying inflammatory process drives significant changes in metabolism that can be measured in the joint tissue. Therefore, the outcome of this study may be helpful for understanding the mechanism of metabolic processes in RA. This may be also helpful for the development of advanced diagnostic methods and therapy for RA.

  11. Chronic hydrocephalus-induced hypoxia: increased expression of VEGFR-2+ and blood vessel density in hippocampus.

    Science.gov (United States)

    Dombrowski, S M; Deshpande, A; Dingwall, C; Leichliter, A; Leibson, Z; Luciano, M G

    2008-03-18

    Chronic hydrocephalus (CH) is a neurological disease characterized by increased cerebrospinal fluid volume and pressure that is often associated with impaired cognitive function. By and large, CH is a complex and heterogeneous cerebrospinal fluid (CSF) disorder where the exact site of brain insult is uncertain. Several mechanisms including neural compression, fiber stretch, and local or global hypoxia have been implicated in the underlying pathophysiology of CH. Specifically, the hippocampus, which plays a significant role in memory processing and is in direct contact with expanding CSF ventricles, may be involved. Using our model of chronic hydrocephalus, we quantified the density of vascular endothelial growth factor receptor 2 (VEGFR-2(+)) neurons, glial, endothelial cells, and blood vessels in hippocampal regions CA1, CA2-3, dentate gyrus and hilus using immunohistochemical and stereological methods. Density and %VEGFR-2(+) cell populations were estimated for CH animals (2-3 weeks vs. 12-16 weeks) and surgical controls (SC). Overall, we found approximately six- to eightfold increase in the cellular density of VEGFR-2(+) and more than double blood vessel density (BVd) in the hippocampus of CH compared with SC. There were no significant regional differences in VEGFR-2(+) cellular and BVd expression in the CH group. VEGFR-2(+) and BVds were significantly related to changes in CSF volume (Pinduced

  12. Tolerance to disulfiram induced by chronic alcohol intake in the rat.

    Science.gov (United States)

    Tampier, Lutske; Quintanilla, María Elena; Israel, Yedy

    2008-06-01

    Disulfiram, an inhibitor of aldehyde dehydrogenase used in the treatment of alcoholism, is an effective medication when its intake is supervised by a third person. However, its therapeutic efficacy varies widely, in part due to the fact that disulfiram is a pro-drug that requires its transformation into an active form and because it shows a wide range of secondary effects which often prevent the use of doses that ensure full therapeutic effectiveness. In this preclinical study in rats we report the development of tolerance to disulfiram induced by the chronic ingestion of ethanol, an additional source of variation for the actions of disulfiram with possible therapeutic significance, We also addresses the likely mechanism of this effect. Wistar-derived rats bred for generations as high ethanol drinkers (UChB) were trained for either 3 days (Group A) or 30 days (Group B) to choose between ethanol (10% v/v) or water, which were freely available from 2 bottles on a 24-hour basis. Subsequently, animals in both groups were administered disulfiram or cyanamide (another inhibitor of aldehyde dehydrogenase) and ethanol intake in this free choice paradigm was determined. Animals were also administered a standard dose of 1 g ethanol/kg (i.p) and arterial blood acetaldehyde was measured. Disulfiram (12.5 and 25 mg/kg) and cyanamide (10 mg/kg) markedly inhibited ethanol intake (up to 60 to 70%) in animals that had ethanol access for only 3 days (Group A). However both drugs were inactive in inhibiting ethanol intake in animals that had consumed ethanol for 30 days (Group B). Following the injection of 1 g ethanol/kg, arterial blood acetaldehyde levels reached levels of 150 and 300 microM for disulfiram and cyanamide respectively, values which were virtually identical regardless of the length of prior ethanol intake of the animals. Chronic ethanol intake in high-drinker rats leads to marked tolerance to the aversive effects of disulfiram and cyanamide on ethanol intake despite

  13. Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

    International Nuclear Information System (INIS)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1983-01-01

    Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD

  14. Stevia Prevents Acute and Chronic Liver Injury Induced by Carbon Tetrachloride by Blocking Oxidative Stress through Nrf2 Upregulation

    Science.gov (United States)

    Ramos-Tovar, Erika; Hernández-Aquino, Erika; Casas-Grajales, Sael; Buendia-Montaño, Laura D.; Tsutsumi, Víctor

    2018-01-01

    The effect of stevia on liver cirrhosis has not been previously investigated. In the present study, the antioxidant and anti-inflammatory properties of stevia leaves were studied in male Wistar rats with carbon tetrachloride- (CCl4-) induced acute and chronic liver damage. Acute and chronic liver damage induced oxidative stress, necrosis, and cholestasis, which were significantly ameliorated by stevia. Chronic CCl4 treatment resulted in liver cirrhosis, as evidenced by nodules of hepatocytes surrounded by thick bands of collagen and distortion of the hepatic architecture, and stevia significantly prevented these alterations. Subsequently, the underlying mechanism of action of the plant was analyzed. Our study for the first time shows that stevia upregulated Nrf2, thereby counteracting oxidative stress, and prevented necrosis and cholestasis through modulation of the main proinflammatory cytokines via NF-κB inhibition. These multitarget mechanisms led to the prevention of experimental cirrhosis. Given the reasonable safety profile of stevia, our results indicated that it may be useful for the clinical treatment of acute and chronic liver diseases. PMID:29849889

  15. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

    Directory of Open Access Journals (Sweden)

    Gang Xin

    2015-11-01

    Full Text Available Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue “unhelped” CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells “help” the CD8 response during chronic infection via IL-21-induced BATF expression.

  16. Effects of Shuyusan on monoamine neurotransmitters expression in a rat model of chronic stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Zhang; Jianjun Jia; Liping Chen; Zhitao Han; Yulan Zhao; Honghong Zhang; Yazhuo Hu

    2011-01-01

    Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.

  17. Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus.

    Science.gov (United States)

    Hennebelle, Marie; Champeil-Potokar, Gaëlle; Lavialle, Monique; Vancassel, Sylvie; Denis, Isabelle

    2014-02-01

    Chronic stress causes the release of glucocorticoids, which greatly influence cerebral function, especially glutamatergic transmission. These stress-induced changes in neurotransmission could be counteracted by increasing the dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Numerous studies have described the capacity of n-3 PUFAs to help protect glutamatergic neurotransmission from damage induced by stress and glucocorticoids, possibly preventing the development of stress-related disorders such as depression or anxiety. The hippocampus contains glucocorticoid receptors and is involved in learning and memory. This makes it particularly sensitive to stress, which alters certain aspects of hippocampal function. In this review, the various ways in which n-3 PUFAs may prevent the harmful effects of chronic stress, particularly the alteration of glutamatergic synapses in the hippocampus, are summarized. © 2014 International Life Sciences Institute.

  18. Cartilage oligomeric matrix protein deficiency promotes early onset and the chronic development of collagen-induced arthritis

    DEFF Research Database (Denmark)

    Geng, Hui; Carlsen, Stefan; Nandakumar, Kutty

    2008-01-01

    ABSTRACT: INTRODUCTION: Cartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage. The development of arthritis, like collagen-induced arthritis (CIA), involves cartilage as a target tissue. We have investigated the development of CIA in COMP-deficient mice. METHODS: COMP......-deficient mice in the 129/Sv background were backcrossed for 10 generations against B10.Q mice, which are susceptible to chronic CIA. COMP-deficient and wild-type mice were tested for onset, incidence, and severity of arthritis in both the collagen and collagen antibody-induced arthritis models. Serum anti......-collagen II and anti-COMP antibodies as well as serum COMP levels in arthritic and wild-type mice were measured by enzyme-linked immunosorbent assay. RESULTS: COMP-deficient mice showed a significant early onset and increase in the severity of CIA in the chronic phase, whereas collagen II-antibody titers were...

  19. Chronic early postnatal scream sound stress induces learning deficits and NMDA receptor changes in the hippocampus of adult mice.

    Science.gov (United States)

    Hu, Lili; Han, Bo; Zhao, Xiaoge; Mi, Lihua; Song, Qiang; Wang, Jue; Song, Tusheng; Huang, Chen

    2016-04-13

    Chronic scream sounds during adulthood affect spatial learning and memory, both of which are sexually dimorphic. The long-term effects of chronic early postnatal scream sound stress (SSS) during postnatal days 1-21 (P1-P21) on spatial learning and memory in adult mice as well as whether or not these effects are sexually dimorphic are unknown. Therefore, the present study examines the performance of adult male and female mice in the Morris water maze following exposure to chronic early postnatal SSS. Hippocampal NR2A and NR2B levels as well as NR2A/NR2B subunit ratios were tested using immunohistochemistry. In the Morris water maze, stress males showed greater impairment in spatial learning and memory than background males; by contrast, stress and background females performed equally well. NR2B levels in CA1 and CA3 were upregulated, whereas NR2A/NR2B ratios were downregulated in stressed males, but not in females. These data suggest that chronic early postnatal SSS influences spatial learning and memory ability, levels of hippocampal NR2B, and NR2A/NR2B ratios in adult males. Moreover, chronic early stress-induced alterations exert long-lasting effects and appear to affect performance in a sex-specific manner.

