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Sample records for encephalomyelitis disseminata klinik

  1. Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics

    Science.gov (United States)

    2013-01-01

    Background ‘Encephalomyelitis disseminata’ (multiple sclerosis) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are both classified as diseases of the central nervous system by the World Health Organization. This review aims to compare the phenomenological and neuroimmune characteristics of MS with those of ME/CFS. Discussion There are remarkable phenomenological and neuroimmune overlaps between both disorders. Patients with ME/CFS and MS both experience severe levels of disabling fatigue and a worsening of symptoms following exercise and resort to energy conservation strategies in an attempt to meet the energy demands of day-to-day living. Debilitating autonomic symptoms, diminished cardiac responses to exercise, orthostatic intolerance and postural hypotension are experienced by patients with both illnesses. Both disorders show a relapsing-remitting or progressive course, while infections and psychosocial stress play a large part in worsening of fatigue symptoms. Activated immunoinflammatory, oxidative and nitrosative (O+NS) pathways and autoimmunity occur in both illnesses. The consequences of O+NS damage to self-epitopes is evidenced by the almost bewildering and almost identical array of autoantibodies formed against damaged epitopes seen in both illnesses. Mitochondrial dysfunctions, including lowered levels of ATP, decreased phosphocreatine synthesis and impaired oxidative phosphorylation, are heavily involved in the pathophysiology of both MS and ME/CFS. The findings produced by neuroimaging techniques are quite similar in both illnesses and show decreased cerebral blood flow, atrophy, gray matter reduction, white matter hyperintensities, increased cerebral lactate and choline signaling and lowered acetyl-aspartate levels. Summary This review shows that there are neuroimmune similarities between MS and ME/CFS. This further substantiates the view that ME/CFS is a neuroimmune illness and that patients with MS are immunologically primed to

  2. Pembuatan Sistem Informasi Manajemen Klinik dengan Rekam Medis: Studi Kasus di Klinik Kebon Arum Boyolali

    Directory of Open Access Journals (Sweden)

    Yanuar Wisnu Triaji

    2017-01-01

    Proses pendaftaran, pemeriksaan, pembayaran, pelaporan dan karyawan administrasi di klinik sangat tidak efisien, dibutuhkan suatu sistem untuk membantu dan mempermudah pengguna dalam proses rekam medis. Tujuan dari penelitian ini adalah mengembangkan sistem informasi manajemen untuk klinik, yaitu klinik Kebon Arum di Boyolali. Metode pengembangan sistem yang digunakan dalam penelitian ini adalah metode Waterfall yang terdiri dari rencana kebutuhan, proses desain, dan implementasi. Aplikasi ini dibangun dengan bahasa pemrograman PHP, codeigniter framework, serta basis data MySQL. Hasil dari penelitian ini adalah sebuah aplikasi sistem informasi manajemen klinik dan sistem ini dapat mengatasi masalah pada pendaftaran klinik, antrian, layanan, pembayaran dan data pasien.

  3. Leiomyomatosis peritonealis disseminata in association with Currarino syndrome?

    Directory of Open Access Journals (Sweden)

    Mignogna Chiara

    2006-05-01

    Full Text Available Abstract Background Leiomyomatosis peritonealis disseminata (LPD is a rare disease in which multiple smooth muscle or smooth muscle-like nodules develop subperitoneally in any part of the abdominal cavity. No reports of multiple congenital malformations associated with LPD have been found in the English literature. Case presentation A 27 year-old patient referred to our gynaecology unit for pelvic pain, amenorrhoea, stress incontinence, chronic constipation and recurrent intestinal and urinary infections. Multiple congenital malformations had previously been diagnosed. Most of these had required surgical treatment in her early life: anorectal malformation with rectovestibular fistula, ectopic right ureteral orifice, megadolichoureter and hemisacrum. An ultrasound scan and computed tomography performed in our department showed an irregular, polylobate, complex 20 cm mass originating from the right pelvis that reached the right hypochondrium and the epigastrium. The patient underwent laparotomy. The three largest abdominal-pelvic masses and multiple independent nodules within the peritoneum were progressively removed. The histological diagnosis was of LPD. Conclusion The case we report is distinctive in that a rare acquired disease, LPD, coexists with multiple congenital malformations recalling a particular subgroup of caudal regression syndrome: the Currarino syndrome.

  4. Iatrogenic parasitic leiomyoma and leiomyomatosis peritonealis disseminata following uterine morcellation.

    Science.gov (United States)

    Lu, Bingjian; Xu, Jing; Pan, Zimin

    2016-08-01

    To assess the impact of morcellation on the spread of uterine leiomyoma. Cases of parasitic leiomyoma involving prior laparoscopy were collected between 2012 and 2015 in a tertiary women's hospital in China. Their clinicopathological features and the associated reports were reviewed. All six patients with parasitic leiomyoma had laparoscopic myomectomy or hysterectomy with power morcellation 39-132 months previously. Patient 1 had widely disseminated tumors in the peritoneum and pelvis, in keeping with leiomyomatosis peritonealis disseminata (LPD). She received debulking of peritoneal tumors and lived with disease for 22 months. The implanting sites of the other parasitic tumors (patients 2-6) included the mesentery (n = 2), intestine (n = 1), pelvic parietal (n = 1), bladder (n = 1), and musculus rectus abdominis (n = 1). The diameter varied from 1 cm to 6 cm. The patients underwent abdominal subtotal hysterectomy, cervicectomy or tumor debulking and the postoperative course was unremarkable for a period of 2-32 months. Pathologically, these disseminated or parasitic leiomyomas did not show any evidence of malignancy. There were no morphological or immunohistochemical differences between the original tumor and the following seeding tumors. On literature review, 11 iatrogenic LPD have been reported after laparoscopic surgery for uterine leiomyoma. These cases may provide an alternative pathogenic mechanism for a distinct variant of LPD. Laparoscopic hysterectomy with tumor morcellation may increase the chance of tumor implantation and dissemination. Both clinicians and pathologists should be alert to this rare complication. © 2016 Japan Society of Obstetrics and Gynecology.

  5. EVALUASI KHASIAT DAN KEAMANAN OBAT (UJI KLINIK

    Directory of Open Access Journals (Sweden)

    Rahmatini Rahmatini

    2010-05-01

    Full Text Available AbstrakUji klinik adalah suatu pengujian khasiat obat baru pada manusia, dimana sebelumnya diawali oleh pengujian pada binatang atau uji pra klinik. Pada dasarnya uji klinik memastikan efektivitas, keamanan dan gambaran efek samping yang sering timbul pada manusia akibat pemberian suatu obat. Bila uji klinik tidak dilakukan maka dapat terjadi malapetaka pada banyak orang bila langsung dipakai secara umum seperti pernah terjadi dengan talidomid (1959-1962 dan obat kontrasepsi pria (gosipol di Cina. Setiap obat yang ditemukan melalui eksperimen in vitro atau hewan coba tidak terjamin bahwa khasiatnya benar-benar akan terlihat pada penderita. Pengujian pada manusia sendirilah yang dapat “menjamin” apakah hasil in vitro atau hewan sama dengan manusia.Uji klinik terdiri dari 4 fase, yaitu uji klinik fase I.Uji klinik fase II, uji klinik fase III dan uji klinik fase IV. Uji klinik fase I dilakukan pada manusia sehat, bertujuan untuk menentukan dosis tunggal yang dapat diterima, Uji klinik fase II, dilakukan pada 100-200 orang penderita untuk melihat apakah efek farmakologik yang tampak pada fase I berguna atau tidak untuk pengobatan. Uji klinik fase III dilakukan pada sekitar 500 penderita yang bertujuan untuk memastikan bahwa suatu obat baru benar-benar berkhasiat. Uji klinik fase IV merupakan pengamatan terhadap obat yang telah dipasarkan. Fase ini bertujuan menentukan pola penggunaan obat di masyarakat serta pola efektifitas dan keamanannya pada penggunaan yang sebenarnya.Uji klinik yang baik dilakukan dengan prosedur yang sudah digariskan dan komponen- komponennya disiapkan dengan matang sehingga hasilnya betul- betul dapat dimanfaatkan sebagai acuan pengobatan.Kata kunci : Khasiat- keamanan- uji klinikAbstractClinical trials is a new drug efficacy testing in humans, which previously preceded by testing on animals or pre-clinical testing. Basically, clinical trials confirm description of effectiveness, safety and side effects that often arise

  6. Melatonin ve Klinik Önemi

    OpenAIRE

    Fehmi, Özgüner; Özcankaya, Ramazan; Delibaş, Namık; Koyu, Ahmet; Çalışkan, Sadettin

    2009-01-01

    SüleymanDemirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 1995 Aralık; 2(4) Melatonin ve Klinik Önemi Fehmi Özgüner Ramazan Özcankaya Namık Delibaş Ahmet Koyu Sadettin Çalışkan . Özet Melatonin karanlık periyotta sentezlenir ve salınır, ayrıca karanlığın süresi hakkındaki bilginin değerlendirilmesine aracılık eder. Melatonin sirkadiyan ritmi, gençlerde oldukça düzenlidir, yaşlılıkta sıklıkla siklus bozulma gösterir ve bir hipomelatoninemi sendromu ola...

  7. ANALISIS KEPUASAN PASIEN TERHADAP KUALITAS PELAYANAN PERAWATAN GIGI DI KLINIK GIGI MY DENTAL CARE SURABAYA

    Directory of Open Access Journals (Sweden)

    Adityarani Putranti

    2016-10-01

    Full Text Available Kebutuhan masyarakat yang semakin tinggi akan jasa layanan kesehatan membuat ekspektasi masyarakat terhadap layanan kesehatan yang baik juga semakin tinggi. Pelayanan gigi dan mulut, merupakan salah satu pelayanan kesehatan dasar pada masyarakat. Klinik gigi My Dental Care Surabaya merupakan salah satu klinik gigi yang terletak di Surabaya Selatan. Klinik Gigi My Dental Care memiliki permasalahan belum tercapainya target jumlah kunjungan pasien sebesar 120 pasien per bulan selama tahun 2013-2014. Jenis penelitian ini adalah penelitian analitik observasional dengan pengumpulan data secara cross sectional. Pengambilan sampel dengan metode simple random sampling dan jumlah sampel sebesar 30 orang. Penelitian ini dilakukan pada pasien yang melakukan perawatan gigi di Klinik Gigi My Dental Care Surabaya. Kata Kunci: Kepuasan Pelanggan, Kualitas Pelayanan, Klinik Gigi My Dental Care Surabaya

  8. Rabies, encephalomyelitis: MRI findings

    International Nuclear Information System (INIS)

    Peloso, Raul; Gonzalez, Roberto

    2002-01-01

    The authors present a 14 year old patient who started with walking and swallowing difficulty; followed by fever, abdominal and lower back pain. Mechanical breathing difficulties required a respiratory mechanic assistance. The diagnosis of Guillain-Barre syndrome was thought at first. Since the patient have had previous contact with a bat two months before the symptoms began, this suggested rabies as the main diagnosis, which was later confirmed by hair-bulb, cornea, oral mucosa and salival immunofluorescence. The brain and spinal cord MRI showed focal lesions in T2 and FLAIR sequences, compatible with encephalomyelitis. (author)

  9. Uji Klinik Fase II Ramuan Jamu sebagai Pelindung Fungsi Hati

    Directory of Open Access Journals (Sweden)

    zuraida - zulkarnain

    2017-07-01

    Full Text Available AbstractThe human liver is susceptible to interference due to its complex function. The development ofhepatoprotective from jamu formula is still needed as to produce more effective, cheaper andsafer hepatoprotective. The result of previous study showed that the hepatoprotective from jamuformula was safe and efficacious. This phase 2 trial was conducted to evaluate the efficacy andsafety of hepatoprotective from jamu formula which consists of Curcuma longa rhizomes, Curcumaxanthorrhiza rhizomes, and Taraxacum officinale leaves. The design was open label randomizedclinical trial with silimarin as a comparison for 42 days intervention. Two hundreds of humansubjects participated in this study. The trial held in 2015 and involved 50 physician members ofSaintifikasi Jamu Network at several regencies in Indonesia. The parameters for assessing efficacywere SGPT, SGOT and as for safety were routine blood, urea, and creatinine. Clinical symptoms andpossible side effects were also observed. The results showed that the jamu formula can reduce theaverage value of SGPT and SGOT equal to silimarin. Jamu formula can relieve clinical symptomsarising from liver function disruption, and it is safe, it does not alter kidney function, hemoglobin,leukocyte count and platelet count in its use for 42 days.Keywords: hepatoprotective, Saintifikasi Jamu, Curcuma longa, Curcuma AbstrakHati mudah mengalami gangguan disebabkan fungsinya yang kompleks. Saat ini masih diperlukanpengembangan ramuan jamu untuk melindungi dan memperbaiki sel-sel hati (hepatoprotektor yanglebih efektif, murah dan aman. Hasil penelitian observasi klinik terdahulu menunjukkan bahwaformula jamu untuk hepatoprotektor aman dan berkhasiat sehingga dilanjutkan dengan uji klinik fase2. Tujuan uji ini untuk menilai khasiat dan keamanan ramuan jamu sebagai hepatoprotektor dengankomposisi rimpang temulawak, rimpang kunyit, dan daun jombang. Rancangan uji adalah open labelrandomised clinical trial dengan

  10. Penerapan Konsep Model View Controller Pada Rancang Bangun Sistem Informasi Klinik Kesehatan Berbasis Web

    Directory of Open Access Journals (Sweden)

    Devy Ferdiansyah

    2018-05-01

    Full Text Available Klinik merupakan sebuah institusi layanan publik yang bergerak dalam bidang jasa kesehatan. Saat ini, masih banyak klinik yang mencatat kegiatan operasional harian secara manual dalam arsip kertas, seperti pendaftaran pasien, pengelolaan data rekam medik, dan sebagainya. Arsip berbagai data klinik menjadi bertumpuk, sehingga membutuhkan ruang penyimpanan yang lebih luas dan pemeliharaan yang lebih ekstra agar kertas catatan tersebut tidak hilang atau mudah rusak. Proses pencarian data pasien dan rekam medik membutuhkan waktu lama, akibat berada di tumpukan arsip yang semakin banyak. Tujuan penelitian adalah membangun sebuah sistem informasi klinik kesehatan berbasis web untuk membantu staff dalam mengelola data klinik kesehatan. Pembangunan Sistem berbasis web ini menggunakan bahasa pemrograman PHP dan database MySQL, dengan menerapkan konsep  Model View Controller(MVC dalam teknik pemrogramannya. Penerapan metode MVC bertujuan untuk memberikan kemudahan bagi pemrogram web dalam membangun website, karena memisahkan data (Model dari tampilannya (View dan cara bagaimana mengolahnya (Controller. Penelitian ini menghasilkan sebuah aplikasi sistem informasi klinik kesehatan berbasis web, yang merubah pola kerja staff dari cara manual dan membutuhkan waktu lama, menjadi terkomputerisasi dengan waktu kerja yang lebih cepat, serta cara kerja yang lebih praktis dan efisien. Penelitian ini memberikan arahan yang jelas tentang bagaimana sebaiknya membangun sebuah sistem informasi berbasis web dengan baik, sehingga tidak menyulitkan pemrogram web saat harus memperbaiki atau mengembangkan sistem di kemudian hari.

  11. Acute disseminated encephalomyelitis

    International Nuclear Information System (INIS)

    Seki, Hareaki; Shiga, Yusei; Ichikawa, Nobumichi.

    1988-01-01

    A previously healthy 39-year-old woman suddenly became stuporous following a slight upper respiratory infection. She went into a coma within a few hours. On admission to our hospital, adenine arabinoside was administered upon the diagnosis of herpes simplex encephalitis, but it had no apparent effect. The patient showed moderate leukocytosis, but no other abnormal laboratory data. Serological examinations for virus titer were all negative. A CT scan on the 9th day showed a diffuse low-density area extending into the cerebral and cerebellar white matter, but no contrast-enhancement effect or midline shift was observed. She has since remained in a coma, and repeated CT scans have revealed marked ventricular dilatation. The clinical course, laboratory data, and CT findings suggest acute disseminated encephalomyelitis, but acute hemorrhagic leukoencephalitis cannot exactly be ruled out. Magnetic resonance imaging demonstrated a widespread white-matter lesion, while positron-emission CT demonstrated a dysfunction in both the white and gray matter. (author)

  12. Interferon-¿ regulates oxidative stress during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C.; Penkowa, Milena; Saez-Torres, I.

    2002-01-01

    Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress......Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress...

  13. MRI in acute disseminated encephalomyelitis

    International Nuclear Information System (INIS)

    Caldemeyer, K.S.; Smith, R.R.; Harris, T.M.; Edwards, M.K.

    1994-01-01

    A retrospective analysis of CT and MRI studies in 12 patients with a clinical diagnosis of acute disseminated encephalomyelitis (ADEM) was performed. MRI was the definitive modality for the assessment of the lesions of ADEM: all patients had abnormalities consistent with the clinical diagnosis. Ten had abnormalities in the brain, three spinal cord lesions, and three showed evidence of optic neuritis. CT was normal in 6 of the 7 patients in which it was performed. (orig.)

  14. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Diagnosis

    Science.gov (United States)

    ... Controls Search Form Controls Cancel Submit Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Note: Javascript is disabled or is not supported ... Facebook Tweet Share Compartir To diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a patient’s doctor or healthcare provider ...

  15. Implementasi Business Intelligence untuk Menganalisis Data Persalinan Anak di Klinik Ani Padang dengan Menggunakan Aplikasi Tableau Public

    Directory of Open Access Journals (Sweden)

    Afdhal Zikri

    2017-07-01

    Full Text Available Pengelolaan data merupakan hal penting dari sebuah perusahaan namun prosesnya tidaklah mudah. Seiring dengan perkembangan teknologi, terciptalah banyak cara dalam mengolah dan mengatur data salah satunya yaitu Business intelligence (BI yang merupakan sebuah proses untuk melakukan ekstrasi data-data operasional perusahaan dan mengumpulkannya  dalam sebuah data warehouse. BI tidak hanya digunakan untuk perusahaan saja tetapi bisa diterapkan pada hal lainnya. Klinik Ani merupakan klinik yang telah berdiri sebelum tahun 2000. Klinik tersebut memiliki record data dari tiap pasien yang telah ditanganinya, salah satunya persalinan. Namun karena proses yang digunakan masih berbentuk manual, klinik tersebut masih belum bisa meningkatkan efektifitas dak efisiensinya sebaik mungkin. Penelitian ini bertujuan untuk memberikan informasi-informasi yang berguna untuk meningkatkan efektifitas dan efisiensi pada klinik tersebut dengan dasar Business intelligence. Dalam penelitian ini, analisis data dilakukan dengan menggunakan aplikasi Tableau Public. Tableau Public adalah perangkat lunak bisnis intelijen yang mudah untuk digunakan, terutama dalam hal membuat visualisasi data, analisis data, dan pelaporan. Dengan metodologi deskriptif  yang didapatkan dari hasil observasi terhadap data yang ada, akan didapatkan sebuah output berupa informasi tentang tren kelahiran/persalinan anak dalam empat semester terakhir di Klinik Ani Padang Sumatera Barat.

  16. Konseling Psikologi dan Kecemasan pada Penderita Hipertiroid di Klinik Litbang Gaki Magelang

    Directory of Open Access Journals (Sweden)

    Diah Yunitawati

    2015-03-01

    Full Text Available KONSELING PSIKOLOGI DAN KECEMASAN PADA PENDERITA HIPERTIROID DI KLINIK LITBANG GAKI MAGELANG Psychological Counseling And Anxiety In Patients With Hyperthyroidism In Klinik Litbang GAKI Magelang ABSTRACT Background. Hyperthyroidism may cause clinical symptoms and physiological changes in thyroid function, and interference in cognitive function, behavioral problems, and a change of feeling (mood and anxiety. Anxiety is negative emotions, which is characterized by feeling worried and fear that is sometimes experienced in different levels. One method to overcome anxiety is by counseling. Counseling is a process of providing information through systematically interpersonal communication. Objective. The aim of this study is determine the effect of psychological counseling and relationships of age, education, and work with the level of anxiety in hyperthyroid patients in Klinik Litbang GAKI Magelang. Method. This study was conducted with pre experimental method with pre-test post-test one group design. The variables are psychological counseling and anxiety. Level of anxiety was measured using the beck anxiety inventory (BAI, which has 21 items and measure physical, cognitive, and emotional aspects. Subjects were asked what she felt for four weeks. Total score indicates the level of anxiety. The subjects were 45 women of childbearing age with hyperthyroid in Klinik Litbang GAKI Magelang. Screening is done by examining level of TSH thyroid stimulating hormone (TSH and free Tetraiodothyronin (fT4. Results. Subjects who have severe disease and are pregnant were excluded. There was a change between the percentage of each category of anxiety before and after counseling. The analysis showed that anxiety scores after and before counseling process have a statistically significant difference. Age, education, and jobs not related to anxiety in patients with hyperthyroidism. Conclusion. Psychological counseling may be an option to reduce the level of anxiety in

  17. 21 CFR 866.3240 - Equine encephalomyelitis virus serological reagents.

    Science.gov (United States)

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents... these viruses. Equine encephalomyelitis viruses are transmitted to humans by the bite of insects, such...

  18. Acute Disseminated Encephalomyelitis: A case series and review of literatures

    Directory of Open Access Journals (Sweden)

    Mohammad Sadegh Rezai

    2013-05-01

    Full Text Available Acute disseminated encephalomyelitis is a rare immune mediated and demyelinating disease of the central nervous system that usually affects children. It is a monophasic disorder related with multifocal neurologic symptoms. In this paper, we report seven cases of Acute disseminated encephalomyelitis in pediatrics in addition; a review of literatures is presented.

  19. REKOMENDASI PENINGKATAN PEMANFAATAN LAYANAN PERSALINAN NORMAL DI KLINIK PRATAMA RAWAT INAP RUMAH BERSALIN GRATIS RUMAH ZAKAT

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    Am Maisarah Disrinama

    2016-06-01

    Full Text Available Intention of buying product or service is very important thing on purchasing stage. It depends on alternatives evaluation process on pre purchasing stage.  K4 Pregnant woman has to decide the place to birth. The objective of this study is to create recommendation to increase Normal Labour on K4 Pregnant Women using Brand Image Analysis dan Three Stage Model of Service Consumption in Klinik Pratama Rawat Inap Rumah Bersalin Gratis Rumah Zakat. This research uses observasional analytic and prospective cohort. The primary data is collected two times, before and after delivery process. There are 54 respondents, whether all of K4 pregnant women with pregnancy age are more than 32 weeks. The samples were taken from March to August 2014. The result shows that some characteristics have relationship with purchasing decision. The recommendations consist of product, place, promotion, people, process, and physical evidence. Overall, the head of branch needs to fix the service for mother and child evaluation soon.

  20. [Can acute disseminated encephalomyelitis progress in a deferred way?].

    Science.gov (United States)

    Gener, B; Garaizar-Axpe, C; Ruiz Espinosa, C; Prats-Viñas, J M

    To report on the heterogeneity with regard to the clinical course of the acute disseminated encephalomyelitis (ADEM). A 5 year old boy suffered of acute disseminated encephalomyelitis of unknown origin. This child suffered two episodes of different neurologic symptoms separated by several weeks. Based on the clinical manifestations and typical appearance of magnetic resonance imaging findings and the absence of oligoclonal bands in CSF immunoglobulins, multiple sclerosis (MS) was ruled out. We postulate that the recurrent symptoms in our patient could be explained as a multiphasic disseminated encephalomyelitis (MDEM). Favourable outcome after simultaneous treatment with methylprednisolone and intravenous immunoglobulin is emphasized in this report.

  1. Epstein-Barr virus encephalitis and encephalomyelitis: MR findings

    International Nuclear Information System (INIS)

    Shian, W.J.; Chi, C.S.

    1996-01-01

    The purpose of this project is to investigate the clinical and brain MR characteristics of Epstein-Barr virus (EBV) encephalitis and encephalomyelitis. Clinical and 30 MR findings of 29 patients with EBV encephalitis or encephalomyelitis were retrospectively reviewed. Patients included 24 with encephalitis, 3 with encephalomyelitis, and 2 with brain-stem encephalitis. Altered consciousness, seizures, visual hallucination, and acute psychotic reaction were the common presentations. Eight patients had positive MR findings. These included T2 prolongation over gray and white matter, periventricular leukomalacia, and brain atrophy. Transient T2 prolongation over gray and white matter was found in one patient. Our results indicate that EBV encephalitis and encephalomyelitis have a wide range of both clinical and MR findings. The MR lesions may disappear in a short period, so the timing for the MR scan may be critical. (orig.). With 5 figs., 2 tabs

  2. Epstein-Barr virus encephalitis and encephalomyelitis: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Shian, W.J. [Department of Pediatrics, Tao-Yuan Veterans Hospital, No. 100, Sec 3, Cheng-Kung Rd, City of Tao-Yuan, Taiwan (Taiwan, Province of China); Chi, C.S. [Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan (Taiwan, Province of China)

    1996-09-01

    The purpose of this project is to investigate the clinical and brain MR characteristics of Epstein-Barr virus (EBV) encephalitis and encephalomyelitis. Clinical and 30 MR findings of 29 patients with EBV encephalitis or encephalomyelitis were retrospectively reviewed. Patients included 24 with encephalitis, 3 with encephalomyelitis, and 2 with brain-stem encephalitis. Altered consciousness, seizures, visual hallucination, and acute psychotic reaction were the common presentations. Eight patients had positive MR findings. These included T2 prolongation over gray and white matter, periventricular leukomalacia, and brain atrophy. Transient T2 prolongation over gray and white matter was found in one patient. Our results indicate that EBV encephalitis and encephalomyelitis have a wide range of both clinical and MR findings. The MR lesions may disappear in a short period, so the timing for the MR scan may be critical. (orig.). With 5 figs., 2 tabs.

  3. Acute Disseminated Encephalomyelitis: Typical Radiologic Findings: Case Report

    International Nuclear Information System (INIS)

    Pulgarin R, Luis G; Posada A, Marcela; Sanchez M, Luisa C

    2011-01-01

    A 28-year-old female patient developed neurological symptoms after a classical episode of dengue. The physical examination reveled no fever, no neurological focalization, and an altered mental status (Glasgow 12/15). Magnetic resonance imaging confirmed the diagnosis of acute disseminated encephalomyelitis. The patient showed clinical improvement following treatment with steroids. Acute disseminated encephalomyelitis (ADEM) is classically described as a uniphasic syndrome occurring in association with systemic viral infection (parainfectious encephalomyelitis) or immunization or vaccination (post vaccination encephalomyelitis). Pathologically, there is perivascular inflammation, edema, and demyelination within the CNS. Clinically, patients present with rapidly progressing focal or multifocal neurologic dysfunction. The treatment for ADEM is targeted at suppressing inflammation in the brain through the use of anti-inflammatory drugs such as intravenous corticosteroids.

  4. Acute disseminated encephalomyelitis in dengue viral infection.

    Science.gov (United States)

    Wan Sulaiman, Wan Aliaa; Inche Mat, Liyana Najwa; Hashim, Hasnur Zaman; Hoo, Fan Kee; Ching, Siew Mooi; Vasudevan, Ramachandran; Mohamed, Mohd Hazmi; Basri, Hamidon

    2017-09-01

    Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. PENCAPAIAN BRAND CORPORATE MELALUI BRAND ACTIVATION PENDEKATAN EXPERIENTIAL MARKETING ( STUDI KASUS LABORATORIUM KLINIK

    Directory of Open Access Journals (Sweden)

    Mahdalena Lubis

    2017-07-01

    ditujukan untuk mengetahui bagaimana pencapaian brand corporate melalui brand activation experiential marketing yang dilakukan oleh Laboratorium Klinik dengan objek PT. Prodia Widyahusada Tbk. Penelitian dengan metode studi kasus deskriptif ini memperoleh data melalui wawancara dan pengamatan. Penelitian ini menemukan fakta bahwa perusahaan melakukan brand activation untuk mencapai brand corporate dilakukan secara holistic untuk memaksimalkan brand di persaingan kompetitif, namun untuk menciptakan experiential marketing, perusahaan dapat menekankan poin-poin tertentu sesuai dengan tujuan yang diinginkan oleh perusahaan. Sekaligus bantahan terhadap teori Schmitt yang menyatakan kejutan (think adalah yang paling penting, berbeda dengan yang dilakukan di objek penelitian bahwa sense dan feel adalah yang paling kuat sesuai dengan kebutuhan atau sasaran pelanggan perusahaan. Pemanfaatan brand activation experiential marketing dapat menciptakan kepercayaan, engagement, loyalitas, akuisisi, share, pembeda dengan kompetitor dan bermuara pada pencapaian brand corporate berupa reputasi.

  6. Profil Pasien HIV di Klinik VCT Sehati RSUD Dr. T.C. Hillers Maumere Tahun 2014

    Directory of Open Access Journals (Sweden)

    Lidwina Anissa

    2015-12-01

    Full Text Available Infeksi HIV merupakan masalah kesehatan dunia. Terdapat peningkatan jumlah infeksi baru di Indonesia. Penelitian ini bertujuan untuk mengetahui profil  pasien HIV di area rural. Studi ini merupakan studi potong lintang dengan data register pasien dalam periode Januari – Desember 2014. HIV di Klinik VCT Sehati RSUD Dr.TC Hillers Maumere, Kabupaten Sikka. Terdapat 104 pasien  yang terdiagnosis HIV positif, 64,4% di antaranya adalah laki-laki. Tingkat pendidikan terbanyak adalah tingkat pendidikan menengah (46,2% dan rendah (44,2%. Rute transmisi terbanyak adalah hubungan seksual heteroseksual (74%. Gejala terbanyak yang dikeluhkan pasien adalah batuk lama, penurunan berat badan dan demam naik turun. Infeksi oportunistik terbanyak adalah TB paru dan kandidosis oral. Infeksi HIV membutuhkan penangan secara holistik yang menjamin kualitas hidup pasien baik dari aspek fisik dan psikis. Edukasi kesehatan reproduksi terutama HIV dan infeksi menular seksual lainnya memegang peranan penting dalam rangka upaya meningkatkan wawasan mengenai HIV sekaligus sebagai upaya pencegahan infeksi baru dan pemutusan rantai penularan. Dukungan peer group memiliki peranan penting dalam peningkatan kualitas hidup pasien. Kata kunci: HIV, heteroseksual, homoseksual, infeksi oportunistik, rute transmisi.   HIV Patients’ Profile in Sehati VCT Clinic Dr.T.C. Hillers Maumere in 2014 Abstract HIV infection is one of global health problems. The number of new infection is increasing in Indonesia. This research aims to study the profile of HIV patients in rural area. This reasearch is a cross-sectional study on patients registers in Sehati Voluntary Counseling Testing / HIV care unit in Dr.TC Hillers District General Hospital, Sikka Regency during January untill December 2014 period. There were 104 subjects diagnosed as HIV positive and 64.4% of them were male. The most common education level was middle school (46.2% and elementary school (44.2%. The most frequent

  7. Acute disseminated encephalomyelitis; Akute disseminierte Enzephalomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Politi, M.; Papanagiotou, P.; Grunwald, I.Q.; Roth, C.; Reith, W. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2008-06-15

    Acute disseminated encephalomyelitis (ADEM) is an acute widespread autoimmune demyelinating condition, which principally affects the white matter of the brain and spinal cord. It usually follows an infection or vaccination. The typical presentation is that of multifocal neurologic disturbances accompanied by change in mental status. CSF analysis reveals lymphocytic pleocytosis and elevated protein content, but may also yield normal results. MRI is regarded as the diagnostic imaging modality of choice and typically demonstrates involvement of deep cerebral hemispheric and subcortical white matter as well as lesions in the basal ganglia, gray-white junction, diencephalon, brainstem, cerebellum and spinal cord. Unlike multiple sclerosis (MS), ADEM has a monophasic course and a favorable long-term prognosis. (orig.) [German] Die akute disseminierte Enzephalomyelitis (ADEM) ist eine akut auftretende autoimmune demylinisierende Erkrankung der weissen Substanz, die hauptsaechlich Gehirn und Rueckenmark befaellt. Ueblicherweise tritt sie nach einer Infektion oder Impfung auf. Die Entwicklung einer fokalen oder multifokalen neurologischen Funktionsstoerung ist das Kennzeichen der klinischen Praesentation der ADEM. Lymphozytaere Pleozytose und Eiweisserhoehung sind typische Befunde in der Liquoruntersuchung. Die Magnetresonanztomographie (MRT) ist die Untersuchungsmethode der Wahl. Die ADEM-Laesionen sind typischerweise gross, multipel und asymmetrisch. Sie koennen in den Gross- und Kleinhirnhemisphaeren, im Hirnstamm und im Rueckenmark lokalisiert sein. Die subkortikale und die zentrale weisse Substanz sind am haeufigsten befallen. Weniger haeufig ist die graue Substanz der Thalami und der Basalganglien betroffen. Im Gegensatz zur Multiplen Sklerose (MS) ist die Prognose der ADEM im Allgemeinen guenstig. (orig.)

  8. MRI findings of acute disseminated encephalomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sei Jung; Suh, Jung Ho; Kim, Dong Ik; Chung, Tae Sub; Lee, So Jin [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1993-07-15

    Acute disseminate encephalomyelitis (ADEM) is a demyelinating disease of probable autoimmune etiology. The MR images of patients with clinically suspected ADEM were retrospectively reviewed. The clinical symptoms occurred 5 days to 1 month after viral upper respiratory infection (4) and Coxsakie viral infection (1). The symptoms had begun with fever (3), headache (3), sore throat (1), and drowsy mental state (1), which progressed with monophasic course to altered mental change (2), extremity weakness (2), seizure (1) and/or cerebellar symptom (1). MRI findings of ADEM showed patchy (4), non hemorrhagic (5), asymmetric (5) high signal intensity lesions on T2-weighted images. The number of the lesions was mostly multiple (4). The lesions mainly involved the brain stem (3) and subcortical while matter (3). Follow-up MR images of 13 days to 20 days after high dose steroid therapy showed marked improvement in two of three, which well corrected with clinical manifestations. MR finding of multiple, patchy, nonhemorrhagic and asymmetric lesions in subcortical white matter and brain stem on T2-weighted images seem to be characteristic features of ADEM, but nonspecific. Therefore, clinical correlation is required in evaluating ADEM.

  9. Vasogenic edema characterizes pediatric acute disseminated encephalomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Zuccoli, Giulio; Panigrahy, Ashok; Sreedher, Gayathri; Bailey, Ariel [Children' s Hospital of Pittsburgh of UPMC, Department of Radiology, Section of Neuroradiology, Pittsburgh, PA (United States); Laney, Ernest John [Children' s Hospital of Pittsburgh of UPMC, Department of Radiology, Section of Neuroradiology, Pittsburgh, PA (United States); Rush University Medical Center, Department of Diagnostic Radiology, Chicago, IL (United States); La Colla, Luca [University of Parma, Department of Anesthesiology, Parma (Italy); UPMC Shadyside Hospital, Department of Emergency Medicine, Pittsburgh, PA (United States); Alper, Gulay [Children' s Hospital of Pittsburgh of UPMC, Department of Pediatric Neurology, Neuroimmunology Clinic, Pittsburgh, PA (United States)

    2014-08-15

    MR imaging criteria for diagnosing acute disseminated encephalomyelitis (ADEM) have not been clearly established. Due to the wide spectrum of differential considerations, new imaging features allowing early and accurate diagnosis for ADEM are needed. We hypothesized that ADEM lesions would be characterized by vasogenic edema due to the potential reversibility of the disease. Sixteen patients who met the diagnostic criteria for ADEM proposed by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) and had complete MR imaging studies performed at our institution during the acute phase of the disease were identified retrospectively and evaluated by experienced pediatric neuroradiologists. Vasogenic edema was demonstrated on diffusion-weighted imaging (DWI) and corresponding apparent diffusion coefficient (ADC) maps in 12 out of 16 patients; cytotoxic edema was identified in two patients while the other two patients displayed no changes on DWI/ADC. ADC values for lesions and normal-appearing brain tissue were 1.39 ± 0.45 x 10{sup -3} and 0.81 ± 0.09 x 10{sup -3} mm/s{sup 2}, respectively (p = 0.002). When considering a cutoff of 5 days between acute and subacute disease, no difference between ADC values in acute vs. subacute phase was depicted. However, we found a significant correlation and an inverse and significant relationship between time and ADC value. We propose that vasogenic edema is a reliable diagnostic sign of acute neuroinflammation in ADEM. (orig.)

  10. Vasogenic edema characterizes pediatric acute disseminated encephalomyelitis

    International Nuclear Information System (INIS)

    Zuccoli, Giulio; Panigrahy, Ashok; Sreedher, Gayathri; Bailey, Ariel; Laney, Ernest John; La Colla, Luca; Alper, Gulay

    2014-01-01

    MR imaging criteria for diagnosing acute disseminated encephalomyelitis (ADEM) have not been clearly established. Due to the wide spectrum of differential considerations, new imaging features allowing early and accurate diagnosis for ADEM are needed. We hypothesized that ADEM lesions would be characterized by vasogenic edema due to the potential reversibility of the disease. Sixteen patients who met the diagnostic criteria for ADEM proposed by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) and had complete MR imaging studies performed at our institution during the acute phase of the disease were identified retrospectively and evaluated by experienced pediatric neuroradiologists. Vasogenic edema was demonstrated on diffusion-weighted imaging (DWI) and corresponding apparent diffusion coefficient (ADC) maps in 12 out of 16 patients; cytotoxic edema was identified in two patients while the other two patients displayed no changes on DWI/ADC. ADC values for lesions and normal-appearing brain tissue were 1.39 ± 0.45 x 10 -3 and 0.81 ± 0.09 x 10 -3 mm/s 2 , respectively (p = 0.002). When considering a cutoff of 5 days between acute and subacute disease, no difference between ADC values in acute vs. subacute phase was depicted. However, we found a significant correlation and an inverse and significant relationship between time and ADC value. We propose that vasogenic edema is a reliable diagnostic sign of acute neuroinflammation in ADEM. (orig.)

  11. 9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ..., Killed Virus. 113.208 Section 113.208 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian Encephalomyelitis Vaccine, Killed Virus. Avian...

  12. Bovine epizootic encephalomyelitis caused by Akabane virus in southern Japan

    Directory of Open Access Journals (Sweden)

    Tanaka Shogo

    2008-06-01

    Full Text Available Abstract Background Akabane virus is a member of the genus Orthobunyavirus in the family Bunyaviridae. It is transmitted by hematophagous arthropod vectors such as Culicoides biting midges and is widely distributed in temperate to tropical regions of the world. The virus is well known as a teratogenic pathogen which causes abortions, stillbirths, premature births and congenital abnormalities with arthrogryposis-hydranencephaly syndrome in cattle, sheep and goats. On the other hand, it is reported that the virus rarely induces encephalomyelitis in cattle by postnatal infection. A first large-scale epidemic of Akabane viral encephalomyelitis in cattle occurred in the southern part of Japan from summer to autumn in 2006. The aim of this study is to define the epidemiological, pathological and virological properties of the disease. Results Nonsuppurative encephalomyelitis was observed in cattle that showed neurological symptoms such as astasia, ataxia, opisthotonus and hypersensitivity in beef and dairy farms by histopathological analysis. Akabane viral antigen and genome were consistently detected from the central nervous system of these animals, and the virus was isolated not only from them but also from the blood samples of clinically healthy calves in the epidemic area. The isolates were classified into genogroup I a containing the Iriki strain, which caused encephalitis of calves almost twenty years ago in Japan. Most of the affected cattle possessed the neutralizing antibody against Akabane virus. Seroconversion of the cohabitated and sentinel cattle in the epidemic area was also confirmed during an outbreak of the disease. Conclusion The ecological and epidemiological data we have obtained so far demonstrated that the Akabane virus is not endemic in Japan. No evidence of Akabane virus circulation was observed in 2005 through nation-wide serological surveillance, suggesting that a new strain belonging to genogroup I a invaded southern Japan

  13. Persistent pseudobulbar affect secondary to acute disseminated encephalomyelitis

    OpenAIRE

    Li, Zhendong; Luo, Shijian; Ou, Jianying; Huang, Rihe; Wang, Ying

    2015-01-01

    Pseudobulbar affect (PBA) is a common complication of central nervous system diseases such as stroke, multiple sclerosis, and other neurological diseases, but it remains under-recognized and under-treated in the clinic. PBA caused by acute disseminated encephalomyelitis (ADEM) has rarely been reported. Here, we report a 30-year-old Chinese woman who has experienced PBA from ADEM for 7 years. The patient’s principal manifestations were extreme emotions or tears when she saw, heard, or spoke ab...