  20. Vagus nerve stimulation mitigates intrinsic cardiac neuronal remodeling and cardiac hypertrophy induced by chronic pressure overload in guinea pig

    Science.gov (United States)

    Beaumont, Eric; Wright, Gary L.; Southerland, Elizabeth M.; Li, Ying; Chui, Ray; KenKnight, Bruce H.; Armour, J. Andrew

    2016-01-01

    Our objective was to determine whether chronic vagus nerve stimulation (VNS) mitigates pressure overload (PO)-induced remodeling of the cardioneural interface. Guinea pigs (n = 48) were randomized to right or left cervical vagus (RCV or LCV) implant. After 2 wk, chronic left ventricular PO was induced by partial (15–20%) aortic constriction. Of the 31 animals surviving PO induction, 10 were randomized to RCV VNS, 9 to LCV VNS, and 12 to sham VNS. VNS was delivered at 20 Hz and 1.14 ± 0.03 mA at a 22% duty cycle. VNS commenced 10 days after PO induction and was maintained for 40 days. Time-matched controls (n = 9) were evaluated concurrently. Echocardiograms were obtained before and 50 days after PO. At termination, intracellular current-clamp recordings of intrinsic cardiac (IC) neurons were studied in vitro to determine effects of therapy on soma characteristics. Ventricular cardiomyocyte sizes were assessed with histology along with immunoblot analysis of selected proteins in myocardial tissue extracts. In sham-treated animals, PO increased cardiac output (34%, P < 0.004), as well as systolic (114%, P < 0.04) and diastolic (49%, P < 0.002) left ventricular volumes, a hemodynamic response prevented by VNS. PO-induced enhancements of IC synaptic efficacy and muscarinic sensitivity of IC neurons were mitigated by chronic VNS. Increased myocyte size, which doubled in PO (P < 0.05), was mitigated by RCV. PO hypertrophic myocardium displayed decreased glycogen synthase (GS) protein levels and accumulation of the phosphorylated (inactive) form of GS. These PO-induced changes in GS were moderated by left VNS. Chronic VNS targets IC neurons accompanying PO to obtund associated adverse cardiomyocyte remodeling. PMID:26993230

  1. Aldehyde Dehydrogenase-2 (ALDH2) Ameliorates Chronic Alcohol Ingestion-Induced Myocardial Insulin Resistance and Endoplasmic Reticulum Stress

    OpenAIRE

    Li, Shi-Yan; Gilbert, Sara A.B.; Li, Qun; Ren, Jun

    2009-01-01

    Chronic alcohol intake leads to insulin resistance and alcoholic cardiomyopathy, which appears to be a result of the complex interaction between genes and environment. This study was designed to examine the impact of aldehyde dehydrogenase-2 (ALDH2) transgenic overexpression on alcohol-induced insulin resistance and myocardial injury. ALDH2 transgenic mice were produced using chicken β-actin promoter. Wild-type FVB and ALDH2 mice were fed a 4% alcohol or control diet for 12 wks. Cell shorteni...

  2. Novel Pharmacological Approaches for Treatment of Neurotoxicity Induced by Chronic Exposure to Depleted Uranium

    National Research Council Canada - National Science Library

    Lasley, Stephen M

    2008-01-01

    .... This hypothesis is consistent with previous observations ensuing from chronic intramuscular DU pellet implants in rats, and is based on the anticipation that specific pharmacological agents will...

  3. Features of blood serum protein spectrum and cytokine spectrum of rats with chronic carrageenan-induced intestinal inflammation

    Directory of Open Access Journals (Sweden)

    A. S. Tkachenko

    2014-04-01

    Full Text Available It has been established that features of modern diet might be considered as a possible source of inflammatory diseases of gastrointestinal tract. Particular attention is paid to the role of different food additives in the development of intestinal inflammation, including the food additive E407, known as carrageenan. A model of chronic carrageenan-induced gastroenterocolitis of moderate severity has been elaborated, which allows us to study carrageenan-induced intestinal inflammation. In particular, the features of blood serum protein spectrum and cytokine spectrum in chronic carrageenan-induced intestinal inflammation are not studied. The female Wistar rats have been used for the experiment. Chronic carrageenan-induced gastroenterocolitis has been reproduced by the free access of animals to 1% solution of carrageenan in drinking water. Laboratory animals have been divided into 3 groups. Group № 1 consisted of experimental animals, who consumed food additive carrageenan during 2 weeks and group № 2 included experimental animals, who consumed food additive carrageenan during 4 weeks. Group № 3 consisted of intact healthy animals. The development of gastroenterocolitis has been proved morphologically and biochemically. Manipulations with animals have been carried out in accordance with the provisions of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 1986. It has been established that the disease has been associated with dysproteinemia. The level of α1-globulins increased after 2 weeks of carrageenan consumption and has been normalized in animals, who consumed carrageenan during 4 weeks. The similar changes have been observed for α2-globulins level. It could be explained by production of acute phase proteins, such as α1-acid glycoprotein, C-reactive protein, fibrinogen, α2-macroglobulin, ceruloplasmin, etc. The intake of carrageenan also caused

  4. Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

    Directory of Open Access Journals (Sweden)

    Fernando B. R. da Silva

    2018-05-01

    Full Text Available Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF, pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

  5. Chronic ethanol feeding promotes azoxymethane and dextran sulfate sodium-induced colonic tumorigenesis potentially by enhancing mucosal inflammation

    International Nuclear Information System (INIS)

    Shukla, Pradeep K.; Chaudhry, Kamaljit K.; Mir, Hina; Gangwar, Ruchika; Yadav, Nikki; Manda, Bhargavi; Meena, Avtar S.; Rao, RadhaKrishna

    2016-01-01

    Alcohol consumption is one of the major risk factors for colorectal cancer. However, the mechanism involved in this effect of alcohol is unknown. We evaluated the effect of chronic ethanol feeding on azoxymethane and dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in mouse colon. Inflammation in colonic mucosa was assessed at a precancerous stage by evaluating mucosal infiltration of neutrophils and macrophages, and analysis of cytokine and chemokine gene expression. Chronic ethanol feeding significantly increased the number and size of polyps in colon of AOM/DSS treated mice. Confocal microscopic and immunoblot analyses showed a significant elevation of phospho-Smad, VEGF and HIF1α in the colonic mucosa. RT-PCR analysis at a precancerous stage indicated that ethanol significantly increases the expression of cytokines IL-1α, IL-6 and TNFα, and the chemokines CCL5/RANTES, CXCL9/MIG and CXCL10/IP-10 in the colonic mucosa of AOM/DSS treated mice. Confocal microscopy showed that ethanol feeding induces a dramatic elevation of myeloperoxidase, Gr1 and CD68-positive cells in the colonic mucosa of AOM/DSS-treated mice. Ethanol feeding enhanced AOM/DSS-induced suppression of tight junction protein expression and elevated cell proliferation marker, Ki-67 in the colonic epithelium. This study demonstrates that chronic ethanol feeding promotes colonic tumorigenesis potentially by enhancing inflammation and elevation of proinflammatory cytokines and chemokines

  6. In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc

    Science.gov (United States)

    McCanless, Jonathan D.

    Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

  7. Lumbar Facet Joint Compressive Injury Induces Lasting Changes in Local Structure, Nociceptive Scores, and Inflammatory Mediators in a Novel Rat Model

    Directory of Open Access Journals (Sweden)

    James L. Henry

    2012-01-01

    Full Text Available Objective. To develop a novel animal model of persisting lumbar facet joint pain. Methods. Sprague Dawley rats were anaesthetized and the right lumbar (L5/L6 facet joint was exposed and compressed to ~1 mm with modified clamps applied for three minutes; sham-operated and naïve animals were used as control groups. After five days, animals were tested for hind-paw sensitivity using von Frey filaments and axial deep tissue sensitivity by algometer on assigned days up to 28 days. Animals were sacrificed at selected times for histological and biochemical analysis. Results. Histological sections revealed site-specific loss of cartilage in model animals only. Tactile hypersensitivity was observed for the ipsi- and contralateral paws lasting 28 days. The threshold at which deep tissue pressure just elicited vocalization was obtained at three lumbar levels; sensitivity at L1>L3/4>L6. Biochemical analyses revealed increases in proinflammatory cytokines, especially TNF-α, IL-1α, and IL-1β. Conclusions. These data suggest that compression of a facet joint induces a novel model of local cartilage loss accompanied by increased sensitivity to mechanical stimuli and by increases in inflammatory mediators. This new model may be useful for studies on mechanisms and treatment of lumbar facet joint pain and osteoarthritis.

  8. Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory.

    Science.gov (United States)

    Lee, Vallent; MacKenzie, Georgina; Hooper, Andrew; Maguire, Jamie

    2016-10-01

    It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAA R) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells, whereas there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAA R δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAA R δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAA R δ subunit-mediated tonic inhibition

  9. Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory

    Science.gov (United States)

    Hooper, Andrew; Maguire, Jamie

    2016-01-01

    It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAAR) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells; whereas, there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAAR δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAAR δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAAR δ subunit-mediated tonic inhibition in

  10. Coronary artery calcification scores improve contrast-induced nephropathy risk assessment in chronic kidney disease patients.

    Science.gov (United States)

    Osugi, Naohiro; Suzuki, Susumu; Shibata, Yohei; Tatami, Yosuke; Harata, Shingo; Ota, Tomoyuki; Hayashi, Mutsuharu; Yasuda, Yoshinari; Ishii, Hideki; Shimizu, Atsuya; Murohara, Toyoaki

    2017-06-01

    Coronary artery calcification (CAC) is an independent predictor of cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. The aim of the present study was to evaluate the predictive value of CAC scores for the incidence of contrast-induced nephropathy (CIN) after cardiac catheterization in non-dialyzed CKD patients. The present study evaluated a total of 140 CKD patients who underwent cardiac catheterization. Patients were stratified into two groups based on the optimal cut-off value of the CAC score, which was graded by a non-triggered, routine diagnostic chest computed tomography scan: CAC score ≥8 (high CAC group); and CAC score 10 % in the baseline serum cystatin C level at 24 h after contrast administration. The mean estimated glomerular filtration rate levels were 41.1 mL/min/1.73 m 2 , and the mean contrast dose administered was 37.5 mL. Patients with high CAC scores exhibited a higher incidence of CIN than patients with low CAC scores (25.5 vs. 3.2 %, p < 0.001). After multivariate adjustment for confounders, the CAC score predicted CIN (odds ratio 1.68, 95 % confidence interval 1.28-2.21, p < 0.001). Moreover, the C-index for CIN prediction significantly increased when the CAC scores were added to the Mehran risk score (0.855 vs. 0.760, p = 0.023). CAC scores, as evaluated using semi-quantitative methods, are a simple and powerful predictor of CIN. Incorporating the CAC score in the Mehran risk score significantly improved the predictive ability to predict CIN incidence.

  11. Mechanism of subdural effusion evolves into chronic subdural hematoma: IL-8 inducing neutrophil oxidative burst.

    Science.gov (United States)

    Tao, Zhiqiang; Lin, Yingying; Hu, Maotong; Ding, Shenghong; Li, Jianwei; Qiu, Yongming

    2016-01-01

    Chronic subdural hematoma (CSDH) is still a mysterious disease. Though great success has been has achieved by neuro-surgery treatment, the origin and development of CSDH remains unknown. Tremendous clinical observations have found the correlation of subdural effusion (SDE) and CSDH. However, systematic elucidation of CSDH's origin and progression is lacking while almost all the current hypothesis only explained partial phenomenon. This hypothesis proposes Interleukin (IL)-8 inducing neutrophil respiratory burst is the crucial impact when SDE evolves into CSDH. IL-8 initially secreted by dural border layer cells, accumulates and the concentration of IL-8 rises in the SDE cavity. Accompanied by the formation of neo-membrane under the dura meninges, IL-8 firstly prompts to establish the neo-vasculature in it, and then attracts lymphocytes aggregation in the neo-membrane. Both the newly recruited lymphocytes and endothelial cells assist the further elevation of local IL-8 concentration. When the IL-8 concentration elevated to a particular level, it attracts neutrophils to the inner wall of neo-vessels and primes them to oxidative burst. Lysosomes and superoxide released by these neutrophils make the fragile neo-capillary became leaky, and subsequently the plasma and blood cells run into SDE. However, as long as the erythrocytes come into the cavity, they shall bind large quantity of IL-8 and decrease IL-8 concentration to a lower level relatively that reduce the neutrophils recruit. When this negative feedback is stagnancy, for example, the SDE space is so large in elder man who is experiencing brain atrophy, the neo-vessels have to release more erythrocytes to bind IL-8, the liquid cavity will expand and the high intracranial pressure symptoms appeared. Our hypothesis holds potential for the proper therapeutic intervention of CSDH. IL-8 antagonist and other anti-inflammation drugs like macrolides antibiotics, glucocorticoid and atorvastatin might be optional to resist

  12. Chronic Renin-Angiotensin System (RAS) Blockade May Not Induce Hypotension During Anaesthesia for Bariatric Surgery.

    Science.gov (United States)

    Salvetti, Guido; Di Salvo, Claudio; Ceccarini, Giovanni; Abramo, Antonio; Fierabracci, Paola; Magno, Silvia; Piaggi, Paolo; Vitti, Paolo; Santini, Ferruccio

    2016-06-01

    The use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) for the treatment of hypertensive obese patients is steadily increasing. Some studies have reported that the use of these drugs was associated with an increased risk of hypotensive episodes, during general anaesthesia. The number of bariatric procedures is also increasing worldwide, but there is a lack of studies investigating the hypotensive effect of renin-angiotensin system (RAS) blockers in severely obese patients during general anaesthesia for bariatric surgery. The aim of this pilot study was to evaluate hemodynamic changes induced by general anaesthesia in obese patients chronically treated with ACE-I or ARB compared to a control group not treated with antihypertensive therapy. Fourteen obese subjects (mean body mass index (BMI) 47.5 kg/m(2)) treated with ACE-I or ARB and twelve obese (mean BMI 45.7 kg/m2) controls not treated with antihypertensive therapy underwent general anaesthesia to perform laparoscopic bariatric surgery. Systolic blood pressure, diastolic blood pressure, and heart rate were monitored continuously and registered at different time points: T0 before induction, then at 2, 5, 7, 10, 15, 20, 30, 60, 90, 120, and 150 min after induction, and the last time point taken following recovery from anaesthesia. A progressive reduction of both systolic and diastolic blood pressure values was observed without significant differences between the two groups. A similar trend of heart rate values was observed. In conclusion, our pilot study suggests that RAS blockers may be continued during the perioperative period in patients undergoing bariatric surgery, without increasing the risk of hypotensive episodes.

  13. A Novel Natural Product, KL-21, Inhibits Proliferation and Induces Apoptosis in Chronic Lymphocytic Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Aysun Adan Gökbulut

    2015-06-01

    Full Text Available INTRODUCTION: The aims of this study were to examine the cytotoxic and apoptotic effects of KL-21, a novel plant product (produced by Naturin Natural Products, İzmir, Turkey, on 232B4 chronic lymphocytic leukemia (CLL cells and to determine the cytotoxic effects on healthy BEAS-2B human bronchial epithelial cells. METHODS: The cytotoxic effect of KL-21 was determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using the caspase-3 colorimetric assay. Changes in mitochondrial membrane potential were determined using the JC-1 dye-based method. Annexin V-FITC/PI double staining was performed to measure the apoptotic cell population. Effects of KL-21 on cell cycle profiles of CLL cells were investigated by flow cytometry. RESULTS: We detected time- and concentration-dependent increases in the cytotoxic effect of KL-21 on 232B4 CLL cells. However, we also showed that, especially at higher concentrations, KL-21 was less cytotoxic towards BEAS-2B healthy cells than towards CLL cells. Annexin-V/PI double staining results showed that the apoptotic cell population increased in 232B4 cells. Increasing concentrations of KL-21 increased caspase-3 enzyme activity and induced loss of mitochondrial membrane potential. KL-21 administration resulted in small increases in the percentage of the cells in the G0/G1 phase while it decreased the S phase cell population up to 1 mg/mL. At the highest concentration, most of the cells accumulated in the G0/G1 phase. DISCUSSION AND CONCLUSION: KL-21 has a growth-inhibitory effect on 232B4 CLL cells. KL-21 causes apoptosis and cell cycle arrest at G0/G1.

  14. Mechanism of vasoconstriction induced by chronic inhibition of nitric oxide in rats.

    Science.gov (United States)

    Bank, N; Aynedjian, H S; Khan, G A

    1994-09-01

    Either acute or chronic inhibition of nitric oxide synthesis by L-arginine analogues results in increases in mean arterial pressure and reductions in renal blood flow. The role of endogenous vasoconstrictors in mediating these effects is not entirely clear. In the present study, nitric oxide was inhibited in male Sprague-Dawley rats by oral administration of nitro-L-arginine for 3 weeks. At the end of this time, mean arterial pressure was 30 to 40 mm Hg higher than in normal controls, renal blood flow and glomerular filtration rate were 25% to 30% lower, and renal vascular resistance was markedly increased. Intravenous infusion of receptor antagonists for angiotensin II, thromboxane, epinephrine, and endothelin-1 had no significant effect on the hypertension. Inhibition of prostaglandin synthesis and furosemide-induced diuresis in the presence of angiotensin blockade also had no effect on blood pressure. Renal vascular resistance was also unaffected by these interventions, except that saralasin did reduce renal resistance in both control and nitric oxide-inhibited groups. However, the absolute level of renal vascular resistance remained higher in the latter group. Calcium channel blockade partially corrected blood pressure and renal resistance, but the levels remained significantly higher than in control animals. The findings are consistent with the view that the increase in vascular smooth muscle tone caused by inhibition of nitric oxide synthesis cannot be accounted for by overexpression of common endogenous vasoconstrictors. Rather, the generalized increase in vascular smooth muscle tone appears to be due to a direct effect of reduced nitric oxide availability, which may lead to an increase in intracellular calcium concentration or sensitivity.

  15. Estimating chronic wasting disease susceptibility in cervids using real-time quaking-induced conversion.

    Science.gov (United States)

    Haley, Nicholas J; Rielinger, Rachel; Davenport, Kristen A; O'Rourke, Katherine; Mitchell, Gordon; Richt, Jürgen A

    2017-11-01

    In mammals, susceptibility to prion infection is primarily modulated by the host's cellular prion protein (PrP C ) sequence. In the sheep scrapie model, a graded scale of susceptibility has been established both in vivo and in vitro based on PrP C amino acids 136, 154 and 171, leading to global breeding programmes to reduce the prevalence of scrapie in sheep. Chronic wasting disease (CWD) resistance in cervids is often characterized as decreased prevalence and/or protracted disease progression in individuals with specific alleles; at present, no PrP C allele conferring absolute resistance in cervids has been identified. To model the susceptibility of various naturally occurring and hypothetical cervid PrP C alleles in vitro, we compared the amplification rates and amyloid extension efficiencies of eight distinct CWD isolates in recombinant cervid PrP C substrates using real-time quaking-induced conversion. We hypothesized that the in vitro conversion characteristics of these isolates in cervid substrates would correlate to in vivo susceptibility - permitting susceptibility prediction for the rare alleles found in nature. We also predicted that hypothetical alleles with multiple resistance-associated codons would be more resistant to in vitro conversion than natural alleles with a single resistant codon. Our studies demonstrate that in vitro conversion metrics align with in vivo susceptibility, and that alleles with multiple amino acid substitutions, each influencing resistance independently, do not necessarily contribute additively to conversion resistance. Importantly, we found that the naturally occurring whitetail deer QGAK substrate exhibited the slowest amplification rate among those evaluated, suggesting that further investigation of this allele and its resistance in vivo is warranted.