  14. Bauran Pemasaran (4P+Physical Evidence Dan Pengaruhnya Terhadap Keputusan Konsumen Dalam Menggunakan Jasa Laboratorium Klinik Prodia Surakarta

    Directory of Open Access Journals (Sweden)

    Sarsi Hartiningsih

    2017-01-01

    Full Text Available ABSTRACT This research is a descriptive study, provides an overview of the influence of the dimensions of the marketing mix consisting of product, price, promotion, distribution channels/locations and the physical evidence against the customers decisions. The purpose of this study was to determine the effect of each variable product, price, promotion, distribution channels/locations and the physical evidence against the customers decision in using the services of Prodia Clinical Laboratory in Surakarta. The samples used were 75 consumers. Instument test result data indicates that every marketing mix variables (5P has the highest r count>r table and Cronbach's alpha values>0.60 so that the data is valid and reliable and can be used for further research. Hypothesis test results show that each variable product, price, promotion, distribution channels/locations and physical evidence has the value t count>t table with a significance value of r tabel dan nilai cronbach’s alpha > 0.60 sehingga data bersifat valid dan reliabel dan dapat digunakan untuk penelitian selanjutnya. Hasil uji hipotesis menunjukkan bahwa masing-masing variabel produk, harga, promosi, saluran distribusi/lokasi dan bukti fisik mempunyai nilai t hitung > t tabel dengan nilai signifikasi < 0.05 sehingga dapat disimpulkan bahwa produk, harga, promosi, saluran distribusi/lokasi dan bukti fisik berpengaruh positif dan signifikan terhadap keputusan konsumen dalam menggunakan jasa Laboratorium Klinik Prodia Kata kunci  : produk, harga, promosi, saluran distribusi/lokasi dan bukti fisik keputusan konsumen.

  15. Functional brain imaging - baric and clinical questions; Funktionelle Bildgebung in der Psychiatrie - Fragestellungen der Klinik und der Forschung

    Energy Technology Data Exchange (ETDEWEB)

    Mager, T. [Psychiatrische Klinik und Poliklinik, Klinikum Innenstadt, Muenchen Univ. (Germany); Moeller, H.J. [Psychiatrische Klinik und Poliklinik, Klinikum Innenstadt, Muenchen Univ. (Germany)

    1997-06-01

    The advancing biological knowledge of disease processes plays a central part in the progress of modern psychiatry. An essential contribution comes from the functional and structural brain imaging techniques (CT, MRI, SPECT, PET). Their application is important for biological oriented research in psychiatry and there is also a growing relevance in clinical aspects. This development is taken into account by recent diagnostic classification systems in psychiatry. The capabilities and limitations of functional brain imaging in the context of research and clinic will be presented and discussed by examples and own investigations. (orig.) [Deutsch] Der Fortschritt in der Psychiatrie der letzten Jahre ist eng verknuepft mit neuen biologischen Erkenntnissen ueber Krankheitsprozesse. Einen wesentlichen Beitrag hierzu leistet die moderne funktionelle und strukturelle Bildgebung, deren Anwendung ein wichtiger Bestandteil biologischer Forschung ist und zunehmend auch an klinischer Bedeutung gewinnt. In den neuen Klassifikationssystemen der Psychiatrie wird diese Entwicklung beruecksichtigt. Moeglichkeiten und Grenzen funktioneller Bildgebung fuer die Psychiatrie werden mit Blick auf die Klinik und wissenschaftliche Fragestellungen im folgenden anhand von Beispielen und eigenen Untersuchungen skizziert und diskutiert. (orig.)

  16. ANALISIS SURVIVAL PENINGKATAN DENSITAS MINERAL TULANG PASIEN PEREMPUAN YANG MENDERITA OSTEOPOROSIS PRIMER DENGAN TERAPI SESUAI TATA LAKSANA KLINIK MTIE (MAKMAL TERPADU IMMUNOENDOKRINOLOGI

    Directory of Open Access Journals (Sweden)

    Halimah Halimah

    2012-11-01

    Full Text Available Background: Life expectacy in Indonesia was increasing every year as impact of access to health services. On 2004 number of elderly people is 16.5 million, 52.6% is female. The most health problem facing by female elderly was osteoporosis that it proved by incidence of osteoporosis among female was higher than male. In fact of that one out of three female tends to have osteoporosis; meanwhile the incidence among male is one out of seven. The objective of this study was to know the length of time for bone development in order to increase the mineral bone density up to 1.5% and 3 percentages in three measurement locations (lumbal, femur, radius. Method: The study has probed as well as the influence factors of bone growth among the osteoporosis patients who were examinated their bone at Klinik Makmal Terpadu Imunoendokrinologi FK UI. This is a longitudinal study with scope in clinical area which include the secondary data analysis form medical record data. The total sample was 52 osteoporosis patients. Analysis survival application is performed for data analysis by using variable time and event from January 2004 to December 2007. The analysis in this study is univariate, bivariate,Kaplan-Meier method, and multivariate with double regresi cox. The factors related with time of remodeling bone were medication standard operating procedure (SOP, and body mass index (BMI. Results: Medication SOP in Klinik Makmal has faster time of remodeling bone and significant result comparing with SOP in other policlinic; on lumbal (event 1.5% and 3% and femur (event 1.5%. Patients with BMI <25 has faster time remodeling bone than patients BMI >25 on femur 1.5%. Contraception group and patient’s age have not enough provided the different time of remodeling bone in those measurement. SOP hazard ratio on lumbal was 3.359, it means patient who receive therapy in Klinik Makmal has 3.36 times chance to have lumbal remodeling bone up to 1.5%. Meanwhile, medication SOP

  17. PROBABILITAS PULIH PADA BALITA KURUS DAN KURUS SEKALI MENURUT KEPATUHAN MENGIKUTI PEMULIHAN SECARA RAWAT JALAN DI KLINIK GIZI BOGOR

    Directory of Open Access Journals (Sweden)

    Sri Muljati

    2012-11-01

    Full Text Available THE PROBABILITY OF NUTRITIONAL STATUS IMPROVEMENT AMONG WASTING CHILDREN ACCORDING TO ROUTINE VISITS TO KLINIK GIZI BOGOR.Background: Prevalence of malnutrition on todler in Indonesia still high. It's an indication that nutrition prevention is not yet safisfiying. SKRT 2004 data shows that 9.3% todler in the cities and 11.1% In the village include in category at thin and very thin. Data from departement of health of RI 2005, Prevalence of malnutrition on todler is still on 19.2% and severe malnutrition is 8.8%. Bogor nutritional clinic is already develop severe malnutrition treament by out patient.Aims: To analize data of nutritional clinic visitors on 2001-2005. To now the probability of cured until Z_skore ≥ -2.5 SD dan Z_skore ≥ -2.0 SD, by using weight for height index on thin todlers and very thin todlers after six months of treatment. Methods: 294 todlers are devided in to two categories, which are 192 thin subject (≥-3SD s/d <-2 SD and 102 very thin (<-3 SD or thin with clinical indication. Inclution criteria in this anallsis, that the subject doesn't have such as down syndrome, heart disorder, thalasemia, hydrocephalus and microcephalus. Results: The study revealed that father education, mother age, todler age and compliance of treatment were correlated with probability of cured until Z_skore ≥ -2.5 SD dan Z_skore ≥ -2.0 SD, on thin todlers and very thin todlers after six months of treatment.Keywords: severe wasting, under five years, compliance

  18. Adverse effects of immunotherapy. Clinical aspects, radiological and nuclear medicine results; Unerwuenschte Wirkungen der Immuntherapie. Klinik, radiologische und nuklearmedizinische Befunde

    Energy Technology Data Exchange (ETDEWEB)

    Widmann, G.; Plaickner, J.; Jaschke, W. [Medizinische Universitaet Innsbruck, Universitaetsklinik fuer Radiologie, Innsbruck (Austria); Nguyen, V.A. [Medizinische Universitaet Innsbruck, Universitaetsklinik fuer Dermatologie, Venerologie und Allergologie, Innsbruck (Austria)

    2017-10-15

    The increasing use of immunotherapy in oncology increases the need for radiologic evaluation of frequent and severe immune-related adverse events. Determination of the incidence and manifestation of radiologic and nuclear medicine findings of immune-related adverse events. Literature review of clinical and imaging findings of immune-related adverse events induced by the immune checkpoint inhibitors ipilimumab, nivolumab and pembrolizumab. Findings are illustrated with pictorial examples and contrasted to other relevant differential diagnoses. The most frequent imaging manifestations are colitis, hepatitis, pancreatitis, hypophysitis, pneumonitis, arthritis and sarcoid-like lymphadenopathy. Severe to life-threatening complications may result from colitis, pneumonitis and hypophysitis. A clear differentiation from other autoimmune diseases and discrimination of immune-related and infectious pulmonary findings can be very difficult and need close multidisciplinary collaboration. Knowledge of clinical and imaging findings of adverse events induced by immunotherapy is essential for timely and adequate therapeutic decisions. In addition to staging and follow-up imaging, identification and monitoring of immune-related adverse events adds to the radiologic responsibility in oncologic care. (orig.) [German] Mit zunehmendem Einsatz von Immuntherapien in der Onkologie steigt die Bedeutung der radiologischen Beurteilung haeufiger und schwerwiegender immunbedingter Nebenwirkungen. Inzidenz und Manifestation radiologischer und nuklearmedizinischer Befunde der immunbedingten Nebenwirkungen. Literaturuebersicht zu Klinik und bildgebenden Befunden immunbedingter Nebenwirkungen der Immuncheckpointinhibitoren Ipilimumab, Nivolumab und Pembrolizumab. Veranschaulichung mit Bildbeispielen und Gegenuebergestellung mit anderen relevanten Differenzialdiagnosen. Die haeufigsten bildgebenden Manifestationen sind Kolitis, Hepatitis, Pankreatitis, Hypophysitis, Pneumonitis, Arthritis und die

  19. Effects of ultraviolet laser radiation on Venezuelan equine encephalomyelitis virus

    International Nuclear Information System (INIS)

    Nikogosyan, D.N.; Kapituletz, S.P.; Smirnov, Y.A.

    1991-01-01

    The effects of usual low-intensity continuous (λ = 254 nm,I = 10 W/m 2 ) UV radiation and high-intensity laser nanosecond (λ = 266 nm, τ p = 10 ns, I = 10 9 W/m 2 ) or picosecond (λ = 266 nm, τ p = 23 ps, I = 10 12 W/m 2 ) UV radiation on Venezuelan equine encephalomyelitis virus (a member of the Togaviridae family) were compared. The quantum yields of infectivity inactivation, pyrimidine dimer formation and RNA-protein crosslinking were determined. (author)

  20. Bioluminescence in vivo imaging of autoimmune encephalomyelitis predicts disease

    Directory of Open Access Journals (Sweden)

    Steinman Lawrence

    2008-02-01

    Full Text Available Abstract Background Experimental autoimmune encephalomyelitis is a widely used animal model to understand not only multiple sclerosis but also basic principles of immunity. The disease is scored typically by observing signs of paralysis, which do not always correspond with pathological changes. Methods Experimental autoimmune encephalomyelitis was induced in transgenic mice expressing an injury responsive luciferase reporter in astrocytes (GFAP-luc. Bioluminescence in the brain and spinal cord was measured non-invasively in living mice. Mice were sacrificed at different time points to evaluate clinical and pathological changes. The correlation between bioluminescence and clinical and pathological EAE was statistically analyzed by Pearson correlation analysis. Results Bioluminescence from the brain and spinal cord correlates strongly with severity of clinical disease and a number of pathological changes in the brain in EAE. Bioluminescence at early time points also predicts severity of disease. Conclusion These results highlight the potential use of bioluminescence imaging to monitor neuroinflammation for rapid drug screening and immunological studies in EAE and suggest that similar approaches could be applied to other animal models of autoimmune and inflammatory disorders.

  1. Ageing and recurrent episodes of neuroinflammation promote progressive experimental autoimmune encephalomyelitis in Biozzi ABH mice

    NARCIS (Netherlands)

    Peferoen, Laura A. N.; Breur, Marjolein; van de Berg, Sarah; Peferoen-Baert, Regina; Boddeke, Erik H. W. G. M.; van der Valk, Paul; Pryce, Gareth; van Noort, Johannes M.; Baker, David; Amor, Sandra

    2016-01-01

    Current therapies for multiple sclerosis (MS) reduce the frequency of relapses by modulating adaptive immune responses but fail to limit the irreversible neurodegeneration driving progressive disability. Experimental autoimmune encephalomyelitis (EAE) in Biozzi ABH mice recapitulates clinical

  2. Individual behavioral characteristics of wild-type rats predict susceptibility to experimental autoimmune encephalomyelitis

    NARCIS (Netherlands)

    Kavelaars, A; Heijnen, CJ; Tennekes, R; Bruggink, JE; Koolhaas, JM

    1999-01-01

    Neuroendocrine-immune interactions are thought to be important in determining susceptibility to autoimmune disease. Animal studies have revealed that differences in susceptibility to experimental autoimmune encephalomyelitis (EAE) are related to:reactivity in the hypothalamo-pituitary-adrenal axis.

  3. Minocycline Effects on the Cerebrospinal Fluid Proteome of Experimental Autoimmune Encephalomyelitis Rats

    NARCIS (Netherlands)

    Stoop, Marcel P.; Rosenling, Therese; Attali, Amos; Meesters, Roland J. W.; Stingl, Christoph; Dekker, Lennard J.; van Aken, Hans; Suidgeest, Ernst; Hintzen, Rogier Q.; Tuinstra, Tinka; van Gool, Alain; Luider, Theo M.; Bischoff, Rainer

    2012-01-01

    To identify response biomarkers for pharmaceutical treatment of multiple sclerosis, we induced experimental autoimmune encephalomyelitis (EAE) in rats and treated symptomatic animals with minocycline. Cerebrospinal fluid (CSF) samples were collected 14 days after EAE induction at the peak of

  4. Minocycline effects on the cerebrospinal fluid proteome of experimental autoimmune encephalomyelitis rats

    NARCIS (Netherlands)

    Stoop, M.P.; Rosenling, T.; Attali, A.; Meesters, R.J.; Stingl, C.; Dekker, L.J.; van Aken, H.; Suidgeest, E.; Hintzen, R.Q.; Tuinstra, T.; Gool, A.J. van; Luider, T.M.; Bischoff, R.

    2012-01-01

    To identify response biomarkers for pharmaceutical treatment of multiple sclerosis, we induced experimental autoimmune encephalomyelitis (EAE) in rats and treated symptomatic animals with minocycline. Cerebrospinal fluid (CSF) samples were collected 14 days after EAE induction at the peak of

  5. Amelioration of ongoing experimental autoimmune encephalomyelitis with fluoxetine.

    Science.gov (United States)

    Bhat, Roopa; Mahapatra, Sidharth; Axtell, Robert C; Steinman, Lawrence

    2017-12-15

    In patients with multiple sclerosis, the selective serotonin reuptake inhibitor, fluoxetine, resulted in less acute disease activity. We tested the immune modulating effects of fluoxetine in a mouse model of multiple sclerosis, i.e. experimental autoimmune encephalomyelitis (EAE). We show that fluoxetine delayed the onset of disease and reduced clinical paralysis in mice with established disease. Fluoxetine had abrogating effects on proliferation of immune cells and inflammatory cytokine production by both antigen-presenting cells and T cells. Specifically, in CD 4 T cells, fluoxetine increased Fas-induced apoptosis. We conclude that fluoxetine possesses immune-modulating effects resulting in the amelioration of symptoms in EAE. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Costimulatory signal blockade in murine relapsing experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Schaub, M; Issazadeh-Navikas, Shohreh; Stadlbauer, T H

    1999-01-01

    Blockade of the CD28-B7 or CD40L-CD40 T cell costimulatory signals prevents induction of experimental autoimmune encephalomyelitis (EAE). However, the effect of simultaneous blockade of these signals in EAE is unknown. We show that administration of either MR1 (to block CD40L) or CTLA4Ig (to block...... B7) after immunization or after the first attack protects from EAE. Treatment with a combination of CTLA4Ig and MR1 provides additive protection, and is associated with complete absence of mononuclear cell infiltrates in the central nervous system, and marked suppression of proliferation of primed T...... cells in the periphery. Selective B7-1 blockade did not protect from EAE. These observations have implications for therapy of autoimmune diseases....

  7. Acute disseminated encephalomyelitis: a case report of effective early immunotherapy

    Science.gov (United States)

    Ritarwan, K.; Ramayani, O. R.; Eyanoer, P.

    2018-03-01

    Acute disseminated encephalomyelitis (ADEM) is a monophasic acute non-vasculitic inflammatory demyelinating disorder of the central nervous system characterized by diffuse neurologic signs and symptoms coupled with evidence of multifocal lesions of demyelination on neuroimaging. Despite the long-standing recognition of ADEM as a specific entity, no consensus definition of ADEM had been reached until recently. Historically, different definitions of ADEM have been in published cases of pediatric and adult patients, which varied as to whether events required (1) monofocal or multifocal clinical features, (2) a change in mental status, and (3) a documentation of previous infection or immunization. The treatment has been given to the patient such as supportive therapy and high dose corticosteroids.

  8. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis.

    LENUS (Irish Health Repository)

    Fletcher, J M

    2012-02-01

    Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS), which involves autoimmune responses to myelin antigens. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have provided convincing evidence that T cells specific for self-antigens mediate pathology in these diseases. Until recently, T helper type 1 (Th1) cells were thought to be the main effector T cells responsible for the autoimmune inflammation. However more recent studies have highlighted an important pathogenic role for CD4(+) T cells that secrete interleukin (IL)-17, termed Th17, but also IL-17-secreting gammadelta T cells in EAE as well as other autoimmune and chronic inflammatory conditions. This has prompted intensive study of the induction, function and regulation of IL-17-producing T cells in MS and EAE. In this paper, we review the contribution of Th1, Th17, gammadelta, CD8(+) and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes.

  9. R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice.

    Science.gov (United States)

    Schmitz, Katja; de Bruin, Natasja; Bishay, Philipp; Männich, Julia; Häussler, Annett; Altmann, Christine; Ferreirós, Nerea; Lötsch, Jörn; Ultsch, Alfred; Parnham, Michael J; Geisslinger, Gerd; Tegeder, Irmgard

    2014-11-01

    R-flurbiprofen is the non-cyclooxygenase inhibiting R-enantiomer of the non-steroidal anti-inflammatory drug flurbiprofen, which was assessed as a remedy for Alzheimer's disease. Because of its anti-inflammatory, endocannabinoid-modulating and antioxidative properties, combined with low toxicity, the present study assessed R-flurbiprofen in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis in mice. Oral R-flurbiprofen prevented and attenuated primary progressive EAE in C57BL6/J mice and relapsing-remitting EAE in SJL mice, even if the treatment was initiated on or after the first flare of the disease. R-flurbiprofen reduced immune cell infiltration and microglia activation and inflammation in the spinal cord, brain and optic nerve and attenuated myelin destruction and EAE-evoked hyperalgesia. R-flurbiprofen treatment increased CD4(+)CD25(+)FoxP3(+) regulatory T cells, CTLA4(+) inhibitory T cells and interleukin-10, whereas the EAE-evoked upregulation of pro-inflammatory genes in the spinal cord was strongly reduced. The effects were associated with an increase of plasma and cortical endocannabinoids but decreased spinal prostaglandins, the latter likely due to R to S inversion. The promising results suggest potential efficacy of R-flurbiprofen in human MS, and its low toxicity may justify a clinical trial. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  10. THE TRANSMISSION OF EQUINE ENCEPHALOMYELITIS VIRUS BY AEDES AEGYPTI.

    Science.gov (United States)

    Merrill, M H; Tenbroeck, C

    1935-10-31

    In confirming Kelser's work on the transmission of equine encephalomyelitis of the western type by Aëdes aegypti it has been learned that the mosquitoes must be fed virus of high titer if positive results are to be secured. A period of from 4 to 5 days after feeding either on infected guinea pigs or on brain containing virus must elapse before the disease is transmitted by biting, but after this time transmission regularly results for a period of about 2 months. By inoculation, virus can be demonstrated in the bodies of infected mosquitoes for the duration of life. Although virus multiplies in the mosquitoes and is generally distributed in their bodies, repeated attempts to demonstrate it in the eggs from females known to be infected as well as in larvae, pupae, and adults from such eggs have been uniformly negative. Larvae have not taken up virus added to the water in which they were living. Male mosquitoes have been infected with virus by feeding but they have not transmitted the virus to normal females, nor have males transmitted the virus from infected to normal females. When virus of the eastern instead of the western type is used transmission experiments with Aëdes aegypti are negative. Apparently this virus is incapable of penetrating the intestinal mucosa of the mosquito. If, however, it is inoculated into the body cavity by needle puncture it persists and transmission experiments are positive.

  11. Persistent pseudobulbar affect secondary to acute disseminated encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Zhendong Li

    2015-03-01

    Full Text Available Pseudobulbar affect (PBA is a common complication of central nervous system diseases such as stroke, multiple sclerosis, and other neurological diseases, but it remains under-recognized and under-treated in the clinic. PBA caused by acute disseminated encephalomyelitis (ADEM has rarely been reported. Here, we report a 30-year-old Chinese woman who has experienced PBA from ADEM for 7 years. The patient's principal manifestations were extreme emotions or tears when she saw, heard, or spoke about sad news or other sad things; the durations of these unmanageable emotions were often less than 30 sec, and they occurred at frequencies that ranged from one to several times a day. Occasionally, she laughed uncontrollably while people were talking despite a lack of funny or sad stimuli in the conversation or the surrounding environment. Thus, her social functioning was impaired. This case indicates that the long-term PBA can occur secondarily to ADEM, and this possibility should be considered clinically to ensure timely identification and treatment.

  12. IL-12p35 Inhibits Neuroinflammation and Ameliorates Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Jin Kyeong Choi

    2017-10-01

    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease in which cytokines produced by immune cells that infiltrate the brain and spinal cord play a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL-35 cytokine, might be an effective biologic for suppressing neuroinflammatory responses and ameliorating the pathology of experimental autoimmune encephalomyelitis (EAE, the mouse model of human MS. We further show that IL-12p35 conferred protection from neuropathy by inhibiting the expansion of pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells into the brain and spinal cord. In addition, in vitro exposure of encephalitogenic cells to IL-12p35 suppressed their capacity to induce EAE by adoptive transfer. Importantly, the IL-12p35-mediated expansion of Treg and Breg cells and its amelioration of EAE correlated with inhibition of cytokine-induced activation of STAT1/STAT3 pathways. Moreover, IL-12p35 inhibited lymphocyte proliferation by suppressing the expressions of cell-cycle regulatory proteins. Taken together, these results suggest that IL-12p35 can be exploited as a novel biologic for treating central nervous system autoimmune diseases and offers the promise of ex vivo production of large amounts of Tregs and Bregs for immunotherapy.

  13. Metabolism of 32P-phosphate in guinea pig cerebrum and cerebellum in experimental allergic encephalomyelitis

    International Nuclear Information System (INIS)

    Mezes, V.; Bukovsky, V.; Drgova, A.; Mezesova, V.

    1984-01-01

    The metabolism of intraventricularly administered 32 P-phosphate in the cerebral and cerebellar tissue of guinea pigs was analyzed in the acute state of experimental allergic encephalomyelitis. One and six hours following administration of 32 P-phosphate into the right lateral ventricle of the brain no differences were found in the specific activity of phosphates of the acid-soluble fraction of the brain tissue in the compared series of guinea pigs. The cerebellar tissue in experimental allergic encephalomyelitis displayed the specific activity of the total phosphorus of the acid-soluble fraction reduced by 27% one hour after administration and by 37% after six hours, and the specific activity of inorganic phosphates was reduced by 40% and by 45%, respectively. Experimental allergic encephalomyelitis does not affect the content of total phosphorus in the acid-soluble fraction and in the fraction of inorganic phosphates in the cerebrum and cerebellum of guinea pigs. (author)

  14. Increased KPI containing amyloid precursor protein in experimental autoimmune encephalomyelitis brains.

    Science.gov (United States)

    Beilin, Orit; Karussis, Dimitrios M; Korczyn, Amos D; Gurwitz, David; Aronovich, Ramona; Mizrachi-Kol, Rachel; Chapman, Joab

    2007-04-16

    Amyloid precursor protein can be translated from three alternatively spliced mRNAs. We measured levels of amyloid precursor protein isoforms containing the Kunitz protease inhibitor domain (KPIAPP), and amyloid precursor protein without the Kunitz protease inhibitor domain (KPIAPP) in brain homogenates of acute experimental autoimmune encephalomyelitis mice. At the preclinical phase of the disease, both KPIAPP and KPIAPP levels were significantly higher in homogenates from brains of autoimmune encephalomyelitis mice, whereas at the acute phase of the disease only KPIAPP remained significantly elevated compared with controls. At the recovery phase, no differences were observed between the groups. The early and isoform-specific elevation of KPIAPP in autoimmune encephalomyelitis mice suggests a possible role for amyloid precursor protein in the immune response mediating the disease.

  15. Reversible paraneoplastic encephalomyelitis as the presenting feature of ovarian teratoma: A clinicopathological correlate

    Directory of Open Access Journals (Sweden)

    Rajappa Senthil

    2007-01-01

    Full Text Available Paraneoplastic encephalomyelitis (PEM is a well-characterized neurological syndrome. Its association with ovarian teratoma is rare. A young lady presented with features suggestive of encephalomyelitis with predominant cerebellar syndrome. Magnetic resonance imaging brain was normal. Cerebrospinal fluid showed lymphocytic pleocytosis. Computerized tomography scan of the pelvis revealed a complex left ovarian cyst. With a clinical diagnosis of PEM she underwent a left salpingo-oopherectomy. This was followed by total recovery of the PEM in two weeks. The histopathology revealed immature teratoma. The interesting feature was the clinicopathological correlation between the finding of fetal cerebellar tissue in the tumor and the PEM with predominant cerebellar features.

  16. MR findings in acute disseminated encephalomyelitis in children

    International Nuclear Information System (INIS)

    Kim, Wha Young; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo

    2006-01-01

    We reviewed the distribution of lesion and the characteristics of the MR findings of acute disseminated encephalomyelitis (ADEM) in children. We evaluated the differences in the imaging findings and the clinical outcomes between the patients with deep gray matter involvement and the patients without deep gray matter involvement. We retrospectively reviewed the 62 MR examinations of 21 patients who were discharged with the clinical diagnosis of ADEM. The patients were aged from 13 months to 12 years old (mean age: 4.5 years). Follow-up MR examinations were done one to 5 times (mean: 3 times) for 2 weeks to 4 years (mean: 3 months) after the initial examination. We compared the signal intensity on T2WI, the enhancement and residue on the MR images and the clinical outcomes between the patients with deep gray matter involvement and the patients without deep gray matter involvement. A total of 21 patients had white matter abnormalities on their initial MR. Fifteen patients (71%) had foci of increased signal intensity on T2WI in the deep gray matter: thalamus (n=15), globus pallidus (n=14) and putamen (n=10). On the follow-up images, all patients showed decreased signal intensity and enhancement of their lesion. We could not find the significant differences in signal intensity, enhancement and residue on the MRIs and also the clinical outcomes between the patients with deep gray matter involvement and the patients without deep gray matter involvement (<.05). There were no significant differences in the characteristics of the imaging and the clinical outcomes between the ADEM patients with deep gray matter involvement and those ADEM patients without deep gray matter involvement

  17. Chondroitin 6-O-sulfate ameliorates experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Miyamoto, Katsuichi; Tanaka, Noriko; Moriguchi, Kota; Ueno, Rino; Kadomatsu, Kenji; Kitagawa, Hiroshi; Kusunoki, Susumu

    2014-05-01

    Chondroitin sulfate proteoglycans (CSPGs) are the main component of the extracellular matrix in the central nervous system (CNS) and influence neuroplasticity. Although CSPG is considered an inhibitory factor for nerve repair in spinal cord injury, it is unclear whether CSPG influences the pathogenetic mechanisms of neuroimmunological diseases. We induced experimental autoimmune encephalomyelitis (EAE) in chondroitin 6-O-sulfate transferase 1-deficient (C6st1(-/-)) mice. C6ST1 is the enzyme that transfers sulfate residues to position 6 of N-acetylgalactosamine in the sugar chain of CSPG. The phenotypes of EAE in C6st1(-/-) mice were more severe than those in wild-type (WT) mice were. In adoptive-transfer EAE, in which antigen-reactive T cells from WT mice were transferred to C6st1(-/-) and WT mice, phenotypes were significantly more severe in C6st1(-/-) than in WT mice. The recall response of antigen-reactive T cells was not significantly different among the groups. Furthermore, the number of pathogenic T cells within the CNS was also not considerably different. When EAE was induced in C6ST1 transgenic mice with C6ST1 overexpression, the mice showed considerably milder symptoms compared with those in WT mice. In conclusion, the presence of sulfate at position 6 of N-acetylgalactosamine of CSPG may influence the effecter phase of EAE to prevent the progression of pathogenesis. Thus, modification of the carbohydrate residue of CSPG may be a novel therapeutic strategy for neuroimmunological diseases such as multiple sclerosis.

  18. CT-verified intracranial calcifications and contrast enhancement in acute disseminated encephalomyelitis: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Ipsen, P. [Department of Neuroradiology, Aarhus University Hospital (Denmark)

    1998-08-01

    Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease which follows viral infection or vaccination. We report the CT findings in a 13-year-old boy with ADEM after infection with Epstein-Barr virus. After 11 days, the patient developed intracranial calcifications in addition to demyelinating lesions. This is a rare finding in ADEM. (orig.) With 4 figs., 15 refs.

  19. CT-verified intracranial calcifications and contrast enhancement in acute disseminated encephalomyelitis: a case report

    International Nuclear Information System (INIS)

    Ipsen, P.

    1998-01-01

    Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease which follows viral infection or vaccination. We report the CT findings in a 13-year-old boy with ADEM after infection with Epstein-Barr virus. After 11 days, the patient developed intracranial calcifications in addition to demyelinating lesions. This is a rare finding in ADEM. (orig.)

  20. 9 CFR 113.207 - Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus.

    Science.gov (United States)

    2010-01-01

    ..., Western, and Venezuelan, Killed Virus. 113.207 Section 113.207 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.207 Encephalomyelitis...

  1. The role of perivascular and meningeal macrophages in experimental allergic encephalomyelitis

    NARCIS (Netherlands)

    Polfliet, Machteld M. J.; van de Veerdonk, F.; Döpp, Ed A.; van Kesteren-Hendrikx, Esther M. L.; van Rooijen, Nico; Dijkstra, Christine D.; van den Berg, Timo K.

    2002-01-01

    The perivascular (PVM) and meningeal (MM) macrophages constitute a major population of resident macrophages in the central nervous system (CNS). To investigate a possible role of PVM and MM during CNS inflammation, we have analysed PVM and MM during experimental allergic encephalomyelitis (EAE), an

  2. 78 FR 15371 - Drug Development for Chronic Fatigue Syndrome and Myalgic Encephalomyelitis; Public Workshop

    Science.gov (United States)

    2013-03-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0962] Drug Development for Chronic Fatigue Syndrome and Myalgic Encephalomyelitis; Public Workshop AGENCY... therapies to treat signs and symptoms related to chronic fatigue syndrome (CFS) and myalgic...

  3. Encephalomyelitis following rabies vaccination - report of a case and review of the literature

    International Nuclear Information System (INIS)

    Turtelli, Celso Montenegro; Leon, Hector L. Coraspe; Francisco, Luis Miguel; Leite, Luciana S. Batista

    1997-01-01

    Encephalomyelitis is a rare complication following rabies vaccination. In patients with acute or subacute central nervous system illnesses such event must be considered in the differential diagnosis. Computed tomography and magnetic resonance imaging play important role in diagnosis and prognosis. (author)

  4. Neurologic and MRI Abnormalities in Acute Disseminated Encephalomyelitis and Response to Plasmapheresis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-08-01

    Full Text Available The relation between the clinical course and MRI findings and response to plasmapheresis were determined by a retrospective record review of 13 children with acute disseminated encephalomyelitis (ADEM admitted to St Christopher’s Hospital for Children, Philadelphia, PA, during 1998-2003.

  5. Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease.

    Science.gov (United States)

    Underhill, R A

    2015-12-01

    The etiology of myalgic encephalomyelitis also known as chronic fatigue syndrome or ME/CFS has not been established. Controversies exist over whether it is an organic disease or a psychological disorder and even the existence of ME/CFS as a disease entity is sometimes denied. Suggested causal hypotheses have included psychosomatic disorders, infectious agents, immune dysfunctions, autoimmunity, metabolic disturbances, toxins and inherited genetic factors. Clinical, immunological and epidemiological evidence supports the hypothesis that: ME/CFS is an infectious disease; the causal pathogen persists in patients; the pathogen can be transmitted by casual contact; host factors determine susceptibility to the illness; and there is a population of healthy carriers, who may be able to shed the pathogen. ME/CFS is endemic globally as sporadic cases and occasional cluster outbreaks (epidemics). Cluster outbreaks imply an infectious agent. An abrupt flu-like onset resembling an infectious illness occurs in outbreak patients and many sporadic patients. Immune responses in sporadic patients resemble immune responses in other infectious diseases. Contagion is shown by finding secondary cases in outbreaks, and suggested by a higher prevalence of ME/CFS in sporadic patients' genetically unrelated close contacts (spouses/partners) than the community. Abortive cases, sub-clinical cases, and carrier state individuals were found in outbreaks. The chronic phase of ME/CFS does not appear to be particularly infective. Some healthy patient-contacts show immune responses similar to patients' immune responses, suggesting exposure to the same antigen (a pathogen). The chronicity of symptoms and of immune system changes and the occurrence of secondary cases suggest persistence of a causal pathogen. Risk factors which predispose to developing ME/CFS are: a close family member with ME/CFS; inherited genetic factors; female gender; age; rest/activity; previous exposure to stress or toxins

  6. The psychological impact of dependency in adults with chronic fatigue syndrome/myalgic encephalomyelitis: A qualitative exploration.

    Science.gov (United States)

    Williams, Ashley Mai; Christopher, Gary; Jenkinson, Elizabeth

    2016-04-01

    Chronic fatigue syndrome/myalgic encephalomyelitis can limit functional capacity, producing various degrees of disability and psychological distress. Semi-structured interviews explored the experiences of adults with chronic fatigue syndrome/myalgic encephalomyelitis being physically dependent on other people for help in daily life, and whether physical dependency affects their psychological well-being. Thematic analysis generated six themes: loss of independence and self-identity, an invisible illness, anxieties of today and the future, catch-22, internalised anger, and acceptance of the condition. The findings provide insight into the psychological impact of dependency. Implications for intervention include better education relating to chronic fatigue syndrome/myalgic encephalomyelitis for family members, carers, and friends; ways to communicate their needs to others who may not understand chronic fatigue syndrome/myalgic encephalomyelitis; and awareness that acceptance of the condition could improve psychological well-being.

  7. HAMBATAN DALAM MENDAPATKAN PENGALAMAN BELAJAR KLINIS PADA KEPANITERAAN KLINIK DI UNIT GAWAT DARURAT (UGD BAGI MAHASISWA FAKULTAS KEDOKTERAN UNIVERSITAS ANDALAS PADANG

    Directory of Open Access Journals (Sweden)

    Hardisman Hardisman

    2009-05-01

    Full Text Available AbstrakPenatalaksanaan gawat darurat merupakan kompetensi yang vital dan harus dimiliki oleh setiap dokter. Selain itu, sejak tahun ajaran 2007/2008 pada tahapan klinik, FK-UNAND melakukan penataan lebih baik pada sistim kepaniteraan. Oleh karea itu perlu dilihat apakah peroses pendidikan di UGD juga telah memberikan pengalaman belajar klinis yang optimal? Serta apa hambatan dalam mendapatkan pengalaman klinis tersebut?.Desain penelitian ini adalah cross sectional study dan dilaksanakan pada bulan September 2007 - Maret 2008. Instrument pengumpulan data adalah kuisioner terstruktur dan sebagian besar menggunakan sistim skala. Populasi dan sampel penelitian ini adalah seluruh mahasiswa yang sedang menjalankan rotasi kepaniteraan klinik di Instalasi Gawat darurat (IGD yang diambil pada dua siklus. Data-data kuantitatif dianalisa secara deskriptif. Untuk melihat bagaimana perbedaan gender dalam mendapatkan pengalaman belajar klinis dianalisa secara statistik (t-test.Kesempatan belajar memperoleh pengalaman klinis oleh mahasiswa mencapai skala 3 lebih (sedang dan tidak ada perbedaan antara laki-laki dan perempuan (p>0,05. Secara sepesifik, kesempatan melakukan tindakan penatalaksanaan jalan nafas (airway management merupakan kesempatan yang paling jarang didapatkan (skala 2,11. Kesempatan melakukan penatalaksanaan dan menjahit luka serta melakukan injeksi cukup sering, dengan skala 4,05 dan 4,25. Hambatan utama dalam memperoleh pengalaman klinis adalah karena jumlah pasein yang kurang (39,7% kurangnya bimbingan (32,9% dan sikap penerimaan atau penolakan dari staf perawat (16,4%.Kesempatan mendapatkan pengalaman dan pencapaian kompetensi klinis mahasiswa di UGD belumlah optimal. Hal ini dipengaruhi oleh beberapa hambatan seperti jumlah pasien dan bimbingan yang kurang serta sikap penerimaan dan kerjasama staf perawat.Kata Kunci: Pengalaman belajar klinis dan pendidikan kedokteran.ARTIKEL PENELITIAN9AbstractClinical competency in management of

  8. THE ROLE OF CONTARST ENHANCEMENT IN VISUALIZATION OF ACUTE DISSEMINATED ENCEPHALOMYELITIS

    Directory of Open Access Journals (Sweden)

    A.A. Alikhanov

    2008-01-01

    Full Text Available It has been described the results of MRI and ct neurovisualization with contrast enhancement in 38 children with clinical diagnosis acute disseminated encephalomyelitis (ADE. The distribution of contrast agents in regions of ADE has been studied and the role of contrast enhancement in diagnosis of its has been estimated. Contrast media application allows to detect brain lesions, to identificate the real volume of cerebral tissue included in pathological process and to estimate the efficacy of treatment of ADE. Investigated variants of MRCM (gadopentetate dimeglumine, gadobutrol and RCM (iopromide distribution in zones of brain lesions in patients with ade are the basis for specificity increase of ADE diagnosis.Key words: acute disseminated encephalomyelitis, contrast enhancement, children.

  9. Relapsing acute disseminated encephalomyelitis associated with chronic Epstein-Barr virus infection: MRI findings

    International Nuclear Information System (INIS)

    Shoji, H.; Kusuhara, T.; Honda, Y.; Hino, H.; Kojima, K.; Abe, T.; Watanabe, M.

    1992-01-01

    A 25-year-old women had a fever, left cervical lymphadenopathy, neurological symptoms and signs, CSF pleocytosis and persistent high serum antibodies to the Epstein-Barr virus (EBV); she had a recurrence 1 year later. She was thought to have relapsing acute disseminated encephalomyelitis associated with chronic EBV infection. MRI revealed abnormalities, mainly in the right basal ganglia and left midbrain. At the time of the recurrence, further abnormalities appeared in the opposite basal ganglia and right cerebral white matter. (orig.)