  16. Overexpression of extracellular superoxide dismutase protects against brain injury induced by chronic hypoxia.

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    Nahla Zaghloul

    Full Text Available Extracellular superoxide dismutase (EC-SOD is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1% for 10 days (H-KI and compared to transgenic animals housed in room air (RA-KI, wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT. Overall brain metabolism evaluated by positron emission tomography (PET showed that H-WT mice had significantly higher uptake of 18FDG in the brain particularly the hippocampus, hypothalamus, and cerebellum. H-KI mice had comparable uptake to the RA-KI and RA-WT groups. To investigate the functional state of the hippocampus, electrophysiological techniques in ex vivo hippocampal slices were performed and showed that H-KI had normal synaptic plasticity, whereas H-WT were severely affected. Markers of oxidative stress, GFAP, IBA1, MIF, and pAMPK showed similar values in the H-KI and RA-WT groups, but were significantly increased in the H-WT group. Caspase-3 assay and histopathological studies showed significant apoptosis/cell damage in the H-WT group, but no significant difference in the H-KI group compared to the RA groups. The data suggest that EC-SOD has potential prophylactic and therapeutic roles in diseases with compromised brain oxygenation.

  17. Chronic postnatal stress induces voluntary alcohol intake and modifies glutamate transporters in adolescent rats.

    Science.gov (United States)

    Odeon, María Mercedes; Andreu, Marcela; Yamauchi, Laura; Grosman, Mauricio; Acosta, Gabriela Beatriz

    2015-01-01

    Postnatal stress alters stress responses for life, with serious consequences on the central nervous system (CNS), involving glutamatergic neurotransmission and development of voluntary alcohol intake. Several drugs of abuse, including alcohol and cocaine, alter glutamate transport (GluT). Here, we evaluated effects of chronic postnatal stress (CPS) on alcohol intake and brain glutamate uptake and transporters in male adolescent Wistar rats. For CPS from postnatal day (PD) 7, pups were separated from their mothers and exposed to cold stress (4 °C) for 1 h daily for 20 days; controls remained with their mothers. Then they were exposed to either voluntary ethanol (6%) or dextrose (1%) intake for 7 days (5-7 rats per group), then killed. CPS: (1) increased voluntary ethanol intake, (2) did not affect body weight gain or produce signs of toxicity with alcohol exposure, (3) increased glutamate uptake by hippocampal synaptosomes in vitro and (4) reduced protein levels (Western measurements) in hippocampus and frontal cortex of glial glutamate transporter-1 (GLT-1) and excitatory amino-acid transporter-3 (EAAT-3) but increased glutamate aspartate transporter (GLAST) levels. We propose that CPS-induced decrements in GLT-1 and EAAT-3 expression levels are opposed by activation of a compensatory mechanism to prevent excitotoxicity. A greater role for GLAST in total glutamate uptake to prevent enlarged extracellular glutamate levels is inferred. Although CPS strongly increased intake of ethanol, this had little impact on effects of CPS on brain glutamate uptake or transporters. However, the impact of early life adverse events on glutamatergic neurotransmission may underlie increased alcohol consumption in adulthood.

  18. Having your cake and eating it too: a habit of comfort food may link chronic social stress exposure and acute stress-induced cortisol hyporesponsiveness.

    Science.gov (United States)

    Tryon, M S; DeCant, Rashel; Laugero, K D

    2013-04-10

    Stress has been tied to changes in eating behavior and food choice. Previous studies in rodents have shown that chronic stress increases palatable food intake which, in turn, increases visceral fat and inhibits acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity. The effect of chronic stress on eating behavior in humans is less understood, but it may be linked to HPA responsivity. The purpose of this study was to investigate the influence of chronic social stress and acute stress reactivity on food choice and food intake. Forty-one women (BMI=25.9±5.1 kg/m(2), age range=41 to 52 years) were subjected to the Trier Social Stress Test or a control task (nature movie) to examine HPA responses to an acute laboratory stressor and then invited to eat from a buffet containing low- and high-calorie snacks. Women were also categorized as high chronic stress or low chronic stress based on Wheaton Chronic Stress Inventory scores. Women reporting higher chronic stress and exhibiting low cortisol reactivity to the acute stress task consumed significantly more calories from chocolate cake on both stress and control visits. Chronic stress in the low cortisol reactor group was also positively related to total fat mass, body fat percentage, and stress-induced negative mood. Further, women reporting high chronic stress consumed significantly less vegetables, but only in those aged 45 years and older. Chronic stress in women within the higher age category was positively related to total calories consumed at the buffet, stress-induced negative mood and food craving. Our results suggest an increased risk for stress eating in persons with a specific chronic stress signature and imply that a habit of comfort food may link chronic social stress and acute stress-induced cortisol hyporesponsiveness. Published by Elsevier Inc.

  19. Physical Activity Protects the Human Brain against Metabolic Stress Induced by a Postprandial and Chronic Inflammation

    NARCIS (Netherlands)

    Pruimboom, Leo; Raison, Charles L.; Muskiet, Frits A. J.

    2015-01-01

    In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often

  20. Nilotinib induced avascular necrosis of femoral head in an adult chronic myeloid leukemia patient.

    Science.gov (United States)

    Thekkudan, Shinto Francis; Nityanand, Soniya

    2018-06-01

    We report a rare case of avascular necrosis of femoral head (AVNFH) in an adult chronic myeloid leukemia - chronic phase (CML-CP) patient during due course of therapy with second line Tyrosine Kinase Inhibitor (TKI), Nilotinib. A high index of clinical suspicion should be kept in any symptomatic CML patient on TKI's.

  1. Trachlight management of succinylcholine-induced subluxation of the Temporo-mandibular joint: a case report and review of the literature.

    Science.gov (United States)

    Roze des Ordons, Amanda; Townsend, Derek R

    2008-09-01

    We present a case of spontaneous subluxation of the Temporo-mandibular joint (TMJ) induced by succinylcholine, to compare our experience with previous cases reported in the literature, and to review the pathophysiology, preoperative screening, and intraoperative management of TMJ instability. A 39-yr-old female with primary hyperparathyroidism and a normal airway examination presented for elective parathyroidectomy. Following induction of anesthesia and the administration of succinylcholine prior to jaw manipulation, her mouth could not be opened, and we suspected spontaneous subluxation of the TMJ. We secured the airway with the use of a Trachlight and, subsequently, reduced the joint. Postoperatively, a history of mild TMJ-related symptoms was elicited. Instability of the TMJ is not uncommon, and has several implications for airway management, highlighting the importance of preoperative screening. Limited mouth opening, due to spontaneous subluxation of the TMJ following succinylcholine-induced muscle relaxation in the absence of airway manipulation, has only twice been reported in the literature. This report highlights how tracheal intubation may be accomplished using the Trachlight, in order to secure the airway prior to reduction of the subluxed joint.

  2. Radiosynoviorthesis in haemaphilic joint disease

    International Nuclear Information System (INIS)

    Pad Bosch, P.J.I. van't; Putte, L.B.A. van de; Boerbooms, A.M.T.; Geerdink, P.J.

    1981-01-01

    The effects of radiosynoviorthesis on chronic haemophilic arthropathic joints were studied in six patients with severe haemophilia by a follow up study which spanned two and a half years. On clinical grounds the treatment was successful because pain and bleeding frequency diminished, although radiographic examination showed further deterioration of the treated joint. Chromosome damage was not detected. We conclude that radiosynoviorthesis is apparently changing the bleeding pattern of articular tissues without arresting the destruction and deformation of joints. (orig.) [de

  3. Chronic sleep restriction induces long-lasting changes in adenosine and noradrenaline receptor density in the rat brain.

    Science.gov (United States)

    Kim, Youngsoo; Elmenhorst, David; Weisshaupt, Angela; Wedekind, Franziska; Kroll, Tina; McCarley, Robert W; Strecker, Robert E; Bauer, Andreas

    2015-10-01

    Although chronic sleep restriction frequently produces long-lasting behavioural and physiological impairments in humans, the underlying neural mechanisms are unknown. Here we used a rat model of chronic sleep restriction to investigate the role of brain adenosine and noradrenaline systems, known to regulate sleep and wakefulness, respectively. The density of adenosine A1 and A2a receptors and β-adrenergic receptors before, during and following 5 days of sleep restriction was assessed with autoradiography. Rats (n = 48) were sleep-deprived for 18 h day(-1) for 5 consecutive days (SR1-SR5), followed by 3 unrestricted recovery sleep days (R1-R3). Brains were collected at the beginning of the light period, which was immediately after the end of sleep deprivation on sleep restriction days. Chronic sleep restriction increased adenosine A1 receptor density significantly in nine of the 13 brain areas analysed with elevations also observed on R3 (+18 to +32%). In contrast, chronic sleep restriction reduced adenosine A2a receptor density significantly in one of the three brain areas analysed (olfactory tubercle which declined 26-31% from SR1 to R1). A decrease in β-adrenergic receptors density was seen in substantia innominata and ventral pallidum which remained reduced on R3, but no changes were found in the anterior cingulate cortex. These data suggest that chronic sleep restriction can induce long-term changes in the brain adenosine and noradrenaline receptors, which may underlie the long-lasting neurocognitive impairments observed in chronic sleep restriction. © 2015 European Sleep Research Society.