  10. Relapsing acute disseminated encephalomyelitis associated with chronic Epstein-Barr virus infection: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Shoji, H.; Kusuhara, T.; Honda, Y.; Hino, H. (1. Dept. (Neurology) of Internal Medicine, Kurume Univ. School of Medicine (Japan)); Kojima, K.; Abe, T. (Dept. of Radiology, Kurume Univ. School of Medicine (Japan)); Watanabe, M. (Dept. of Neurosurgery, Koyanagi Hospital, Saga (Japan))

    1992-08-01

    A 25-year-old women had a fever, left cervical lymphadenopathy, neurological symptoms and signs, CSF pleocytosis and persistent high serum antibodies to the Epstein-Barr virus (EBV); she had a recurrence 1 year later. She was thought to have relapsing acute disseminated encephalomyelitis associated with chronic EBV infection. MRI revealed abnormalities, mainly in the right basal ganglia and left midbrain. At the time of the recurrence, further abnormalities appeared in the opposite basal ganglia and right cerebral white matter. (orig.).

  11. Factors Influencing Virulence and Plaque Properties of Attenuated Venezuelan Equine Encephalomyelitis Virus Populations

    Science.gov (United States)

    Hearn, Henry J.; Seliokas, Zenonas V.; Andersen, Arthur A.

    1969-01-01

    A minority of stable large-plaque virus increased proportionally in stored unstable attenuated (9t) Venezuelan equine encephalomyelitis virus populations. L-cell-grown progeny (9t2) of stored 9t showed large amounts of large-plaque virus and increased virulence. Small-plaque virus inhibited large-plaque virus but not the reverse. Serial passage of small-plaque virus from 9t2 yielded a strain (20t) that was more attenuated than 9t. PMID:5823235

  12. Acute disseminated encephalomyelitis in children. A descriptive study in Tehran, Iran

    International Nuclear Information System (INIS)

    Samile, N; Hassan, T.

    2007-01-01

    To determine the frequency, etiology (viral infection or vaccination), presenting signs and symptoms, response to therapy, complication and course of acute disseminated encephalomyelitis (ADEM) in our hospitals. A 2-year retrospective, descriptive, chart review of children with final diagnosis of ADEM in 2 hospitals (Hazrat Rasool and Mofid in Tehran, Iran during 2000-2002) was carried out. The diagnosis is based upon clinical presentation, physical examination and ruling out of other disease (imaging, laboratories and so forth) of expert pediatric neurologists. Acute disseminated encephalomyelitis was documented in all cases by characteristics MRI changes included inflammation and demyelination in subcortical or periventricular regions. Acute disseminated encephalomyelitis were diagnosed in 15 patients. More than half of patients were between 9-14 years old. It was rare in 1-5 years old children. It had an abrupt onset, preceding infection/vaccination with no gender differences. Approximately 46.4% of cases had a recent upper respiratory tract illness. Varicella zoster virus infection, urinary tract infection, and mycoplasma pneumoniae were observed. Presentation signs included ataxia, decreased consciousness, fever plus nausea/vomiting, cranial nerve involvement, dysarthric speech, convulsion, hemiparesis, paresthesia, meningismus, and headache. We identified inflammation and demyelination in subcortical than periventricular lesions by magnetic resonance imaging. Prognosis was excellent with low mortality rate (6.6%). Acute disseminated encephalomyelitis is common in our children, possibly because of the high prevalence of causative infections. Due to advances in control of traditional exanthematous diseases such as measle, rubella and so forth, most cases of ADEM in this study followed non-specific upper respiratory infections. Differentiation of ADEM from a single episode of multiple sclerosis is difficult. Diagnosis of multiple sclerosis should be carried out

  13. Housebound versus nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome.

    Science.gov (United States)

    Pendergrast, Tricia; Brown, Abigail; Sunnquist, Madison; Jantke, Rachel; Newton, Julia L; Strand, Elin Bolle; Jason, Leonard A

    2016-12-01

    The objective of this study was to examine individuals with myalgic encephalomyelitis and chronic fatigue syndrome who are confined to their homes due to severe symptomatology. The existing literature fails to address differences between this group, and less severe, nonhousebound patient populations. Participants completed the DePaul Symptom Questionnaire, a measure of myalgic encephalomyelitis and chronic fatigue syndrome symptomology, and the SF-36, a measure of health impact on physical/mental functioning. ANOVAs and, where appropriate, MANCOVAS were used to compare housebound and nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome across areas of functioning, symptomatology, and illness onset characteristics. Findings indicated that the housebound group represented one quarter of the sample, and were significantly more impaired with regards to physical functioning, bodily pain, vitality, social functioning, fatigue, postexertional malaise, sleep, pain, neurocognitive, autonomic, neuroendocrine, and immune functioning compared to individuals who were not housebound. Findings indicated that housebound patients have more impairment on functional and symptom outcomes compared to those who were not housebound. Understanding the differences between housebound and not housebound groups holds implications for physicians and researchers as they develop interventions intended for patients who are most severely affected by this chronic illness. © The Author(s) 2016.

  14. Diffusion Tensor Imaging as a Biomarker to Differentiate Acute Disseminated Encephalomyelitis From Multiple Sclerosis at First Demyelination.

    Science.gov (United States)

    Aung, Wint Yan; Massoumzadeh, Parinaz; Najmi, Safa; Salter, Amber; Heaps, Jodi; Benzinger, Tammie L S; Mar, Soe

    2018-01-01

    There are no clinical features or biomarkers that can reliably differentiate acute disseminated encephalomyelitis from multiple sclerosis at the first demyelination attack. Consequently, a final diagnosis is sometimes delayed by months and years of follow-up. Early treatment for multiple sclerosis is recommended to reduce long-term disability. Therefore, we intend to explore neuroimaging biomarkers that can reliably distinguish between the two diagnoses. We reviewed prospectively collected clinical, standard MRI and diffusion tensor imaging data from 12 pediatric patients who presented with acute demyelination with and without encephalopathy. Patients were followed for an average of 6.5 years to determine the accuracy of final diagnosis. Final diagnosis was determined using 2013 International Pediatric MS Study Group criteria. Control subjects consisted of four age-matched healthy individuals for each patient. The study population consisted of six patients with central nervous system demyelination with encephalopathy with a presumed diagnosis of acute disseminated encephalomyelitis and six without encephalopathy with a presumed diagnosis of multiple sclerosis or clinically isolated syndrome at high risk for multiple sclerosis. During follow-up, two patients with initial diagnosis of acute disseminated encephalomyelitis were later diagnosed with multiple sclerosis. Diffusion tensor imaging region of interest analysis of baseline scans showed differences between final diagnosis of multiple sclerosis and acute disseminated encephalomyelitis patients, whereby low fractional anisotropy and high radial diffusivity occurred in multiple sclerosis patients compared with acute disseminated encephalomyelitis patients and the age-matched controls. Fractional anisotropy and radial diffusivity measures may have the potential to serve as biomarkers for distinguishing acute disseminated encephalomyelitis from multiple sclerosis at the onset. Copyright © 2017 Elsevier Inc. All

  15. Arg deficiency does not influence the course of Myelin Oligodendrocyte Glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Jacobsen, Freja Aksel; Hulst, Camilla; Bäckström, Thomas

    2016-01-01

    Background: Inhibition of Abl kinases has an ameliorating effect on the rodent model for multiple sclerosis, experimental autoimmune encephalomyelitis, and arrests lymphocyte activation. The family of Abl kinases consists of the Abl1/Abl and Abl2/Arg tyrosine kinases. While the Abl kinase has bee...... encephalomyelitis is not dependent on Arg, but Arg plays a role for the number of B cells in immunized mice. This might suggest a novel role for the Arg kinase in B-cell trafficking or regulation. Furthermore, the results suggest that Arg is important for normal embryonic development....

  16. Acute Disseminated Encephalomyelitis: A Review of Eleven Cases in Childhood in North of Iran

    Directory of Open Access Journals (Sweden)

    Ali Nikkhah

    2016-01-01

    Full Text Available Background: Acute disseminated encephalomyelitis (ADEM is an inflammatory demyelinating disorder. The pathogenesis is unclear, but it is thought to be immune-mediated. The prognosis is favorable, with most children making a full recovery. Objectives: The present report analyzed different clinical presentations, response to treatment and outcome in a series of 11 patients with ADEM who referred to our tertiary center in north of Iran from 2010 to 2014. Materials and Methods: In this retrospective simple descriptive review, eleven cases with ADEM admitted in the neurology ward from 2010 to 2014 were enrolled. The clinical findings and laboratory and imaging results of patients were reviewed. All of these cases were evaluated with neurological examination, serologic tests for bacterial meningitis and viral encephalitis (especially, herpes simplex virus and brain MRI without contrast. After discharge, patients were followed for at least six months (6 to 12 months clinically and radiologically. Results: Of 11 children, 8 were male and 3 female. Their ages ranged between 4 and 10 years. The mean interval between the preceding infection and symptoms of encephalomyelitis was nine days. The most common presenting symptoms were ataxia in 45.4%, fever and headache in 36.4% and altered consciousness in 18.2% of patients. Neurological examination revealed pyramidal motor signs such as brisk deep tendon reflexes (hyperreflexia (81.8%, cranial nerve involvement (18.2%, dysarthria (9.1% and abnormal movements (9.1%. We followed up these patients in long-term for 6 to 12 months. Only in 1 child who received IVIG, mild ataxia had reminded. Conclusions: The prognosis of acute disseminated encephalomyelitis (ADEM is favorable. Early diagnosis and prompt treatment of ADEM would probably reduce morbidity.

  17. NEUROPHYSIOLOGY PARAMETERS IN DIAGNOSTICS OF MULTIPLE SCLEROSIS AND ACUTE DISSEMINATED ENCEPHALOMYELITIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    V. B. Voitenkov

    2017-01-01

    Full Text Available Our research objective was to evaluate the importance of neurophysiological methods in diagnosing the state of visual, somatosensory and motor pathways condition in the early stages of multiple sclerosis (MS and acute disseminated encephalomyelitis (ADEM in children.Materials and methods. Twenty-four children with a debut of multiple sclerosis, 15 children with debute of acute disseminated encephalomyelitis and 20 neurologically healthy children of the comparison group were examined. All patients were evaluated by neurologist, brain MRI and CSF analysis (isoelectrofocusing to oligoclonal IgG, oligoclonal bands test, visual evoked potentials (VEP, transcranial magnetic stimulation (TMS and somatosensory evoked potentials (SSEP.Results. In children with MS asymmetry of the conduction along the motor pathways on the spinal level was higher than in patients with ADEM and controls, functional state of somatosensory cortex neurons was lower and conduction along somatosensory pathways on the spinal level was slower – all differences significant. According to the visual evoked potentials, in more than half of the cases, there was an increase in the latency of the P100 peak. Also in MS group there was a significant disruption of the visual pathway in 54% of the cases. Neurophysiological changes in 58% of cases were demyelinating, and violations of the axonal type occurred in 37% of cases.Conclusions. Neurophysiological diagnostic methods such as transcranial magnetic stimulation, visual evoked potentials, somatosensory evoked potentials are highly informative for the differential diagnosis of multiple sclerosis and acute disseminated encephalomyelitis. More pronounced spinal lesions in early stages of MS than in ADEM in children may be the cause of the neurophysiologic differences, and prevalence of the sensory system involvement at this stage may be the reason behind more extended SSEP abnormalities comparing with TMS. VEP changes may reflect primary

  18. Two Cases of Acute Disseminated Encephalomyelitis Following Vaccination Against Human Papilloma Virus

    Science.gov (United States)

    Sekiguchi, Kenji; Yasui, Naoko; Kowa, Hisatomo; Kanda, Fumio; Toda, Tatsushi

    2016-01-01

    We herein present two cases of acute disseminated encephalomyelitis (ADEM) following vaccination against human papilloma virus (HPV). Case 1 experienced diplopia and developed an unstable gait 14 days after a second vaccination of Cervarix. Brain magnetic resonance imaging (MRI) showed an isolated small, demyelinating lesion in the pontine tegmentum. Case 2 experienced a fever and limb dysesthesia 16 days after a second vaccination of Gardasil. Brain MRI revealed hyperintense lesion in the pons with slight edema on a T2-weighted image. Both cases resolved completely. It is important to accumulate further data on confirmed cases of ADEM temporally associated with HPV vaccination. PMID:27803416

  19. The murine gammaherpesvirus-68 chemokine-binding protein M3 inhibits experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Millward, Jason M; Holst, Peter J; Høgh-Petersen, Mette

    2010-01-01

    M3 (AdM3) directly to the CNS to evaluate the capacity of this protein to inhibit neuroinflammation using the experimental autoimmune encephalomyelitis (EAE) model. Treatment with the AdM3 vector significantly reduced the clinical severity of EAE, attenuated CNS histopathology, and reduced numbers......Chemokines are critical mediators of immune cell entry into the central nervous system (CNS), as occurs in neuroinflammatory disease such as multiple sclerosis. Chemokines are also implicated in the immune response to viral infections. Many viruses encode proteins that mimic or block chemokine...... of immune cells infiltrating the CNS. These results suggest that M3 may represent a novel therapeutic approach to neuroinflammatory disease....

  20. Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C; Carrasco, J; Hidalgo, J

    2001-01-01

    Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein......-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflammatory cytokine, in the control of metallothioneins expression...

  1. Transfer of experimental allergic encephalomyelitis to bone marrow chimeras. Endothelial cells are not a restricting element

    International Nuclear Information System (INIS)

    Hinrichs, D.J.; Wegmann, K.W.; Dietsch, G.N.

    1987-01-01

    The adoptive transfer of clinical and histopathologic signs of experimental allergic encephalomyelitis (EAE) requires MHC compatibility between cell donor and cell recipient. The results of adoptive transfer studies using F1 to parent bone marrow chimeras as recipients of parental-derived BP-sensitive spleen cells indicate that this restriction is not expressed at the level of the endothelial cell but is confined to the cells of bone marrow derivation. Furthermore, these results indicate that the development of EAE is not dependent on the activity of MHC-restricted cytotoxic cells

  2. Key metalloproteinases are expressed by specific cell types in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Toft-Hansen, Henrik; Nuttall, Robert K; Edwards, Dylan R

    2004-01-01

    animal model, experimental autoimmune encephalomyelitis (EAE). We used real-time RT-PCR to profile the expression of all 22 known mouse MMPs, seven ADAMs, and all four known TIMPs in spinal cord from SJL/J mice and mice with adoptively transferred myelin basic protein (MBP)-specific EAE. A significant...... cellular sources of these strongly affected proteins in the inflamed CNS, we isolated macrophages, granulocytes, microglia, and T cells by cell sorting from the CNS of mice with EAE and analyzed their expression by real-time RT-PCR. This identified macrophages as a major source of MMP-12 and TIMP-1...

  3. Progressive Encephalomyelitis with Rigidity and Myoclonus in an Intellectually Disabled Patient Mimicking Neuroleptic Malignant Syndrome

    Directory of Open Access Journals (Sweden)

    Zheyu Xu

    2017-05-01

    Full Text Available We present a case of 32-year-old male with profound mental retardation and autism spectrum disorder who had presented with seizures, rigidity and elevated creatine kinase and was initially diagnosed as neuroleptic malignant syndrome (NMS. The patient subsequently had a complicated clinical course, developing refractory status epilepticus, which lead to the eventual diagnosis of progressive encephalomyelitis with rigidity and myoclonus (PERM. We discuss the clinical similarities and differences between NMS and PERM, and highlight the need to consider alternative diagnoses when the clinical picture of NMS is atypical, particularly in this patient group where the history and clinical examination may be challenging.

  4. A retrospective data acquisition and evaluation on the characterization and prognosis for 776 patients with differentiated thyroid carcinomas in the Klinik und Poliklinik fuer Nuklearmedizin der Universitaet zu Koeln in the period from 1990 to 2005

    International Nuclear Information System (INIS)

    Meixner, Markus

    2011-01-01

    The author describes the retrospective data acquisition and evaluation on the characterization and prognosis for 776 patients (average age 40:1 years) with differentiated thyroid carcinomas in the Klinik und Poliklinik fuer Nuklearmedizin der Universitaet zu Koeln in the period from 1990 to 2005. The methodology includes patient-relevant data, examination data, imaging techniques and biochemical tests. Clinically important differences were found for papillary and follicular thyroid carcinoma. Further differences concern the localization of metastases. The author discusses the prognostic significance of the primary tumor radius in comparison with the so-called TNM classification for papillary and follicular thyroid carcinomas. It is concluded that the new version of the TNM classification offers only slight advantages with respect to the former version. It was also shown that the primary tumor size is adequate for prognostic estimations.

  5. Devital dişlerin ıntrakoronal ağartmasında kullanılan iki farklı materyalin klinik etkinliğinin karşılaştırılması

    OpenAIRE

    Keçeci, Diljin

    2009-01-01

    SüleymanDemirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 2006 Eylül; 13(3) Devital dişlerin ıntrakoronal ağartmasında kullanılan iki farklı materyalin klinik etkinliğinin karşılaştırılması Diljin Keçeci Devital diş renklenmeleri diş dizisinde kolayca ayırt edilebildiği için özellikle ön dişlerde estetik sorunlara yol açmaktadır. Bu çalışmada kanal tedavisi uygulanmış veya travmaya maruz kalmış, ön dişlerde ortaya çıkan renklenmelerin ağartılması amacıyla bir sodyum perborat (Starbrite, Dentr...

  6. Bipolar tip-II bozuklukta ötimik dönemde psikososyal işlevselliğin klinik ve bilişsel yordayıcıları

    OpenAIRE

    İLHAN, Rifat Serav

    2014-01-01

    Amaç: Bipolar bozukluğu (BB) olan hastaların, iyileşme dönemlerinde de psikososyal işlevsellik kusuru yaşadıkları bildirilmektedir. Klinik belirtilerin ve bilişsel işlevlerdeki bozulmanın, hastaların ötimik dönemde psikososyal işlevselliğindeki bozulmayı yordadığı üzerinde durulmaktadır. Ancak bu konuya ilişkin bilgiler çoğunlukla, bipolar tip I bozuk...

  7. Hoftedysplasi: klinik, billeddiagnostik og henvisning

    DEFF Research Database (Denmark)

    Troelsen, Anders; Rømer, Lone; Søballe, Kjeld

    2007-01-01

    Hip dysplasia is a common congenital disorder, and identified as a source of pain, functional impairment and increased risk for development of osteoarthritis. Early diagnosis and reference is essential in symptomatic hip dysplasia, since patients may be candidates for joint preserving surgery....... Assessment concentrates on history, physical examination and plain radiography. If radiography confirms the diagnosis (CE-angle hip dysplasia should be well-known to GPs, orthopaedics and radiologists. Udgivelsesdato: 2007...

  8. A retrospective data acquisition and evaluation on the characterization and prognosis for 776 patients with differentiated thyroid carcinomas in the Klinik und Poliklinik fuer Nuklearmedizin der Universitaet zu Koeln in the period from 1990 to 2005; Eine retrospektive Datenerhebung und Auswertung zur Charakterisierung und Prognose von 776 Patienten mit differenziertem Schilddruesenkarzinom der Klinik und Poliklinik fuer Nuklearmedizin der Universitaet zu Koeln im Zeitraum von 1990-2005

    Energy Technology Data Exchange (ETDEWEB)

    Meixner, Markus

    2011-06-22

    The author describes the retrospective data acquisition and evaluation on the characterization and prognosis for 776 patients (average age 40:1 years) with differentiated thyroid carcinomas in the Klinik und Poliklinik fuer Nuklearmedizin der Universitaet zu Koeln in the period from 1990 to 2005. The methodology includes patient-relevant data, examination data, imaging techniques and biochemical tests. Clinically important differences were found for papillary and follicular thyroid carcinoma. Further differences concern the localization of metastases. The author discusses the prognostic significance of the primary tumor radius in comparison with the so-called TNM classification for papillary and follicular thyroid carcinomas. It is concluded that the new version of the TNM classification offers only slight advantages with respect to the former version. It was also shown that the primary tumor size is adequate for prognostic estimations.

  9. Computerized training improves verbal working memory in patients with myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study.

    Science.gov (United States)

    Maroti, Daniel; Westerberg, Annika Fryxell; Saury, Jean-Michel; Bileviciute-Ljungar, Indre

    2015-08-18

    Patients with myalgic encephalomyelitis/chronic fatigue syndrome experience cognitive difficulties. The aim of this study was to evaluate the effect of computerized training on working memory in this syndrome. Non-randomized (quasi-experimental) study with no-treatment control group and non-equivalent dependent variable design in a myalgic encephalomyelitis/chronic fatigue syndrome-cohort. Patients with myalgic encephalomyelitis/chronic fatigue syndrome who participated in a 6-month outpatient rehabilitation programme were included in the study. Eleven patients who showed signs of working memory deficit were recruited for additional memory training and 12 patients with no working memory deficit served as controls. Cognitive training with computerized working memory tasks of increasing difficulty was performed 30-45 min/day, 5 days/week over a 5-week period. Short-term and working memory tests (Digit Span - forward, backward, total) were used as primary outcome measures. Nine of the 11 patients were able to complete the training. Cognitive training increased working memory (p = 0.003) and general attention (p = 0.004) to the mean level. Short-term memory was also improved, but the difference was not statistically significant (p = 0.052) vs prior training. The control group did not show any significant improvement in primary outcome measures. Cognitive training may be a new treatment for patients with myalgic encephalomyelitis/chronic fatigue syndrome.

  10. Phenotype of Antigen Unexperienced TH Cells in the Inflamed Central Nervous System in Experimental Autoimmune Encephalomyelitis.

    Science.gov (United States)

    Franck, Sophia; Paterka, Magdalena; Birkenstock, Jerome; Zipp, Frauke; Siffrin, Volker; Witsch, Esther

    2017-06-01

    Multiple sclerosis is a chronic, disseminated inflammation of the central nervous system which is thought to be driven by autoimmune T cells. Genetic association studies in multiple sclerosis and a large number of studies in the animal model of the disease support a role for effector/memory T helper cells. However, the mechanisms underlying relapses, remission and chronic progression in multiple sclerosis or the animal model experimental autoimmune encephalomyelitis, are not clear. In particular, there is only scarce information on the role of central nervous system-invading naive T helper cells in these processes. By applying two-photon laser scanning microscopy we could show in vivo that antigen unexperienced T helper cells migrated into the deep parenchyma of the inflamed central nervous system in experimental autoimmune encephalomyelitis, independent of their antigen specificity. Using flow cytometric analyses of central nervous system-derived lymphocytes we found that only antigen-specific, formerly naive T helper cells became activated during inflammation of the central nervous system encountering their corresponding antigen.

  11. Receptors for Theiler's murine encephalomyelitis virus: characterization by using rabbit antiviral antiserum

    International Nuclear Information System (INIS)

    Rubio, N.; Cuesta, A.

    1988-01-01

    An immunological assay was developed to characterize the binding of Theiler's murine encephalomyelitis virus to BHK-21 cell receptors. After absorption of the virus and formaldehyde fixation, rabbit antibodies and Staphylococcus aureus protein A labeled with 125 I formed a specific complex on the surfaces of the cells. The optimal multiplicity of infection in this system was 10 PFU per cell. The virus was internalized at 33 and 37 0 C, but internalization did not take place at 25 or 4 0 C. The binding was proportional to the number of cells and was significant within 30 s. Cell surface receptors were still active after fixation, and only intact viruses were bound, as demonstrated by the lack of binding of the purified, isolated virion proteins VP1, VP2, and VP3

  12. "United We Stand": Framing Myalgic Encephalomyelitis in a Virtual Symbolic Community.

    Science.gov (United States)

    Lian, Olaug S; Nettleton, Sarah

    2015-10-01

    In this article, we report on a study that seeks to explore how the contested chronic condition myalgic encephalomyelitis (ME), one of the current medical diagnoses for medically unexplained long-term exhaustion, is negotiated within the context of Norwegian internet sites. From an analysis of discussions on 14 internet forums sustained by and for people living with ME, we seek to understand how their online activity sustains a virtual symbolic community (VSC). After exploring the content on these sites, we identified four discursive domains, or fields of conversation, that are demarcated by a discursive frame, or norms, values, and goals that define and reinforce the boundaries of the community. Interpreting discursive domains and their discursive frame provides insight not only to the culture of the ME VSC but also to its role in an international social health movement, including its potential for becoming politically influential. © The Author(s) 2014.

  13. Evidence for a prolonged role of alpha 4 integrin throughout active experimental allergic encephalomyelitis.

    Science.gov (United States)

    Keszthelyi, E; Karlik, S; Hyduk, S; Rice, G P; Gordon, G; Yednock, T; Horner, H

    1996-10-01

    The leukocyte integrin receptor, alpha 4 beta 1, and its endothelial cell ligand, vascular cell adhesion molecule 1, appear to be of critical importance in the leukocyte trafficking that accompanies CNS damage in experimental allergic encephalomyelitis (EAE). In this study, the persistence of the role for alpha 4 beta 1/VCAM-1 in EAE was established by observing antibody-mediated disease reversal up to 1 month following disease onset. Limited treatment with a monoclonal antibody against alpha 4 integrin, GG5/3, resulted in a significant decrease in both clinical and histopathologic signs. This was not observed in isotype control experiments. In the latter phase of progressive disease, widespread demyelination occurred in the animals that did not respond to 6 days of anti-alpha 4 treatment. These results demonstrate an essential role for alpha 4 beta 1 interactions throughout active EAE and illustrate the difference between reversible clinical deficits caused by edema and irreversible deficits associated with demyelination.

  14. Cytokine production by cells in cerebrospinal fluid during experimental allergic encephalomyelitis in SJL/J mice

    DEFF Research Database (Denmark)

    Renno, T; Lin, J Y; Piccirillo, C

    1994-01-01

    Cytokine production by T cells in the cerebrospinal fluid (CSF) and central nervous system (CNS) of SJL/J mice during myelin basic protein (MBP)-induced experimental allergic encephalomyelitis (EAE) was examined. Reverse transcriptase/polymerase chain reaction (RT/PCR) was used to measure...... interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) mRNA levels from perfused CNS tissue (brain and spinal cord) and from cells isolated from CSF. Animals were grouped according to EAE severity, ranging from asymptomatic (adjuvant only) to severe disease (paralysis or severe paresis). Cytokine signals......, normalized to actin, were almost undetectable in control tissues, and only slightly elevated in whole CNS tissue from animals with mild EAE. Both cytokine messages were strongly upregulated in CNS tissues derived from severely affected animals, consistent with previous observations correlating disease...

  15. Total glucosides of peony attenuates experimental autoimmune encephalomyelitis in C57BL/6 mice.

    Science.gov (United States)

    Huang, Qiling; Ma, Xiaomeng; Zhu, Dong Liang; Chen, Li; Jiang, Ying; Zhou, Linli; Cen, Lei; Pi, Rongbiao; Chen, Xiaohong

    2015-07-15

    Total glucosides of peony (TGP), an active compound extracted from the roots of Paeonia lactiflora Pall, has wide pharmacological effects on nervous system. Here we examined the effects of TGP on experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). The results showed that TGP can reduce the severity and progression of EAE in C57 BL/6 mice. In addition, TGP also down-regulated the Th1/Th17 inflammatory response and prevented the reduced expression of brain-derived neurotrophic factor and 2',3'-cyclic nucleotide 3'-phosphodiesterase of EAE. These findings suggest that TGP could be a potential therapeutic agent for MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Detection of eastern equine encephalomyelitis virus RNA in North American snakes.

    Science.gov (United States)

    Bingham, Andrea M; Graham, Sean P; Burkett-Cadena, Nathan D; White, Gregory S; Hassan, Hassan K; Unnasch, Thomas R

    2012-12-01

    The role of non-avian vertebrates in the ecology of eastern equine encephalomyelitis virus (EEEV) is unresolved, but mounting evidence supports a potential role for snakes in the EEEV transmission cycle, especially as over-wintering hosts. To determine rates of exposure and infection, we examined serum samples from wild snakes at a focus of EEEV in Alabama for viral RNA using quantitative reverse transcription polymerase chain reaction. Two species of vipers, the copperhead (Agkistrodon contortrix) and the cottonmouth (Agkistrodon piscivorus), were found to be positive for EEEV RNA using this assay. Prevalence of EEEV RNA was more frequent in seropositive snakes than seronegative snakes. Positivity for the quantitative reverse transcription polymerase chain reaction in cottonmouths peaked in April and September. Body size and sex ratios were not significantly different between infected and uninfected snakes. These results support the hypothesis that snakes are involved in the ecology of EEEV in North America, possibly as over-wintering hosts for the virus.

  17. Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Current Applications and Future Perspectives

    Science.gov (United States)

    Lang, Yue

    2018-01-01

    The gut environment and gut microbiome dysbiosis have been demonstrated to significantly influence a range of disorders in humans, including obesity, diabetes, rheumatoid arthritis, and multiple sclerosis (MS). MS is an autoimmune disease affecting the central nervous system (CNS). The etiology of MS is not clear, and it should involve both genetic and extrinsic factors. The extrinsic factors responsible for predisposition to MS remain elusive. Recent studies on MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have found that gastrointestinal microbiota may play an important role in the pathogenesis of MS/EAE. Thus, gut microbiome adjustment may be a future direction of treatment in MS. In this review, we discuss the characteristics of the gut microbiota, the connection between the brain and the gut, and the changes in gut microbiota in MS/EAE, and we explore the possibility of applying microbiota therapies in patients with MS. PMID:29805314

  18. Experimental autoimmune encephalomyelitis from a tissue energy perspective [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Roshni A Desai

    2017-11-01

    Full Text Available Increasing evidence suggests a key role for tissue energy failure in the pathophysiology of multiple sclerosis (MS. Studies in experimental autoimmune encephalomyelitis (EAE, a commonly used model of MS, have been instrumental in illuminating the mechanisms that may be involved in compromising energy production. In this article, we review recent advances in EAE research focussing on factors that conspire to impair tissue energy metabolism, such as tissue hypoxia, mitochondrial dysfunction, production of reactive oxygen/nitrogen species, and sodium dysregulation, which are directly affected by energy insufficiency, and promote cellular damage. A greater understanding of how inflammation affects tissue energy balance may lead to novel and effective therapeutic strategies that ultimately will benefit not only people affected by MS but also people affected by the wide range of other neurological disorders in which neuroinflammation plays an important role.

  19. Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Martínez-Cáceres, E M

    2003-01-01

    Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells......, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue...... repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain....

  20. A role for VAV1 in experimental autoimmune encephalomyelitis and multiple sclerosis

    DEFF Research Database (Denmark)

    Jagodic, Maja; Colacios, Celine; Nohra, Rita

    2009-01-01

    Multiple sclerosis, the most common cause of progressive neurological disability in young adults, is a chronic inflammatory disease. There is solid evidence for a genetic influence in multiple sclerosis, and deciphering the causative genes could reveal key pathways influencing the disease. A genome...... region on rat chromosome 9 regulates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Using interval-specific congenic rat lines and association of single-nucleotide polymorphisms with inflammatory phenotypes, we localized the gene of influence to Vav1, which codes for a signal......-transducing protein in leukocytes. Analysis of seven human cohorts (12,735 individuals) demonstrated an association of rs2546133-rs2617822 haplotypes in the first VAV1 intron with multiple sclerosis (CA: odds ratio, 1.18; CG: odds ratio, 0.86; TG: odds ratio, 0.90). The risk CA haplotype also predisposed for higher...

    1. Strain-related effects of fenbendazole treatment on murine experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Ramp, A A; Hall, C; Orian, J M

      2010-07-01

      Parasitic infections are a concern in animal facilities, in view of their influence on physiological processes and the immune status of animals. Pinworms are effectively controlled with the anthelminthic fenbendazole (FBZ, [5-(phenylthio)-1H-benzamidazol-2-yl]carbamic acid methyl ester; C(15)H(13)N(3)O(2)S); however, questions remain as to whether prolonged FBZ exposure alters the disease course in specific experimental models, such as those pertaining to the immune system. We report that a three-month regimen of FBZ-medicated feed severely affected the onset and disease severity of murine experimental autoimmune encephalomyelitis (EAE), a disease that mimics multiple sclerosis. Differences were recorded between mouse strains used. Our data suggest that where the use of FBZ is mandatory, its full effect should be verified on the particular EAE variant adopted by the laboratory.

    2. Outbreaks of Neuroinvasive Astrovirus Associated with Encephalomyelitis, Weakness, and Paralysis among Weaned Pigs, Hungary.

      Science.gov (United States)

      Boros, Ákos; Albert, Mihály; Pankovics, Péter; Bíró, Hunor; Pesavento, Patricia A; Phan, Tung Gia; Delwart, Eric; Reuter, Gábor

      2017-12-01

      A large, highly prolific swine farm in Hungary had a 2-year history of neurologic disease among newly weaned (25- to 35-day-old) pigs, with clinical signs of posterior paraplegia and a high mortality rate. Affected pigs that were necropsied had encephalomyelitis and neural necrosis. Porcine astrovirus type 3 was identified by reverse transcription PCR and in situ hybridization in brain and spinal cord samples in 6 animals from this farm. Among tissues tested by quantitative RT-PCR, the highest viral loads were detected in brain stem and spinal cord. Similar porcine astrovirus type 3 was also detected in archived brain and spinal cord samples from another 2 geographically distant farms. Viral RNA was predominantly restricted to neurons, particularly in the brain stem, cerebellum (Purkinje cells), and cervical spinal cord. Astrovirus was generally undetectable in feces but present in respiratory samples, indicating a possible respiratory infection. Astrovirus could cause common, neuroinvasive epidemic disease.

    3. Enterovirus 71-related encephalomyelitis: usual and unusual magnetic resonance imaging findings

      Energy Technology Data Exchange (ETDEWEB)

      Jang, Seonah; Suh, Sang-Il; Ha, Su Min; Seol, Hae-Young [Korea University Guro Hospital, Korea University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Byeon, Jung Hye; Eun, Baik-Lin [Korea University Guro Hospital, Korea University College of Medicine, Department of Pediatrics, Seoul (Korea, Republic of); Lee, Young Hen; Seo, Hyung Suk [Korea University Ansan Hospital, Korea University College of Medicine, Department of Radiology, Ansan (Korea, Republic of); Eun, So-Hee [Korea University Ansan Hospital, Korea University College of Medicine, Department of Pediatrics, Ansan (Korea, Republic of)

      2012-03-15

      Most enterovirus (EV) 71 infections manifest as mild cases of hand-foot-mouth disease (HFMD)/herpangina with seasonal variations, having peak incidence during the summer. Meanwhile, EV 71 may involve the central nervous system (CNS), causing severe neurologic disease. In many cases, enteroviral encephalomyelitis involves the central midbrain, posterior portion of the medulla oblongata and pons, bilateral dentate nuclei of the cerebellum, and the ventral roots of the cervical spinal cord, and the lesions show hyperintensity on T2-weighted and fluid-attenuation inversion recovery (FLAIR) images. Our goal was to review usual and unusual magnetic resonance (MR) findings in CNS involvement of enteroviral infection. Among consecutive patients who had HFMD and clinically suspected encephalitis or myelitis and who underwent brain or spinal MR imaging, five patients revealed abnormal MR findings. Diffusion-weighted and conventional MR and follow-up MR images were obtained. From cerebrospinal fluid, stool, or nasopharyngeal swabs, EV 71 was confirmed in all patients. MR imaging studies of two patients showed hyperintensity in the posterior portion of the brainstem on T2-weighted and FLAIR images, which is the well-known MR finding of EV 71 encephalitis. The remaining three cases revealed unusual manifestations: leptomeningeal enhancement, abnormal enhancement along the ventral roots at the conus medullaris level without brain involvement, and hyperintensity in the left hippocampus on T2/FLAIR images. EV 71 encephalomyelitis shows relatively characteristic MR findings; therefore, imaging can be helpful in radiologic diagnosis. However, physicians should also be aware of unusual radiologic manifestations of EV 71. (orig.)

    4. Clinical features and outcome of acute disseminated encephalomyelitis (ADEM: An outlook from South India

      Directory of Open Access Journals (Sweden)

      Maramattom Boby

      2006-01-01

      Full Text Available Introduction: Acute disseminated encephalomyelitis (ADEM is an uncommon inflammatory demyelinating encephalomyelitis that may follow infections, vaccinations or occur spontaneously. Most of the large series of this disorder were published in the pre-MRI era. Subsequently there has been a paucity of data regarding this entity. Aims: We sought to describe our experience with ADEM across 2 hospitals from Kerala, Sree chitra tirunal institute of medical sciences, thiruvanthapuram and the Indo-american Brain and spine center, Vaikom. We wanted to look at the clinico-radiological parameters of this patient population as well as the functional outcome following ADEM. Materials and Methods: A total of 45 patients seen in these two centers over a period of 9 years from 1995 to 2003 were analyzed in a retrospective-prospective design. MRI, CT scans, laboratory investigations, nerve conduction parameters and modified rankin outcome scores at last follow up were also noted. Results: The clinico-radiological profile of our patients was comparable to that of patients described in the literature. Relapse was uncommon although transient reappearance of prior symptoms during subsequent illness was common. Possible multiple sclerosis could be diagnosed only in one patient during follow up. Mortality was low ( Conclusions: ADEM deserves to be distinguished from MS in our population as there seems to be a low likelihood of recurrence or relapse. Although mortality rates have improved greatly, survivors are left with a plethora of disabilities and are functionally impaired. Future studies should focus on specific disabilities and treatment options to further improve outcomes in ADEM

    5. Enterovirus 71-related encephalomyelitis: usual and unusual magnetic resonance imaging findings

      International Nuclear Information System (INIS)

      Jang, Seonah; Suh, Sang-Il; Ha, Su Min; Seol, Hae-Young; Byeon, Jung Hye; Eun, Baik-Lin; Lee, Young Hen; Seo, Hyung Suk; Eun, So-Hee

      2012-01-01

      Most enterovirus (EV) 71 infections manifest as mild cases of hand-foot-mouth disease (HFMD)/herpangina with seasonal variations, having peak incidence during the summer. Meanwhile, EV 71 may involve the central nervous system (CNS), causing severe neurologic disease. In many cases, enteroviral encephalomyelitis involves the central midbrain, posterior portion of the medulla oblongata and pons, bilateral dentate nuclei of the cerebellum, and the ventral roots of the cervical spinal cord, and the lesions show hyperintensity on T2-weighted and fluid-attenuation inversion recovery (FLAIR) images. Our goal was to review usual and unusual magnetic resonance (MR) findings in CNS involvement of enteroviral infection. Among consecutive patients who had HFMD and clinically suspected encephalitis or myelitis and who underwent brain or spinal MR imaging, five patients revealed abnormal MR findings. Diffusion-weighted and conventional MR and follow-up MR images were obtained. From cerebrospinal fluid, stool, or nasopharyngeal swabs, EV 71 was confirmed in all patients. MR imaging studies of two patients showed hyperintensity in the posterior portion of the brainstem on T2-weighted and FLAIR images, which is the well-known MR finding of EV 71 encephalitis. The remaining three cases revealed unusual manifestations: leptomeningeal enhancement, abnormal enhancement along the ventral roots at the conus medullaris level without brain involvement, and hyperintensity in the left hippocampus on T2/FLAIR images. EV 71 encephalomyelitis shows relatively characteristic MR findings; therefore, imaging can be helpful in radiologic diagnosis. However, physicians should also be aware of unusual radiologic manifestations of EV 71. (orig.)

    6. Longitudinal in vivo magnetic resonance imaging studies in experimental allergic encephalomyelitis: effect of a neurotrophic treatment on cortical lesion development

      Energy Technology Data Exchange (ETDEWEB)

      Gispen, W.H. [Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Medical Faculty, Utrecht University Utrecht (Netherlands); Nicolay, K. [Department of in vivo NMR, Bijvoet Center, Utrecht University Utrecht (Netherlands); Verhaagen, J. [Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Medical Faculty, Utrecht University Utrecht (Netherlands); Muller, H.J. [Department of in vivo NMR, Bijvoet Center, Utrecht University Utrecht (Netherlands); Duckers, H.J. [Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Medical Faculty, Utrecht University Utrecht (Netherlands)

      1997-02-14

      Proton magnetic resonance imaging enables non-invasive monitoring of lesion formation in multiple sclerosis and has an important role in assessing the potential effects of therapy. T2-weighted and short {tau} inversion recovery magnetic resonance imaging were used to assess the effect of a neurotrophic adrenocorticotrophic hormone{sub 4-9} analogue [H-Met(O{sub 2})-Glu-His-Phe-d-Lys-Phe-OH] on the volume of lesions in the brains of rats suffering from chronic experimental allergic encephalomyelitis, an animal equivalent of multiple sclerosis. Lesion volume was monitored during a five-month period. Magnetic resonance imaging indicated that treatment with the adrenocorticotrophic hormone{sub 4-9} analogue significantly reduced the lesion volume by 84 and 85% 10 and 20 weeks after lesion induction, respectively. Furthermore, peptide treatment significantly reduced chronic experimental allergic encephalomyelitis-related neurological symptoms during the chronic phase of the disease (week 3 until week 20 after lesion induction). Both functional and morphological recovery were considerably advanced by peptide treatment. Twenty weeks after lesion induction rats with chronic experimental allergic encephalomyelitis were killed for histological analysis, to correlate magnetic resonance imaging findings with morphological changes. The regions of abnormally high signal intensities on T2-weighted magnetic resonance images coincided with areas of demyelination and concomitant widespread inflammatory infiltration, oedema formation and enlarged ventricles.The improved neurological status and the 84% reduction in the lesion volume in the cerebrum of rats chronic experimental allergic encephalomyelitis point to the potential value of trophic peptides in the development of strategies for limiting the damage caused by central demyelinating lesions in syndromes such as multiple sclerosis. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

    7. Specific and strain-independent effects of dexamethasone in the prevention and treatment of experimental autoimmune encephalomyelitis in rodents

      DEFF Research Database (Denmark)

      Donia, M; Mangano, K; Quattrocchi, C

      2010-01-01

      Experimental autoimmune encephalomyelitis in rodents (EAE) is a generally accepted in vivo model for immunopathogenic mechanisms underlying multiple sclerosis (MS). There are, however, different forms of rodent EAE, and therapeutic regimens may affect these forms differently. We have therefore te...... predictors of drug efficacy in at least some variants of human MS. Better understanding of the clinical and immunopharmacologic features of these models might prove useful when testing new drug candidates for MS treatment....

    8. Particular experiences: a psychosocial exploration of myalgic encephalomyelitis (ME) and its relationship with self, environment and the material world

      OpenAIRE

      Fellenor, John

      2015-01-01

      Myalgic encephalomyelitis (ME), also referred to as chronic fatigue syndrome (CFS), is a symptomatically defined and debilitating condition that presents as a range of physiological and psychological effects. Post-exertional fatigue and ongoing low energy levels are cardinal features. Whilst ME-like conditions have been recognised for at least two hundred years, they have been characterised over recent decades by a fiercely contested debate as to whether aetiology is primarily psychological o...

    9. Longitudinal in vivo magnetic resonance imaging studies in experimental allergic encephalomyelitis: effect of a neurotrophic treatment on cortical lesion development

      International Nuclear Information System (INIS)

      Gispen, W.H.; Nicolay, K.; Verhaagen, J.; Muller, H.J.; Duckers, H.J.

      1997-01-01

      Proton magnetic resonance imaging enables non-invasive monitoring of lesion formation in multiple sclerosis and has an important role in assessing the potential effects of therapy. T2-weighted and short τ inversion recovery magnetic resonance imaging were used to assess the effect of a neurotrophic adrenocorticotrophic hormone 4-9 analogue [H-Met(O 2 )-Glu-His-Phe-d-Lys-Phe-OH] on the volume of lesions in the brains of rats suffering from chronic experimental allergic encephalomyelitis, an animal equivalent of multiple sclerosis. Lesion volume was monitored during a five-month period. Magnetic resonance imaging indicated that treatment with the adrenocorticotrophic hormone 4-9 analogue significantly reduced the lesion volume by 84 and 85% 10 and 20 weeks after lesion induction, respectively. Furthermore, peptide treatment significantly reduced chronic experimental allergic encephalomyelitis-related neurological symptoms during the chronic phase of the disease (week 3 until week 20 after lesion induction). Both functional and morphological recovery were considerably advanced by peptide treatment. Twenty weeks after lesion induction rats with chronic experimental allergic encephalomyelitis were killed for histological analysis, to correlate magnetic resonance imaging findings with morphological changes. The regions of abnormally high signal intensities on T2-weighted magnetic resonance images coincided with areas of demyelination and concomitant widespread inflammatory infiltration, oedema formation and enlarged ventricles.The improved neurological status and the 84% reduction in the lesion volume in the cerebrum of rats chronic experimental allergic encephalomyelitis point to the potential value of trophic peptides in the development of strategies for limiting the damage caused by central demyelinating lesions in syndromes such as multiple sclerosis. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

    10. Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

      OpenAIRE

      Maes, Michael; Kubera, Marta; Uytterhoeven, Marc; Vrydags, Nicolas; Bosmans, Eugene

      2011-01-01

      Summary Background There is evidence that myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by activation of immune, inflammatory, oxidative and nitrosative stress (IO&NS) pathways. The present study was carried out in order to examine whether ME/CFS is accompanied by increased levels of plasma peroxides and serum oxidized LDL (oxLDL) antibodies, two biomarkers of oxidative stress. Material/Methods Blood was collected from 56 patients with ME/CFS and 37 normal volun...

    11. Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis.

      Science.gov (United States)

      Martin, Nina M; Griffin, Diane E

      2018-03-15

      Alphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053-16058, 2014, https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4 + T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10 -/- mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain. IMPORTANCE Alphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence

    12. Epidemiological characteristics of chronic fatigue- syndrome/myalgic encephalomyelitis in Australian patients

      Directory of Open Access Journals (Sweden)

      Johnston SC

      2016-05-01

      Full Text Available Samantha C Johnston1,2 Donald R Staines1 Sonya M Marshall-Gradisnik1,2 1National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute Queensland, 2School of Medical Sciences, Griffith University, Parklands, QLD, Australia Background: No epidemiological investigations have previously been conducted in Australia according to the current clinical definitions of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME. The aim of this study was to describe sociodemographic and illness characteristics of Australian patients with CFS/ME.Methods: A cross-sectional survey on the medical history of patients enrolled in an Australian CFS/ME research database between April 2013 and April 2015. Participants were classified according to Fukuda criteria and International Consensus Criteria.Results: A total of 535 patients diagnosed with CFS/ME by a primary care physician were identified. The mean age of all patients was 46.4 years (standard deviation 12.0; the majority were female (78.61%, Caucasian, and highly educated. Of these, 30.28% met Fukuda criteria. A further 31.96% met both Fukuda criteria and International Consensus Criteria. There were 14.58% reporting chronic fatigue but did not meet criteria for CFS/ME and 23.18% were considered noncases due to exclusionary conditions. Within those meeting CFS/ME criteria, the most common events prior to illness included cold or flu, gastrointestinal illness, and periods of undue stress. Of the 60 symptoms surveyed, fatigue, cognitive, and short-term memory symptoms, headaches, muscle and joint pain, unrefreshed sleep, sensory disturbances, muscle weakness, and intolerance to extremes of temperature were the most commonly occurring symptoms (reported by more than two-thirds of patients. Significant differences in symptom occurrence between Fukuda- and International Consensus Criteria-defined cases were also identified.Conclusion: This is the first study to summarize sociodemographic and

    13. Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodeling

      Science.gov (United States)

      Tambalo, Stefano; Peruzzotti-Jametti, Luca; Rigolio, Roberta; Fiorini, Silvia; Bontempi, Pietro; Mallucci, Giulia; Balzarotti, Beatrice; Marmiroli, Paola; Sbarbati, Andrea; Cavaletti, Guido

      2015-01-01

      Cortical reorganization occurring in multiple sclerosis (MS) patients is thought to play a key role in limiting the effect of structural tissue damage. Conversely, its exhaustion may contribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel-based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS. SIGNIFICANCE STATEMENT Since the early 2000s, functional MRI (fMRI) has demonstrated profound modifications in the recruitment of cortical areas during motor, cognitive, and sensory tasks in multiple sclerosis (MS) patients. Experimental autoimmune

    14. Protective influences on experimental autoimmune encephalomyelitis by MHC class I and class II alleles

      DEFF Research Database (Denmark)

      Mustafa, M; Vingsbo, C; Olsson, T

      1994-01-01

      are resistant. Interestingly, rats with the MHC u haplotype develop an immune response to the MBP 63-88, but do not get EAE. In this study we have used intra-MHC recombinant rat strains to compare the influences of the MHC u with the a haplotype. We discovered the following: 1) The class II region of the MHC...... a haplotype permits EAE and a Th1 type of immune response as measured by IFN-gamma production after in vitro challenge of in vivo-primed T cells with MBP 63-88. 2) The class II region of the u haplotype is associated with a disease-protective immune response characterized by production of not only IFN......Experimental autoimmune encephalomyelitis (EAE) is influenced by polymorphism of the MHC. We have previously found that Lewis rats with certain MHC haplotypes are susceptible to disease induced with the myelin basic protein (MBP) peptide 63-88, whereas Lewis rats with other MHC haplotypes...

    15. High-throughput sequencing of plasma microRNA in chronic fatigue syndrome/myalgic encephalomyelitis.

      Directory of Open Access Journals (Sweden)

      Ekua W Brenu

      Full Text Available BACKGROUND: MicroRNAs (miRNAs are known to regulate many biological processes and their dysregulation has been associated with a variety of diseases including Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME. The recent discovery of stable and reproducible miRNA in plasma has raised the possibility that circulating miRNAs may serve as novel diagnostic markers. The objective of this study was to determine the role of plasma miRNA in CFS/ME. RESULTS: Using Illumina high-throughput sequencing we identified 19 miRNAs that were differentially expressed in the plasma of CFS/ME patients in comparison to non-fatigued controls. Following RT-qPCR analysis, we were able to confirm the significant up-regulation of three miRNAs (hsa-miR-127-3p, hsa-miR-142-5p and hsa-miR-143-3p in the CFS/ME patients. CONCLUSION: Our study is the first to identify circulating miRNAs from CFS/ME patients and also to confirm three differentially expressed circulating miRNAs in CFS/ME patients, providing a basis for further study to find useful CFS/ME biomarkers.

    16. High-Throughput Sequencing of Plasma MicroRNA in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

      Science.gov (United States)

      Brenu, Ekua W.; Ashton, Kevin J.; Batovska, Jana; Staines, Donald R.; Marshall-Gradisnik, Sonya M.

      2014-01-01

      Background MicroRNAs (miRNAs) are known to regulate many biological processes and their dysregulation has been associated with a variety of diseases including Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). The recent discovery of stable and reproducible miRNA in plasma has raised the possibility that circulating miRNAs may serve as novel diagnostic markers. The objective of this study was to determine the role of plasma miRNA in CFS/ME. Results Using Illumina high-throughput sequencing we identified 19 miRNAs that were differentially expressed in the plasma of CFS/ME patients in comparison to non-fatigued controls. Following RT-qPCR analysis, we were able to confirm the significant up-regulation of three miRNAs (hsa-miR-127-3p, hsa-miR-142-5p and hsa-miR-143-3p) in the CFS/ME patients. Conclusion Our study is the first to identify circulating miRNAs from CFS/ME patients and also to confirm three differentially expressed circulating miRNAs in CFS/ME patients, providing a basis for further study to find useful CFS/ME biomarkers. PMID:25238588

    17. 5-Androstenediol Ameliorates Pleurisy, Septic Shock, and Experimental Autoimmune Encephalomyelitis in Mice

      Directory of Open Access Journals (Sweden)

      Ferdinando Nicoletti

      2010-01-01

      Full Text Available Androstenediol (androst-5-ene-3β,17β-diol; 5-AED, a natural adrenal steroid, has been shown to suppress experimental autoimmune encephalomyelitis (EAE in female SJL/J mice. We here report that 5-AED limits inflammation and proinflammatory cytokines including TNFα in murine models of carrageenan-induced pleurisy and lippopolysaccaride- (LPS induced septic shock. 5-AED binds to and transactivates sex steroid receptors with the same general rank order of potency (ERβ > ERα ≫ AR. 5-AED provides benefit in EAE in a dose-dependent fashion, even when treatment is delayed until onset of disease. The minimally effective dose may be as low as 4 mg/kg in mice. However, benefit was not observed when 5-AED was given in soluble formulation, leading to a short half-life and rapid clearance. These observations suggest that treatment with 5-AED limits the production of pro-inflammatory cytokines in these animal models and, ultimately, when formulated and administered properly, may be beneficial for patients with multiple sclerosis and other Th1-driven autoimmune diseases.

    18. Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Systemic Exertion Intolerance Disease: Three Distinct Clinical Entities

      Directory of Open Access Journals (Sweden)

      Frank N.M. Twisk

      2018-04-01

      Full Text Available Many researchers consider chronic fatigue syndrome (CFS to be a synonym of Myalgic Encephalomyelitis (ME. However, the case criteria of ME and CFS define two distinct clinical entities. Although some patients will meet both case criteria, other patients can meet the diagnosis of ME and not fulfil the case criteria for CFS, while the diagnosis of CFS is largely insufficient to be qualified as a ME patient. ME is a neuromuscular disease with distinctive muscular symptoms, including prolonged muscle weakness after exertion, and neurological signs implicating cerebral dysfunction, including cognitive impairment and sensory symptoms. The only mandatory symptom of CFS is chronic fatigue. Chronic fatigue must be accompanied by at least four out of eight nonspecific symptoms: substantial impairment in short-term memory or concentration, a sore throat, tender lymph nodes, muscle pain, multijoint pain, a new type of headaches, unrefreshing sleep, and postexertional “malaise” lasting more than 24 h. So, regardless whether the name ME is appropriate or not, ME is not synonymous to CFS. That is not a matter of opinion, but a matter of definition. Due to the definitions of ME and CFS, “ME/CFS” does not exist and cannot be replaced by a new clinical entity (SEID: Systemic Exertion Intolerance Disease, as recently suggested.

    19. The experimental autoimmune encephalomyelitis disease course is modulated by nicotine and other cigarette smoke components.

      Directory of Open Access Journals (Sweden)

      Zhen Gao

      Full Text Available Epidemiological studies have reported that cigarette smoking increases the risk of developing multiple sclerosis (MS and accelerates its progression. However, the molecular mechanisms underlying these effects remain unsettled. We have investigated here the effects of the nicotine and the non-nicotine components in cigarette smoke on MS using the experimental autoimmune encephalomyelitis (EAE model, and have explored their underlying mechanism of action. Our results show that nicotine ameliorates the severity of EAE, as shown by reduced demyelination, increased body weight, and attenuated microglial activation. Nicotine administration after the development of EAE symptoms prevented further disease exacerbation, suggesting that it might be useful as an EAE/MS therapeutic. In contrast, the remaining components of cigarette smoke, delivered as cigarette smoke condensate (CSC, accelerated and increased adverse clinical symptoms during the early stages of EAE, and we identify a particular cigarette smoke compound, acrolein, as one of the potential mediators. We also show that the mechanisms underlying the opposing effects of nicotine and CSC on EAE are likely due to distinct effects on microglial viability, activation, and function.

    20. Helminth Products Potently Modulate Experimental Autoimmune Encephalomyelitis by Downregulating Neuroinflammation and Promoting a Suppressive Microenvironment

      Directory of Open Access Journals (Sweden)

      Alberto N. Peón

      2017-01-01

      Full Text Available A negative correlation between the geographical distribution of autoimmune diseases and helminth infections has been largely associated in the last few years with a possible role for such type of parasites in the regulation of inflammatory diseases, suggesting new pathways for drug development. However, few helminth-derived immunomodulators have been tested in experimental autoimmune encephalomyelitis (EAE, an animal model of the human disease multiple sclerosis (MS. The immunomodulatory activities of Taenia crassiceps excreted/secreted products (TcES that may suppress EAE development were sought for. Interestingly, it was discovered that TcES was able to suppress EAE development with more potency than dexamethasone; moreover, TcES treatment was still effective even when inoculated at later stages after the onset of EAE. Importantly, the TcES treatment was able to induce a range of Th2-type cytokines, while suppressing Th1 and Th17 responses. Both the polyclonal and the antigen-specific proliferative responses of lymphocytes were also inhibited in EAE-ill mice receiving TcES in association with a potent recruitment of suppressor cell populations. Peritoneal inoculation of TcES was able to direct the normal inflammatory cell traffic to the site of injection, thus modulating CNS infiltration, which may work along with Th2 immune polarization and lymphocyte activation impairment to downregulate EAE development.

    1. Effects of Intermittent Fasting on Experimental Autoimune Encephalomyelitis in C57BL/6 Mice.

      Science.gov (United States)

      Razeghi Jahromi, Soodeh; Ghaemi, Amir; Alizadeh, Akram; Sabetghadam, Fatemeh; Moradi Tabriz, Hedieh; Togha, Mansoureh

      2016-06-01

      Several religions recommend periods of fasting. One of the most frequently asked questions of MS patients before the holy month of Ramadan is weather fasting might have an unfavorable effect on their disease course. This debate became more challenging after the publication of experimental studies suggesting that calorie restriction prior to disease induction attenuates disease severity. We conducted this study to assess early and late effects of fasting on the animal model of MS, known as autoimmune encephalomyelitis. EAE was induced in the C57BL/6 mice, using Myelin Oligodendrocyte Glycopeptide  (MOG) 35-55 and they fasted every other day either after the appearance of the first clinical sign or 30 days after disease induction for ten days. Thereafter, the mice were sacrificed for further histological and immunological evaluations. Intermittent fasting after the establishment of EAE did not have any unfavorable effect on the course of disease. Moreover, fasting at the early phase of disease alleviated EAE severity by ameliorating spinal cord demyelination. Fasting suppressed the secretion of IFN-γ, TNF-α and raised IL-10 production in splenocytes. Fasting was also associated with a lower percent of cytotoxicity. Intermittent fasting not only had no unfavorable effect on EAE but also reduced EAE severity if started at early phase of disease.

    2. Differential effects of B7-1 blockade in the rat experimental autoimmune encephalomyelitis model

      DEFF Research Database (Denmark)

      Gallon, L; Chandraker, A; Issazadeh-Navikas, Shohreh

      1997-01-01

      that CD28-B7 blockade by systemic administration of CTLA4Ig prevents actively induced EAE. Since CTLA4Ig binds to both B7-1 and B7-2, we used a mutant form of CTLA4Ig (CTLA4IgY100F) that binds only B7-1, to study the role of B7-1 blockade in this model. Such a reagent avoids the potential of signaling...... treated with systemic CTLA4gY100F did not. More importantly, systemic administration of CTLA4IgY100F abrogated the protective effect of ex vivo treated APCs. These data suggest an important regulatory role for B7-1, perhaps through binding to CTLA4, in this model of EAE. Understanding the role......Blocking the CD28-B7 T cell costimulatory activation pathway protects animals from developing experimental autoimmune encephalomyelitis (EAE). In the mouse EAE model, selective blockade of B7-1 by specific mAbs has been shown to protect animals from EAE. In the Lewis rat model, we have shown...

    3. Acute disseminated encephalomyelitis complicating dengue infection with neuroimaging mimicking multiple sclerosis: A report of two cases.

      Science.gov (United States)

      Viswanathan, S; Botross, N; Rusli, B N; Riad, A

      2016-11-01

      Acute disseminated encephalomyelitis (ADEM) complicating dengue infection is still exceedingly rare even in endemic countries such as Malaysia. Here we report two such cases, the first in an elderly female patient and the second in a young man. Both presented with encephalopathy, brainstem involvement and worsening upper and lower limb weakness. Initial magnetic resonance imaging (MRI) of the brain was normal in the first case. Serum for dengue Ig M and NS-1 was positive in both cases. Cerebrospinal fluid (CSF) showed pleocytosis in both with Dengue IgM and NS-1 positive in the second case but not done in the first. MRI brain showed changes of perpendicular subcortical palisading white matter, callosal and brainstem disease mimicking multiple sclerosis (MS) in both patients though in the former case there was a lag between the onset of clinical symptoms and MRI changes which was only clarified on reimaging. The temporal evolution and duration of the clinical symptoms, CSF changes and neuroimaging were more suggestive of Dengue ADEM rather than an encephalitis though initially the first case began as dengue encephalitis. Furthermore in dengue encephalitis neuroimaging is usually normal or rarely edema, haemorrhage, brainstem, thalamic or focal lesions are seen. Therefore, early recognition of ADEM as a sequelae of dengue infection with neuroimaging mimicking MS and repeat imaging helped in identifying these two cases. Treatment with intravenous steroids followed by maintenance oral steroids produced good outcome in both patients. Copyright © 2016 Elsevier B.V. All rights reserved.

    4. Infection Elicited Autoimmunity and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An Explanatory Model

      Science.gov (United States)

      Blomberg, Jonas; Gottfries, Carl-Gerhard; Elfaitouri, Amal; Rizwan, Muhammad; Rosén, Anders

      2018-01-01

      Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS. PMID:29497420

    5. Identification of gene expression patterns crucially involved in experimental autoimmune encephalomyelitis and multiple sclerosis

      Directory of Open Access Journals (Sweden)

      Martin M. Herrmann

      2016-10-01

      Full Text Available After encounter with a central nervous system (CNS-derived autoantigen, lymphocytes leave the lymph nodes and enter the CNS. This event leads only rarely to subsequent tissue damage. Genes relevant to CNS pathology after cell infiltration are largely undefined. Myelin-oligodendrocyte-glycoprotein (MOG-induced experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a chronic autoimmune disease of the CNS that results in disability. To assess genes that are involved in encephalitogenicity and subsequent tissue damage mediated by CNS-infiltrating cells, we performed a DNA microarray analysis from cells derived from lymph nodes and eluted from CNS in LEW.1AV1 (RT1av1 rats immunized with MOG 91-108. The data was compared to immunizations with adjuvant alone or naive rats and to immunizations with the immunogenic but not encephalitogenic MOG 73-90 peptide. Here, we show involvement of Cd38, Cxcr4 and Akt and confirm these findings by the use of Cd38-knockout (B6.129P2-Cd38tm1Lnd/J mice, S1P-receptor modulation during EAE and quantitative expression analysis in individuals with MS. The hereby-defined underlying pathways indicate cellular activation and migration pathways mediated by G-protein-coupled receptors as crucial events in CNS tissue damage. These pathways can be further explored for novel therapeutic interventions.

    6. SAP Suppresses the Development of Experimental Autoimmune Encephalomyelitis in C57BL6 Mice

      Science.gov (United States)

      Ji, Zhe; Ke, Zun-Ji; Geng, Jian-Guo

      2012-01-01

      Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated disease of the CNS. Serum amyloid P component (SAP) is a highly conserved plasma protein named for its universal presence in amyloid deposits. Here we report SAP transgenic mice had unexpectedly attenuated EAE due to impaired encephalitogenic responses. Following induction with myelin oligodendroglial glycoprotein (MOG) peptide 35–55 in CFA, SAP transgenic mice showed reduced spinal cord inflammation with lower severity of EAE attacks as compared with control C57BL/6 mice. However in SAP-KO mice, the severity of EAE is enhanced. Adoptive transfer of Ag-restimulated T cells from wild-type to SAP transgenic mice or transfer of SAP transgenic Ag-restimulated T cells to control mice induced milder EAE. T cells from MOG-primed SAP transgenic mice showed weak proliferative responses. Furthermore, in SAP transgenic mice, there is little infiltration of CD45-positive cells in the spinal cord. In vitro, SAP suppressed the secretion of IL-2 stimulated by P-selectin, and blocked P-selectin binding to T cells. Moreover, SAP could change the affinity between α4-integrin and T cells. These data suggested that SAP could antagonize the development of the acute phase of inflammation accompanying EAE by modulating the function of P-selectin. PMID:21647172

    7. Magnetic resonance imaging and peripheral blood abnormalities in experimental allergic encephalomyelitis

      International Nuclear Information System (INIS)

      Rose, L.M.; Alvord, E.C. Jr.; Richards, T.L.

      1989-01-01

      Experimental allergic encephalomyelitis (EAE) was induced in twelve cynomologous macaques (Macaca fascicularis) by sensitization to autologous myelin basic protein (BP) in complete Freund's adjuvant (CFA). The white blood cell (WBC) count, absolute number of lymphocytes and absolute numbers of CD4 + and CD8 + T-cell subsets were measured weekly. Using magnetic resonance imaging (MRI), the animals were monitored twice weekly for the development of central nervous system (CNS) lesions. Conventional spin-warp imaging was performed using a General Electric CSI-II NMR imager/spectrometer (2 Tesla magnet). CNS lesions were detected by MRI in all of the animals sensitized to myelin BP. Longitudinal analysis of their peripheral blood leukocytes revealed a progressive leukocytosis and lymphopenia, which always preceded the onset of clinical signs and almost always also preceded the formation of detectable CNS lesions. These results suggest that frequent analysis of T-cell subsets may provide a more accurate means of predicting episodes of disease activity than clinical or MRI evaluation

    8. Evaluation of Marijuana Compounds on Neuroimmune Endpoints in Experimental Autoimmune Encephalomyelitis.

      Science.gov (United States)

      Kaplan, Barbara L F

      2018-02-21

      Cannabinoid compounds refer to a group of more than 60 plant-derived compounds in Cannabis sativa, more commonly known as marijuana. Exposure to marijuana and cannabinoid compounds has been increasing due to increased societal acceptance for both recreational and possible medical use. Cannabinoid compounds suppress immune function, and while this could compromise one's ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases. It is critical, therefore, to understand the effects and mechanisms by which cannabinoid compounds alter immune function, especially immune responses induced in autoimmune disease. Therefore, this unit will describe induction and assessment of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and its potential alteration by cannabinoid compounds. The unit includes three approaches to induce EAE, two of which provide correlations to two forms of MS, and the third specifically addresses the role of autoreactive T cells in EAE. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

    9. The mechanism of effective electroacupuncture on T cell response in rats with experimental autoimmune encephalomyelitis.

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      Yumei Liu

      Full Text Available Previously, we demonstrated that electroacupuncture (EA decreased lymphocyte infiltration into the spinal cords of rats presenting with experimental autoimmune encephalomyelitis (EAE, a disease model used in the study of multiple sclerosis (MS. The aim of this study was to characterize the effects of EA on the EAE. Female Lewis rats were divided into either CFA, EAE, EA, or injection with naloxone after electroacupuncture (NAL groups. Electroacupuncture was administered every day for 21 days. To evaluate proliferation and apoptosis, lymphocytes from rats presenting with EAE were collected and cultured with β-endorphin. Immunohistochemisty, flow cytometry and radio-immunity methods were applied to detect the expression of β-endorphin. Results presented in this report demonstrate that the beneficial anti-inflammatory effects of EA on EAE were related to β-endorphin production that balances the Thl/Th2 and Th17/Treg responses. These results suggest that β-endorphin could be an important component in the development of EA-based therapies used for the treatment of EAE.

    10. Immune mechanisms in the transfer of experimental autoimmune encephalomyelitis without adjuvant

      International Nuclear Information System (INIS)

      Silberg, D.G.

      1985-01-01

      Experimental autoimmune encephalomyelitis (EAE) can be induced in Lewis rats without the use of adjuvant. Spleen cells of naive rats were sensitized to myelin basic protein (MBP) in vitro. Transfer of these cells did not result in the development of EAE. However, spleen cells from primary recipients, taken 10 days post transfer, and cultured with MBP (secondary culture, transferred EAE to secondary recipients. EAE can be induced in primary recipients by the transfer of secondary cultured cells or cultured cells or challenge with MBP in complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA) 10 days after injection of naive cultured cells. The finding that MBP-CFA challenged 1' recipients developed EAE, suggests that the rats have been primed to MBP through the naive cultured cell transfer. The cells from naive culture that sensitize the primary recipient were radioresistant (1500 R), probably macrophages. This is in contrast to the cells transferring EAE to the secondary recipient, which were radiosensitive. Unlike the spleen cells which transfer EAE from MBP-CFA sensitized rats, the cells in the secondary transfer could not be activated to transfer EAE when cultured with concanavalin A. Clinical EAE in the secondary recipient was more severe when these rats were irradiated (200 R) prior to transfer. There is evidence that low dose irradiation eliminates naturally occurring suppressor cells. EAE also developed in lethally irradiated (850 R) recipients of secondary cultured cells, suggesting that the transferred cells can induce EAE alone or by recruiting radioresistant cells in the secondary host

    11. Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.

      Science.gov (United States)

      Raddatz, Barbara B; Sun, Wenhui; Brogden, Graham; Sun, Yanyong; Kammeyer, Patricia; Kalkuhl, Arno; Colbatzky, Florian; Deschl, Ulrich; Naim, Hassan Y; Baumgärtner, Wolfgang; Ulrich, Reiner

      2016-01-01

      High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection. © 2015 International Society of Neuropathology.

    12. Detection of antibodies against Theiler's murine encephalomyelitis virus GDVII strain in experimental guinea pigs.

      Science.gov (United States)

      Häger, C; Glage, S; Held, N; Bleich, E M; Burghard, A; Mähler, M; Bleich, André

      2016-10-01

      A disease affecting guinea pigs called 'guinea pig lameness' characterized by clinical signs of depression, lameness of limbs, flaccid paralysis, weight loss and death within a few weeks was first described by Römer in 1911. After a research group in our facility kept laboratory guinea pigs from two different origins together in one room, lameness was observed in two animals. Further investigations revealed a serological immune response against Theiler's murine encephalomyelitis virus (TMEV; GDVII strain) in these animals. Histopathology of the lumbar spinal cord of these animals showed mononuclear cell infiltration and necrotic neurons in the anterior horn. Therefore, all guinea pigs from this contaminated animal unit, from other units in our facility, as well as from different European institutions and breeding centres were screened for antibodies directed against GDVII. Our investigations showed that approximately 80% of all guinea pigs from the contaminated animal unit were seropositive for GDVII, whereas animals from other separate units were completely negative. In addition, 43% of tested sera from the different European institutions and breeding centres contained antibodies against GDVII. The present data confirm that an unknown viral infection causes an immune response in experimental guinea pigs leading to seroconversion against GDVII and that guinea pigs from a commercial breeder are the source of the infection. © The Author(s) 2015.

    13. Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis.

      Directory of Open Access Journals (Sweden)

      Amal Elfaitouri

      Full Text Available Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome, a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60 occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen. The anti-HSP60 humoral (IgG and IgM immune response was studied in 69 ME patients and 76 blood donors (BD (the Training set with recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like activity, but these and other HSP60 peptides also bound IgG and IgM with an ME preference, theoretically indicating a competition between HSP60 function and antibody binding. A HSP60-based panel of 25 antigens was selected. When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients, a peptide from Chlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24% of ME, and in 1 of 399 non-ME at a high cutoff (p<0.0001. IgM to specific cross-reactive epitopes of human and microbial HSP60 occurs in a subset of ME, compatible with infection-induced autoimmunity.

    14. Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.

      Science.gov (United States)

      Stanisavljević, Suzana; Dinić, Miroslav; Jevtić, Bojan; Đedović, Neda; Momčilović, Miljana; Đokić, Jelena; Golić, Nataša; Mostarica Stojković, Marija; Miljković, Đorđe

      2018-01-01

      Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.

    15. Autophagy regulates the therapeutic potential of mesenchymal stem cells in experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Dang, Shipeng; Xu, Huanbai; Xu, Congfeng; Cai, Wei; Li, Qian; Cheng, Yiji; Jin, Min; Wang, Ru-Xing; Peng, Yongde; Zhang, Yi; Wu, Changping; He, Xiaozhou; Wan, Bing; Zhang, Yanyun

      2014-07-01

      Mesenchymal stem cell (MSC)-based therapy is a promising approach to treat various inflammatory disorders including multiple sclerosis. However, the fate of MSCs in the inflammatory microenvironment is largely unknown. Experimental autoimmune encephalomyelitis (EAE) is a well-studied animal model of multiple sclerosis. We demonstrated that autophagy occurred in MSCs during their application for EAE treatment. Inflammatory cytokines, e.g., interferon gamma and tumor necrosis factor, induced autophagy in MSCs synergistically by inducing expression of BECN1/Beclin 1. Inhibition of autophagy by knockdown of Becn1 significantly improved the therapeutic effects of MSCs on EAE, which was mainly attributable to enhanced suppression upon activation and expansion of CD4(+) T cells. Mechanistically, inhibition of autophagy increased reactive oxygen species generation and mitogen-activated protein kinase 1/3 activation in MSCs, which were essential for PTGS2 (prostaglandin-endoperoxide synthase 2 [prostaglandin G/H synthase and cyclooxygenase]) and downstream prostaglandin E2 expression to exert immunoregulatory function. Furthermore, pharmacological treatment of MSCs to inhibit autophagy increased their immunosuppressive effects on T cell-mediated EAE. Our findings indicate that inflammatory microenvironment-induced autophagy downregulates the immunosuppressive function of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel strategy to improve MSC-based immunotherapy.

    16. Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Stanisavljević, S; Lukić, J; Momčilović, M; Miljković, M; Jevtić, B; Kojić, M; Golić, N; Mostarica Stojković, M; Miljković, D

      2016-06-01

      Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.

    17. T Follicular Helper-Like Cells Are Involved in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

      Directory of Open Access Journals (Sweden)

      Jun Guo

      2018-05-01

      Full Text Available Multiple sclerosis (MS and experimental autoimmune encephalomyelitis (EAE have been proved to be T cell-mediated autoimmune diseases. Recent researches indicate that humoral immunity is also involved in the pathogenesis of these disorders. T follicular helper (Tfh cells are critical for B cell differentiation and antibody production. However, the role of Tfh cells in MS and EAE remains unclear. Here, we found elevated frequencies of CD4+CXCR5+PD-1+ Tfh-like cells in both MS patients and EAE. In EAE mice, Tfh-like cells, together with B cells, were found in the ectopic lymphoid structures in spinal cords. Moreover, Tfh-like cells promoted the antibody production via IL-21/IL-21R and CD40 ligand/CD40 interaction and the synergy effect of STAT3 and non-canonical NF-κB signaling pathway inside B cells. Moreover, adoptive transfer of Tfh-like cells could increase the severity and delay the remission of EAE. In conclusion, our data indicate that Tfh-like cells contribute to the pathogenesis of EAE.

    18. Childhood acute disseminated encephalomyelitis: the role of brain and spinal cord MRI

      International Nuclear Information System (INIS)

      Khong, Pek-Lan; Cheng, Pui-Wai; Chan, Fu-Luk; Ho, Hok-Kung; Wong, Virginia C.N.; Goh, Winnie

      2002-01-01

      Background. It is recognised that the clinical and radiological spectrum of childhood acute disseminated encephalomyelitis (ADEM) is wide. Objective. To determine whether initial MRI features are predictive of clinical outcome and to determine the role of MRI in the management of ADEM. Materials and methods. The MRI scans of ten consecutive children (eight boys, two girls), clinically and radiologically diagnosed to have ADEM, were retrospectively reviewed. Follow-up MRI was available for eight patients. Results. Lesions ranged from small and punctate (<1 cm) to moderate sized and confluent (4-5 cm) to diffuse and extensive. Spinal cord lesions, seen in five of seven children, were contiguous or segmental. Seven children (70%) made good clinical recovery while three children (30%) remained severely handicapped. There was no correlation between the site, extent and pattern of involvement and clinical outcome. However, the evolution of MRI findings on follow-up correlated well with the subsequent clinical course and outcome. Conclusions. Although the extent and site of lesions on initial MRI scans are not predictive of clinical outcome, early MRI of the brain and spine is useful in aiding clinical diagnosis, and subsequent follow-up MRI is helpful in monitoring disease progression. (orig.)

    19. Vorinostat, a histone deacetylase inhibitor, suppresses dendritic cell function and ameliorates experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Ge, Zhenzhen; Da, Yurong; Xue, Zhenyi; Zhang, Kai; Zhuang, Hao; Peng, Meiyu; Li, Yan; Li, Wen; Simard, Alain; Hao, Junwei; Yao, Zhi; Zhang, Rongxin

      2013-03-01

      Vorinostat, a histone deacetylase inhibitor, has been used clinically as an anticancer drug and also has immunosuppressive properties. However, the underlying mechanisms of effects of vorinostat on central nervous system (CNS) inflammatory diseases remain incomplete. Here, this study investigates the effects of vorinostat on human CD14(+) monocyte-derived dendritic cells (DCs) and mouse immature DC in vitro. Furthermore, we explore the therapeutic effects and cellular mechanisms of vorinostat on animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) in vivo. Our findings demonstrate that vorinostat inhibited human CD14(+) monocyte-derived DCs differentiation, maturation, endocytosis, and further inhibited mDCs' stimulation of allogeneic T-cell proliferation. In addition, vorinostat inhibited DC-directed Th1- (Type 1T helper) and Th17-polarizing cytokine production. Furthermore, vorinostat ameliorated Th1- and Th17-mediated EAE by reducing CNS inflammation and demyelination. What's more, Th1 and Th17 cell functions were suppressed in vorinostat-treated EAE mice. Finally, vorinostat suppressed expression of costimulatory molecules of DC in EAE mice. These suggest therapeutic effects of vorinostat on EAE which may by suppress DCs and DCs-mediated Th1 and Th17 cell functions. Our findings warrant further investigation in the potential of vorinostat for the treatment of human multiple sclerosis. Copyright © 2012. Published by Elsevier Inc.

    20. Combined treatment with ribavirin and tiazofurin attenuates response of glial cells in experimental autoimmune encephalomyelitis

      Directory of Open Access Journals (Sweden)

      Nedeljković Nadežda

      2012-01-01

      Full Text Available Experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a human inflammatory and demyelinating disease. Microglia and astrocytes are glial cells of the central nervous system (CNS that play a dual role in MS and EAE pathology. The aim of this study was to examine the effect of combined treatment with two nucleoside analogues, ribavirin and tiazofurin, on microglia and astrocytes in actively induced EAE. Therapeutic treatment with a combination of these two nucleoside analogues reduced disease severity, mononuclear cell infiltration and demyelination. The obtained histological results indicate that ribavirin and tiazofurin changed activated microglia into an inactive type and attenuated astrocyte reactivity at the end of the treatment period. Since reduction of reactive microgliosis and astrogliosis correlated with EAE suppression, the present study also suggests that the obtained beneficial effect of ribavirin and tiazofurin could be a consequence of their action inside as well as outside the CNS. [Acknowledgments. This work was supported by the Serbian Ministry of Education and Science, Project No: III41014.

    1. Experimental Autoimmune Encephalomyelitis (EAE) as Animal Models of Multiple Sclerosis (MS).

      Science.gov (United States)

      Glatigny, Simon; Bettelli, Estelle

      2018-01-08

      Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system (CNS) leading to the progressive destruction of the myelin sheath surrounding axons. It can present with variable clinical and pathological manifestations, which might reflect the involvement of distinct pathogenic processes. Although the mechanisms leading to the development of the disease are not fully understood, numerous evidences indicate that MS is an autoimmune disease, the initiation and progression of which are dependent on an autoimmune response against myelin antigens. In addition, genetic susceptibility and environmental triggers likely contribute to the initiation of the disease. At this time, there is no cure for MS, but several disease-modifying therapies (DMTs) are available to control and slow down disease progression. A good number of these DMTs were identified and tested using animal models of MS referred to as experimental autoimmune encephalomyelitis (EAE). In this review, we will recapitulate the characteristics of EAE models and discuss how they help shed light on MS pathogenesis and help test new treatments for MS patients. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

    2. The expressed needs of people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A systematic review

      Directory of Open Access Journals (Sweden)

      Campion Peter

      2009-12-01

      Full Text Available Abstract Background We aimed to review systematically the needs for support in managing illness and maintaining social inclusion expressed by people with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME Methods We carried out a systematic review of primary research and personal ('own' stories expressing the needs of people with CFS/ME. Structured searches were carried out on Medline, AMED, CINAHL, EMBASE, ASSIA, CENTRAL, and other health, social and legal databases from inception to November 2007. Study inclusion, data extraction and risk of bias were assessed independently in duplicate. Expressed needs were tabulated and a conceptual framework developed through an iterative process. Results Thirty two quantitative and qualitative studies, including the views of over 2500 people with CFS/ME with mainly moderate or severe illness severity, met the inclusion criteria. The following major support needs emerged: 1 The need to make sense of symptoms and gain diagnosis, 2 for respect and empathy from service providers, 3 for positive attitudes and support from family and friends, 4 for information on CFS/ME, 5 to adjust views and priorities, 6 to develop strategies to manage impairments and activity limitations, and 7 to develop strategies to maintain/regain social participation. Conclusions Although the studies were heterogeneous, there was consistent evidence that substantial support is needed to rebuild lives. Gaining support depends - most importantly - on the ability of providers of health and social care, colleagues, friends and relatives, and those providing educational and leisure services, to understand and respond to those needs.