  4. Pain in the hip joint

    Directory of Open Access Journals (Sweden)

    Yuri Aleksandrovich Olyunin

    2013-01-01

    Full Text Available Pathological changes that develop in the hip joints (HJ have different origins and mechanisms of development, but their main manifestation is pain. The nature of this pain cannot be well established on frequent occasions. The English-language medical literature currently classifies such disorders as greater trochanter pain syndrome (GTPS. Its major signs are chronic pain and local palpatory tenderness in the outer part of HJ. The development of GTPS may be associated with inflammation of the synovial bursae situated in the greater tronchanter, as well as with tendinitis, myorrhexis, iliotibial band syndrome, and other local changes in the adjacent tissues or with systemic diseases. So GTPS may be characterized as regional pain syndrome that frequently mimics pain induced by different diseases, including myofascial pain syndrome, osteoarthrosis, spinal diseases, etc.

  5. Metabolically induced liver inflammation leads to NASH and differs from LPS-or IL-1β-induced chronic inflammation

    NARCIS (Netherlands)

    Liang, W.; Lindeman, J.H.; Menke, A.L.; Koonen, D.P.; Morrison, M.; Havekes, L.M.; Hoek, A.M. van den; Kleemann, R.

    2014-01-01

    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β

  6. Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1 beta-induced chronic inflammation

    NARCIS (Netherlands)

    Liang, Wen; Lindeman, Jan H.; Menke, Aswin L.; Koonen, Debby P.; Morrison, Martine; Havekes, Louis M.; van den Hoek, Anita M.; Kleemann, Robert

    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1 beta

  7. Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency.

    Science.gov (United States)

    Regadas, Rommel Prata; Reges, Ricardo; Cerqueira, João Batista Gadelha; Sucupira, Daniel Gabrielle; Jamacaru, Francisco Vagnaldo F; Moraes, Manoel Odorico de; Gonzaga-Silva, Lúcio Flávio

    2014-01-01

    The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME); 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles.

  8. Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

    Directory of Open Access Journals (Sweden)

    Rommel Prata Regadas

    2014-08-01

    Full Text Available Purpose The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO induced by chronic nitric oxide deficiency. Materials and Methods Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME; 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days, all animals were submitted to urodynamic study. Results The administration of L-NAME increased the number of non-voiding contractions (NVC (1.04 ± 0.22, volume threshold (VT (1.86 ± 0.35, and micturition cycle (MC (1.34 ± 0.11 compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30, respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42 and VT (0.76 ± 0.24 compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53 and MC (0.76 ± 0.22 compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18, VT (0.97 ± 0.52 and MC (0.68 ± 0.30 compared with L-NAME group. Conclusion In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles.

  9. Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits.

    Science.gov (United States)

    Bhagya, Venkanna Rao; Srikumar, Bettadapura N; Veena, Jayagopalan; Shankaranarayana Rao, Byrathnahalli S

    2017-08-01

    Exposure to prolonged stress results in structural and functional alterations in the hippocampus including reduced long-term potentiation (LTP), neurogenesis, spatial learning and working memory impairments, and enhanced anxiety-like behavior. On the other hand, enriched environment (EE) has beneficial effects on hippocampal structure and function, such as improved memory, increased hippocampal neurogenesis, and progressive synaptic plasticity. It is unclear whether exposure to short-term EE for 10 days can overcome restraint stress-induced cognitive deficits and impaired hippocampal plasticity. Consequently, the present study explored the beneficial effects of short-term EE on chronic stress-induced impaired LTP, working memory, and anxiety-like behavior. Male Wistar rats were subjected to chronic restraint stress (6 hr/day) over a period of 21 days, and then they were exposed to EE (6 hr/day) for 10 days. Restraint stress reduced hippocampal CA1-LTP, increased anxiety-like symptoms in elevated plus maze, and impaired working memory in T-maze task. Remarkably, EE facilitated hippocampal LTP, improved working memory performance, and completely overcame the effect of chronic stress on anxiety behavior. In conclusion, exposure to EE can bring out positive effects on synaptic plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. [A comparative study on behaviors of two depression models in rats induced by chronic forced swimming stress].

    Science.gov (United States)

    Han, Ming-Fei; Gao, Dong; Sun, Xue-Li

    2010-01-01

    To compare the behaviors of rats with depressions induced by chronic forced swimming stress under two different conditions. Eighteen male rats were randomly divided into 3 groups, with 6 rats in each group. The rats in the control group (C group) were not forced into swimming, while the rats in the stress groups (S1 and S2) were forced to swim for 14 consecutive days. The rats in S1 group and S2 group swam for five minutes every morning, in water with (23 +/- 1) degree C, and (10 +/- 0.5) degree C in temperature, respectively. The weight gain, food intake, open-field test and saccharin solution test were observed on the seventh day and fourteenth day. On the seventh day following chronic swim stress, the rats in the S2 group had significant lower ratio in weight gain and food intake than the controls (P forced swimming. On the fourteenth day, the rats in the S1 group still had lower ratio in weight gain, but had higher ratio in food intake and preference for saccharin solution, and greater number of crossing than the controls. Chronic forced swimming at a lower temperature could induce depression better than at a higher temperature.

  11. Chronic exposure to low concentrations of lead induces metabolic disorder and dysbiosis of the gut microbiota in mice.

    Science.gov (United States)

    Xia, Jizhou; Jin, Cuiyuan; Pan, Zihong; Sun, Liwei; Fu, Zhengwei; Jin, Yuanxiang

    2018-08-01

    Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that can contaminate food and water. In this study, effects of chronic exposure to low concentrations of Pb on metabolism and gut microbiota were evaluated in mice. It was observed that exposure of mice to 0.1mg/L Pb, supplied via drinking water, for 15weeks increased hepatic TG and TCH levels. The levels of some key genes related to lipid metabolism in the liver increased significantly in Pb-treated mice. For the gut microbiota, at the phylum level, the relative abundance of Firmicutes and Bacteroidetes changed obviously in the feces and the cecal contents of mice exposed to 0.1mg/L Pb for 15weeks. In addition, 16s rRNA gene sequencing further discovered that Pb exposure affected the structure and richness of the gut microbiota. Moreover, a 1 H NMR metabolic analysis unambiguously identified 31 metabolites, and 15 metabolites were noticeably altered in 0.1mg/L Pb-treated mice. Taken together, the data indicate that chronic Pb exposure induces dysbiosis of the gut microbiota and metabolic disorder in mice. Chronic Pb exposure induces metabolic disorder, dysbiosis of the gut microbiota and hepatic lipid metabolism disorder in mice. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. New therapeutic aspect for carvedilol: Antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage

    International Nuclear Information System (INIS)

    Hamdy, Nadia; El-Demerdash, Ebtehal

    2012-01-01

    Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-κB). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-κB expression and finally HSC activation. -- Highlights: ► Carvedilol is a beta blocker with antioxidant and antifibrotic

  13. New therapeutic aspect for carvedilol: Antifibrotic effects of carvedilol in chronic carbon tetrachloride-induced liver damage

    Energy Technology Data Exchange (ETDEWEB)

    Hamdy, Nadia [Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); El-Demerdash, Ebtehal, E-mail: ebtehal_dm@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-06-15

    Portal hypertension is a common complication of chronic liver diseases associated with liver fibrosis and cirrhosis. At present, beta-blockers such as carvedilol remain the medical treatment of choice for protection against variceal bleeding and other complications. Since carvedilol has powerful antioxidant properties we assessed the potential antifibrotic effects of carvedilol and the underlying mechanisms that may add further benefits for its clinical usefulness using a chronic model of carbon tetrachloride (CCl4)-induced hepatotoxicity. Two weeks after CCl4 induction of chronic hepatotoxicity, rats were co-treated with carvedilol (10 mg/kg, orally) daily for 6 weeks. It was found that treatment of animals with carvedilol significantly counteracted the changes in liver function and histopathological lesions induced by CCl4. Also, carvedilol significantly counteracted lipid peroxidation, GSH depletion, and reduction in antioxidant enzyme activities; glutathione-S-transferase and catalase that was induced by CCl4. In addition, carvedilol ameliorated the inflammation induced by CCl4 as indicated by reducing the serum level of acute phase protein marker; alpha-2-macroglobulin and the liver expression of nuclear factor-kappa B (NF-κB). Finally, carvedilol significantly reduced liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cell (HSC) activation marker; alpha smooth muscle actin. In conclusion, the present study provides evidences for the promising antifibrotic effects of carvedilol that can be explained by amelioration of oxidative stress through mainly, replenishment of GSH, restoration of antioxidant enzyme activities and reduction of lipid peroxides as well as amelioration of inflammation and fibrosis by decreasing collagen accumulation, acute phase protein level, NF-κB expression and finally HSC activation. -- Highlights: ► Carvedilol is a beta blocker with antioxidant and antifibrotic

  14. Music-induced analgesia in chronic pain conditions: a systematic review and meta- analysis

    DEFF Research Database (Denmark)

    Garza-Villarreal, Eduardo A.; Pando, Victor; Vuust, Peter

    2017-01-01

    Background: Music is increasingly used as an adjuvant for chronic pain management as it is non-invasive, inexpensive, and patients usually report positive experiences with it. However, little is known about its clinical efficacy in chronic pain patients. Objectives: We aimed to determine the effect...... of music as an adjuvant for chronic pain, as well as to identify characteristics of music interventions associated wit positive clinical outcomes. Study Design: In this systematic review and meta-analysis, we investigated randomized controlled trials (RCTs) of adult patients that reported any type of music...... 14 RTCs that fulfilled our criteria. The sample size of the studies varied between 25 and 200 participants. Results: We found that music reduced self-reported chronic pain and depressive symptoms. We also found music had a greater effect when the participant chose the music compared to when...