    3. Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis

      Science.gov (United States)

      Yeste, Ada; Nadeau, Meghan; Burns, Evan J.; Weiner, Howard L.; Quintana, Francisco J.

      2012-01-01

      The immune response is normally controlled by regulatory T cells (Tregs). However, Treg deficits are found in autoimmune diseases, and therefore the induction of functional Tregs is considered a potential therapeutic approach for autoimmune disorders. The activation of the ligand-activated transcription factor aryl hydrocarbon receptor by 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) or other ligands induces dendritic cells (DCs) that promote FoxP3+ Treg differentiation. Here we report the use of nanoparticles (NPs) to coadminister ITE and a T-cell epitope from myelin oligodendrocyte glycoprotein (MOG)35–55 to promote the generation of Tregs by DCs. NP-treated DCs displayed a tolerogenic phenotype and promoted the differentiation of Tregs in vitro. Moreover, NPs carrying ITE and MOG35–55 expanded the FoxP3+ Treg compartment and suppressed the development of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis. Thus, NPs are potential new tools to induce functional Tregs in autoimmune disorders. PMID:22745170

    4. A case of acute disseminated encephalomyelitis with convulsion, gait disturbance, facial palsy and with multifocal CT lesions

      International Nuclear Information System (INIS)

      Nagano, Tetsu; Kurihara, Eiji; Mizuno, Yoshihiko; Tamagawa, Kimiko; Komiya, Kazuhiko; Mizuguchi, Masashi.

      1988-01-01

      A case of acute disseminated encephalomyelitis (ADEM) was presented. The patient was a 4-year-old boy with convulsion, ataxic gait, facial palsy. It was postulated that the influenza vaccine might induce the disease in this case. Cranial CT showed a low density arease in the right temporal lobe, which disappeared afterwards when other low density areas appeared in the right cerebellar hemisphere and in inner portion of the body of the left lateral ventricle. All symptoms disappeared without therapy and the CT findings improved within three months after onset. (author)

    5. Rehabilitation outcomes after combined acute disseminated encephalomyelitis and Guillain-Barré syndrome in a child: a case report.

      Science.gov (United States)

      Korupolu, Radha; Ngo, Thien; Hack, Nawaz; Escott, Edward; Salles, Sara

      2014-01-01

      A 5-year old female presented with acute tetraparesis and areflexia. Initial imaging and cerebrospinal fluid analysis were suggestive of acute disseminated encephalomyelitis (ADEM). Minimal clinical response with intravenous steroids prompted further work up. Limited nerve conduction studies suggested possible acute motor-sensory axonal neuropathy, a rare variant of Guillain-Barré syndrome (GBS). Repeat imaging was compatible with polyradiculopathy indicating concomitance of ADEM and GBS. The patient suffered severe motor deficits and neuropathic pain. Slow but significant functional recovery was noted after intensive inpatient rehabilitation followed by continued rehabilitation via home health services.

    6. Treatment with metallothionein prevents demyelination and axonal damage and increases oligodendrocyte precursors and tissue repair during experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Penkowa, Milena; Hidalgo, Juan

      2003-01-01

      Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human demyelinating disease multiple sclerosis (MS). EAE and MS are characterized by significant inflammation, demyelination, neuroglial damage, and cell death. Metallothionein-I and -II (MT-I + II) are antiinflammatory an......)beta, neurotrophin-3 (NT-3), NT-4/5, and nerve growth factor (NGF). These beneficial effects of Zn-MT-II treatment could not be attributable to its zinc content per se. The present results support further the use of Zn-MT-II as a safe and successful therapy for multiple sclerosis....

    7. Eastern equine encephalomyelitis virus and Culiseta melanura activity at the Patuxent Wildlife Research Center, 1985-90.

      Science.gov (United States)

      Pagac, B B; Turell, M J; Olsen, G H

      1992-09-01

      Mosquito population densities, virus isolations and seroconversion in sentinel quail were used to monitor eastern equine encephalomyelitis virus (EEE) activity at the Patuxent Wildlife Research Center, Laurel, Maryland, from 1985 through 1990. A dramatic increase in the number of Culiseta melanura collected in 1989, as compared with the 3 previous years, was associated with virus isolations from this species (5/75 pools; n = 542 mosquitoes) and with seroconversion in sentinel quail (4/22 birds positive). This was the first detection of EEE virus activity in this area since a 1984 EEE outbreak killed 7 whooping cranes.

    8. The picornavirus avian encephalomyelitis virus possesses a hepatitis C virus-like internal ribosome entry site element

      DEFF Research Database (Denmark)

      Bakhshesh, M.; Groppelli, E.; Willcocks, M.A.

      2008-01-01

      and it is also resistant to an inhibitor of eIF4A. These properties are reminiscent of the recently discovered class of IRES elements within certain other picornaviruses, such as porcine teschovirus 1 (PTV-1). Like the PTV-1 IRES, the AEV IRES shows significant similarity to the hepatitis C virus (HCV) IRES......Avian encephalomyelitis virus (AEV) is a picornavirus that causes disease in poultry worldwide, and flocks must be vaccinated for protection. AEV is currently classified within the hepatovirus genus, since its proteins are most closely related to those of hepatitis A virus (HAV). We now provide...

    9. Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis

      International Nuclear Information System (INIS)

      Massa, P.T.; ter Meulen, V.; Fontana, A.

      1987-01-01

      In search of a phenotypic marker determining genetically controlled susceptibility to delayed-type hypersensitivity (DTH) reactions in the brain-in particular, experimental autoimmune encephalomyelitis (EAE)- the authors have compared the γ-interferon (IFN-γ) induction of Ia molecules on astrocytes and macrophages from rat and mouse strains that are susceptible or resistant to this disease. They focused on Ia expression because DTH reactions to self or foreign antigens are largely mediated by lymphocytes restricted by class II (Ia) antigens of the major histocompatibility complex (MHC). The data demonstrate that Lewis (fully susceptible) and Brown Norway (BN) (fully resistant) rats are very different in that Lewis astrocytes express much higher levels of Ia than BN astrocytes. Similar data were obtained from an analysis of EAE-susceptible and -resistant mouse strains (SJL and BALB/c, respectively), which suggest that this phenomenon may be universal and not limited to only one mammalian species. At least one gene responsible for Ia hyperinduction is located outside the rat RT-1 or the mouse MHC locus. Animals congenic at the RT-1 or MHC locus of the resistant strain but with background genes of the susceptible strain exhibit intermediate levels of Ia compared to fully resistant and susceptible rodents, which fits well with the reduced EAE susceptibility of these congenic animals. Furthermore, hyperinduction of Ia is astrocyte specific, since peritoneal macrophages of susceptible and resistant strains exhibit identical profiles of Ia induction. Thus, astrocyte Ia hyperinducibility may be a major strain- and tissue-specific factor that contributes to Ia-restricted DTH reactions in the brain

    10. Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

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      Ashton Kevin J

      2011-05-01

      Full Text Available Abstract Background Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME is characterised by severe prolonged fatigue, and decreases in cognition and other physiological functions, resulting in severe loss of quality of life, difficult clinical management and high costs to the health care system. To date there is no proven pathomechanism to satisfactorily explain this disorder. Studies have identified abnormalities in immune function but these data are inconsistent. We investigated the profile of markers of immune function (including novel markers in CFS/ME patients. Methods We included 95 CFS/ME patients and 50 healthy controls. All participants were assessed on natural killer (NK and CD8+T cell cytotoxic activities, Th1 and Th2 cytokine profile of CD4+T cells, expression of vasoactive intestinal peptide receptor 2 (VPACR2, levels of NK phenotypes (CD56bright and CD56dim and regulatory T cells expressing FoxP3 transcription factor. Results Compared to healthy individuals, CFS/ME patients displayed significant increases in IL-10, IFN-γ, TNF-α, CD4+CD25+ T cells, FoxP3 and VPACR2 expression. Cytotoxic activity of NK and CD8+T cells and NK phenotypes, in particular the CD56bright NK cells were significantly decreased in CFS/ME patients. Additionally granzyme A and granzyme K expression were reduced while expression levels of perforin were significantly increased in the CFS/ME population relative to the control population. These data suggest significant dysregulation of the immune system in CFS/ME patients. Conclusions Our study found immunological abnormalities which may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool.

    11. Partial deficiency of sphingosine-1-phosphate lyase confers protection in experimental autoimmune encephalomyelitis.

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      Andreas Billich

      Full Text Available BACKGROUND: Sphingosine-1-phosphate (S1P regulates the egress of T cells from lymphoid organs; levels of S1P in the tissues are controlled by S1P lyase (Sgpl1. Hence, Sgpl1 offers a target to block T cell-dependent inflammatory processes. However, the involvement of Sgpl1 in models of disease has not been fully elucidated yet, since Sgpl1 KO mice have a short life-span. METHODOLOGY: We generated inducible Sgpl1 KO mice featuring partial reduction of Sgpl1 activity and analyzed them with respect to sphingolipid levels, T-cell distribution, and response in models of inflammation. PRINCIPAL FINDINGS: The partially Sgpl1 deficient mice are viable but feature profound reduction of peripheral T cells, similar to the constitutive KO mice. While thymic T cell development in these mice appears normal, mature T cells are retained in thymus and lymph nodes, leading to reduced T cell numbers in spleen and blood, with a skewing towards increased proportions of memory T cells and T regulatory cells. The therapeutic relevance of Sgpl1 is demonstrated by the fact that the inducible KO mice are protected in experimental autoimmune encephalomyelitis (EAE. T cell immigration into the CNS was found to be profoundly reduced. Since S1P levels in the brain of the animals are unchanged, we conclude that protection in EAE is due to the peripheral effect on T cells, leading to reduced CNS immigration, rather than on local effects in the CNS. SIGNIFICANCE: The data suggest Sgpl1 as a novel therapeutic target for the treatment of multiple sclerosis.

    12. Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE).

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      Benson, Curtis; Paylor, John W; Tenorio, Gustavo; Winship, Ian; Baker, Glen; Kerr, Bradley J

      2015-09-01

      Multiple sclerosis (MS) is classically defined by motor deficits, but it is also associated with the secondary symptoms of pain, depression, and anxiety. Up to this point modifying these secondary symptoms has been difficult. There is evidence that both MS and the animal model experimental autoimmune encephalomyelitis (EAE), commonly used to study the pathophysiology of the disease, can be modulated by exercise. To examine whether limited voluntary wheel running could modulate EAE disease progression and the co-morbid symptoms of pain, mice with EAE were allowed access to running wheels for 1h every day. Allowing only 1h every day of voluntary running led to a significant delay in the onset of clinical signs of the disease. The development of mechanical allodynia was assessed using Von Frey hairs and indicated that wheel running had a modest positive effect on the pain hypersensitivity associated with EAE. These behavioral changes were associated with reduced numbers of cFOS and phosphorylated NR1 positive cells in the dorsal horn of the spinal cord compared to no-run EAE controls. In addition, within the dorsal horn, voluntary wheel running reduced the number of infiltrating CD3(+) T-cells and reduced the overall levels of Iba1 immunoreactivity. Using high performance liquid chromatography (HPLC), we observed that wheel-running lead to significant changes in the spinal cord levels of the antioxidant glutathione. Oxidative stress has separately been shown to contribute to EAE disease progression and neuropathic pain. Together these results indicate that in mice with EAE, voluntary motor activity can delay the onset of clinical signs and reduce pain symptoms associated with the disease. Copyright © 2015 Elsevier Inc. All rights reserved.

    13. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer

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      Peter C. Rowe

      2017-06-01

      Full Text Available Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS is a complex disease that affects children and adolescents as well as adults. The etiology has not been established. While many pediatricians and other health-care providers are aware of ME/CFS, they often lack essential knowledge that is necessary for diagnosis and treatment. Many young patients experience symptoms for years before receiving a diagnosis. This primer, written by the International Writing Group for Pediatric ME/CFS, provides information necessary to understand, diagnose, and manage the symptoms of ME/CFS in children and adolescents. ME/CFS is characterized by overwhelming fatigue with a substantial loss of physical and mental stamina. Cardinal features are malaise and a worsening of symptoms following minimal physical or mental exertion. These post-exertional symptoms can persist for hours, days, or weeks and are not relieved by rest or sleep. Other symptoms include cognitive problems, unrefreshing or disturbed sleep, generalized or localized pain, lightheadedness, and additional symptoms in multiple organ systems. While some young patients can attend school, on a full or part-time basis, many others are wheelchair dependent, housebound, or bedbound. Prevalence estimates for pediatric ME/CFS vary from 0.1 to 0.5%. Because there is no diagnostic test for ME/CFS, diagnosis is purely clinical, based on the history and the exclusion of other fatiguing illnesses by physical examination and medical testing. Co-existing medical conditions including orthostatic intolerance (OI are common. Successful management is based on determining the optimum balance of rest and activity to help prevent post-exertional symptom worsening. Medications are helpful to treat pain, insomnia, OI and other symptoms. The published literature on ME/CFS and specifically that describing the diagnosis and management of pediatric ME/CFS is very limited. Where published studies are lacking, recommendations

    14. Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids.

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      Pryce, Gareth; Riddall, Dieter R; Selwood, David L; Giovannoni, Gavin; Baker, David

      2015-06-01

      Multiple sclerosis (MS) is the major immune-mediated, demyelinating, neurodegenerative disease of the central nervous system. Compounds within cannabis, notably Δ9-tetrahydrocannabinol (Δ9-THC) can limit the inappropriate neurotransmissions that cause MS-related problems and medicinal cannabis is now licenced for the treatment of MS symptoms. However, the biology indicates that the endocannabinoid system may offer the potential to control other aspects of disease. Although there is limited evidence that the cannabinoids from cannabis are having significant immunosuppressive activities that will influence relapsing autoimmunity, we and others can experimentally demonstrate that they may limit neurodegeneration that drives progressive disability. Here we show that synthetic cannabidiol can slow down the accumulation of disability from the inflammatory penumbra during relapsing experimental autoimmune encephalomyelitis (EAE) in ABH mice, possibly via blockade of voltage-gated sodium channels. In addition, whilst non-sedating doses of Δ9-THC do not inhibit relapsing autoimmunity, they dose-dependently inhibit the accumulation of disability during EAE. They also appear to slow down clinical progression during MS in humans. Although a 3 year, phase III clinical trial did not detect a beneficial effect of oral Δ9-THC in progressive MS, a planned subgroup analysis of people with less disability who progressed more rapidly, demonstrated a significant slowing of progression by oral Δ9-THC compared to placebo. Whilst this may support the experimental and biological evidence for a neuroprotective effect by the endocannabinoid system in MS, it remains to be established whether this will be formally demonstrated in further trials of Δ9-THC/cannabis in progressive MS.

    15. Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study.

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      Floris, S; Blezer, E L A; Schreibelt, G; Döpp, E; van der Pol, S M A; Schadee-Eestermans, I L; Nicolay, K; Dijkstra, C D; de Vries, H E

      2004-03-01

      Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood-brain barrier leakage is an early event and precedes massive cellular infiltration in the development of acute experimental allergic encephalomyelitis (EAE), the animal correlate of multiple sclerosis. Cerebrovascular leakage and monocytes infiltrates were separately monitored by quantitative in vivo MRI during the course of the disease. Magnetic resonance enhancement of the contrast agent gadolinium diethylenetriaminepentaacetate (Gd-DTPA), reflecting vascular leakage, occurred concomitantly with the onset of neurological signs and was already at a maximal level at this stage of the disease. Immunohistochemical analysis also confirmed the presence of the serum-derived proteins such as fibrinogen around the brain vessels early in the disease, whereas no cellular infiltrates could be detected. MRI further demonstrated that Gd-DTPA leakage clearly preceded monocyte infiltration as imaged by the contrast agent based on ultra small particles of iron oxide (USPIO), which was maximal only during full-blown EAE. Ultrastructural and immunohistochemical investigation revealed that USPIOs were present in newly infiltrated macrophages within the inflammatory lesions. To validate the use of USPIOs as a non-invasive tool to evaluate therapeutic strategies, EAE animals were treated with the immunomodulator 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitor, lovastatin, which ameliorated clinical scores. MRI showed that the USPIO load in the brain was significantly diminished in lovastatin-treated animals. Data indicate that cerebrovascular leakage and monocytic trafficking into the brain are two distinct processes in the development of inflammatory lesions during multiple sclerosis, which can

    16. Treatment and management of chronic fatigue syndrome/myalgic encephalomyelitis: all roads lead to Rome

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      Sáez‐Francàs, Naia; Santillo, Dafna; Alegre, Jose

      2017-01-01

      This review explores the current evidence on benefits and harms of therapeutic interventions in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and makes recommendations. CFS/ME is a complex, multi‐system, chronic medical condition whose pathophysiology remains unknown. No established diagnostic tests exist nor are any FDA‐approved drugs available for treatment. Because of the range of symptoms of CFS/ME, treatment approaches vary widely. Studies undertaken have heterogeneous designs and are limited by sample size, length of follow‐up, applicability and methodological quality. The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. Similarly, adaptive pacing appears to offer some benefits, but the results are debatable: so is the use of nutritional supplements, which may be of value to CFS/ME patients with biochemically proven deficiencies. To summarize, the recommended treatment strategies should include proper administration of nutritional supplements in CFS/ME patients with demonstrated deficiencies and personalized pacing programs to relieve symptoms and improve performance of daily activities, but a larger randomized controlled trial (RCT) evaluation is required to confirm these preliminary observations. At present, no firm conclusions can be drawn because the few RCTs undertaken to date have been small‐scale, with a high risk of bias, and have used different case definitions. Further, RCTs are now urgently needed with rigorous experimental designs and appropriate data analysis, focusing particularly on the comparison of outcomes measures according to clinical presentation, patient characteristics, case criteria and degree of disability (i.e. severely ill ME cases or bedridden). PMID:28052319

    17. A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis.

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      Harris, Sarah; Gilbert, Matthew; Beasant, Lucy; Linney, Catherine; Broughton, Jessica; Crawley, Esther

      2017-01-01

      An estimated 10% of children and adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) experience eating difficulties; however, little is known about why these difficulties develop, what the impact is or how to manage them. Semi-structured interviews were conducted with adolescents (aged 12-17 years) attending a specialist service who have a primary diagnosis of CFS/ME and experience nausea, abdominal pain and/or eating difficulties. A total of 11 adolescents were interviewed (eight female, mean age: 15 years). Transcripts were analysed thematically using techniques of constant comparison which commenced soon after data collection and informed further interview protocols. Adolescents perceived their eating difficulties were caused by abdominal symptoms, being too fatigued to eat and changes to their senses of taste and smell. Some of the adolescents recognised how their eating difficulties were exacerbated and maintained by psychological factors of low mood and anxiety. The adolescents eating difficulties had a negative impact on their weight, fatigue, socialising and family life. They perceived helpful interventions to include modifying their diets, families adjusting and also medical interventions (e.g. medication). Adolescents identified that early education and support about diet and eating habits would have been helpful. If adolescents diagnosed with CFS/ME develop eating difficulties, this has a significant impact on their quality of life, illness and on their families. Not eating increases fatigue, low mood and anxiety which further exacerbates the eating difficulties. Clinicians should screen for eating difficulties in those with symptoms of nausea and abdominal pain, warn adolescents and their families of the risk of developing eating difficulties and provide interventions and support as early as possible.

    18. A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome.

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      Morris, Gerwyn; Maes, Michael

      2013-12-01

      This paper proposes a neuro-immune model for Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). A wide range of immunological and neurological abnormalities have been reported in people suffering from ME/CFS. They include abnormalities in proinflammatory cytokines, raised production of nuclear factor-κB, mitochondrial dysfunctions, autoimmune responses, autonomic disturbances and brain pathology. Raised levels of oxidative and nitrosative stress (O&NS), together with reduced levels of antioxidants are indicative of an immuno-inflammatory pathology. A number of different pathogens have been reported either as triggering or maintaining factors. Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve. Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage. The subsequent ATP deficit together with inflammation and O&NS are responsible for the landmark symptoms of ME/CFS, including post-exertional malaise. Raised levels of O&NS subsequently cause progressive elevation of autoimmune activity facilitated by molecular mimicry, bystander activation or epitope spreading. These processes provoke central nervous system (CNS) activation in an attempt to restore immune homeostatsis. This model proposes that the antagonistic activities of the CNS response to peripheral inflammation, O&NS and chronic immune activation are responsible for the remitting-relapsing nature of ME/CFS. Leads for future research are suggested based on this

    19. Effect of dimethyl fumarate on heme oxygenase-1 expression in experimental allergic encephalomyelitis in rats

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      Kaja Kasarełło

      2017-12-01

      Full Text Available Multiple sclerosis (MS is an autoimmunological disease leading to neurodegeneration. The etiology of the disease remains unknown, which strongly impedes the development of effective therapy. Most MS treatments focus on modulating the activity of the immune system. Dimethyl fumarate (DMF exerts a broad spectrum of action, such as modulating immune cell differentiation towards anti-inflammatory subtypes, influencing cytokine production, regulating immune cell migration into the central nervous system, and activating intracellular antioxidant mechanisms. It is well established that activation of the nuclear factor E2 (Nrf2-dependent pathway, leading to expression of the second-phase antioxidant enzymes, is influenced by DMF. In our experiments we used female Lewis rats in an animal model of MS – experimental allergic encephalomyelitis (EAE. The rats were fed with dimethyl fumarate to test the expression of heme oxygenase-1 (HO-1, one of the second-phase antioxidant enzymes, at specific time points of the symptomatic phases of the disease: on the first day of the occurrence of clinical symptoms (10th day post immunization, DPI; at the peak of clinical symptoms (14th DPI; and at the end of the relapse (21st DPI. The results showed that HO-1 expression, at both the mRNA and protein level, is influenced by DMF administration only at the very beginning of the symptomatic phase of EAE, and not at the peak of clinical symptoms, nor at the end of the relapse. This indicates that the regulation of the Nrf2-dependent antioxidant pathway by DMF occurs at a certain time interval (early EAE/MS and strongly underlines the importance of the earliest introduction of the therapy to the patient.

    20. The prevalence of chronic fatigue syndrome/ myalgic encephalomyelitis: a meta-analysis

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      Johnston S

      2013-03-01

      Full Text Available Samantha Johnston,1 Ekua W Brenu,1 Donald Staines,1,2 Sonya Marshall-Gradisnik1 1Griffith Health Institute, School of Medical Sciences, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Parklands, QLD, Australia; 2Gold Coast Public Health Unit, Queensland Health, Robina, QLD, Australia Purpose: To perform a meta-analysis to examine variability among prevalence estimates for CFS/ME, according to the method of assessment used. Methods: Databases were systematically searched for studies on CFS/ME prevalence in adults that applied the 1994 Centers for Disease Control (CDC case definition.1 Estimates were categorized into two methods of assessment: self-reporting of symptoms versus clinical assessment of symptoms. Meta-analysis was performed to pool prevalences by assessment using random effects modeling. This was stratified by sample setting (community or primary care and heterogeneity was examined using the I2 statistic. Results: Of 216 records found, 14 studies were considered suitable for inclusion. The pooled prevalence for self-reporting assessment was 3.28% (95% CI: 2.24–4.33 and 0.76% (95% CI: 0.23–1.29 for clinical assessment. High variability was observed among self-reported estimates, while clinically assessed estimates showed greater consistency. Conclusion: The observed heterogeneity in CFS/ME prevalence may be due to differences in method of assessment. Stakeholders should be cautious of prevalence determined by the self-reporting of symptoms alone. The 1994 CDC case definition appeared to be the most reliable clinical assessment tool available at the time of these studies. Improving clinical case definitions and their adoption internationally will enable better comparisons of findings and inform health systems about the true burden of CFS/ME. Keywords: chronic fatigue syndrome, myalgic encephalomyelitis, prevalence, meta-analysis

    1. Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

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      Norbert W Lutz

      Full Text Available Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE and adjuvant arthritis (AA in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA and spinal-cord homogenate (SC-H, whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group. Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE or extra-cerebral (AA inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and

    2. Exercise training attenuates experimental autoimmune encephalomyelitis by peripheral immunomodulation rather than direct neuroprotection.

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      Einstein, Ofira; Fainstein, Nina; Touloumi, Olga; Lagoudaki, Roza; Hanya, Ester; Grigoriadis, Nikolaos; Katz, Abram; Ben-Hur, Tamir

      2018-01-01

      Conflicting results exist on the effects of exercise training (ET) on Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise impacts on disease progression. We examined whether ET ameliorates the development of EAE by modulating the systemic immune system or exerting direct neuroprotective effects on the CNS. Healthy mice were subjected to 6weeks of motorized treadmill running. The Proteolipid protein (PLP)-induced transfer EAE model in mice was utilized. To assess effects of ET on systemic autoimmunity, lymph-node (LN)-T cells from trained- vs. sedentary donor mice were transferred to naïve recipients. To assess direct neuroprotective effects of ET, PLP-reactive LN-T cells were transferred into recipient mice that were trained prior to EAE transfer or to sedentary mice. EAE severity was assessed in vivo and the characteristics of encephalitogenic LN-T cells derived from PLP-immunized mice were evaluated in vitro. LN-T cells obtained from trained mice induced an attenuated clinical and pathological EAE in recipient mice vs. cells derived from sedentary animals. Training inhibited the activation, proliferation and cytokine gene expression of PLP-reactive T cells in response to CNS-derived autoantigen, but strongly enhanced their proliferation in response to Concanavalin A, a non-specific stimulus. However, there was no difference in EAE severity when autoreactive encephalitogenic T cells were transferred to trained vs. sedentary recipient mice. ET inhibits immune system responses to an auto-antigen to attenuate EAE, rather than generally suppressing the immune system, but does not induce a direct neuro-protective effect against EAE. Copyright © 2017 Elsevier Inc. All rights reserved.

    3. RAE-1 expression is induced during experimental autoimmune encephalomyelitis and is correlated with microglia cell proliferation.

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      Djelloul, Mehdi; Popa, Natalia; Pelletier, Florence; Raguénez, Gilda; Boucraut, José

      2016-11-01

      Retinoic acid early induced transcript-1 (RAE-1) glycoproteins are ligands of the activating immune receptor NKG2D. They are known as stress molecules induced in pathological conditions. We previously reported that progenitor cells express RAE-1 in physiological conditions and we described a correlation between RAE-1 expression and cell proliferation. In addition, we showed that Raet1 transcripts are induced in the spinal cord of experimental autoimmune encephalomyelitis (EAE) mice. EAE is a model for multiple sclerosis which is accompanied by microglia proliferation and activation, recruitment of immune cells and neurogenesis. We herein studied the time course expression of the two members of the Raet1 gene family present in C57BL/6 mice, namely Raet1d and Raet1e, in the spinal cord during EAE. We report that Raet1d and Raet1e genes are induced early upon EAE onset and reach a maximal expression at the peak of the pathology. We show that myeloid cells, i.e. macrophages as well as microglia, are cellular sources of Raet1 transcripts. We also demonstrate that only Raet1d expression is induced in microglia, whereas macrophages expressed both Raet1d and Raet1e. Furthermore, we investigated the dynamics of RAE-1 expression in microglia cultures. RAE-1 induction correlated with cell proliferation but not with M1/M2 phenotypic orientation. We finally demonstrate that macrophage colony-stimulating factor (M-CSF) is a major factor controlling RAE-1 expression in microglia. Copyright © 2016 Elsevier Inc. All rights reserved.

    4. Transplantation of autologous adipose stem cells lacks therapeutic efficacy in the experimental autoimmune encephalomyelitis model.

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      Xiujuan Zhang

      Full Text Available Multiple sclerosis (MS, characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE, a murine model of MS. ASCs from EAE mice and their syngeneic wild-type mice were cultured, expanded, and characterized for their cell morphology, surface antigen expression, osteogenic and adipogenic differentiation, colony forming units, and inflammatory cytokine and chemokine levels in vitro. Furthermore, the therapeutic efficacy of the cells was assessed in vivo by transplantation into EAE mice. The results indicated that the ASCs from EAE mice displayed a normal phenotype, typical MSC surface antigen expression, and in vitro osteogenic and adipogenic differentiation capacity, while their osteogenic differentiation capacity was reduced in comparison with their unafflicted control mice. The ASCs from EAE mice also demonstrated increased expression of pro-inflammatory cytokines and chemokines, specifically an elevation in the expression of monocyte chemoattractant protein-1 and keratin chemoattractant. In vivo, infusion of wild type ASCs significantly ameliorate the disease course, autoimmune mediated demyelination and cell infiltration through the regulation of the inflammatory responses, however, mice treated with autologous ASCs showed no therapeutic improvement on the disease progression.

    5. Delayed onset of experimental autoimmune encephalomyelitis in Olig1 deficient mice.

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      Xiaoli Guo

      Full Text Available BACKGROUND: Olig1 is a basic helix-loop-helix (bHLH transcription factor that is essential for oligodendrogenesis and efficient remyelination. However, its role in neurodegenerative disorders has not been well-elucidated. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the effects of Olig1 deficiency on experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. We show that the mean disease onset of myelin oligodendrocyte glycoprotein (MOG-induced EAE in Olig1(-/- mice is significantly slower than wide-type (WT mice (19.8 ± 2.2 in Olig1(-/- mice and 9.5 ± 0.3 days in WT mice. In addition, 10% of Olig1(-/- mice did not develop EAE by the end of the observation periods (60 days. The severity of EAE, the extent of demyelination, and the activation of microglial cells and astrocytes in spinal cords, were significantly milder in Olig1(-/- mice compared with WT mice in the early stage. Moreover, the visual function, as assessed by the second-kernel of multifocal electroretinograms, was better preserved, and the number of degenerating axons in the optic nerve was significantly reduced in Olig1(-/- mice. Interestingly, Olig1 deficiency had no effect on T cell response capability, however, it reduced the expression of myelin proteins such as MOG, myelin basic protein (MBP and myelin-associated glycoprotein (MAG. The expression of Olig2 remained unchanged in the optic nerve and brain, and it was reduced in the spinal cord of Olig1(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the Olig1 signaling pathways may be involved in the incidence rate and the severity of neurological symptoms in MS.

    6. Epitope-Specific Tolerance Modes Differentially Specify Susceptibility to Proteolipid Protein-Induced Experimental Autoimmune Encephalomyelitis

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      Lei Wang

      2017-11-01

      Full Text Available Immunization with myelin components can elicit experimental autoimmune encephalomyelitis (EAE. EAE susceptibility varies between mouse strains, depending on the antigen employed. BL/6 mice are largely resistant to EAE induction with proteolipid protein (PLP, probably a reflection of antigen-specific tolerance. However, the extent and mechanism(s of tolerance to PLP remain unclear. Here, we identified three PLP epitopes in PLP-deficient BL/6 mice. PLP-sufficient mice did not respond against two of these, whereas tolerance was “leaky” for an epitope with weak predicted MHCII binding, and only this epitope was encephalitogenic. In TCR transgenic mice, the “EAE-susceptibility-associated” epitope was “ignored” by specific CD4 T cells, whereas the “resistance-associated” epitope induced clonal deletion and Treg induction in the thymus. Central tolerance was autoimmune regulator dependent and required expression and presentation of PLP by thymic epithelial cells (TECs. TEC-specific ablation of PLP revealed that peripheral tolerance, mediated by dendritic cells through recessive tolerance mechanisms (deletion and anergy, could largely compensate for a lack of central tolerance. However, adoptive EAE was exacerbated in mice lacking PLP in TECs, pointing toward a non-redundant role of the thymus in dominant tolerance to PLP. Our findings reveal multiple layers of tolerance to a central nervous system autoantigen that vary among epitopes and thereby specify disease susceptibility. Understanding how different modalities of tolerance apply to distinct T cell epitopes of a target in autoimmunity has implications for antigen-specific strategies to therapeutically interfere with unwanted immune reactions against self.

    7. [Acute disseminated encephalomyelitis following influenza vaccination: report of a case with callosal disconnection syndrome].

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      Arai, Motomi; Takagi, Daisuke; Nagao, Ryosuke

      2014-01-01

      We present a case of callosal disconnection syndrome as a rare manifestation of acute disseminated encephalomyelitis (ADEM). A dextral 48-year-old Japanese woman received trivalent inactivated influenza vaccine in mid-November 2011. Twenty days later, she was found to be in a daze. Subsequently, she developed abnormal behavior and gait disturbance, and she was disoriented regarding time and place. Nystagmus and abnormal ocular movements were absent. Upper limb power was normal, whereas her lower limbs were mildly weak. Tendon reflexes were normally evoked without pathological reflexes. There was no sensory impairment. Serum CRP levels were slightly elevated; other routine laboratory tests, thyroid functions, and vitamin B1 levels were within the normal range. Cerebrospinal fluid examination revealed that it was acellular with a protein level of 54 mg/dl and high myelin basic protein level. Fluid-attenuated inversion recovery MR images revealed a large hyperintense lesion in the corpus callosum, but the lower part of the splenium was spared. Flow voids were observed in the pericallosal arteries. She was diagnosed with post-vaccination ADEM and vigorously treated with an intravenous infusion of methylprednisolone (1 g/day for 6 days) and immunoglobulin (1.2 g/kg). Gait disturbance and disorientation rapidly improved; however, tactile anomia, ideomotor apraxia, ideational apraxia, and agraphia of the left hand were present one month after onset. She had no aphasia or alexia.Interestingly, the patient's left unilateral agraphia was more prominent in kana than kanji (an article in Japanese text) for polysyllabic words, whereas she could write kana characters to dictation. Changes in the sequential order of kana characters within a word were observed. These findings were similar to those observed in pure agraphia associated with lesions in the posterior part of the left middle frontal gyrus. Thus, an interhemispheric mechanism is probably involved in the selection and

    8. Mechanisms of action of cannabidiol in adoptively transferred experimental autoimmune encephalomyelitis.

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      González-García, Coral; Torres, Irene Moreno; García-Hernández, Ruth; Campos-Ruíz, Lucía; Esparragoza, Luis Rodríguez; Coronado, María José; Grande, Aranzazu García; García-Merino, Antonio; Sánchez López, Antonio J

      2017-12-01

      Cannabidiol (CBD) is one of the most important compounds in Cannabis sativa, lacks psychotropic effects, and possesses a high number of therapeutic properties including the amelioration of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyse the relative efficacy of CBD in adoptively transferred EAE (at-EAE), a model that allows better delineation of the effector phase of EAE. Splenocytes and lymph nodes from mice with actively induced EAE were cultured in the presence of MOG 35-55 and IL-12 and inoculated intraperitoneally in recipient female C57BL/6J mice. The effects of CBD were evaluated using clinical scores and magnetic resonance imaging (MRI). In the central nervous system, the extent of cell infiltration, axonal damage, demyelination, microglial activation and cannabinoid receptors expression was assessed by immunohistochemistry. Lymph cell viability, apoptosis, oxidative stress and IL-6 production were measured in vitro. Preventive intraperitoneal treatment with CBD ameliorated the clinical signs of at-EAE, and this improvement was accompanied by a reduction of the apparent diffusion coefficient in the subiculum area of the brain. Inflammatory infiltration, axonal damage, and demyelination were reduced, and cannabinoid receptor expression was modulated. Incubation with CBD decreased encephalitogenic cell viability, increasing early apoptosis and reactive oxygen species (ROS) and decreasing IL-6 production. The reduction in viability was not mediated by CB 1 , CB 2 or GPR55 receptors. CBD markedly improved the clinical signs of at-EAE and reduced infiltration, demyelination and axonal damage. The CBD-mediated decrease in the viability of encephalitogenic cells involves ROS generation, apoptosis and a decrease in IL-6 production and may contribute to the therapeutic effect of this compound. Copyright © 2017 Elsevier Inc. All rights reserved.

    9. Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

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      Lutz, Norbert W; Fernandez, Carla; Pellissier, Jean-François; Cozzone, Patrick J; Béraud, Evelyne

      2013-01-01

      Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA) and spinal-cord homogenate (SC-H), whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group). Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE) or extra-cerebral (AA) inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and/or due to the

    10. Acute disseminated encephalomyelitis onset: evaluation based on vaccine adverse events reporting systems.

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      Paolo Pellegrino

      Full Text Available OBJECTIVE: To evaluate epidemiological features of post vaccine acute disseminated encephalomyelitis (ADEM by considering data from different pharmacovigilance surveillance systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS database and the EudraVigilance post-authorisation module (EVPM were searched to identify post vaccine ADEM cases. Epidemiological features including sex and related vaccines were analysed. RESULTS: We retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40±21.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines. CONCLUSIONS: This study has a high epidemiological power as it is based on information on adverse events having occurred in over one billion people. It suffers from lack of rigorous case verification due to the weakness intrinsic to the surveillance databases used. At variance with previous reports on a prevalence of ADEM in childhood we demonstrate that it may occur at any age when post vaccination. This study also shows that the diminishing trend in post vaccine ADEM reporting related to Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B and human papilloma virus vaccine groups is most likely not [corrected] due to a decline in vaccine coverage indicative of a reduced attention to this adverse drug reaction.

    11. In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed.

      Science.gov (United States)

      Vainchtein, I D; Vinet, J; Brouwer, N; Brendecke, S; Biagini, G; Biber, K; Boddeke, H W G M; Eggen, B J L

      2014-10-01

      Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of microglia, the resident macrophages of the CNS, remains ambiguous. Therefore, we have compared the phenotypes of microglia and macrophages in a mouse model for MS, experimental autoimmune encephalomyelitis (EAE). In order to properly discriminate between these two cell types, microglia were defined as CD11b(pos) CD45(int) Ly-6C(neg) , and infiltrated macrophages as CD11b(pos) CD45(high) Ly-6C(pos) . During clinical EAE, microglia displayed a weakly immune-activated phenotype, based on the expression of MHCII, co-stimulatory molecules (CD80, CD86, and CD40) and proinflammatory genes [interleukin-1β (IL-1β) and tumour necrosis factor- α (TNF-α)]. In contrast, CD11b(pos) CD45(high) Ly-6C(pos) infiltrated macrophages were strongly activated and could be divided into two populations Ly-6C(int) and Ly-6C(high) , respectively. Ly-6C(high) macrophages contained less myelin than Ly-6C(int) macrophages and expression levels of the proinflammatory cytokines IL-1β and TNF-α were higher in Ly-6C(int) macrophages. Together, our data show that during clinical EAE, microglia are only weakly activated whereas infiltrated macrophages are highly immune reactive. © 2014 Wiley Periodicals, Inc.

    12. Excess circulating alternatively activated myeloid (M2 cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.

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      Ilan Vaknin

      Full Text Available Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs, representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease.We tested this working hypothesis in amyotrophic lateral sclerosis (ALS and its mouse model, which are characterized by a rapid progression once clinical symptoms are evident. Adaptive transfer of alternatively activated myeloid (M2 cells, which homed to the spleen and exhibited immune suppressive activity in G93A mutant superoxide dismutase-1 (mSOD1 mice at a stage before emergence of disease symptoms, resulted in earlier appearance of disease symptoms and shorter life expectancy. The same protocol mitigated the inflammation-induced disease model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE, which requires circulating T cells for disease induction. Analysis of whole peripheral blood samples obtained from 28 patients suffering from sporadic ALS (sALS, revealed a two-fold increase in the percentage of circulating MDSCs (LIN(-/LowHLA-DR(-CD33(+ compared to controls.Taken together, these results emphasize the distinct requirements for fighting the inflammatory neurodegenerative disease, multiple sclerosis, and the neurodegenerative disease, ALS, though both share a local inflammatory component. Moreover, the increased levels of circulating MDSCs in ALS patients indicates the operation of systemic mechanisms that might lead to an impairment of T cell reactivity needed to overcome the disease conditions within the CNS. This high level of suppressive immune cells might

    13. Regulation of Th1 cells and experimental autoimmune encephalomyelitis (EAE) by glycogen synthase kinase-3

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      Beurel, Eléonore; Kaidanovich-Beilin, Oksana; Yeh, Wen-I; Song, Ling; Palomo, Valle; Michalek, Suzanne M.; Woodgett, James R.; Harrington, Laurie E.; Eldar-Finkelman, Hagit; Martinez, Ana; Jope, Richard S.