  15. Can mesenchymal stem cells reverse chronic stress-induced impairment of lung healing following traumatic injury?

    Science.gov (United States)

    Gore, Amy V; Bible, Letitia E; Livingston, David H; Mohr, Alicia M; Sifri, Ziad C

    2015-04-01

    One week following unilateral lung contusion (LC), rat lungs demonstrate full histologic recovery. When animals undergo LC plus the addition of chronic restraint stress (CS), wound healing is significantly delayed. Mesenchymal stem cells (MSCs) are pluripotent cells capable of immunomodulation, which have been the focus of much research in wound healing and tissue regeneration. We hypothesize that the addition of MSCs will improve wound healing in the setting of CS. Male Sprague-Dawley rats (n = 6-7 per group) were subjected to LC/CS with or without the injection of MSCs. MSCs were given as a single intravenous dose of 5 × 10 cells in 1 mL Iscove's Modified Dulbecco's Medium at the time of LC. Rats were subjected to 2 hours of restraint stress on Days 1 to 6 following LC. Seven days following injury, rats were sacrificed, and the lungs were examined for histologic evidence of wound healing using a well-established histologic lung injury score (LIS) to grade injury. LIS examines inflammatory cells/high-power field (HPF) averaged over 30 fields, interstitial edema, pulmonary edema, and alveolar integrity, with scores ranging from 0 (normal) to 11 (highly damaged). Peripheral blood was analyzed by flow cytometry for the presence of T-regulatory (C4CD25FoxP3) cells. Data were analyzed by analysis of variance followed by Tukey's multiple comparison test, expressed as mean (SD). As previously shown, 7 days following isolated LC, LIS has returned to 0.83 (0.41), with a subscore of zero for inflammatory cells/HPF. The addition of CS results in an LIS of 4.4 (2.2), with a subscore of 1.9 (0.7) for inflammatory cells/HPF. Addition of MSC to LC/CS decreased LIS to 1.7 (0.8), with a subscore of zero for inflammatory cells/HPF. Furthermore, treatment of animals undergoing LC/CS with MSCs increased the %T-regulatory cells by 70% in animals undergoing LC/CS alone (12.9% [2.4]% vs. 6.2% [1.3%]). Stress-induced impairment of wound healing is reversed by the addition of MSCs given

  16. A rat model of chronic syringomyelia induced by epidural compression of the lumbar spinal cord.

    Science.gov (United States)

    Lee, Ji Yeoun; Kim, Shin Won; Kim, Saet Pyoul; Kim, Hyeonjin; Cheon, Jung-Eun; Kim, Seung-Ki; Paek, Sun Ha; Pang, Dachling; Wang, Kyu-Chang

    2017-10-01

    OBJECTIVE There has been no established animal model of syringomyelia associated with lumbosacral spinal lipoma. The research on the pathophysiology of syringomyelia has been focused on Chiari malformation, trauma, and inflammation. To understand the pathophysiology of syringomyelia associated with occult spinal dysraphism, a novel animal model of syringomyelia induced by chronic mechanical compression of the lumbar spinal cord was created. METHODS The model was made by epidural injection of highly concentrated paste-like kaolin solution through windows created by partial laminectomy of L-1 and L-5 vertebrae. Behavioral outcome in terms of motor (Basso-Beattie-Bresnahan score) and urinary function was assessed serially for 12 weeks. Magnetic resonance images were obtained in some animals to confirm the formation of a syrinx and to monitor changes in its size. Immunohistochemical studies, including analysis for glial fibrillary acidic protein, NeuN, CC1, ED-1, and caspase-3, were done. RESULTS By 12 weeks after the epidural compression procedure, syringomyelia formation was confirmed in 85% of the rats (34 of 40) on histology and/or MRI. The syrinx cavities were found rostral to the epidural compression. Motor deficit of varying degrees was seen immediately after the procedure in 28% of the rats (11 of 40). In 13 rats (33%), lower urinary tract dysfunction was seen. Motor deficit improved by 5 weeks after the procedure, whereas urinary dysfunction mostly improved by 2 weeks. Five rats (13%, 5 of 40) died 1 month postoperatively or later, and 3 of the 5 had developed urinary tract infection. At 12 weeks after the operation, IHC showed no inflammatory process, demyelination, or accelerated apoptosis in the spinal cords surrounding the syrinx cavities, similar to sham-operated animals. CONCLUSIONS A novel experimental model for syringomyelia by epidural compression of the lumbar spinal cord has been created. The authors hope that it will serve as an important research

  17. Contrast-induced nephropathy in patients with chronic kidney disease and peripheral arterial disease

    International Nuclear Information System (INIS)

    Kroneberger, Christian; Enzweiler, Christian N; Schmidt-Lucke, Andre; Rückert, Ralph-Ingo; Teichgräber, Ulf; Franiel, Tobias

    2015-01-01

    The risk for contrast-induced nephropathy (CIN) after intra-arterial application of an iodine-based contrast material is unknown for patients with chronic kidney disease (CKD) and peripheral arterial disease (PAD). To investigate the incidence of CIN in patients with CKD and PAD. This retrospective study was approved by the local ethics committee. One hundred and twenty patients with 128 procedures (73 with baseline eGFR in the range of 45–60 mL/min/1.73m 2 , 55 with eGFR < 45 mL/min/1.73m 2 ) were evaluated. All patients received intra-arterially an iodine-based low-osmolar contrast material (CM) after adequate intravenous hydration with isotonic NaCl 0.9% solution. CIN was defined as an increase in serum creatinine of more than 44 μmol/L within 4 days. The influence of patient-related risk factors (age, weight, body mass index, eGFR, serum creatinine, hypertension, diabetes mellitus, coronary heart disease, heart failure) and therapy-related risk factors (amount of CM, nephrotoxic drugs, number of CM applications) on CIN were examined. CIN developed in 0% (0/73) of procedures in patients with PAD and an eGFR in the range of 45–60 mL/min/1.73m 2 and in 10.9% (6/55) of procedures in patients with an eGFR <45 mL/min/1.73m 2 . No risk factor significantly influenced the development of CIN, although baseline serum creatinine (P = 0.06) and baseline eGFR (P = 0.10) showed a considerable dependency. Patients with an eGFR in the range of 45–60 mL/min/1.73m 2 and PAD seem not at risk for CIN after intra-arterial CM application and adequate hydration. Whereas, an eGFR < 45 mL/min/1.73m 2 correlated with a risk of 10.9% for a CIN

  18. Protective effects of antidepressants against chronic fatigue syndrome-induced behavioral changes and biochemical alterations.

    Science.gov (United States)

    Kumar, Anil; Garg, Ruchika

    2009-02-01

    Chronic fatigue syndrome (CFS) is characterized by profound fatigue, which substantially interferes with daily activities. The aim of this study was to explore the protective effects of antidepressants in an animal model of CFS in mice. Male albino mice were forced to swim individually for a period of 6-min session each for 7 days. Imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg) and citalopram (5 and 10 mg/kg) were administered 30 min before forced swimming test on each day. Various behavior tests (immobility time, locomotor activity, anxiety-like behavior by plus maze and mirror chamber) followed by biochemical parameters (lipid peroxidation, reduced glutathione, catalase and nitrite level) were assessed in chronic stressed mice. Chronic forced swimming for 7 days significantly caused increase in immobility period, impairment in locomotor activity, anxiety-like behavior, and oxidative stress (raised lipid peroxidation, nitrite activity and reduced glutathione and catalase activity) as compared with naïve mice (P immobility time, improved locomotor activity and anti-anxiety effect (in both plus maze and mirror chamber test), and attenuated oxidative stress in chronic stressed mice as compared with control (chronic fatigues) (P < 0.05). These results suggested that these drugs have protective effect and could be used in the management of chronic fatigue like conditions.

  19. Inducible expression of A Disintegrin and Metalloproteinase 8 in chronic periodontitis and gingival epithelial cells.