      2013-01-01

      Experimental autoimmune encephalomyelitis (EAE) is a rodent model of multiple sclerosis (MS), a debilitating autoimmune disease of the central nervous system, for which only limited therapeutic interventions are available. Since MS is mediated in part by autoreactive T cells, particularly Th17 and Th1 cells, in the present study, we tested if inhibitors of glycogen synthase kinase-3 (GSK3), previously reported to reduce Th17 cell generation, also alter Th1 cell production or ameliorate EAE. GSK3 inhibitors were found to impede the production of Th1 cells by reducing STAT1 activation. Molecularly reducing the expression of either of the two GSK3 isoforms demonstrated that Th17 cell production was sensitive to reduced levels of GSK3β, and Th1 cell production was inhibited in GSK3α-deficient cells. Administration of the selective GSK3 inhibitors TDZD-8, VP2.51, VP0.7, or L803-mts, significantly reduced the clinical symptoms of MOG35-55-induced EAE in mice, nearly eliminating the chronic progressive phase, and reduced the number of Th17 and Th1 cells in the spinal cord. Administration of TDZD-8 or L803-mts after the initial disease episode ameliorated clinical symptoms in a relapsing/remitting model of PLP139-151-induced EAE. Furthermore, deletion of GSK3β specifically in T cells was sufficient to ameliorate MOG35-55-induced EAE. These results demonstrate isoform-selective effects of GSK3 on T cell generation, therapeutic effects of GSK3 inhibitors in EAE, and that GSK3 inhibition in T cells is sufficient to reduce the severity of EAE, suggesting that GSK3 may be a feasible target for developing new therapeutic interventions for MS. PMID:23606540

    14. Cell Fusion along the Anterior-Posterior Neuroaxis in Mice with Experimental Autoimmune Encephalomyelitis.

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      Sreenivasa R Sankavaram

      Full Text Available It is well documented that bone marrow-derived cells can fuse with a diverse range of cells, including brain cells, under normal or pathological conditions. Inflammation leads to robust fusion of bone marrow-derived cells with Purkinje cells and the formation of binucleate heterokaryons in the cerebellum. Heterokaryons form through the fusion of two developmentally differential cells and as a result contain two distinct nuclei without subsequent nuclear or chromosome loss.In the brain, fusion of bone marrow-derived cells appears to be restricted to the complex and large Purkinje cells, raising the question whether the size of the recipient cell is important for cell fusion in the central nervous system. Purkinje cells are among the largest neurons in the central nervous system and accordingly can harbor two nuclei.Using a well-characterized model for heterokaryon formation in the cerebellum (experimental autoimmune encephalomyelitis - a mouse model of multiple sclerosis, we report for the first time that green fluorescent protein-labeled bone marrow-derived cells can fuse and form heterokaryons with spinal cord motor neurons. These spinal cord heterokaryons are predominantly located in or adjacent to an active or previously active inflammation site, demonstrating that inflammation and infiltration of immune cells are key for cell fusion in the central nervous system. While some motor neurons were found to contain two nuclei, co-expressing green fluorescent protein and the neuronal marker, neuron-specific nuclear protein, a number of small interneurons also co-expressed green fluorescent protein and the neuronal marker, neuron-specific nuclear protein. These small heterokaryons were scattered in the gray matter of the spinal cord.This novel finding expands the repertoire of neurons that can form heterokaryons with bone marrow-derived cells in the central nervous system, albeit in low numbers, possibly leading to a novel therapy for spinal cord

    15. Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels.

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      Yixin He

      Full Text Available Multiple sclerosis (MS is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the pathogenesis of MS. In current study, astragaloside IV (ASI, a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.

    16. Astragaloside IV attenuates experimental autoimmune encephalomyelitis of mice by counteracting oxidative stress at multiple levels.

      Science.gov (United States)

      He, Yixin; Du, Min; Gao, Yan; Liu, Hongshuai; Wang, Hongwei; Wu, Xiaojun; Wang, Zhengtao

      2013-01-01

      Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory disease found mostly in young adults in the western world. Oxidative stress induced neuronal apoptosis plays an important role in the pathogenesis of MS. In current study, astragaloside IV (ASI), a natural saponin molecule isolated from Astragalus membranceus, given at 20 mg/kg daily attenuated the severity of experimental autoimmune encephalomyelitis (EAE) in mice significantly. Further studies disclosed that ASI treatment inhibited the increase of ROS and pro-inflammatory cytokine levels, down-regulation of SOD and GSH-Px activities, and elevation of iNOS, p53 and phosphorylated tau in central nervous system (CNS) as well as the leakage of BBB of EAE mice. Meanwhile, the decreased ratio of Bcl-2/Bax was reversed by ASI. Moreover, ASI regulated T-cell differentiation and infiltration into CNS. In neuroblast SH-SY5Y cells, ASI dose-dependently reduced cellular ROS level and phosphorylation of tau in response to hydrogen peroxide challenge by modulation of Bcl-2/Bax ratio. ASI also inhibited activation of microglia both in vivo and in vitro. iNOS up-regulation induced by IFNγ stimulation was abolished by ASI dose-dependently in BV-2 cells. In summary, ASI prevented the severity of EAE progression possibly by counterbalancing oxidative stress and its effects via reduction of cellular ROS level, enhancement of antioxidant defense system, increase of anti-apoptotic and anti-inflammatory pathways, as well as modulation of T-cell differentiation and infiltration into CNS. The study suggested ASI may be effective for clinical therapy/prevention of MS.

    17. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer

      Science.gov (United States)

      Rowe, Peter C.; Underhill, Rosemary A.; Friedman, Kenneth J.; Gurwitt, Alan; Medow, Marvin S.; Schwartz, Malcolm S.; Speight, Nigel; Stewart, Julian M.; Vallings, Rosamund; Rowe, Katherine S.

      2017-01-01

      Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that affects children and adolescents as well as adults. The etiology has not been established. While many pediatricians and other health-care providers are aware of ME/CFS, they often lack essential knowledge that is necessary for diagnosis and treatment. Many young patients experience symptoms for years before receiving a diagnosis. This primer, written by the International Writing Group for Pediatric ME/CFS, provides information necessary to understand, diagnose, and manage the symptoms of ME/CFS in children and adolescents. ME/CFS is characterized by overwhelming fatigue with a substantial loss of physical and mental stamina. Cardinal features are malaise and a worsening of symptoms following minimal physical or mental exertion. These post-exertional symptoms can persist for hours, days, or weeks and are not relieved by rest or sleep. Other symptoms include cognitive problems, unrefreshing or disturbed sleep, generalized or localized pain, lightheadedness, and additional symptoms in multiple organ systems. While some young patients can attend school, on a full or part-time basis, many others are wheelchair dependent, housebound, or bedbound. Prevalence estimates for pediatric ME/CFS vary from 0.1 to 0.5%. Because there is no diagnostic test for ME/CFS, diagnosis is purely clinical, based on the history and the exclusion of other fatiguing illnesses by physical examination and medical testing. Co-existing medical conditions including orthostatic intolerance (OI) are common. Successful management is based on determining the optimum balance of rest and activity to help prevent post-exertional symptom worsening. Medications are helpful to treat pain, insomnia, OI and other symptoms. The published literature on ME/CFS and specifically that describing the diagnosis and management of pediatric ME/CFS is very limited. Where published studies are lacking, recommendations are based on the

    18. Huperzine A inhibits CCL2 production in experimental autoimmune encephalomyelitis mice and in cultured astrocyte.

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      Tian, G X; Zhu, X Q; Chen, Y; Wu, G C; Wang, J

      2013-01-01

      The active role of chemokines and inflammatory cytokines in the central nervous system (CNS) during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been clearly established. Recent studies from our laboratory reported that Huperzine A (HupA) can attenuate the disease process in EAE by the inhibition of inflammation, demyelination, and axonal injury in the spinal cord as well as encephalomyelitic T-cell proliferation. In this study, the effects of low dose HupA on CCL2, TNF-alpha, IL-6, and IL-1beta expression were evaluated in EAE. The effect of HupA on lipopolysachharide (LPS)-induced inflammatory molecule secretion was investigated in cultured-astrocytes in vitro. In MOG35-55-induced EAE mice, intraperitoneal injections of HupA (0.1 mg/kg•d−1) significantly suppressed the expression of CCL2, IL-6, TNF-alpha, and IL-1beta in the spinal cord. HupA also repressed LPS-induced CCL2 production, but with little influence on pro-inflammatory cytokines in primary cultured astrocytes. The inhibition effect of HupA on CCL2 is PPARgamma-dependent and nicotine receptor-independent. Conditioned culture media from HupA-treated astrocyte decreased PBMC migration in vitro. Collectively, these results suggest that HupA can ameliorate EAE by inhibiting CCL2 production in astrocyte, which may consequently decrease inflammatory cell infiltration in the spinal cord. HupA may have a potential therapeutic value for the treatment of MS and other neuroinflammatory diseases.

    19. Acute disseminated encephalomyelitis in children: differential diagnosis from multiple sclerosis on the basis of clinical course

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      Yun Jin Lee

      2011-06-01

      Full Text Available Acute disseminated encephalomyelitis (ADEM is a demyelinating disease of the central nervous system (CNS that typically presents as a monophasic disorder associated with multifocal neurologic symptoms and encephalopathy. ADEM is considered an autoimmune disorder that is triggered by an environmental stimulus in genetically susceptible individuals. The diagnosis of ADEM is based on clinical and radiological features. Most children with ADEM initially present with fever, meningeal signs, and acute encephalopathy. The level of consciousness ranges from lethargy to frank coma. Deep and subcortical white-matter lesions and gray-matter lesions such as thalami and basal ganglia on magnetic resonance imaging (MRI are associated with ADEM. In a child who presents with signs of encephalitis, bacterial and viral meningitis or encephalitis must be ruled out. Sequential MRI is required to confirm the diagnosis of ADEM, as relapses with the appearance of new lesions on MRI may suggest either multiphasic ADEM or multiple sclerosis (MS. Pediatric MS, defined as onset of MS before the age of 16, is being increasingly recognized. MS is characterized by recurrent episodes of demyelination in the CNS separated in space and time. The McDonald criteria for diagnosis of MS include evidence from MRI and allow the clinician to make a diagnosis of clinically definite MS on the basis of the interval preceding the development of new white matter lesions, even in the absence of new clinical findings. The most important alternative diagnosis to MS is ADEM. At the initial presentation, the 2 disorders cannot be distinguished with certainty. Therefore, prolonged follow-up is needed to establish a diagnosis.

    20. Severe T-cell depletion from the PALS leads to altered spleen composition in common marmosets with experimental autoimmune encephalomyelitis (EAE)

      NARCIS (Netherlands)

      De Vos, Alex F; van Riel, Debby A J; van Meurs, Marjan; Brok, Herbert P M; Boon, Louis; Hintzen, Rogier Q; Claassen, Eric H J H M; 't Hart, Bert A; Laman, Jon D

      Recent data suggest that the spleen is a crucial component of the immune system in the development of experimental autoimmune encephalomyelitis (EAE) in marmoset monkeys. Using immunohistochemistry, we investigated changes in the distribution of leukocytes in the spleen associated with clinical

    1. Deficient p75 low-affinity neurotrophin receptor expression does alter the composition of cellular infiltrate in experimental autoimmune encephalomyelitis in C57BL/6 mice

      NARCIS (Netherlands)

      Kust, B; Mantingh-Otter, [No Value; Boddeke, E; Copray, S

      We have shown earlier that induction of experimental autoimmune encephalomyelitis (EAE)-a model for the human disease multiple sclerosis-in C5713L/6 wild-type mice resulted in the expression of the p75 low-affinity neurotrophin receptor (p75(NTR)) in endothelial cells in the CNS. In comparison to

    2. Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis.

      Science.gov (United States)

      Castro-Marrero, Jesús; Zaragozá, Maria C; González-Garcia, Sergio; Aliste, Luisa; Sáez-Francàs, Naia; Romero, Odile; Ferré, Alex; Fernández de Sevilla, Tomás; Alegre, José

      2018-05-16

      Non-restorative sleep is a hallmark symptom of chronic fatigue syndrome/myalgic encephalomyelitis. However, little is known about self-reported sleep disturbances in these subjects. This study aimed to assess the self-reported sleep quality and its impact on quality of life in a Spanish community-based chronic fatigue syndrome/myalgic encephalomyelitis cohort. A prospective cross-sectional cohort study was conducted in 1,455 Spanish chronic fatigue syndrome/myalgic encephalomyelitis patients. Sleep quality, fatigue, pain, functional capacity impairment, psychopathological status, anxiety/depression and health-related quality of life were assessed using validated subjective measures. The frequencies of muscular, cognitive, neurological, autonomic and immunological symptom clusters were above 80%. High scores were recorded for pain, fatigue, psychopathological status, anxiety/depression, and low scores for functional capacity and quality of life, all of which correlated significantly (all p quality of sleep as measured by the Pittsburgh Sleep Quality Index. Multivariate regression analysis showed that after adjusting for age and gender, the pain intensity (odds ratio, 1.11; p quality of life (odds ratio, 0.96; both p quality. These findings suggest that this large chronic fatigue syndrome/myalgic encephalomyelitis sample presents poor sleep quality, as assessed by the Pittsburgh Sleep Quality Index, and that this poor sleep quality is associated with many aspects of quality of life. © 2018 European Sleep Research Society.

    3. Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA.

      Science.gov (United States)

      Wong, K T; Ng, K Y; Ong, K C; Ng, W F; Shankar, S K; Mahadevan, A; Radotra, B; Su, I J; Lau, G; Ling, A E; Chan, K P; Macorelles, P; Vallet, S; Cardosa, M J; Desai, A; Ravi, V; Nagata, N; Shimizu, H; Takasaki, T

      2012-08-01

      To investigate if two important epidemic viral encephalitis in children, Enterovirus 71 (EV71) encephalomyelitis and Japanese encephalitis (JE) whose clinical and pathological features may be nonspecific and overlapping, could be distinguished. Tissue sections from the central nervous system of infected cases were examined by light microscopy, immunohistochemistry and in situ hybridization. All 13 cases of EV71 encephalomyelitis collected from Asia and France invariably showed stereotyped distribution of inflammation in the spinal cord, brainstem, hypothalamus, cerebellar dentate nucleus and, to a lesser extent, cerebral cortex and meninges. Anterior pons, corpus striatum, thalamus, temporal lobe, hippocampus and cerebellar cortex were always uninflamed. In contrast, the eight JE cases studied showed inflammation involving most neuronal areas of the central nervous system, including the areas that were uninflamed in EV71 encephalomyelitis. Lesions in both infections were nonspecific, consisting of perivascular and parenchymal infiltration by inflammatory cells, oedematous/necrolytic areas, microglial nodules and neuronophagia. Viral inclusions were absent. Immunohistochemistry and in situ hybridization assays were useful to identify the causative virus, localizing viral antigens and RNA, respectively, almost exclusively to neurones. The stereotyped distribution of inflammatory lesions in EV71 encephalomyelitis appears to be very useful to help distinguish it from JE. © 2011 The Authors. Neuropathology and Applied Neurobiology © 2011 British Neuropathological Society.

    4. Natural Docosahexaenoic Acid in the Triglyceride Form Attenuates In Vitro Microglial Activation and Ameliorates Autoimmune Encephalomyelitis in Mice

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      Pilar Mancera

      2017-06-01

      Full Text Available Many neurodegenerative diseases are associated, at least in part, to an inflammatory process in which microglia plays a major role. The effect of the triglyceride form of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (TG-DHA was assayed in vitro and in vivo to assess the protective and anti-inflammatory activity of this compound. In the in vitro study, BV-2 microglia cells were previously treated with TG-DHA and then activated with Lipopolysaccharide (LPS and Interferon-gamma (IFN-γ. TG-DHA treatment protected BV-2 microglia cells from oxidative stress toxicity attenuating NO production and suppressing the induction of inflammatory cytokines. When compared with DHA in the ethyl-ester form, a significant difference in the ability to inhibit NO production in favor of TG-DHA was observed. TG-DHA inhibited significantly splenocyte proliferation but isolated CD4+ lymphocyte proliferation was unaffected. In a mice model of autoimmune encephalomyelitis (EAE, 250 mg/kg/day oral TG-DHA treatment was associated with a significant amelioration of the course and severity of the disease as compared to untreated animals. TG-DHA-treated EAE mice showed a better weight profile, which is a symptom related to a better course of encephalomyelitis. TG-DHA may be a promising therapeutic agent in neuroinflammatory processes and merit to be more extensively studied in human neurodegenerative disorders.

    5. Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis

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      Brenu Ekua W

      2012-05-01

      Full Text Available Abstract Background Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME is an etiologically unexplained disorder characterised by irregularities in various aspects of the immunological function. Presently, it is unknown whether these immunological changes remain consistent over time. This study investigates Natural Killer (NK cell cytotoxic activity, NK cell subsets (CD56brightCD16- and CD56dimCD16+ and cytokines, over the course of a12 month period in patients with CFS/ME. Methods The participants in the study comprised 65 (47.2 ± 11.5 years CFS/ME participants and 21 (45.2 ±9.3 years non-fatigued controls. Flow cytometry protocols were used to assess NK subsets and NK cytotoxic activity at various time points that included baseline (T1, 6 (T2 and 12 months (T3. Cytokine secretions were measured following mitogenic stimulation of peripheral blood mononuclear cells. Results NK cytotoxic activity was significantly decreased in the CFS/ME patients at T1, T2 and T3 compared to the non-fatigued group. Additionally, in comparison to the non-fatigued controls, the CFS/ME group had significantly lower numbers of CD56brightCD16- NK cells at both T1 and T2. Interestingly, following mitogenic stimulation, cytokine secretion revealed significant increases in IL-10, IFN-γ and TNF-α at T1 in the CFS/ME group. A significant decrease was observed at T2 in the CFS/ME group for IL-10 and IL-17A while at T3, IL-2 was increased in the CFS/ME group in comparison to the non-fatigued controls. Overall cytotoxic activity was significantly decreased at T3 compared to T1 and T2. CD56brightCD16- NK cells were much lower at T2 compared to T1 and T3. IL-10 and IL-17A secretion was elevated at T2 in comparison to T1 and T3. Conclusion These results confirm decreases in immune function in CFS/ME patients, suggesting an increased susceptibility to viral and other infections. Furthermore, NK cytotoxic activity may be a suitable biomarker for diagnosing CFS

    6. Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis.

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      Rodolfo Thomé

      Full Text Available BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg cells and suppressive Dendritic Cells (DCs, to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ, an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE, an experimental model for human Multiple Sclerosis, was investigated as well. METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55 peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of

    7. Gray Matter Hypoxia in the Brain of the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis

      Science.gov (United States)

      Johnson, Thomas W.; Wu, Ying; Nathoo, Nabeela; Rogers, James A.; Wee Yong, V.; Dunn, Jeff F.

      2016-01-01

      Background Multiple sclerosis (MS) has a significant inflammatory component and may have significant gray matter (GM) pathophysiology. Brain oxygenation is a sensitive measurement of the balance between metabolic need and oxygen delivery. There is evidence that inflammation and hypoxia are interdependent. In this paper, we applied novel, implanted PO2 sensors to measure hypoxia in cortical and cerebellar GM, in an inflammation-induced mouse model of MS. Objective Quantify oxygenation in cortical and cerebellar GM in the awake, unrestrained experimental autoimmune encephalomyelitis (EAE) mouse model and to relate the results to symptom level and disease time-course. Methods C57BL/6 mice were implanted with a fiber-optic sensor in the cerebellum (n = 13) and cortex (n = 24). Animals were induced with stimulation of the immune response and sensitization to myelin oligodendrocyte glycoprotein (MOG). Controls did not have MOG. We measured PO2 in awake, unrestrained animals from pre-induction (baseline) up to 36 days post-induction for EAE and controls. Results There were more days with hypoxia than hyperoxia (cerebellum: 34/67 vs. 18/67 days; cortex: 85/112 vs. 22/112) compared to time-matched controls. The average decline in PO2 on days that were significantly lower than time-matched controls was -8.8±6.0 mmHg (mean ± SD) for the cerebellum and -8.0±4.6 for the cortex. Conversely, the average increase in PO2 on days that were significantly hyperoxic was +3.2±2.8 mmHg (mean ± SD) for the cerebellum and +0.8±2.1 for the cortex. Cortical hypoxia related to increased behavioral deficits. Evidence for hypoxia occurred before measurable behavioral deficits. Conclusions A highly inflammatory condition primed to a white matter (WM) autoimmune response correlates with significant hypoxia and increased variation in oxygenation in GM of both cerebellum and cortex in the mouse EAE model of MS. PMID:27907119

    8. Epigenetic modifications and glucocorticoid sensitivity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

      Science.gov (United States)

      de Vega, Wilfred C; Herrera, Santiago; Vernon, Suzanne D; McGowan, Patrick O

      2017-02-23

      Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating idiopathic disease characterized by unexplained fatigue that fails to resolve with sufficient rest. Diagnosis is based on a list of symptoms and exclusion of other fatigue-related health conditions. Despite a heterogeneous patient population, immune and hypothalamic-pituitary-adrenal (HPA) axis function differences, such as enhanced negative feedback to glucocorticoids, are recurring findings in ME/CFS studies. Epigenetic modifications, such as CpG methylation, are known to regulate long-term phenotypic differences and previous work by our group found DNA methylome differences in ME/CFS, however the relationship between DNA methylome modifications, clinical and functional characteristics associated with ME/CFS has not been examined. We examined the DNA methylome in peripheral blood mononuclear cells (PBMCs) of a larger cohort of female ME/CFS patients using the Illumina HumanMethylation450 BeadChip Array. In parallel to the DNA methylome analysis, we investigated in vitro glucocorticoid sensitivity differences by stimulating PBMCs with phytohaemagglutinin and suppressed growth with dexamethasone. We explored DNA methylation differences using bisulfite pyrosequencing and statistical permutation. Linear regression was implemented to discover epigenomic regions associated with self-reported quality of life and network analysis of gene ontology terms to biologically contextualize results. We detected 12,608 differentially methylated sites between ME/CFS patients and healthy controls predominantly localized to cellular metabolism genes, some of which were also related to self-reported quality of life health scores. Among ME/CFS patients, glucocorticoid sensitivity was associated with differential methylation at 13 loci. Our results indicate DNA methylation modifications in cellular metabolism in ME/CFS despite a heterogeneous patient population, implicating these processes in immune and HPA

    9. Natural course of chronic fatigue syndrome/myalgic encephalomyelitis in adolescents.

      Science.gov (United States)

      Norris, Tom; Collin, Simon M; Tilling, Kate; Nuevo, Roberto; Stansfeld, Stephen A; Sterne, Jonathan Ac; Heron, Jon; Crawley, Esther

      2017-06-01

      Little is known about persistence of or recovery from chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adolescents. Previous studies have small sample sizes, short follow-up or have focused on fatigue rather than CFS/ME or, equivalently, chronic fatigue, which is disabling. This work aimed to describe the epidemiology and natural course of CFS/ME in adolescents aged 13-18 years. Longitudinal follow-up of adolescents enrolled in the Avon Longitudinal Study of Parents and Children. Avon, UK. We identified adolescents who had disabling fatigue of >6 months duration without a known cause at ages 13, 16 and 18 years. We use the term 'chronic disabling fatigue' (CDF) because CFS/ME was not verified by clinical diagnosis. We used multiple imputation to obtain unbiased estimates of prevalence and persistence. The estimated prevalence of CDF was 1.47% (95% CI 1.05% to 1.89%) at age 13, 2.22% (1.67% to 2.78%) at age 16 and 2.99% (2.24% to 3.75%) at age 18. Among adolescents with CDF of 6 months duration at 13 years 75.3% (64.0% to 86.6%) were not classified as such at age 16. Similar change was observed between 16 and 18 years (75.0% (62.8% to 87.2%)). Of those with CDF at age 13, 8.02% (0.61% to 15.4%) presented with CDF throughout the duration of adolescence. The prevalence of CDF lasting 6 months or longer (a proxy for clinically diagnosed CFS/ME) increases from 13 to 18 years. However, persistent CDF is rare in adolescents, with approximately 75% recovering after 2-3 years. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

    10. Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome.

      Science.gov (United States)

      Nagy-Szakal, Dorottya; Williams, Brent L; Mishra, Nischay; Che, Xiaoyu; Lee, Bohyun; Bateman, Lucinda; Klimas, Nancy G; Komaroff, Anthony L; Levine, Susan; Montoya, Jose G; Peterson, Daniel L; Ramanan, Devi; Jain, Komal; Eddy, Meredith L; Hornig, Mady; Lipkin, W Ian

      2017-04-26

      Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the

    11. A cannabigerol derivative suppresses immune responses and protects mice from experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Carrillo-Salinas, Francisco J; Navarrete, Carmen; Mecha, Miriam; Feliú, Ana; Collado, Juan A; Cantarero, Irene; Bellido, María L; Muñoz, Eduardo; Guaza, Carmen

      2014-01-01

      Phytocannabinoids that do not produce psychotropic effects are considered of special interest as novel therapeutic agents in CNS diseases. A cannabigerol quinone, the compound VCE-003, has been shown to alleviate symptoms in a viral model of multiple sclerosis (MS). Hence, we studied T cells and macrophages as targets for VCE-003 and its efficacy in an autoimmune model of MS. Proliferation, cell cycle, expression of activation markers was assessed by FACs in human primary T cells, and cytokine and chemokine production was evaluated. Transcription was studied in Jurkat cells and RAW264.7 cells were used to study the effects of VCE-003 on IL-17-induced macrophage polarization to a M1 phenotype. Experimental autoimmune encephalomyelitis (EAE) was induced by myelin oligodendrocyte glycoprotein (MOG₃₅₋₅₅) immunization and spinal cord pathology was assessed by immunohistochemistry. Neurological impairment was evaluated using disease scores. We show here that VCE-003 inhibits CD3/CD28-induced proliferation, cell cycle progression and the expression of the IL-2Rα and ICAM-1 activation markers in human primary T cells. VCE-003 inhibits the secretion of Th1/Th17 cytokines and chemokines in primary murine T cells, and it reduces the transcriptional activity of the IL-2, IL-17 and TNFα promoters induced by CD3/CD28. In addition, VCE-003 and JWH-133, a selective CB2 agonist, dampened the IL-17-induced polarization of macrophages to a pro-inflammatory M1 profile. VCE-003 also prevented LPS-induced iNOS expression in microglia. VCE-003 ameliorates the neurological defects and the severity of MOG-induced EAE in mice through CB2 and PPARγ receptor activation. A reduction in cell infiltrates, mainly CD4+ T cells, was observed, and Th1 and Th17 responses were inhibited in the spinal cord of VCE-003-treated mice, accompanied by weaker microglial activation, structural preservation of myelin sheets and reduced axonal damage. This study highlights the therapeutic potential

    12. Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.

      Directory of Open Access Journals (Sweden)

      Zhengqi Lu

      Full Text Available BACKGROUND: Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM, neuromyelitis optica (NMO, and multiple sclerosis (MS. OBJECTIVES: To investigate comparative brain stem lesions on magnetic resonance imaging (MRI among adult patients with ADEM, NMO, and MS. METHODS: Sixty-five adult patients with ADEM (n = 17, NMO (n = 23, and MS (n = 25 who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. RESULTS: Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001 and MS (94.1% vs. 40.0%, P<0.001; patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001 and ADEM (34.8% vs. 70.6%, P = 0.025; and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001 and MS (91.3% vs. 36.0%, P<0.001. On the axial section of the brain stem, the majority (82.4% of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%; and lesions in patients with MS were found in both the ventral (44.0% and dorsal (56.0% parts. The lesions in patients with ADEM (100% and NMO (91.3% had poorly defined margins, while lesions of patients with MS (76.0% had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%, while lesions in patients with NMO (87.0% and MS (92.0% were asymmetrical or unilateral. CONCLUSIONS: Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

    13. Diffusion-weighted imaging and proton MR spectroscopy in the characterization of acute disseminated encephalomyelitis

      International Nuclear Information System (INIS)

      Balasubramanya, K.S.; Kovoor, J.M.E.; Jayakumar, P.N.; Ravishankar, S.; Kamble, R.B.; Panicker, J.; Nagaraja, D.

      2007-01-01

      Acute disseminated encephalomyelitis (ADEM) is usually a monophasic illness characterized by multiple lesions involving gray and white matter. Quantitative MR techniques were used to characterize and stage these lesions. Eight patients (seven males and one female; mean age 19 years, range 5 to 36 years) were studied using conventional MRI (T2- and T1-weighted and FLAIR sequences), diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS). Apparent diffusion coefficient (ADC) values and MRS ratios were calculated for the lesion and for normal-appearing white matter (NAWM). Three patients were imaged in the acute stage (within 7 days of the onset of neurological symptoms) and five in the subacute stage (after 7 days from the onset of symptoms). ADC values in NAWM were in the range 0.7-1.24 x 10 -3 mm/s 2 (mean 0.937 ± 0.17 mm/s 2 ). ADC values of ADEM lesions in the acute stage were in the range 0.37-0.68 x 10 -3 mm/s 2 (mean 0.56 ± 0.16 mm/s 2 ) and 1.01-1.31 x 10 -3 mm/s 2 (mean 1.24 ± 0.13 mm/s 2 ) in the subacute stage. MRS ratios were obtained for all patients. NAA/Cho ratios were in the range 1.1-3.5 (mean 1.93 ± 0.86) in the NAWM. NAA/Cho ratios within ADEM lesions in the acute stage were in the range 0.63-1.48 (mean 1.18 ± 0.48) and 0.29-0.84 (mean 0.49 ± 0.22) in the subacute stage. The ADC values, NAA/Cho and Cho/Cr ratios were significantly different between lesions in the acute and subacute stages (P < 0.001, P < 0.027, P < 0.047, respectively). ADC values were significantly different between lesions in the acute (P < 0.009) and subacute stages (P < 0.005) with NAWM. In addition, NAA/Cho and Cho/Cr ratios were significantly different between lesions in the subacute stage and NAWM (P < 0.006, P < 0.007, respectively). ADEM lesions were characterized in the acute stage by restricted diffusion and in the subacute stage by free diffusion and a decrease in NAA/Cho ratios. Restricted diffusion and progressive decrease in NAA

    14. Diffusion-weighted imaging and proton MR spectroscopy in the characterization of acute disseminated encephalomyelitis

      Energy Technology Data Exchange (ETDEWEB)

      Balasubramanya, K.S.; Kovoor, J.M.E.; Jayakumar, P.N.; Ravishankar, S.; Kamble, R.B. [National Institute of Mental Health and Neurosciences, Department of Neuroimaging and Interventional Radiology, Bangalore, Karnataka (India); Panicker, J.; Nagaraja, D. [National Institute of Mental Health and Neurosciences, Department of Neurology, Bangalore (India)

      2007-02-15

      Acute disseminated encephalomyelitis (ADEM) is usually a monophasic illness characterized by multiple lesions involving gray and white matter. Quantitative MR techniques were used to characterize and stage these lesions. Eight patients (seven males and one female; mean age 19 years, range 5 to 36 years) were studied using conventional MRI (T2- and T1-weighted and FLAIR sequences), diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS). Apparent diffusion coefficient (ADC) values and MRS ratios were calculated for the lesion and for normal-appearing white matter (NAWM). Three patients were imaged in the acute stage (within 7 days of the onset of neurological symptoms) and five in the subacute stage (after 7 days from the onset of symptoms). ADC values in NAWM were in the range 0.7-1.24 x 10{sup -3} mm/s{sup 2} (mean 0.937 {+-} 0.17 mm/s{sup 2}). ADC values of ADEM lesions in the acute stage were in the range 0.37-0.68 x 10{sup -3} mm/s{sup 2} (mean 0.56 {+-} 0.16 mm/s{sup 2}) and 1.01-1.31 x 10{sup -3} mm/s{sup 2} (mean 1.24 {+-} 0.13 mm/s{sup 2}) in the subacute stage. MRS ratios were obtained for all patients. NAA/Cho ratios were in the range 1.1-3.5 (mean 1.93 {+-} 0.86) in the NAWM. NAA/Cho ratios within ADEM lesions in the acute stage were in the range 0.63-1.48 (mean 1.18 {+-} 0.48) and 0.29-0.84 (mean 0.49 {+-} 0.22) in the subacute stage. The ADC values, NAA/Cho and Cho/Cr ratios were significantly different between lesions in the acute and subacute stages (P < 0.001, P < 0.027, P < 0.047, respectively). ADC values were significantly different between lesions in the acute (P < 0.009) and subacute stages (P < 0.005) with NAWM. In addition, NAA/Cho and Cho/Cr ratios were significantly different between lesions in the subacute stage and NAWM (P < 0.006, P < 0.007, respectively). ADEM lesions were characterized in the acute stage by restricted diffusion and in the subacute stage by free diffusion and a decrease in NAA/Cho ratios

    15. Correlation of gut microbiota composition with resistance to experimental autoimmune encephalomyelitis in rats

      Directory of Open Access Journals (Sweden)

      Suzana Stanisavljevic

      2016-12-01

      Full Text Available Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS. It is widely accepted that autoimmune response against the antigens of the CNS is the essential pathogenic force in the disease. It has recently become increasingly appreciated that activated encephalitogenic cells tend to migrate towards gut associated lymphoid tissues (GALT and that interrupted balance between regulatory and inflammatory immunity within the GALT might have decisive role in the initiation and propagation of the CNS autoimmunity. Gut microbiota composition and function has the major impact on the balance in the GALT. Thus, our aim was to perform analyses of gut microbiota in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis. Albino Oxford (AO rats that are highly resistant to EAE induction and Dark Agouti (DA rats that develop EAE after mild immunization were compared for gut microbiota composition in different phases after EAE induction. Microbial analyses of the genus Lactobacillus and related lactic acid bacteria showed higher diversity of Lactobacillus spp. in EAE-resistant AO rats, while some members of Firmicutes and Proteobacteria (Undibacterium oligocarboniphilum were detected only in faeces of DA rats at the peak of the disease (between 13 and 16 days after induction. Interestingly, Turicibacter sp. that was found exclusively in non-immunized AO, but not in DA rats in our previous study was detected in DA rats that remained healthy 16 days after induction. Similar observation was obtained for the members of Lachnospiraceae. As dominant presence of the members of Lachnospiraceae family in gut microbial community has been linked with mild symptoms of various diseases, it is tempting to assume that Turicibacter sp. and Lachnospiraceae contribute to the prevention of EAE development and the alleviation of the disease symptoms. Further, production of a typical regulatory cytokine interleukin-10 was

    16. GM-CSF-Producing Th Cells in Rats Sensitive and Resistant to Experimental Autoimmune Encephalomyelitis.

      Science.gov (United States)

      Stojić-Vukanić, Zorica; Pilipović, Ivan; Vujnović, Ivana; Nacka-Aleksić, Mirjana; Petrović, Raisa; Arsenović-Ranin, Nevena; Dimitrijević, Mirjana; Leposavić, Gordana

      2016-01-01

      Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+IFN-γ+, IL-17+IFN-γ-, and IL-17-IFN-γ+ cells accompanied by higher frequency of IL-17-IFN-γ- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+IFN-γ+ Th17 cells in SC) on GM-CSF+IFN-γ+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+IFN-γ+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1β, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45hi cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms

    17. A cannabigerol derivative suppresses immune responses and protects mice from experimental autoimmune encephalomyelitis.

      Directory of Open Access Journals (Sweden)

      Francisco J Carrillo-Salinas

      Full Text Available Phytocannabinoids that do not produce psychotropic effects are considered of special interest as novel therapeutic agents in CNS diseases. A cannabigerol quinone, the compound VCE-003, has been shown to alleviate symptoms in a viral model of multiple sclerosis (MS. Hence, we studied T cells and macrophages as targets for VCE-003 and its efficacy in an autoimmune model of MS. Proliferation, cell cycle, expression of activation markers was assessed by FACs in human primary T cells, and cytokine and chemokine production was evaluated. Transcription was studied in Jurkat cells and RAW264.7 cells were used to study the effects of VCE-003 on IL-17-induced macrophage polarization to a M1 phenotype. Experimental autoimmune encephalomyelitis (EAE was induced by myelin oligodendrocyte glycoprotein (MOG₃₅₋₅₅ immunization and spinal cord pathology was assessed by immunohistochemistry. Neurological impairment was evaluated using disease scores. We show here that VCE-003 inhibits CD3/CD28-induced proliferation, cell cycle progression and the expression of the IL-2Rα and ICAM-1 activation markers in human primary T cells. VCE-003 inhibits the secretion of Th1/Th17 cytokines and chemokines in primary murine T cells, and it reduces the transcriptional activity of the IL-2, IL-17 and TNFα promoters induced by CD3/CD28. In addition, VCE-003 and JWH-133, a selective CB2 agonist, dampened the IL-17-induced polarization of macrophages to a pro-inflammatory M1 profile. VCE-003 also prevented LPS-induced iNOS expression in microglia. VCE-003 ameliorates the neurological defects and the severity of MOG-induced EAE in mice through CB2 and PPARγ receptor activation. A reduction in cell infiltrates, mainly CD4+ T cells, was observed, and Th1 and Th17 responses were inhibited in the spinal cord of VCE-003-treated mice, accompanied by weaker microglial activation, structural preservation of myelin sheets and reduced axonal damage. This study highlights the

    18. Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review

      Directory of Open Access Journals (Sweden)

      Jun-liang Yuan

      2016-01-01

      Full Text Available Acute disseminated encephalomyelitis (ADEM is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM.

    19. Serological evidence of avian encephalomyelitis virus and Pasteurella multocida infections in free-range indigenous chickens in Southern Mozambique.

      Science.gov (United States)

      Taunde, Paula; Timbe, Palmira; Lucas, Ana Felicidade; Tchamo, Cesaltina; Chilundo, Abel; Dos Anjos, Filomena; Costa, Rosa; Bila, Custodio Gabriel

      2017-06-01

      A total of 398 serum samples from free-range indigenous chickens originating from four villages in Southern Mozambique were tested for the presence of avian encephalomyelitis virus (AEV) and Pasteurella multocida (PM) antibodies through commercial enzyme-linked immunosorbent assay (ELISA) kits. AEV and PM antibodies were detected in all villages surveyed. The proportion of positive samples was very high: 59.5% (95% confidence interval (CI) 51.7-67.7%) for AEV and 71.5% (95% CI 67.7-77.3%) for PM. Our findings revealed that these pathogens are widespread among free-range indigenous chickens in the studied villages and may represent a threat in the transmission of AEV and PM to wild, broiler or layer chickens in the region. Further research is warranted on epidemiology of circulating strains and impact of infection on the poultry industry.

    20. Selective enrichment of Th1 CD45RBlow CD4+ T cells in autoimmune infiltrates in experimental allergic encephalomyelitis

      DEFF Research Database (Denmark)

      Renno, T; Zeine, R; Girard, J M

      1994-01-01

      The cytokine effector status of CD4+ T cells from lymph nodes (LN) and the central nervous system (CNS) of SJL/J mice immunized with autoantigen in adjuvant for the induction of experimental allergic encephalomyelitis (EAE) was compared. CD4+ T cells were FACS sorted based on the levels...... in the sorted populations. CD45RBlow cells constituted a minority of CD4+ cells in the LN and expressed elevated levels of IL-2, IFN-gamma, and IL-4 mRNA, whereas the CD45RBlow CD4+ population did not express detectable message for these cytokines under linear PCR conditions. By contrast to the LN, CD4+ cells...... of expression of the activation marker CD45RB. Low levels of expression of this surface marker are induced by antigen recognition and are associated with 'effector' T cell function. Reverse transcriptase polymerase chain reaction (PCR) was used to analyze the expression of different T cell cytokine genes...

    1. MR imaging of acute disseminated encephalomyelitis, cerebellitis and myelitis in infancy: likely topographic variant of a single process

      International Nuclear Information System (INIS)

      Fortuno, J. R.; Menor, F.; Esteban, M. J.; Pamies, J.; Gomez-Gosalvez, F. A.; Jover, J.

      2003-01-01

      To describe MR images of acute disseminated encephalomyelitis (ADE) in a paediatric group, particularly focused on its likely topographic variants, cerebellitis and myelitis, its evolution, and the differential diagnosis between it an an initial outbreak of multiple sclerosis. Initial and follow-up cranial MR images were retrospectively reviewed for 14 paediatric patients diagnosed with either ADE, cerebellitis or myelitis. In 9 patients, a spinal cord monitoring was included. Three topographic variants have been considered: ADE (7 patients). In the case of ADE, the supratentorial white matter was always affected, the brain stem in five (71%) and the cerebellum in two (28,5%). Basal ganglionic lesions were detected in 5 patients (71%) and cortical lesions in one (14%). Associated spinal cord abnormality was found in five of the six cases in which this study was included (83%). ADE lesions tended to be nodular and poorly differentiated whereas in cerebellitis and myelitis the predominant pattern was one of diffuse damage. Evolution of the lesions was toward reduction/resolution. Follow-up using MR in the medium-term in 6 patients (four ADE and two cerebellitis) did not detect any new lesions. Clinical follow-up of the patients did not show any neurological recurrences in any of them. ADE, cerebillits and myelitis could be topographic variants of a single process with a common pathogeny. As the spinal cord often seems to play a role in ADE, spinal cord monitoring would be recommended, even in the absence of the above-mentioned symptoms. This spinal cord abnormality, which is usually diffuse, plus deep gray matter damage, as well as the disease of monophase course, corroborated by a sequential MR follow-up, is all helpful in the differential diagnosis with multiple sclerosis. Nonetheless, the differential diagnosis between a recurring form of ADE and an encephalomyelitis is practically impossible to make. (Author) 33 refs

    2. XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Du, Sienmi; Itoh, Noriko; Askarinam, Sahar; Hill, Haley; Arnold, Arthur P; Voskuhl, Rhonda R

      2014-02-18

      Women are more susceptible to multiple sclerosis (MS) and have more robust immune responses than men. However, men with MS tend to demonstrate a more progressive disease course than women, suggesting a disconnect between the severity of an immune attack and the CNS response to a given immune attack. We have previously shown in an MS model, experimental autoimmune encephalomyelitis, that autoantigen-sensitized XX lymph node cells, compared with XY, are more encephalitogenic. These studies demonstrated an effect of sex chromosomes in the induction of immune responses, but did not address a potential role of sex chromosomes in the CNS response to immune-mediated injury. Here, we examined this possibility using XX versus XY bone marrow chimeras reconstituted with a common immune system of one sex chromosomal type. We found that experimental autoimmune encephalomyelitis mice with an XY sex chromosome complement in the CNS, compared with XX, demonstrated greater clinical disease severity with more neuropathology in the spinal cord, cerebellum, and cerebral cortex. A candidate gene on the X chromosome, toll-like receptor 7, was then examined. Toll-like receptor 7 expression in cortical neurons was higher in mice with XY compared with mice with XX CNS, consistent with the known neurodegenerative role for toll-like receptor 7 in neurons. These results suggest that sex chromosome effects on neurodegeneration in the CNS run counter to effects on immune responses, and may bear relevance to the clinical enigma of greater MS susceptibility in women but faster disability progression in men. This is a demonstration of a direct effect of sex chromosome complement on neurodegeneration in a neurological disease.

    3. Psychosocial factors involved in memory and cognitive failures in people with myalgic encephalomyelitis/chronic fatigue syndrome

      Directory of Open Access Journals (Sweden)

      Attree EA

      2014-02-01

      Full Text Available Elizabeth A Attree,1 Megan A Arroll,1 Christine P Dancey,1 Charlene Griffith,1 Amolak S Bansal1,2 1Chronic Illness Research Team, School of Psychology, University of East London, London, UK; 2Department of Immunology and the Sutton CFS Service, St Helier Hospital, Carshalton, UK Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS is characterized by persistent emotional, mental, and physical fatigue accompanied by a range of neurological, autonomic, neuroendocrine, immune, and sleep problems. Research has shown that psychosocial factors such as anxiety and depression as well as the symptoms of the illness, have a significant impact on the quality of life of people with ME/CFS. In addition, individuals may suffer from deficits in memory and concentration. This study set out to explore the relationships between variables which have been found to contribute to cognitive performance, as measured by prospective and retrospective memory, and cognitive failures. Methods: Eighty-seven people with ME/CFS answered questionnaires measuring fatigue, depression, anxiety, social support, and general self-efficacy. These were used in a correlational design (multiple regression to predict cognitive function (self-ratings on prospective and retrospective memory, and cognitive failures. Results: Our study found that fatigue, depression, and general self-efficacy were directly associated with cognitive failures and retrospective (but not prospective memory. Conclusion: Although it was not possible in this study to determine the cause of the deficits, the literature in this area leads us to suggest that although the pathophysiological mechanisms of ME/CFS are unclear, abnormalities in the immune system, including proinflammatory cytokines, can lead to significant impairments in cognition. We suggest that fatigue and depression may be a result of the neurobiological effects of ME/CFS and in addition, that the neurobiological effects of the illness

    4. Tinjauan Anatomi Klinik dan Manajemen Bell's Palsy

      OpenAIRE

      Nur Mujaddidah

      2017-01-01

      Bell's Palsy is a peripheral facial nerve weakness (facial nerve) with acute onset on one side of the face. This condition causes the inability of the patient to move half of his face consciously (volunter) on the affected side. The Bell's Palsy incidence is 20-30 cases out of 100.000 people and accounts for 60-70% of all cases of unilateral facial paralysis. The disease is self-limited, but causes great suffering for patients who are not treated properly. Controversy in the management is sti...

    5. Tinjauan Anatomi Klinik dan Manajemen Bell's Palsy

      Directory of Open Access Journals (Sweden)

      Nur Mujaddidah

      2017-07-01

      Full Text Available Bell's Palsy is a peripheral facial nerve weakness (facial nerve with acute onset on one side of the face. This condition causes the inability of the patient to move half of his face consciously (volunter on the affected side. The Bell's Palsy incidence is 20-30 cases out of 100.000 people and accounts for 60-70% of all cases of unilateral facial paralysis. The disease is self-limited, but causes great suffering for patients who are not treated properly. Controversy in the management is still debated, and the cause is still unknown. The underlying hypothesis is ischemic, vascular, viral, bacterial, hereditary, and immunologic. Therapy done so far is to improve facial nerve function and healing process. The management of the therapy used will be closely related to the structure of the anatomy and its functions and associated abnormalities. The modalities of Bell's Palsy therapy are with corticosteroids and antivirals, facial exercises, electrostimulation, physiotherapy and decompression operations. Approximately 80-90% of patients with Bell's palsy recover completely within 6 months, even in 50-60% of cases improved within 3 weeks. Approximately 10% experienced persistent facial muscle asymmetry, and 5% experienced severe sequelae, and 8% of cases were recurrent.

    6. Aspek Klinik, Genetik dan Molekuler Osteogensis Imperfekta

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      Mariska Mariska

      2015-10-01

      Full Text Available Osteogenesis imperfects (OI is a heritable disorder of connective tissue that mainly affects the bones. Being always associated with bone fragility, it is also known as "brittle bone" disease. Multiple bone fractures with minimal or absent trauma, dentinogenesis imperfects, short stature, blue slerae, and in adult years, hearing loss. Most cases of OI, which is inherited in an autosomal dominant manner, result from mutations affecting the genes COL1A1 (collagen type I alpha 1 and COL1A2 (collagen type I alpha 2 that encode pro-α 2 chains of type I collagen. The type I collagen molecule accounts for about 90% of the organic matrix of the bone. In addition, collagen forms a family of proteins that strengthen and support many tissues in the body, including cartilage, tendons, skin, and the white part of the eye (sclera. This paper aims to review the genetic contribution to OI.

    7. Herpes zoster: klinik, diagnostik og behandling

      DEFF Research Database (Denmark)

      Kofoed, Kristian; Rønholt, Finn; Gerstoft, Jan

      2011-01-01

      that early recognition and treatment can reduce acute symptoms, that antiviral therapy and corticosteroids shorten the acute illness period, that opioids and anticonvulsants have effect on acute HZ pain and, finally, that tricyclic antidepressants, opioids and anticonvulsants all have proven efficiency...

    8. Perancangan Sistem Basis Data pada Klinik

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      Indrajani Indrajani

      2011-06-01

      Full Text Available The purpose of this research is to analyze and design a database to support Clinic information needs. The methods used in this research are data collection, which uses the search data techniques that includes interviews, documentation, observation, literature study, analysis method and database design that includes conceptual, logical, and physical design. The result of this research is a database system that can save data integrated, clinic information needs, and health services improvement which are patients and community in general. The conclusions that can be drawn from this research are the existence of this database system, so the clinic can manage patient data and checkup transaction, treatment, and payment. 

    9. Det metaboliske syndrom i daglig klinik

      DEFF Research Database (Denmark)

      Beck-Nielsen, Henning

      2010-01-01

      An obesity epidemic has spread all over the world during the past 30-40 years. Persons becoming viscerally obese have a large risk of developing dysmetabolism characterised by ectopic fat accumulation resulting in increased triglyceride content and reduced HDL-cholesterol in the blood, arterial...

    10. Herpes zoster: klinik, diagnostik og behandling

      DEFF Research Database (Denmark)

      Kofoed, Kristian; Rønholt, Finn; Gerstoft, Jan

      2011-01-01

      Herpes zoster (HZ) is a painful vesicular rash localized to one dermatome. Post-herpetic neuralgia (PHN) is persistent pain three months after the rash started. In recent years several Cochrane reviews and clinical studies on how to treat HZ and PHN have been published. These studies show...

    11. A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior

      OpenAIRE

      Morris, Gerwyn; Anderson, George; Galecki, Piotr; Berk, Michael; Maes, Michael

      2013-01-01

      It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gas...

    12. The UK ME/CFS Biobank for biomedical research on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Multiple Sclerosis.

      OpenAIRE

      Lacerda, EM; Bowman, EW; Cliff, JM; Kingdon, CC; King, EC; Lee, JS; Clark, TG; Dockrell, HM; Riley, EM; Curran, H; Nacul, L

      2017-01-01

      : The UK ME/CFS Biobank was launched in August 2011 following extensive consultation with professionals and patient representatives. The bioresource aims to enhance research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), related to pathophysiology, biomarkers and therapeutic approaches. The cohort includes 18-60 year olds, encompassing 284 clinically-confirmed ME/CFS cases, 60 neurologist-diagnosed multiple sclerosis (MS) cases, and 135 healthy individuals. The Biobank contai...

    13. Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis

      OpenAIRE

      de Carvalho Leite Jose C; de L Drachler Maria; Killett Anne; Kale Swati; Nacul Luis; McArthur Maggie; Hong Chia; O'Driscoll Lucy; Pheby Derek; Campion Peter; Lacerda Eliana; Poland Fiona

      2011-01-01

      Abstract Background Needs-based resource allocation is fundamental to equitable care provision, which can meet the often-complex, fluctuating needs of people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This has posed challenges both for those providing and those seeking support providers, in building shared understanding of the condition and of actions to address it. This qualitative study reports on needs for equity in health and social care expressed by adults living w...

    14. Social support needs for equity in health & social care: a thematic analysis of experiences of people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

      OpenAIRE

      Leite, Jose Carlos de Carvalho; Drachler, Maria de L.; Killett, Anne; Kale, Swati; Nacul, Luis; McArthur, Maggie; Hong, Chia Swee; O'Driscoll, Lucy; Pheby, Derek; Campion, Peter; Lacerda, Elliana; Poland, Fiona

      2011-01-01

      Background: Needs-based resource allocation is fundamental to equitable care provision, which can meet the often-complex, fluctuating needs of people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This has posed challenges both for those providing and those seeking support providers, in building shared understanding of the condition and of actions to address it. This qualitative study reports on needs for equity in health and social care expressed by adults living with CFS/...

    15. The role of autonomic function in exercise-induced endogenous analgesia : a case-control study in myalgic encephalomyelitis/chronic fatigue syndrome and healthy people

      OpenAIRE

      Van Oosterwijck, Jessica; Marusic, Uros; De Wandele, Inge; Paul, Lorna; Meeus, Mira; Moorkens, Greta; Lambrecht, Luc; Danneels, Lieven; Nijs, Jo

      2017-01-01

      BACKGROUND: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are unable to activate brain-orchestrated endogenous analgesia (or descending inhibition) in response to exercise. This physiological impairment is currently regarded as one factor explaining post-exertional malaise in these patients. Autonomic dysfunction is also a feature of ME/CFS. OBJECTIVES: This study aims to examine the role of the autonomic nervous system in exercise-induced analgesia in healthy...

    16. Infection dynamics of western equine encephalomyelitis virus (Togaviridae: Alphavirus in four strains of Culex tarsalis (Diptera: Culicidae: an immunocytochemical study

      Directory of Open Access Journals (Sweden)

      Neira Oviedo MV

      2011-04-01

      Full Text Available Marco V Neira Oviedo1,2, William S Romoser1, Calvin BL James1, Farida Mahmood3, William K Reisen31Tropical Disease Institute, Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, OH, USA; 2Oxitec Inc, Oxford, England; 3Center for Vectorborne Diseases, School of Veterinary Medicine, University of California, Davis, CA, USABackground: Vector competence describes the efficiency with which vector arthropods become infected with and transmit pathogens and depends on interactions between pathogen and arthropod genetics as well as environmental factors. For arbovirus transmission, the female mosquito ingests viremic blood, the virus infects and replicates in midgut cells, escapes from the midgut, and disseminates to other tissues, including the salivary glands. Virus-laden saliva is then injected into a new host. For transmission to occur, the virus must overcome several "barriers", including barriers to midgut infection and/or escape and salivary infection and/or escape. By examining the spatial/temporal infection dynamics of Culex tarsalis strains infected with western equine encephalomyelitis virus (WEEV, we identified tissue tropisms and potential tissue barriers, and evaluated the effects of viral dose and time postingestion.Methods: Using immuno-stained paraffin sections, WEEV antigens were tracked in four Cx. tarsalis strains: two recently colonized California field strains – Coachella Valley, Riverside County (COAV and Kern National Wildlife Refuge (KNWR; and two laboratory strains selected for WEEV susceptibility (high viremia producer, HVP, and WEEV resistance (WR.Results and conclusions: Tissues susceptible to WEEV infection included midgut epithelium, neural ganglia, trachea, chorionated eggs, and salivary glands. Neuroendocrine cells in the retrocerebral complex were occasionally infected, indicating the potential for behavioral effects. The HVP and COAV strains vigorously supported viral growth

    17. Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice.

      Science.gov (United States)

      Li, Bin; Cui, Wei; Liu, Jia; Li, Ru; Liu, Qian; Xie, Xiao-Hua; Ge, Xiao-Li; Zhang, Jing; Song, Xiu-Juan; Wang, Ying; Guo, Li

      2013-12-01

      Sulforaphane (SFN) is an organosulfur compound present in vegetables and has potent anti-oxidant and anti-inflammatory activities. This study was aimed at investigating the effect of treatment with SFN on inflammation and oxidative stress, and the potential mechanisms underlying the action of SFN in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Treatment with SFN significantly inhibited the development and severity of EAE in mice, accompanied by mitigating inflammatory infiltration and demyelination in the spinal cord of mice. The protective effect of SFN was associated with significantly improved distribution of claudin-5 and occludin, and decreased levels of MMP-9 expression, preserving the blood-brain barrier. Furthermore, the protection of SFN was also related to decreased levels of oxidative stress in the brains of mice by enhanced activation of the Nrf2/ARE pathway and increased levels of anti-oxidant HO-1 and NQO1 expression. In addition, treatment with SFN inhibited antigen-specific Th17 responses and enhanced IL-10 responses. Our data indicated that treatment with SFN inhibited EAE development and severity in mice by its anti-oxidant activity and antagonizing autoimmune inflammation. Our findings suggest that SFN and its analogues may be promising reagents for intervention of multiple sclerosis and other autoimmune diseases. © 2013.

    18. The leukotriene B{sub 4} receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis

      Energy Technology Data Exchange (ETDEWEB)

      Kihara, Yasuyuki, E-mail: kihara-yasuyuki@umin.net [Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Yokomizo, Takehiko [Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582 (Japan); Core Research for Embryonic Science and Technology (CREST), Japan Science and Technology Agency (Japan); Kunita, Akiko; Morishita, Yasuyuki; Fukayama, Masashi [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033 (Japan); Ishii, Satoshi; Shimizu, Takao [Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

      2010-04-09

      Leukotriene B{sub 4} (LTB{sub 4}) is a potent chemoattractant and activator of neutrophils, macrophages and T cells. These cells are a key component of inflammation and all express BLT1, a high affinity G-protein-coupled receptor for LTB{sub 4}. However, little is known about the neuroimmune functions of BLT1. In this study, we describe a distinct role for BLT1 in the pathology of experimental autoimmune encephalomyelitis (EAE) and T{sub H}1/T{sub H}17 immune responses. BLT1 mRNA was highly upregulated in the spinal cord of EAE mice, especially during the induction phase. BLT1{sup -/-} mice had delayed onset and less severe symptoms of EAE than BLT1{sup +/+} mice. Additionally, inflammatory cells were recruited to the spinal cord of asymptomatic BLT1{sup +/+}, but not BLT1{sup -/-} mice before the onset of disease. Ex vivo studies showed that both the proliferation and the production of IFN-{gamma}, TNF-{alpha}, IL-17 and IL-6 were impaired in BLT1{sup -/-} cells, as compared with BLT1{sup +/+} cells. Thus, we suggest that BLT1 exacerbates EAE by regulating the migration of inflammatory cells and T{sub H}1/T{sub H}17 immune responses. Our findings provide a novel therapeutic option for the treatment of multiple sclerosis and other T{sub H}17-mediated diseases.

    19. Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by photobiomodulation induced by 670 nm light.

      Directory of Open Access Journals (Sweden)

      Kamaldeen A Muili

      Full Text Available The approved immunomodulatory agents for the treatment of multiple sclerosis (MS are only partially effective. It is thought that the combination of immunomodulatory and neuroprotective strategies is necessary to prevent or reverse disease progression. Irradiation with far red/near infrared light, termed photobiomodulation, is a therapeutic approach for inflammatory and neurodegenerative diseases. Data suggests that near-infrared light functions through neuroprotective and anti-inflammatory mechanisms. We sought to investigate the clinical effect of photobiomodulation in the Experimental Autoimmune Encephalomyelitis (EAE model of multiple sclerosis.The clinical effect of photobiomodulation induced by 670 nm light was investigated in the C57BL/6 mouse model of EAE. Disease was induced with myelin oligodendrocyte glycoprotein (MOG according to standard laboratory protocol. Mice received 670 nm light or no light treatment (sham administered as suppression and treatment protocols. 670 nm light reduced disease severity with both protocols compared to sham treated mice. Disease amelioration was associated with down-regulation of proinflammatory cytokines (interferon-γ, tumor necrosis factor-α and up-regulation of anti-inflammatory cytokines (IL-4, IL-10 in vitro and in vivo.These studies document the therapeutic potential of photobiomodulation with 670 nm light in the EAE model, in part through modulation of the immune response.

    20. BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

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      Sofia Fernanda Gonçalves Zorzella-Pezavento

      2013-01-01

      Full Text Available A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65 after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γ levels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

    1. Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review.

      Science.gov (United States)

      Campagnolo, N; Johnston, S; Collatz, A; Staines, D; Marshall-Gradisnik, S

      2017-06-01

      Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is characterised by unexplained fatigue for at least 6 months accompanied by a diverse but consistent set of symptoms. Diet modification and nutritional supplements could be used to improve patient outcomes, such fatigue and quality of life. We reviewed and discussed the evidence for nutritional interventions that may assist in alleviating symptoms of CFS/ME. Medline, Cinahl and Scopus were systematically searched from 1994 to May 2016. All studies on nutrition intervention were included where CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing). Seventeen studies were included that meet the inclusion criteria. Of these, 14 different interventions were investigated on study outcomes. Many studies did not show therapeutic benefit on CFS/ME. Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10. This review identified insufficient evidence for the use of nutritional supplements and elimination or modified diets to relieve CFS/ME symptoms. Studies were limited by the number of studies investigating the interventions, small sample sizes, study duration, variety of instruments used, and studies not reporting dietary intake method. Further research is warranted in homogeneous CFS/ME populations. © 2017 The Authors. Journal of Human Nutrition and Dietetics published by John Wiley & Sons Ltd on behalf of British Dietetic Association.

    2. Post-infective transverse myelitis following Streptococcus pneumoniae meningitis with radiological features of acute disseminated encephalomyelitis: a case report

      Directory of Open Access Journals (Sweden)

      Williams Thomas

      2012-09-01

      Full Text Available Abstract Introduction Post-infectious autoimmune demyelination of the central nervous system is a rare neurological disorder typically associated with exanthematous viral infections. We report an unusual presentation of the condition and a previously undocumented association with Streptococcus pneumonia meningitis. Case presentation A 50-year-old Caucasian woman presented to our facility with an acute myelopathy three days after discharge following acute Streptococcus pneumoniae meningitis. Imaging studies of the spine ruled out an infective focus and no other lesions were seen within the cord. Diffuse, bilateral white matter lesions were seen within the cerebral hemispheres, and our patient was diagnosed as having a post-infective demyelination syndrome that met the diagnostic criteria for an acute transverse myelitis. Our patient clinically and radiologically improved following treatment with steroids. Conclusions The novel association of a Streptococcus pneumoniae infection with post-infectious autoimmune central nervous system demyelination should alert the reader to the potentially causative role of this common organism, and gives insights into the pathogenesis. The unusual dissociation between the clinical presentation and the location of the radiological lesions should also highlight the potential for the condition to mimic the presentation of others, and stimulates debate on the definitions of acute transverse myelitis and acute disseminated encephalomyelitis, and their potential overlap.

    3. Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling.

      Science.gov (United States)

      Li, Wen; Zhang, Zhihui; Zhang, Kai; Xue, Zhenyi; Li, Yan; Zhang, Zimu; Zhang, Lijuan; Gu, Chao; Zhang, Qi; Hao, Junwei; Da, Yurong; Yao, Zhi; Kong, Ying; Zhang, Rongxin

      2016-10-01

      Arctigenin is a herb compound extract from Arctium lappa and is reported to exhibit pharmacological properties, including neuronal protection and antidiabetic, antitumor, and antioxidant properties. However, the effects of arctigenin on autoimmune inflammatory diseases of the CNS, multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE) are still unclear. In this study, we demonstrated that arctigenin-treated mice are resistant to EAE; the clinical scores of arctigenin-treated mice are significantly reduced. Histochemical assays of spinal cord sections also showed that arctigenin reduces inflammation and demyelination in mice with EAE. Furthermore, the Th1 and Th17 cells in peripheral immune organs are inhibited by arctigenin in vivo. In addition, the Th1 cytokine IFN-γ and transcription factor T-bet, as well as the Th17 cytokines IL-17A, IL-17F, and transcription factor ROR-γt are significantly suppressed upon arctigenin treatment in vitro and in vivo. Interestedly, Th17 cells are obviously inhibited in CNS of mice with EAE, while Th1 cells do not significantly change. Besides, arctigenin significantly restrains the differentiation of Th17 cells. We further demonstrate that arctigenin activates AMPK and inhibits phosphorylated p38, in addition, upregulates PPAR-γ, and finally suppresses ROR-γt. These findings suggest that arctigenin may have anti-inflammatory and immunosuppressive properties via inhibiting Th17 cells, indicating that it could be a potential therapeutic drug for multiple sclerosis or other autoimmune inflammatory diseases.

    4. Perceived Fatigue Interference and Depressed Mood: Comparison of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients with Fatigued Breast Cancer Survivors.

      Science.gov (United States)

      Hall, Daniel L; Antoni, Michael H; Lattie, Emily G; Jutagir, Devika R; Czaja, Sara J; Perdomo, Dolores; Lechner, Suzanne C; Stagl, Jamie M; Bouchard, Laura C; Gudenkauf, Lisa M; Traeger, Lara; Fletcher, MaryAnn; Klimas, Nancy G

      Persistent fatigue and depressive symptoms are both highly prevalent among patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) as well as breast cancer survivors. This study aimed to assess and directly compare perceptions of fatigue as highly interfering in one's daily functioning in both patient populations to better understand their relationships with depressed mood. Participants were 95 female CFS/ME patients and 67 females who were approximately 5 years post-treatment for stage 0-III breast cancer presenting with clinically elevated fatigue severity. Self-report measures were obtained on participants' fatigue-related interference in daily functioning and fatigue severity as well as depressed mood. Hierarchical regression was used to test effects controlling for relevant demographic, psychosocial, and medical covariates. CFS/ME patients endorsed greater depressed mood and fatigue interference than did fatigued breast cancer survivors, p's fatigued breast cancer survivors (β=.18, p =.19). CFS/ME patients reported elevated fatigue symptoms and depression relative to fatigued breast cancer survivors. In the former group, greater depressed mood was highly and significantly associated with greater fatigue-related inference in daily activities. Potential targets for cognitive behavioral interventions are discussed.

    5. Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms

      Science.gov (United States)

      Twisk, Frank NM

      2015-01-01

      Although myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) are considered to be synonymous, the definitional criteria for ME and CFS define two distinct, partially overlapping, clinical entities. ME, whether defined by the original criteria or by the recently proposed criteria, is not equivalent to CFS, let alone a severe variant of incapacitating chronic fatigue. Distinctive features of ME are: muscle weakness and easy muscle fatigability, cognitive impairment, circulatory deficits, a marked variability of the symptoms in presence and severity, but above all, post-exertional “malaise”: a (delayed) prolonged aggravation of symptoms after a minor exertion. In contrast, CFS is primarily defined by (unexplained) chronic fatigue, which should be accompanied by four out of a list of 8 symptoms, e.g., headaches. Due to the subjective nature of several symptoms of ME and CFS, researchers and clinicians have questioned the physiological origin of these symptoms and qualified ME and CFS as functional somatic syndromes. However, various characteristic symptoms, e.g., post-exertional “malaise” and muscle weakness, can be assessed objectively using well-accepted methods, e.g., cardiopulmonary exercise tests and cognitive tests. The objective measures acquired by these methods should be used to accurately diagnose patients, to evaluate the severity and impact of the illness objectively and to assess the positive and negative effects of proposed therapies impartially. PMID:26140274

    6. Inhibition of Myeloperoxidase at the Peak of Experimental Autoimmune Encephalomyelitis Restores Blood-Brain-Barrier Integrity and Ameliorates Disease Severity.

      Science.gov (United States)

      Zhang, Hao; Ray, Avijit; Miller, Nichole M; Hartwig, Danielle; Pritchard, Kirkwood A; Dittel, Bonnie N

      2015-11-12

      Oxidative stress is thought to contribute to disease pathogenesis in the central nervous system (CNS) disease multiple sclerosis (MS). Myeloperoxidase (MPO), a potent peroxidase that generates toxic radicals and oxidants, is increased in the CNS during MS. However, the exact mechanism whereby MPO drives MS pathology is not known. We addressed this question by inhibiting MPO in mice with experimental autoimmune encephalomyelitis (EAE) using our non-toxic MPO inhibitor KYC. We found that therapeutic administration of KYC for five days starting at the peak of disease significantly attenuated EAE disease severity, reduced myeloid cell numbers and permeability of the blood-brain-barrier (BBB). These data indicate that inhibition of MPO by KYC restores BBB integrity thereby limiting migration of myeloid cells into the CNS that drive EAE pathogenesis. In addition, these observations indicate that KYC may be an effective therapeutic agent for the treatment of MS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

    7. Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune Encephalomyelitis through Modulation of Th17/Treg Balance

      Directory of Open Access Journals (Sweden)

      Yan Zhou

      2016-01-01

      Full Text Available It is well known that dendritic cells (DCs play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs, a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG- specific experimental autoimmune encephalomyelitis (EAE model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS. Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs. Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS.

    8. Apoptosis of infiltrating T cells in the central nervous system of mice infected with Theiler's murine encephalomyelitis virus

      International Nuclear Information System (INIS)

      Oleszak, Emilia L.; Hoffman, Brad E.; Chang, J. Robert; Zaczynska, Ewa; Gaughan, John; Katsetos, Christos D.; Platsoucas, Chris D.; Harvey, Nile

      2003-01-01

      Theiler murine encephalomyelitis virus (TMEV), DA strain, induces in susceptible strain of mice a biphasic disease consisting of early acute disease followed by late chronic demyelinating disease. Both phases of the disease are associated with inflammatory infiltrates of the central nervous system (CNS). Late chronic demyelinating disease induced by TMEV serves as an excellent model to study human demyelinating disease, multiple sclerosis. During early acute disease, the virus is partially cleared from the CNS by CD3 + T cells. These T cells express Fas, FasL, negligible levels of Bcl-2 proteins and undergo activation-induced cell death as determined by TUNEL assay leading to resolution of the inflammatory response. In contrast, during late chronic demyelinating disease, and despite dense perivascular and leptomeningeal infiltrates, only very few cells undergo apoptosis. Mononuclear cells infiltrating the CNS express Bcl-2. It appears that the lack of apoptosis of T cells during late chronic demyelinating disease leads to the accumulation of these cells in the CNS. These cells may play a role in the pathogenesis of the demyelinating disease

    9. Comparative Effects of Human Neural Stem Cells and Oligodendrocyte Progenitor Cells on the Neurobehavioral Disorders of Experimental Autoimmune Encephalomyelitis Mice

      Directory of Open Access Journals (Sweden)

      Dae-Kwon Bae

      2016-01-01

      Full Text Available Since multiple sclerosis (MS is featured with widespread demyelination caused by autoimmune response, we investigated the recovery effects of F3.olig2 progenitors, established by transducing human neural stem cells (F3 NSCs with Olig2 transcription factor, in myelin oligodendrocyte glycoprotein- (MOG- induced experimental autoimmune encephalomyelitis (EAE model mice. Six days after EAE induction, F3 or F3.olig2 cells (1 × 106/mouse were intravenously transplanted. MOG-injected mice displayed severe neurobehavioral deficits which were remarkably attenuated and restored by cell transplantation, in which F3.olig2 cells were superior to its parental F3 cells. Transplanted cells migrated to the injured spinal cord, matured to oligodendrocytes, and produced myelin basic proteins (MBP. The F3.olig2 cells expressed growth and neurotrophic factors including brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, ciliary neurotrophic factor (CNTF, and leukemia inhibitory factor (LIF. In addition, the transplanted cells markedly attenuated inflammatory cell infiltration, reduced cytokine levels in the spinal cord and lymph nodes, and protected host myelins. The results indicate that F3.olig2 cells restore neurobehavioral symptoms of EAE mice by regulating autoimmune inflammatory responses as well as by stimulating remyelination and that F3.olig2 progenitors could be a candidate for the cell therapy of demyelinating diseases including MS.

    10. 1H-MRS for the diagnosis of acute disseminated encephalomyelitis: insight into the acute-disease stage

      International Nuclear Information System (INIS)

      Ben Sira, Liat; Miller, Elka; Artzi, Moran; Fattal-Valevski, Aviva; Constantini, Shlomi; Ben Bashat, Dafna

      2010-01-01

      Acute disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the central nervous system (CNS). Differentiating ADEM from other inflammatory disorders, such as multiple sclerosis, is not always conclusive using conventional MRI. To evaluate longitudinal magnetic resonance spectroscopy (MRS) changes that distinguish ADEM from other inflammatory disorders. MRI/MRS scans were performed in seven patients with ADEM during the acute and chronic phases of the disease. Partial recovery was detected between the acute and chronic phases in choline/creatine ratio. Major elevation of lipids and reduction in myo-inositol/creatine ratio was detected in all patients during the acute phase, followed by a reduction in lipids peak and elevation above normal in myo-inositol/creatine ratio during the chronic phase. Consistent and unique MRS changes in metabolite ratios between the acute and chronic presentations of the disease were found. To the best of our knowledge, these patterns have not been described in other inflammatory disorders and might assist in the early diagnosis of ADEM. (orig.)

    11. Perceived Fatigue Interference and Depressed Mood: Comparison of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients with Fatigued Breast Cancer Survivors

      Science.gov (United States)

      Hall, Daniel L.; Antoni, Michael H.; Lattie, Emily G.; Jutagir, Devika R.; Czaja, Sara J.; Perdomo, Dolores; Lechner, Suzanne C.; Stagl, Jamie M.; Bouchard, Laura C.; Gudenkauf, Lisa M.; Traeger, Lara; Fletcher, MaryAnn; Klimas, Nancy G.

      2015-01-01

      Objective Persistent fatigue and depressive symptoms are both highly prevalent among patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) as well as breast cancer survivors. This study aimed to assess and directly compare perceptions of fatigue as highly interfering in one’s daily functioning in both patient populations to better understand their relationships with depressed mood. Methods Participants were 95 female CFS/ME patients and 67 females who were approximately 5 years post-treatment for stage 0-III breast cancer presenting with clinically elevated fatigue severity. Self-report measures were obtained on participants’ fatigue-related interference in daily functioning and fatigue severity as well as depressed mood. Hierarchical regression was used to test effects controlling for relevant demographic, psychosocial, and medical covariates. Results CFS/ME patients endorsed greater depressed mood and fatigue interference than did fatigued breast cancer survivors, p’sfatigued breast cancer survivors (β=.18, p=.19). Conclusions CFS/ME patients reported elevated fatigue symptoms and depression relative to fatigued breast cancer survivors. In the former group, greater depressed mood was highly and significantly associated with greater fatigue-related inference in daily activities. Potential targets for cognitive behavioral interventions are discussed. PMID:26180660

    12. The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis

      DEFF Research Database (Denmark)

      Krakowski, M L; Owens, T

      1997-01-01

      In experimental allergic encephalomyelitis (EAE), CD4+ T cells infiltrate the central nervous system (CNS). We derived CD4+ T cell lines from SJL/J mice that were specific for encephalitogenic myelin basic protein (MBP) peptides and produced both Th1 and Th2 cytokines. These lines transferred EAE...... to naive mice. Peptide-specific cells re-isolated from the CNS only produced Th1 cytokines, whereas T cells in the lymph nodes produced both Th1 and Th2 cytokines. Mononuclear cells isolated from the CNS, the majority of which were microglia, presented antigen to and stimulated MBP-specific T cell lines...... in vitro. Although CNS antigen-presenting cells (APC) supported increased production of interferon (IFN)-gamma mRNA by these T cells, there was no increase in the interleukin (IL)-4 signal, whereas splenic APC induced increases in both IFN-gamma and IL-4. mRNA for IL-12 (p40 subunit) was up...

    13. A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS?

      Directory of Open Access Journals (Sweden)

      Navena Navaneetharaja

      2016-06-01

      Full Text Available Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS is a heterogeneous disorder of significant societal impact that is proposed to involve both host and environmentally derived aetiologies that may be autoimmune in nature. Immune-related symptoms of at least moderate severity persisting for prolonged periods of time are common in ME/CFS patients and B cell depletion therapy is of significant therapeutic benefit. The origin of these symptoms and whether it is infectious or inflammatory in nature is not clear, with seeking evidence of acute or chronic virus infections contributing to the induction of autoimmune processes in ME/CFS being an area of recent interest. This article provides a comprehensive review of the current evidence supporting an infectious aetiology for ME/CFS leading us to propose the novel concept that the intestinal microbiota and in particular members of the virome are a source of the “infectious” trigger of the disease. Such an approach has the potential to identify disease biomarkers and influence therapeutics, providing much-needed approaches in preventing and managing a disease desperately in need of confronting.

    14. The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS)

      DEFF Research Database (Denmark)

      Falk Hvidberg, Michael; Brinth, Louise Schouborg; Olesen, Anne V

      2015-01-01

      INTRODUCTION: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a common, severe condition affecting 0.2 to 0.4 per cent of the population. Even so, no recent international EQ-5D based health-related quality of life (HRQoL) estimates exist for ME/CFS patients. The main purpose...... of this study was to estimate HRQoL scores using the EQ-5D-3L with Danish time trade-off tariffs. Secondary, the aims were to explore whether the results are not influenced by other conditions using regression, to compare the estimates to 20 other conditions and finally to present ME/CFS patient characteristics...... for use in clinical practice. MATERIAL AND METHODS: All members of the Danish ME/CFS Patient Association in 2013 (n=319) were asked to fill out a questionnaire including the EQ-5D-3L. From these, 105 ME/CFS patients were identified and gave valid responses. Unadjusted EQ-5D-3L means were calculated...

    15. The occupational and quality of life consequences of chronic fatigue syndrome/myalgic encephalomyelitis in young people

      Science.gov (United States)

      Taylor, Renee R; O’Brien, Jane; Kielhofner, Gary; Lee, Sun-Wook; Katz, Ben; Mears, Cynthia

      2011-01-01

      Introduction Chronic fatigue syndrome, termed myalgic encephalomyelitis in the United Kingdom (CFS/ME), is a debilitating condition involving severe exhaustion, cognitive difficulties, educational and vocational losses, and disruption of social activities and relationships. CFS/ME may affect volition (that is, value, interest and sense of competence). Purpose To test Model of Human Occupation (MOHO) concepts by comparing young people with and without CFS/ME in terms of occupational participation, volition and health-related quality of life during infection and over time. Method Three hundred and one people (12–18 years old) diagnosed with glandular fever were evaluated at the time of acute infection (baseline). Six months following diagnosis, 39 of them met the criteria for CFS/ME. A further 39 who recovered were randomly selected and matched to CFS/ME participants. Both groups were re-evaluated at 12 months and 24 months. The Occupational Self Assessment and the Child General Health Questionnaire were used to compare occupational participation. Results Those with CFS/ME reported lower levels of perceived competency, more difficulties with physical functioning and poorer general health status than those who recovered. Conclusion Those with CFS/ME report lower perceived competency, and compromises in physical functioning, school performance, social activities, emotional functioning and general health. This supports the MOHO assertion that impairments affect volition and quality of life. PMID:22102767

    16. Regulation of Th1 and Th17 cell differentiation and amelioration of experimental autoimmune encephalomyelitis by natural product compound berberine.

      Science.gov (United States)

      Qin, Xia; Guo, Bingshi T; Wan, Bing; Fang, Lei; Lu, Limin; Wu, Lili; Zang, Ying Qin; Zhang, Jingwu Z

      2010-08-01

      Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as an anti-inflammatory remedy in traditional Chinese medicine. In this study, we showed that BBR was efficacious in the amelioration of experimental autoimmune encephalomyelitis (EAE) through novel regulatory mechanisms involving pathogenic Th1 and Th17 cells. BBR inhibited differentiation of Th17 cells and, to a lesser degree, Th1 cells through direct actions on the JAK/STAT pathway, whereas it had no effect on the relative number of CD4(+)Foxp3(+) regulatory T cells. In addition, BBR indirectly influenced Th17 and Th1 cell functions through its effect on the expression and function of costimulatory molecules and the production of IL-6, which was attributable to the inhibition of NF-kappaB activity in CD11b(+) APCs. BBR treatment completely abolished the encephalitogenicity of MOG(35-55)-reactive Th17 cells in an adoptive transfer EAE model, and the same treatment significantly inhibited the ability of MOG(35-55)-reactive Th1 cells to induce EAE. This study provides new evidence that natural compounds, such as BBR, are of great value in the search for novel anti-inflammatory agents and therapeutic targets for autoimmune diseases.

    17. Hsp65-producing Lactococcus lactis prevents experimental autoimmune encephalomyelitis in mice by inducing CD4+LAP+ regulatory T cells

      Science.gov (United States)

      Rezende, Rafael M.; Oliveira, Rafael P.; Medeiros, Samara R.; Gomes-Santos, Ana C.; Alves, Andrea C.; Loli, Flávia G.; Guimarães, Mauro A.F.; Amaral, Sylvia S.; da Cunha, André P.; Weiner, Howard L.; Azevedo, Vasco; Miyoshi, Anderson; Faria, Ana M.C.