    Science.gov (United States)

    Aung, W P P; Chotjumlong, P; Pata, S; Montreekachon, P; Supanchart, C; Khongkhunthian, S; Sastraruji, T; Krisanaprakornkit, S

    2017-06-01

    The expression of A Disintegrin and Metalloproteinase 8 (ADAM8) is associated with several inflammatory diseases. Elevated ADAM8 levels have been shown in gingival crevicular fluid of patients with chronic periodontitis. The objective of this study was to investigate ADAM8 expression in chronic periodontitis tissues compared with that in normal tissues. ADAM8 expression and its inductive mechanism were examined in human gingival epithelial cells (HGECs) and human gingival fibroblasts. Total RNA and protein were extracted from gingival biopsies of 33 patients with chronic periodontitis and those of 23 healthy volunteers. ADAM8 mRNA and protein expression was analyzed by real-time polymerase chain reaction, immunoblotting and immunohistochemistry. ADAM8 expression in control and stimulated cells in the presence or absence of specific inhibitors for mitogen-activated protein kinase pathways was assayed by real-time polymerase chain reaction, immunoblotting, flow cytometry and immunofluorescence. ADAM8 mRNA and protein expression in chronic periodontitis tissues was significantly greater than that in normal tissues (p chronic periodontitis tissues (p chronic periodontitis tissues and localized within gingival epithelium, consistent with an upregulation of ADAM8 expression in F. nucleatum-stimulated HGECs, suggesting a possible role of ADAM8 in innate immunity of periodontal tissue. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Joint Inflammation and Early Degeneration Induced by High-Force Reaching Are Attenuated by Ibuprofen in an Animal Model of Work-Related Musculoskeletal Disorder

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Driban

    2011-01-01

    Full Text Available We used our voluntary rat model of reaching and grasping to study the effect of performing a high-repetition and high-force (HRHF task for 12 weeks on wrist joints. We also studied the effectiveness of ibuprofen, administered in the last 8 weeks, in attenuating HRHF-induced changes in these joints. With HRHF task performance, ED1+ and COX2+ cells were present in subchondral radius, carpal bones and synovium; IL-1alpha and TNF-alpha increased in distal radius/ulna/carpal bones; chondrocytes stained with Terminal deoxynucleotidyl Transferase- (TDT- mediated dUTP-biotin nick end-labeling (TUNEL increased in wrist articular cartilages; superficial structural changes (e.g., pannus and reduced proteoglycan staining were observed in wrist articular cartilages. These changes were not present in normal controls or ibuprofen treated rats, although IL-1alpha was increased in reach limbs of trained controls. HRHF-induced increases in serum C1,2C (a biomarker of collagen I and II degradation, and the ratio of collagen degradation to synthesis (C1,2C/CPII; the latter a biomarker of collage type II synthesis were also attenuated by ibuprofen. Thus, ibuprofen treatment was effective in attenuating HRHF-induced inflammation and early articular cartilage degeneration.

  1. A Model of Chronic Exposure to Unpredictable Mild Socio-Environmental Stressors Replicates Some Spaceflight-Induced Immunological Changes

    Directory of Open Access Journals (Sweden)

    Fanny Gaignier

    2018-05-01

    Full Text Available During spaceflight, astronauts face radiations, mechanical, and socio-environmental stressors. To determine the impact of chronic socio-environmental stressors on immunity, we exposed adult male mice to chronic unpredictable mild psychosocial and environmental stressors (CUMS model for 3 weeks. This duration was chosen to simulate a long flight at the human scale. Our data show that this combination of stressors induces an increase of serum IgA, a reduction of normalized splenic mass and tends to reduce the production of pro-inflammatory cytokines, as previously reported during or after space missions. However, CUMS did not modify major splenic lymphocyte sub-populations and the proliferative responses of splenocytes suggesting that these changes could be due to other factors such as gravity changes. Thus, CUMS, which is an easy to implement model, could contribute to deepen our understanding of some spaceflight-associated immune alterations and could be useful to test countermeasures.

  2. Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice.

    Science.gov (United States)

    Calas, André-Guilhem; Richard, Olivier; Même, Sandra; Beloeil, Jean-Claude; Doan, Bich-Thuy; Gefflaut, Thierry; Même, William; Crusio, Wim E; Pichon, Jacques; Montécot, Céline

    2008-07-01

    Glufosinate-ammonium (GLA), the active compound of a worldwide-used herbicide, acts by inhibiting the plant glutamine synthetase (GS) leading to a lethal accumulation of ammonia. GS plays a pivotal role in the mammalian brain where it allows neurotransmitter glutamate recycling within astroglia. Clinical studies report that an acute GLA ingestion induces convulsions and memory impairment in humans. Toxicological studies performed at doses used for herbicidal activity showed that GLA is probably harmless at short or medium range periods. However, effects of low doses of GLA on chronically exposed subjects are not known. In our study, C57BL/6J mice were treated during 10 weeks three times a week with 2.5, 5 and 10mg/kg of GLA. Effects of this chronic treatment were assessed at behavioral, structural and metabolic levels by using tests of spatial memory, locomotor activity and anxiety, hippocampal magnetic resonance imaging (MRI) texture analysis, and hippocampal GS activity assay, respectively. Chronic GLA treatments have effects neither on anxiety nor on locomotor activity of mice but at 5 and 10mg/kg induce (1) mild memory impairments, (2) a modification of hippocampal texture and (3) a significant increase in hippocampal GS activity. It is suggested that these modifications may be causally linked one to another. Since glutamate is the main neurotransmitter in hippocampus where it plays a crucial role in spatial memory, hippocampal MRI texture and spatial memory alterations might be the consequences of hippocampal glutamate homeostasis modification revealed by increased GS activity in hippocampus. The present study provides the first data that show cerebral alterations after chronic exposure to GLA.

  3. TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation

    Directory of Open Access Journals (Sweden)

    Belarbi Karim

    2012-01-01

    Full Text Available Abstract Background Chronic neuroinflammation is a hallmark of several neurological disorders associated with cognitive loss. Activated microglia and secreted factors such as tumor necrosis factor (TNF-α are key mediators of neuroinflammation and may contribute to neuronal dysfunction. Our study was aimed to evaluate the therapeutic potential of a novel analog of thalidomide, 3,6'-dithiothalidomide (DT, an agent with anti-TNF-α activity, in a model of chronic neuroinflammation. Methods Lipopolysaccharide or artificial cerebrospinal fluid was infused into the fourth ventricle of three-month-old rats for 28 days. Starting on day 29, animals received daily intraperitoneal injections of DT (56 mg/kg/day or vehicle for 14 days. Thereafter, cognitive function was assessed by novel object recognition, novel place recognition and Morris water maze, and animals were euthanized 25 min following water maze probe test evaluation. Results Chronic LPS-infusion was characterized by increased gene expression of the proinflammatory cytokines TNF-α and IL-1β in the hippocampus. Treatment with DT normalized TNF-α levels back to control levels but not IL-1β. Treatment with DT attenuated the expression of TLR2, TLR4, IRAK1 and Hmgb1, all genes involved in the TLR-mediated signaling pathway associated with classical microglia activation. However DT did not impact the numbers of MHC Class II immunoreactive cells. Chronic neuroinflammation impaired novel place recognition, spatial learning and memory function; but it did not impact novel object recognition. Importantly, treatment with DT restored cognitive function in LPS-infused animals and normalized the fraction of hippocampal neurons expressing the plasticity-related immediate-early gene Arc. Conclusion Our data demonstrate that the TNF-α synthesis inhibitor DT can significantly reverse hippocampus-dependent cognitive deficits induced by chronic neuroinflammation. These results suggest that TNF-α is a

  4. Cannabinoid receptor 2 agonist attenuates pain related behavior in rats with chronic alcohol/high fat diet induced pancreatitis.

    Science.gov (United States)

    Zhang, Liping; Kline, Robert H; McNearney, Terry A; Johnson, Michael P; Westlund, Karin N

    2014-11-17

    Chronic Pancreatitis (CP) is a complex and multifactorial syndrome. Many contributing factors result in development of dysfunctional pain in a significant number of patients. Drugs developed to treat a variety of pain states fall short of providing effective analgesia for patients with chronic pancreatitis, often providing minimal to partial pain relief over time with significant side effects. Recently, availability of selective pharmacological tools has enabled great advances in our knowledge of the role of the cannabinoid receptors in pathophysiology. In particular, cannabinoid receptor 2 (CB2) has emerged as an attractive target for management of chronic pain, as demonstrated in several studies with inflammatory and neuropathic preclinical pain models. In this study, the analgesic efficacy of a novel, highly selective CB2 receptor agonist, LY3038404 HCl, is investigated in a chronic pancreatitis pain model, induced with an alcohol/high fat (AHF) diet. Rats fed the AHF diet developed visceral pain-like behaviors detectable by week 3 and reached a maximum at week 5 that persists as long as the diet is maintained. Rats with AHF induced chronic pancreatitis were treated with LY3038404 HCl (10 mg/kg, orally, twice a day for 9 days). The treated animals demonstrated significantly alleviated pain related behaviors after 3 days of dosing, including increased paw withdrawal thresholds (PWT), prolonged abdominal withdrawal latencies (ABWL), and decreased nocifensive responses to noxious 44°C hotplate stimuli. Terminal histological analysis of pancreatic tissue sections from the AHF chronic pancreatitis animals demonstrated extensive injury, including a global pancreatic gland degeneration (cellular atrophy), vacuolization (fat deposition), and fibrosis. After the LY3038404 HCl treatment, pancreatic tissue was significantly protected from severe damage and fibrosis. LY3038404 HCl affected neither open field exploratory behaviors nor dark/light box preferences as measures

  5. Therapeutic effects of Qian-Yu decoction and its three extracts on carrageenan-induced chronic prostatitis/chronic pelvic pain syndrome in rats.

    Science.gov (United States)

    Zhang, Keda; Zeng, Xiaobin; Chen, Yonggang; Zhao, Rong; Wang, Hui; Wu, Jinhu

    2017-01-25

    Qian-Yu decoction (QYD) is a traditional Chinese medicinal recipe composed of Radix astragali (Astragalus membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P.K. Hsiao, Fabaceae ), Herba epimedii (Epimedium brevicornum Maxim., Berberidaceae), Herba leonuri (Leonurus japonicus Houtt., Lamiaceae), Cortex phellodendri (Phellodendron chinense Schneid., Rutaceae) and Radix achyranthis bidentatae (Achyranthes bidentata Bl., Amaranthaceae). This study aimed to evaluate the therapeutic activity of QYD against carrageenan-induced chronic prostatic/chronic pelvic pain syndrome (CP/CPPS) in rats and further elucidate its effective components. Three types of components, total polysaccharides, total flavonoids and total saponins were separately extracted from QYD. Carrageenan-induced CP/CPPS rats were intragastrically administered with lyophilized product of QYD, individual extracts and all the combined forms of extracts for three weeks. Prostatic index (PI) was determined and histopathological analysis was performed. The levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PEG2) in rat prostate tissues were measured using ELISA. The production of inducible nitric oxide synthase (iNOS) was evaluated by an enzymatic activity assay, and the release of nitric oxide (NO) was determined by a nitrate/nitrite assay. Treatment with QYD significantly ameliorated the histological changes of CP/CPPS rats and reduced the PI by 44.3%, with a marked downregulation of TNF-α (42.8% reduction), IL-1β (45.3%), COX-2 (36.6%), PGE2 (44.2%), iNOS (54.1%) and NO (46.0%). Each of three extracts attenuated the symptom of CP/CPPS, but much more weakly than QYD. The combined administration of three extracts showed efficacy comparable to that of QYD while better than that of any combination of two extracts. A principal component analysis of the six inflammatory mediators as variables indicated that the effects of TS on CP

  6. Molecular monitoring of equine joint homeostasis

    NARCIS (Netherlands)

    de Grauw, J.C.

    2010-01-01

    Chronic joint disorders are a major cause of impaired mobility and loss of quality of life in both humans and horses. Regardless of the primary insult, any joint disorder is characterized by an upset in normal joint homeostasis, the balance between tissue anabolism and catabolism that is normally

  7. THERAPEUTIC EFFECTIVENESS OF THORACIC FACET JOINT INTERVENTIONS IN CHRONIC THORACIC PAIN%X光引导胸椎小关节注射治疗胸背痛的疗效观察

    Institute of Scientific and Technical Information of China (English)

    李晓宏; 李世杰; 黄翔; 富沛勇; 杨承祥

    2013-01-01

    目的:评价小关节注射治疗胸背部疼痛的临床疗效及安全性.方法:60例经保守治疗无效的慢性胸背痛患者,随机分为超激光治疗组(S组,n=30)和介入治疗组(Ⅰ组,n=30).S组患者取俯卧位,超激光照射病变关节部位,每天1次,每次15 rain,共14次;Ⅰ组患者取俯卧位,在X光引导下确定病变小关节平面,穿刺针经皮正确无误到达胸椎后关节突关节间隙,到位后注射消炎镇痛液.对治疗后第1周、2周、1个月、3个月的VAS进行评分、生活质量改善情况及安全性进行评估.结果:与S组比较,Ⅰ组治疗患者术后3个月的VAS评分较治疗前有显著性降低(P<0.05),且未发现有严重并发症.结论:小关节注射治疗胸背痛是一项操作简便、安全,疗效确切、可靠的微创介入治疗方法.%Objective:To determine the clinical effectiveness of zygapophysial joint injections with fluoroscopy in managing chronic mid back or upper back pain of facet joint origin.Methods:A total of 60 patients were randomized divided into two groups,with 30 patients in each of the super laser and facet joint interventions groups.All of the patients met the diagnostic criteria of thoracic facet joint pain by means of the inclusion criteria.Group S patients received thoracic facet joint with super laser,whereas Group Ⅰ patients received thoracic facet joint intervention with bupivacaine and non-particulate betamethasone.The clinical efficacy were assessed by patients with visual analogue scale(VAS).All outcomes were assessed at baseline,1 week,2 weeks,1 month,and 3 months after treatment.Results:In Group S,compared with baseline,patients showed significant pain relief and functional improvement at 1 week (P < 0.05) But there were no significant pain relief after 2 weeks.In Group Ⅰ,patients showed significant pain relief and functional improvement after facet joint injection,a significant change 3 months after treatment from baseline (P < 0

  8. Specific behavioral and cellular adaptations induced by chronic morphine are reduced by dietary omega-3 polyunsaturated fatty acids.

    Directory of Open Access Journals (Sweden)

    Joshua Hakimian

    Full Text Available Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellular and behavioral levels. As omega-3 polyunsaturated fatty acids (n-3 PUFAs play a ubiquitous role in behavioral and cellular processes, we proposed that supplemental n-3 PUFAs, enriched in docosahexanoic acid (DHA, could offset these adaptations following chronic opioid exposure. We used an 8 week regimen of n-3 PUFA supplementation followed by 8 days of morphine in the presence of this diet. We first assessed the effect of morphine in different behavioral measures and found that morphine increased anxiety and reduced wheel-running behavior. These effects were reduced by dietary n-3 PUFAs without affecting morphine-induced analgesia or hyperlocomotion, known effects of this opiate acting at mu opioid receptors. At the cellular level we found that morphine reduced striatal DHA content and that this was reversed by supplemental n-3 PUFAs. Chronic morphine also increased glutamatergic plasticity and the proportion of Grin2B-NMDARs in striatal projection neurons. This effect was similarly reversed by supplemental n-3 PUFAs. Gene analysis showed that supplemental PUFAs offset the effect of morphine on genes found in neurons of the dopamine receptor 2 (D2-enriched indirect pathway but not of genes found in dopamine receptor 1(D1-enriched direct-pathway neurons. Analysis of the D2 striatal connectome by a retrogradely transported pseudorabies virus showed that n-3 PUFA supplementation reversed the effect of chronic morphine on the innervation of D2 neurons by the dorsomedial prefontal and piriform cortices. Together these changes outline specific behavioral and

  9. Chronic Restraint Stress Induces an Isoform-Specific Regulation on the Neural Cell Adhesion Molecule in the Hippocampus

    Science.gov (United States)

    Touyarot, K.; Sandi, C.

    2002-01-01

    Existing evidence indicates that 21-days exposure of rats to restraint stress induces dendritic atrophy in pyramidal cells of the hippocampus. This phenomenon has been related to altered performance in hippocampal-dependent learning tasks. Prior studies have shown that hippocampal expression of cell adhesion molecules is modified by such stress treatment, with the neural cell adhesion molecule (NCAM) decreasing and L1 increasing, their expression, at both the mRNA and protein levels. Given that NCAM comprises several isoforms, we investigated here whether chronic stress might differentially affect the expression of the three major isoforms (NCAM-120, NCAM-140, NCAM-180) in the hippocampus. In addition, as glucocorticoids have been implicated in the deleterious effects induced by chronic stress, we also evaluated plasma corticosterone levels and the hippocampal expression of the corticosteroid mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The results showed that the protein concentration of the NCAM-140 isoform decreased in the hippoampus of stressed rats. This effect was isoform-specific, because NCAM-120 and NCAM-180 levels were not significantly modified. In addition, whereas basal levels of plasma corticosterone tended to be increased, MR and GR concentrations were not significantly altered. Although possible changes in NCAM-120, NCAM-180 and corticosteroid receptors at earlier time points of the stress period cannot be ignored; this study suggests that a down-regulation of NCAM-140 might be implicated in the structural alterations consistently shown to be induced in the hippocampus by chronic stress exposure. As NCAM-140 is involved in cell-cell adhesion and neurite outgrowth, these findings suggest that this molecule might be one of the molecular mechanisms involved in the complex interactions among neurodegeneration-related events. PMID:12757368

  10. Persistent Increase in Microglial RAGE Contributes to Chronic Stress-Induced Priming of Depressive-like Behavior.

    Science.gov (United States)

    Franklin, Tina C; Wohleb, Eric S; Zhang, Yi; Fogaça, Manoela; Hare, Brendan; Duman, Ronald S

    2018-01-01

    Chronic stress-induced inflammatory responses occur in part via danger-associated molecular pattern (DAMP) molecules, such as high mobility group box 1 protein (HMGB1), but the receptor(s) underlying DAMP signaling have not been identified. Microglia morphology and DAMP signaling in enriched rat hippocampal microglia were examined during the development and expression of chronic unpredictable stress (CUS)-induced behavioral deficits, including long-term, persistent changes after CUS. The results show that CUS promotes significant morphological changes and causes robust upregulation of HMGB1 messenger RNA in enriched hippocampal microglia, an effect that persists for up to 6 weeks after CUS exposure. This coincides with robust and persistent upregulation of receptor for advanced glycation end products (RAGE) messenger RNA, but not toll-like receptor 4 in hippocampal microglia. CUS also increased surface expression of RAGE protein on hippocampal microglia as determined by flow cytometry and returned to basal levels 5 weeks after CUS. Importantly, exposure to short-term stress was sufficient to increase RAGE surface expression as well as anhedonic behavior, reflecting a primed state that results from a persistent increase in RAGE messenger RNA expression. Further evidence for DAMP signaling in behavioral responses is provided by evidence that HMGB1 infusion into the hippocampus was sufficient to cause anhedonic behavior and by evidence that RAGE knockout mice were resilient to stress-induced anhedonia. Together, the results provide evidence of persistent microglial HMGB1-RAGE expression that increases vulnerability to depressive-like behaviors long after chronic stress exposure. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

    Science.gov (United States)

    Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

    2017-03-15

    It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identify