      2013-01-01

      Heat shock proteins (Hsps) participate in the cellular response to stress and they are hiperexpressed in inflammatory conditions. They are also known to play a major role in immune modulation, controlling, for instance, autoimmune responses. In this study, we showed that oral administration of a recombinant Lactococcus lactis strain that produces and releases LPS-free Hsp65 prevented the development of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. This was confirmed by the reduced inflammatory cell infiltrate and absence of injury signs in the spinal cord. The effect was associated with reduced IL-17 and increased IL-10 production in mesenteric lymph node and spleen cell cultures. Hsp65-producing-L. lactis-fed mice had a remarkable increase in the number of natural and inducible CD4+Foxp3+ regulatory T (Treg) cells and CD4+LAP+ (Latency-associated peptide) Tregs - which express the membrane-bound TGF-β - in spleen, inguinal and mesenteric lymph nodes as well as in spinal cord. Moreover, many Tregs co-expressed Foxp3 and LAP. In vivo depletion of LAP+ cells abrogated the effect of Hsp65-producing L. lactis in EAE prevention and worsened disease in medium-fed mice. Thus, Hsp65-L.lactis seems to boost this critical regulatory circuit involved in controlling EAE development in mice. PMID:22939403

    18. Methodological Challenges in Protein Microarray and Immunohistochemistry for the Discovery of Novel Autoantibodies in Paediatric Acute Disseminated Encephalomyelitis

      Science.gov (United States)

      Peschl, Patrick; Ramberger, Melanie; Höftberger, Romana; Jöhrer, Karin; Baumann, Matthias; Rostásy, Kevin; Reindl, Markus

      2017-01-01

      Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients. Therefore, we aimed to identify novel autoantibody targets in ADEM patients. Sixteen ADEM patients (11 seronegative, 5 seropositive for MOG antibodies) were analysed for potential new biomarkers, using a protein microarray and immunohistochemistry on rat brain tissue to identify antibodies against intracellular and surface neuronal and glial antigens. Nine candidate antigens were identified in the protein microarray analysis in at least two patients per group. Immunohistochemistry on rat brain tissue did not reveal new target antigens. Although no new autoantibody targets could be found here, future studies should aim to identify new biomarkers for therapeutic and prognostic purposes. The microarray analysis and immunohistochemistry methods used here have several limitations, which should be considered in future searches for biomarkers. PMID:28327523

    19. An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis

      Science.gov (United States)

      Quintana, Francisco J.; Murugaiyan, Gopal; Farez, Mauricio F.; Mitsdoerffer, Meike; Tukpah, Ann-Marcia; Burns, Evan J.; Weiner, Howard L.

      2010-01-01

      The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) participates in the differentiation of FoxP3+ Treg, Tr1 cells, and IL-17–producing T cells (Th17). Most of our understanding on the role of AHR on the FoxP3+ Treg compartment results from studies using the toxic synthetic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin. Thus, the physiological relevance of AHR signaling on FoxP3+ Treg in vivo is unclear. We studied mice that carry a GFP reporter in the endogenous foxp3 locus and a mutated AHR protein with reduced affinity for its ligands, and found that AHR signaling participates in the differentiation of FoxP3+ Treg in vivo. Moreover, we found that treatment with the endogenous AHR ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) given parenterally or orally induces FoxP3+ Treg that suppress experimental autoimmune encephalomyelitis. ITE acts not only on T cells, but also directly on dendritic cells to induce tolerogenic dendritic cells that support FoxP3+ Treg differentiation in a retinoic acid-dependent manner. Thus, our work demonstrates that the endogenous AHR ligand ITE promotes the induction of active immunologic tolerance by direct effects on dendritic and T cells, and identifies nontoxic endogenous AHR ligands as potential unique compounds for the treatment of autoimmune disorders. PMID:21068375

    20. Inhibition of reactive astrocytosis in established experimental autoimmune encephalomyelitis favors infiltration by myeloid cells over T cells and enhances severity of disease

      DEFF Research Database (Denmark)

      Toft-Hansen, Henrik; Füchtbauer, Laila; Owens, Trevor

      2011-01-01

      encephalomyelitis (EAE), an animal model of multiple sclerosis. We made use of transgenic mice, which express herpes simplex virus-derived thymidine kinase under control of a glial fibrillary acidic protein promotor (GFAP HSV-TK mice). Treatment of these mice with ganciclovir leads to inhibition of reactive......-associated molecules TNFα, MMP-12 and TIMP-1 was elevated in spinal cord of GFAP HSV-TK mice treated with ganciclovir. Relative expression of CD3ε was downregulated, and expression levels of IFNγ, IL-4, IL-10, IL-17, and Foxp3 were not significantly changed. mRNA expression of CCL2 was upregulated, and CXL10...

    1. TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis

      DEFF Research Database (Denmark)

      Renno, T; Krakowski, M; Piccirillo, C

      1995-01-01

      in the pathology of multiple sclerosis and its animal model experimental allergic encephalomyelitis (EAE). We used reverse transcriptase (RT)-PCR to study the kinetics, cellular source, and regulation of cytokine gene expression in the central nervous system (CNS) of SJL/J mice with myelin basic protein......, the majority of which were identified as microglia and macrophages by their Mac-1 phenotype. Microglia could be discriminated by their low expression of CD45. Incubation of freshly derived, adult microglia from normal, uninfiltrated, CNS with activated Th1 supernatant induced the production of TNF-alpha m...

    2. Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice

      DEFF Research Database (Denmark)

      Tran, E H; Hoekstra, K; van Rooijen, N

      1998-01-01

      role of peripheral macrophages in experimental allergic encephalomyelitis (EAE), a Th1-mediated demyelinating disease that serves as a an animal model for multiple sclerosis (MS), by their depletion using mannosylated liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP). Here we describe....../J mice was abrogated by Cl2MDP-mnL treatment. CD4+ T cell and MHC II+ B220+ B cell extravasation from blood vessels and Th1 cytokine production were not inhibited. However, invasion of the central nervous system intraparenchymal tissues by lymphocytes, F4/80+, Mac-1+, and MOMA-1+ macrophages was almost...

    3. Mumps virus encephalomyelitis in a 19-year old male patient with an undefined severe combined immunodeficiency post-haematopoietic bone marrow transplantation: a rare fatal complication.

      Science.gov (United States)

      Eyre, Toby A; Pelosi, Emanuela; McQuaid, Stephen; Richardson, Deborah; Newman, Joan; Hill, Kate; Veys, Paul; Davies, Graham; Orchard, Kim H

      2013-06-01

      We describe a rare case of fatal mumps encephalomyelitis occurring in 19-year old male following matched unrelated donor peripheral blood haematopoietic stem cell transplantation (HSCT). The indication for HSCT was for an undefined form of severe combined immunodeficiency (SCID). Molecular typing of the mumps viral RNA isolated from neural tissue indicated that the infection was acquired at the time of a mumps outbreak in England and Wales that occurred between 2004 and 2006. This case highlights the importance of considering mumps in the differential diagnosis of central nervous system infection in highly immunosuppressed patients. Copyright © 2013 Elsevier B.V. All rights reserved.

    4. Perancangan Sistem Informasi Manajemen pada Klinik Skala Kecil (Studi Kasus: Klinik Dr. Jonni

      Directory of Open Access Journals (Sweden)

      Ayuliana Ayuliana

      2014-12-01

      Full Text Available The purpose of this research was to develop a database application at dr. Jonni clinic which can be used for processing and recording of operational data with an attractive user interface. Through the integrated database application, data on dr. Jonni clinic would be more structured, therefore data retrieval will go faster and more accurate, data security administration will be increased, data redundancy will be eliminated and service performance clinic dr. Jonni will also be increased. The method of analysis includes the study of literature, examination of documentation, observation, and interviews. While in the design, the method includes application design using the waterfall method models, database design and data modeling application screens using State Transition Diagrams. The results achieved from this research is an application of data base management hospital. With database applications, all data and information can be integrated well, so that it would improve the quality of  services as well as facilitate storing and accessing data. The conclusions obtained from this research is the application of data base management hospital helps in generating quick and accurate information that is used to support operations and decision-making in the clinic dr. Jonni.

    5. Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 tesla Clinical whole-body system after intraperitoneal contrast injection

      Energy Technology Data Exchange (ETDEWEB)

      Heckl, S.; Naegele, T.; Klose, U. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Herrmann, M.; Gaertner, S.; Weissert, R. [Dept. of Neurology, Medical School, Univ. of Tuebingen (Germany); Schick, F. [Dept. of Radiology, Medical School, Univ. of Tuebingen (Germany); Kueker, W. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Dept. of Neuroradiology, Radcliffe Infirmary, Oxford, England (United Kingdom)

      2004-11-01

      Purpose: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) wholebody MR system. Materials and Methods: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weighted images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. Results: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense area in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. Conclusions: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats. (orig.)

    6. Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 tesla Clinical whole-body system after intraperitoneal contrast injection

      International Nuclear Information System (INIS)

      Heckl, S.; Naegele, T.; Klose, U.; Herrmann, M.; Gaertner, S.; Weissert, R.; Schick, F.; Kueker, W.

      2004-01-01

      Purpose: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) wholebody MR system. Materials and Methods: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weighted images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. Results: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense area in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. Conclusions: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats. (orig.)

    7. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

      Directory of Open Access Journals (Sweden)

      Alan D Curtis

      Full Text Available Atypical models of experimental autoimmune encephalomyelitis (EAE are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS. Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG in complete Freund's adjuvant (CFA followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA. The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in

    8. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

      Science.gov (United States)

      Curtis, Alan D; Taslim, Najla; Reece, Shaun P; Grebenciucova, Elena; Ray, Richard H; Rosenbaum, Matthew D; Wardle, Robert L; Van Scott, Michael R; Mannie, Mark D

      2014-01-01

      Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund's adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and

    9. Immune responses to commercial equine vaccines against equine herpesvirus-1, equine influenza virus, eastern equine encephalomyelitis, and tetanus.

      Science.gov (United States)

      Holmes, Mark A; Townsend, Hugh G G; Kohler, Andrea K; Hussey, Steve; Breathnach, Cormac; Barnett, Craig; Holland, Robert; Lunn, D P

      2006-05-15

      Horses are commonly vaccinated to protect against pathogens which are responsible for diseases which are endemic within the general horse population, such as equine influenza virus (EIV) and equine herpesvirus-1 (EHV-1), and against a variety of diseases which are less common but which lead to greater morbidity and mortality, such as eastern equine encephalomyelitis virus (EEE) and tetanus. This study consisted of two trials which investigated the antigenicity of commercially available vaccines licensed in the USA to protect against EIV, EHV-1 respiratory disease, EHV-1 abortion, EEE and tetanus in horses. Trial I was conducted to compare serological responses to vaccines produced by three manufacturers against EIV, EHV-1 (respiratory disease), EEE, and tetanus given as multivalent preparations or as multiple vaccine courses. Trial II compared vaccines from two manufacturers licensed to protect against EHV-1 abortion, and measured EHV-1-specific interferon-gamma (IFN-gamma) mRNA production in addition to serological evidence of antigenicity. In Trial I significant differences were found between the antigenicity of different commercial vaccines that should be considered in product selection. It was difficult to identify vaccines that generate significant immune responses to respiratory viruses. The most dramatic differences in vaccine performance occurred in the case of the tetanus antigen. In Trial II both vaccines generated significant antibody responses and showed evidence of EHV-1-specific IFN-gamma mRNA responses. Overall there were wide variations in vaccine response, and the vaccines with the best responses were not produced by a single manufacturer. Differences in vaccine performance may have resulted from differences in antigen load and adjuvant formulation.

    10. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis

      KAUST Repository

      Zeitelhofer, Manuel

      2017-02-15

      Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo. Namely, Jak/Stat, Erk/Mapk, and Pi3K/Akt/mTor signaling pathway genes were down-regulated upon vitamin D supplementation. The protective effect associated with epigenetic mechanisms, such as (i) changed levels of enzymes involved in establishment and maintenance of epigenetic marks, i.e., DNA methylation and histone modifications; (ii) genome-wide reduction of DNA methylation, and (iii) up-regulation of noncoding RNAs, including microRNAs, with concomitant down-regulation of their protein-coding target RNAs involved in T-cell activation and differentiation. We further demonstrate that treatment of myelin-specific T cells with vitamin D reduces frequency of Th1 and Th17 cells, down-regulates genes in key signaling pathways and epigenetic machinery, and impairs their ability to transfer EAE. Finally, orthologs of nearly 50% of candidate MS risk genes and 40% of signature genes of myelin-reactive T cells in MS changed their expression in vivo in EAE upon supplementation, supporting the hypothesis that vitamin D may modulate risk for developing MS.

    11. IL17/IL17RA as a Novel Signaling Axis Driving Mesenchymal Stem Cell Therapeutic Function in Experimental Autoimmune Encephalomyelitis

      Directory of Open Access Journals (Sweden)

      Mónica Kurte

      2018-04-01

      Full Text Available The therapeutic effect of mesenchymal stem cells (MSCs in multiple sclerosis (MS and the experimental autoimmune encephalomyelitis (EAE model has been well described. This effect is, in part, mediated through the inhibition of IL17-producing cells and the generation of regulatory T cells. While proinflammatory cytokines such as IFNγ, TNFα, and IL1β have been shown to enhance MSCs immunosuppressive function, the role of IL17 remains poorly elucidated. The aim of this study was, therefore, to investigate the role of the IL17/IL17R pathway on MSCs immunoregulatory effects focusing on Th17 cell generation in vitro and on Th17-mediated EAE pathogenesis in vivo. In vitro, we showed that the immunosuppressive effect of MSCs on Th17 cell proliferation and differentiation is partially dependent on IL17RA expression. This was associated with a reduced expression level of MSCs immunosuppressive mediators such as VCAM1, ICAM1, and PD-L1 in IL17RA−/− MSCs as compared to wild-type (WT MSCs. In the EAE model, we demonstrated that while WT MSCs significantly reduced the clinical scores of the disease, IL17RA−/− MSCs injected mice exhibited a clinical worsening of the disease. The disability of IL17RA−/− MSCs to reduce the progression of the disease paralleled the inability of these cells to reduce the frequency of Th17 cells in the draining lymph node of the mice as compared to WT MSCs. Moreover, we showed that the therapeutic effect of MSCs was correlated with the generation of classical Treg bearing the CD4+CD25+Foxp3+ signature in an IL17RA-dependent manner. Our findings reveal a novel role of IL17RA on MSCs immunosuppressive and therapeutic potential in EAE and suggest that the modulation of IL17RA in MSCs could represent a novel method to enhance their therapeutic effect in MS.

    12. Infection dynamics of western equine encephalomyelitis virus (Togaviridae: Alphavirus) in four strains of Culex tarsalis (Diptera: Culicidae): an immunocytochemical study.

      Science.gov (United States)

      Oviedo, Marco V Neira; Romoser, William S; James, Calvin Bl; Mahmood, Farida; Reisen, William K

      2011-04-18

      BACKGROUND: Vector competence describes the efficiency with which vector arthropods become infected with and transmit pathogens and depends on interactions between pathogen and arthropod genetics as well as environmental factors. For arbovirus transmission, the female mosquito ingests viremic blood, the virus infects and replicates in midgut cells, escapes from the midgut, and disseminates to other tissues, including the salivary glands. Virus-laden saliva is then injected into a new host. For transmission to occur, the virus must overcome several "barriers", including barriers to midgut infection and/or escape and salivary infection and/or escape. By examining the spatial/temporal infection dynamics of Culex tarsalis strains infected with western equine encephalomyelitis virus (WEEV), we identified tissue tropisms and potential tissue barriers, and evaluated the effects of viral dose and time postingestion. METHODS: Using immunostained paraffin sections, WEEV antigens were tracked in four Cx. tarsalis strains: two recently colonized California field strains - Coachella Valley, Riverside County (COAV) and Kern National Wildlife Refuge (KNWR); and two laboratory strains selected for WEEV susceptibility (high viremia producer, HVP), and WEEV resistance (WR). RESULTS AND CONCLUSIONS: Tissues susceptible to WEEV infection included midgut epithelium, neural ganglia, trachea, chorionated eggs, and salivary glands. Neuroendocrine cells in the retrocerebral complex were occasionally infected, indicating the potential for behavioral effects. The HVP and COAV strains vigorously supported viral growth, whereas the WR and KNWR strains were less competent. Consistent with earlier studies, WEEV resistance appeared to be related to a dose-dependent midgut infection barrier, and a midgut escape barrier. The midgut escape barrier was not dependent upon the ingested viral dose. Consistent with midgut infection modulation, disseminated infections were less common in the WR and KNWR

    13. Functional genomics analysis of vitamin D effects on CD4+ T cells in vivo in experimental autoimmune encephalomyelitis

      KAUST Repository

      Zeitelhofer, Manuel; Adzemovic, Milena Z.; Gomez-Cabrero, David; Bergman, Petra; Hochmeister, Sonja; N'diaye, Marie; Paulson, Atul; Ruhrmann, Sabrina; Almgren, Malin; Tegner, Jesper; Ekströ m, Tomas J.; Guerreiro-Cacais, André Ortlieb; Jagodic, Maja

      2017-01-01

      Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo. Namely, Jak/Stat, Erk/Mapk, and Pi3K/Akt/mTor signaling pathway genes were down-regulated upon vitamin D supplementation. The protective effect associated with epigenetic mechanisms, such as (i) changed levels of enzymes involved in establishment and maintenance of epigenetic marks, i.e., DNA methylation and histone modifications; (ii) genome-wide reduction of DNA methylation, and (iii) up-regulation of noncoding RNAs, including microRNAs, with concomitant down-regulation of their protein-coding target RNAs involved in T-cell activation and differentiation. We further demonstrate that treatment of myelin-specific T cells with vitamin D reduces frequency of Th1 and Th17 cells, down-regulates genes in key signaling pathways and epigenetic machinery, and impairs their ability to transfer EAE. Finally, orthologs of nearly 50% of candidate MS risk genes and 40% of signature genes of myelin-reactive T cells in MS changed their expression in vivo in EAE upon supplementation, supporting the hypothesis that vitamin D may modulate risk for developing MS.

    14. Genetic resistance in experimental autoimmune encephalomyelitis. I. Analysis of the mechanism of LeR resistance using radiation chimeras

      International Nuclear Information System (INIS)

      Pelfrey, C.M.; Waxman, F.J.; Whitacre, C.C.

      1989-01-01

      Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease of the central nervous system that has been extensively studied in the rat. The Lewis rat is highly susceptible to the induction of EAE, while the Lewis resistant (LeR) rat is known to be resistant. In this paper, we demonstrate that the LeR rat, which was derived from the Lewis strain by inbreeding of fully resistant animals, is histocompatible with the Lewis strain. Radiation chimeras, a tool for distinguishing between immunologic and nonimmunologic resistance mechanisms, were utilized to analyze the cellular mechanisms involved in genetic resistance to EAE. By transplanting bone marrow cells from LeR rats into irradiated Lewis recipients, Lewis rats were rendered resistant to EAE induction. Likewise, transplanting Lewis bone marrow cells into irradiated LeR recipients rendered LeR rats susceptible. Mixed lymphoid cell chimeras using bone marrow, spleen, and thymus cells in Lewis recipient rats revealed individual lymphoid cell types and cell interactions that significantly affected the incidence and severity of EAE. Our results suggest that LeR resistance is mediated by hematopoietic/immune cells, and that cells located in the spleen appear to play a critical role in the resistance/susceptibility to EAE induction. Depletion of splenic adherent cells did not change the patterns of EAE resistance. In vivo cell mixing studies suggested the presence of a suppressor cell population in the LeR spleen preparations which exerted an inhibitory effect on Lewis autoimmune responses. Thus, the mechanism of LeR resistance appears to be different from that in other EAE-resistant animals

    15. The influence of macrophage growth factors on Theiler's Murine Encephalomyelitis Virus (TMEV) infection and activation of macrophages.

      Science.gov (United States)

      Schneider, Karin M; Watson, Neva B; Minchenberg, Scott B; Massa, Paul T

      2018-02-01

      Macrophages are common targets for infection and innate immune activation by many pathogenic viruses including the neurotropic Theiler's Murine Encephalomyelitis Virus (TMEV). As both infection and innate activation of macrophages are key determinants of viral pathogenesis especially in the central nervous system (CNS), an analysis of macrophage growth factors on these events was performed. C3H mouse bone-marrow cells were differentiated in culture using either recombinant macrophage colony stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), inoculated with TMEV (BeAn) and analyzed at various times thereafter. Cytokine RNA and protein analysis, virus titers, and flow cytometry were performed to characterize virological parameters under these culture conditions. GM-CSF-differentiated macrophages showed higher levels of TMEV viral RNA and proinflammatory molecules compared to infected M-CSF-differentiated cells. Thus, GM-CSF increases both TMEV infection and TMEV-induced activation of macrophages compared to that seen with M-CSF. Moreover, while infectious viral particles decreased from a peak at 12h to undetectable levels at 48h post infection, TMEV viral RNA remained higher in GM-CSF- compared to M-CSF-differentiated macrophages in concert with increased proinflammatory gene expression. Analysis of a possible basis for these differences determined that glycolytic rates contributed to heightened virus replication and proinflammatory cytokine secretion in GM-CSF compared to M-CSF-differentiated macrophages. In conclusion, we provide evidence implicating a role for GM-CSF in promoting virus replication and proinflammatory cytokine expression in macrophages, indicating that GM-CSF may be a key factor for TMEV infection and the induction of chronic TMEV-induced immunopathogenesis in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

    16. Association of T and NK Cell Phenotype With the Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS

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      Jose Luis Rivas

      2018-05-01

      Full Text Available Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS is a pathological condition characterized by incapacitating fatigue and a combination of neurologic, immunologic, and endocrine symptoms. At present its diagnosis is based exclusively on clinical criteria. Several studies have described altered immunologic profiles; therefore, we proposed to further examine the more significant differences, particularly T and NK cell subpopulations that could be conditioned by viral infections, to discern their utility in improving the diagnosis and characterization of the patients. The study included 76 patients that fulfilled the revised Canadian Consensus Criteria (CCC 2010 for ME/CFS and 73 healthy controls, matched for age and gender. Immunophenotyping of different T cell and natural killer cell subpopulations in peripheral blood was determined by flow cytometry. ME/CFS patients showed significantly lower values of T regulatory cells (CD4+CD25++(highFOXP3+ and higher NKT-like cells (CD3+CD16+/−CD56+ than the healthy individuals. Regarding NK phenotypes, NKG2C was significantly lower and NKCD69 and NKCD56 bright were significantly higher in the patients group. A classification model was generated using the more relevant cell phenotype differences (NKG2C and T regulatory cells that was able to classify the individuals as ME/CFS patients or healthy in a 70% of cases. The observed differences in some of the subpopulations of T and NK cells between patients and healthy controls could define a distinct immunological profile that can help in the diagnostic process of ME/CFS patients, contribute to the recognition of the disease and to the search of more specific treatments. However, more studies are needed to corroborate these findings and to contribute to establish a consensus in diagnosis.

    17. Lipocalin 2 is a novel immune mediator of experimental autoimmune encephalomyelitis pathogenesis and is modulated in multiple sclerosis.

      Science.gov (United States)

      Berard, Jennifer L; Zarruk, Juan G; Arbour, Nathalie; Prat, Alexandre; Yong, V Wee; Jacques, Francois H; Akira, Shizuo; David, Samuel

      2012-07-01

      Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of multiple sclerosis (MS), an inflammatory, demyelinating disease of the central nervous system (CNS). EAE pathogenesis involves various cell types, cytokines, chemokines, and adhesion molecules. Given the complexity of the inflammatory response in EAE, it is likely that many immune mediators still remain to be discovered. To identify novel immune mediators of EAE pathogenesis, we performed an Affymetrix gene array screen on the spinal cords of mice at the onset stage of disease. This screening identified the gene encoding lipocalin 2 (Lcn2) as being significantly upregulated. Lcn2 is a multi-functional protein that plays a role in glial activation, matrix metalloproteinase (MMP) stabilization, and cellular iron flux. As many of these processes have been implicated in EAE, we characterized the expression and role of Lcn2 in this disease in C57BL/6 mice. We show that Lcn2 is significantly upregulated in the spinal cord throughout EAE and is expressed predominantly by monocytes and reactive astrocytes. The Lcn2 receptor, 24p3R, is also expressed on monocytes, macrophages/microglia, and astrocytes in EAE. In addition, we show that EAE severity is increased in Lcn2(-/-) mice as compared with wild-type controls. Finally, we demonstrate that elevated levels of Lcn2 are detected in the plasma and cerebrospinal fluid (CSF) in MS and in immune cells in CNS lesions in MS tissue sections. These data indicate that Lcn2 is a modulator of EAE pathogenesis and suggest that it may also play a role in MS. Copyright © 2012 Wiley Periodicals, Inc.

    18. Human periodontal ligament stem cells secretome from multiple sclerosis patients suppresses NALP3 inflammasome activation in experimental autoimmune encephalomyelitis

      Science.gov (United States)

      Soundara Rajan, Thangavelu; Giacoppo, Sabrina; Diomede, Francesca; Bramanti, Placido; Trubiani, Oriana; Mazzon, Emanuela

      2017-01-01

      Research in recent years has largely explored the immunomodulatory effects of mesenchymal stem cells (MSCs) and their secretory products, called “secretome,” in the treatment of neuroinflammatory diseases. Here, we examined whether such immunosuppressive effects might be elicited due to inflammasome inactivation. To this end, we treated experimental autoimmune encephalomyelitis (EAE) mice model of multiple sclerosis (MS) with the conditioned medium or purified exosomes/microvesicles (EMVs) obtained from relapsing-remitting-MS patients human periodontal ligament stem cells (hPDLSCs) and investigated the regulation of NALP3 inflammasome. We noticed enhanced expression of NALP3, Cleaved Caspase 1, interleukin (IL)-1β, and IL-18 in EAE mouse spinal cord. Conversely, hPDLSCs-conditioned medium and EMVs significantly blocked NALP3 inflammasome activation and provided protection from EAE. Reduction in NALP3, Cleaved Caspase 1, IL-1β, and IL-18 level was noticed in conditioned medium and EMVs-treated EAE mice. Pro-inflammatory Toll-like receptor (TLR)-4 and nuclear factor (NF)-κB were elevated in EAE, while hPDLSCs-conditioned medium and EMVs treatment reduced their expression and increased IκB-α expression. Characterization of hPDLSCs-conditioned medium showed substantial level of anti-inflammatory IL-10, transforming growth factor (TGF)-β, and stromal cell–derived factor 1α (SDF-1α). We propose that the immunosuppressive role of hPDLSCs-derived conditioned medium and EMVs in EAE mice may partly attribute to the presence of soluble immunomodulatory factors, NALP3 inflammasome inactivation, and NF-κB reduction. PMID:28764573

    19. Huperzine A ameliorates experimental autoimmune encephalomyelitis via the suppression of T cell-mediated neuronal inflammation in mice.

      Science.gov (United States)

      Wang, Jun; Chen, Fu; Zheng, Peng; Deng, Weijuan; Yuan, Jia; Peng, Bo; Wang, Ruochen; Liu, Wenjun; Zhao, Hui; Wang, Yanqing; Wu, Gencheng

      2012-07-01

      Huperzine A (HupA), a sesquiterpene alkaloid and a potent and reversible inhibitor of acetylcholinesterase, possesses potential anti-inflammatory properties and is used for the treatment of certain neurodegenerative diseases such as Alzheimer's disease. However, it is still unknown whether this chemical is beneficial in the treatment of multiple sclerosis, a progressive inflammatory disease of the central nervous system. In this study, we examined the immunomodulatory properties of HupA in experimental autoimmune encephalomyelitis (EAE), a T-cell mediated murine model of multiple sclerosis. The following results were obtained: (1) intraperitoneal injections of HupA significantly attenuate the neurological severity of EAE in mice. (2) HupA decreases the accumulation of inflammatory cells, autoimmune-related demyelination and axonal injury in the spinal cords of EAE mice. (3) HupA down-regulates mRNA levels of the pro-inflammatory cytokines (IFN-γ and IL-17) and chemokines (MCP-1, RANTES, and TWEAK) while enhancing levels of anti-inflammatory cytokines (IL-4 and IL-10) in the spinal cords of EAE mice. (4) HupA inhibits MOG(35-55) stimulation-induced T-cell proliferation and IFN-γ and IL-17 secretion in cultured splenocytes. (5) HupA inhibition of T-cell proliferation is reversed by the nicotinic acetylcholinergic receptor antagonist mecamylamine. We conclude that HupA can ameliorate EAE by suppressing autoimmune responses, inflammatory reactions, subsequent demyelination and axonal injury in the spinal cord. Therefore, HupA may have a potential therapeutic value for the treatment of multiple sclerosis and as a neuroimmunomodulatory drug to control human CNS pathology. Copyright © 2012 Elsevier Inc. All rights reserved.

    20. Myelin/oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis in common marmosets : the encephalitogenic T cell epitope pMOG24-36 is presented by a monomorphic MHC class II molecule

      NARCIS (Netherlands)

      Brok, H.P.M.; Uccelli, A.; Kerlero De Rosbo, N.; Bontrop, R.E.; Roccatagliata, L.; Groot, de N.G.; Capello, E.; Laman, J.D.; Nicolay, K.; Mancardi, G.L.; Ben-Nun, A.; Hart, 't L.A.

      2000-01-01

      Immunization of common marmosets (Callithrix jacchus) with a single dose of human myelin in CFA, without administration of Bordetella pertussis, induces a form of autoimmune encephalomyelitis (EAE) resembling in its clinical and pathological expression multiple sclerosis in humans. The EAE incidence

    1. Heterogeneous stock mice are susceptible to encephalomyelitis and antibody-initiated arthritis but not to collagen- and G6PI-induced arthritis.

      Science.gov (United States)

      Klaczkowska, D; Raposo, B; Nandakumar, K S

      2011-01-01

      The strategy of using heterogeneous stock (HS) mice has proven to be successful in fine mapping of quantitative trait loci in complex diseases. However, whether these mice can be used for arthritis, encephalomyelitis and autoimmune phenotypes has not been addressed. Here, we screened the Northport HS mice for arthritis phenotypes using three different models: collagen-induced arthritis (CIA), using rat, bovine or chicken collagen type II (CII); recombinant human glucose-6-phosphate isomerase (G6PI)-induced arthritis; and collagen antibody-induced arthritis (CAIA). Irrespective of the origin of collagen, we found HS mice to be fairly resistant to CIA and G6PI-induced arthritis, despite the development of antibodies against the respective antigens. On the other hand, HS mice were found to be susceptible for CAIA. Similarly, these mice developed encephalomyelitis (EAE) induced either with mouse or rat spinal cord homogenate (SCH), or with recombinant rat myelin oligodendrocyte glycoprotein, with elevated antibody levels against CNS proteins. Accordingly, we conclude that the use of HS mice for fine mapping and positional cloning of gene(s) involved in CAIA and EAE is possible, but not for collagen- and G6PI-induced arthritis. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

    2. Analysis of viral protein-2 encoding gene of avian encephalomyelitis virus from field specimens in Central Java region, Indonesia

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      Aris Haryanto

      2016-01-01

      Full Text Available Aim: Avian encephalomyelitis (AE is a viral disease which can infect various types of poultry, especially chicken. In Indonesia, the incidence of AE infection in chicken has been reported since 2009, the AE incidence tends to increase from year to year. The objective of this study was to analyze viral protein 2 (VP-2 encoding gene of AE virus (AEV from various species of birds in field specimen by reverse transcription polymerase chain reaction (RT-PCR amplification using specific nucleotides primer for confirmation of AE diagnosis. Materials and Methods: A total of 13 AEV samples are isolated from various species of poultry which are serologically diagnosed infected by AEV from some areas in central Java, Indonesia. Research stage consists of virus samples collection from field specimens, extraction of AEV RNA, amplification of VP-2 protein encoding gene by RT-PCR, separation of RT-PCR product by agarose gel electrophoresis, DNA sequencing and data analysis. Results: Amplification products of the VP-2 encoding gene of AEV by RT-PCR methods of various types of poultry from field specimens showed a positive results on sample code 499/4/12 which generated DNA fragment in the size of 619 bp. Sensitivity test of RT-PCR amplification showed that the minimum concentration of RNA template is 127.75 ng/μl. The multiple alignments of DNA sequencing product indicated that positive sample with code 499/4/12 has 92% nucleotide homology compared with AEV with accession number AV1775/07 and 85% nucleotide homology with accession number ZCHP2/0912695 from Genbank database. Analysis of VP-2 gene sequence showed that it found 46 nucleotides difference between isolate 499/4/12 compared with accession number AV1775/07 and 93 nucleotides different with accession number ZCHP2/0912695. Conclusions: Analyses of the VP-2 encoding gene of AEV with RT-PCR method from 13 samples from field specimen generated the DNA fragment in the size of 619 bp from one sample with

    3. Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway.

      Science.gov (United States)

      Bakken, Inger J; Tveito, Kari; Aaberg, Kari M; Ghaderi, Sara; Gunnes, Nina; Trogstad, Lill; Magnus, Per; Stoltenberg, Camilla; Håberg, Siri E

      2016-09-02

      Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex condition. Causal factors are not established, although underlying psychological or immunological susceptibility has been proposed. We studied primary care diagnoses for children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups. All Norwegian children born 1992-2012 constituted the study sample. Children with CFS/ME (n = 1670) or T1DM (n = 4937) were identified in the Norwegian Patient Register (NPR) (2008-2014). Children without either diagnosis constituted the general child population comparison group (n = 1337508). We obtained information on primary care diagnoses from the Norwegian Directorate of Health. For each primary care diagnosis, the proportion and 99 % confidence interval (CI) within the three groups was calculated, adjusted for sex and age by direct standardization. Children with CFS/ME were more often registered with a primary care diagnosis of weakness/general tiredness (89.9 % [99 % CI 88.0 to 91.8 %]) than children in either comparison group (T1DM: 14.5 % [99 % CI: 13.1 to 16.0 %], general child population: 11.1 % [99 % CI: 11.0 to 11.2 %]). Also, depressive disorder and anxiety disorder were more common in the CFS/ME group, as were migraine, muscle pain, and infections. In the 2 year period prior to the diagnoses, infectious mononucleosis was registered for 11.1 % (99 % CI 9.1 to 13.1 %) of children with CFS/ME and for 0.5 % (99 % CI (0.2 to 0.8 %) of children with T1DM. Of children with CFS/ME, 74.6 % (1292/1670) were registered with a prior primary care diagnosis of weakness / general tiredness. The time span from the first primary care diagnosis of weakness / general tiredness to the specialist health care diagnosis of CFS/ME was 1 year or longer for 47.8 %. This large nationwide registry linkage study confirms that the clinical picture in CFS

    4. Bee Venom Acupuncture Alleviates Experimental Autoimmune Encephalomyelitis by Upregulating Regulatory T Cells and Suppressing Th1 and Th17 Responses.

      Science.gov (United States)

      Lee, Min Jung; Jang, Minhee; Choi, Jonghee; Lee, Gihyun; Min, Hyun Jung; Chung, Won-Seok; Kim, Jong-In; Jee, Youngheun; Chae, Younbyoung; Kim, Sung-Hoon; Lee, Sung Joong; Cho, Ik-Hyun

      2016-04-01

      The protective and therapeutic mechanism of bee venom acupuncture (BVA) in neurodegenerative disorders is not clear. We investigated whether treatment with BVA (0.25 and 0.8 mg/kg) at the Zusanli (ST36) acupoints, located lateral from the anterior border of the tibia, has a beneficial effect in a myelin basic protein (MBP)(68-82)-induced acute experimental autoimmune encephalomyelitis (EAE) rat model. Pretreatment (every 3 days from 1 h before immunization) with BVA was more effective than posttreatment (daily after immunization) with BVA with respect to clinical signs (neurological impairment and loss of body weight) of acute EAE rats. Treatment with BVA at the ST36 acupoint in normal rats did not induce the clinical signs. Pretreatment with BVA suppressed demyelination, glial activation, expression of cytokines [interferon (IFN)-γ, IL-17, IL-17A, tumor necrosis factor-alpha (TNF-α), and IL-1β], chemokines [RANTES, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1α], and inducible nitric oxide synthase (iNOS), and activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB (p65 and phospho-IκBα) signaling pathways in the spinal cord of acute EAE rats. Pretreatment with BVA decreased the number of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells, but increased the number of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of acute EAE rats. Treatment with BVA at six placebo acupoints (SP9, GB39, and four non-acupoints) did not have a positive effect in acute EAE rats. Interestingly, onset and posttreatment with BVA at the ST36 acupoint markedly attenuated neurological impairment in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE mice compared to treatment with BVA at six placebo acupoints. Our findings strongly suggest that treatment with BVA with ST36 acupoint could delay or attenuate the development and progression of EAE by upregulating regulatory T cells and

    5. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME in adults: a qualitative study of perspectives from professional practice

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      Campion Peter D

      2010-11-01

      Full Text Available Abstract Background Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME can cause profound and prolonged illness and disability, and poses significant problems of uncertainty for healthcare professionals in its diagnosis and management. The aim of this qualitative study was to explore the nature of professional 'best practice' in working with people with CFS/ME. Methods The views and experiences of health care practitioners (HCPs were sought, who had been judged by people with CFS/ME themselves to have been particularly helpful and effective. Qualitative semi-structured interviews following a topic guide were carried out with six health care practitioners. Interviews were audio-recorded, transcribed and subject to thematic analysis. Results Five main themes were developed: 1 Diagnosis; 2 Professional perspectives on living with CFS/ME; 3 Interventions for treatment and management; 4 Professional values and support for people with CFS/ME and their families; 5 Health professional roles and working practices. Key findings related to: the diagnostic process, especially the degree of uncertainty which may be shared by primary care physicians and patients alike; the continued denial in some quarters of the existence of CFS/ME as a condition; the variability, complexity, and serious impact of the condition on life and living; the onus on the person with CFS/ME to manage their condition, supported by HCPs; the wealth of often conflicting and confusing information on the condition and options for treatment; and the vital role of extended listening and trustful relationships with patients. Conclusions While professional frustrations were clearly expressed about the variability of services both in primary and specialist care and continuing equivocal attitudes to CFS/ME as a condition, there were also strong positive messages for people with CFS/ME where the right services are in place. Many of the findings from these practitioners seen by their

    6. Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS.

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      Sanjay K Shukla

      Full Text Available Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation. To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005. There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there

    7. The Health-Related Quality of Life for Patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS.

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      Michael Falk Hvidberg

      Full Text Available Myalgic encephalomyelitis (ME/chronic fatigue syndrome (CFS is a common, severe condition affecting 0.2 to 0.4 per cent of the population. Even so, no recent international EQ-5D based health-related quality of life (HRQoL estimates exist for ME/CFS patients. The main purpose of this study was to estimate HRQoL scores using the EQ-5D-3L with Danish time trade-off tariffs. Secondary, the aims were to explore whether the results are not influenced by other conditions using regression, to compare the estimates to 20 other conditions and finally to present ME/CFS patient characteristics for use in clinical practice.All members of the Danish ME/CFS Patient Association in 2013 (n=319 were asked to fill out a questionnaire including the EQ-5D-3L. From these, 105 ME/CFS patients were identified and gave valid responses. Unadjusted EQ-5D-3L means were calculated and compared to the population mean as well as to the mean of 20 other conditions. Furthermore, adjusted estimates were calculated using ordinary least squares (OLS regression, adjusting for gender, age, education, and co-morbidity of 18 self-reported conditions. Data from the North Denmark Health Profile 2010 was used as population reference in the regression analysis (n=23,392.The unadjusted EQ-5D-3L mean of ME/CFS was 0.47 [0.41-0.53] compared to a population mean of 0.85 [0.84-0.86]. The OLS regression estimated a disutility of -0.29 [-0.21;-0.34] for ME/CFS patients in this study. The characteristics of ME/CFS patients are different from the population with respect to gender, relationship, employment etc.The EQ-5D-3L-based HRQoL of ME/CFS is significantly lower than the population mean and the lowest of all the compared conditions. The adjusted analysis confirms that poor HRQoL of ME/CFS is distinctly different from and not a proxy of the other included conditions. However, further studies are needed to exclude the possible selection bias of the current study.

    8. Moringin activates Wnt canonical pathway by inhibiting GSK3β in a mouse model of experimental autoimmune encephalomyelitis

      Directory of Open Access Journals (Sweden)

      Giacoppo S

      2016-10-01

      Full Text Available Sabrina Giacoppo,1 Thangavelu Soundara Rajan,1 Gina Rosalinda De Nicola,2 Renato Iori,2 Placido Bramanti,1 Emanuela Mazzon1 1IRCCS Centre Neurolesi “Bonino-Pulejo”, Messina, Italy; 2Council for Agricultural Research and Economics, Research Centre for Industrial Crops (CREA-CIN, Bologna, Italy Abstract: Aberrant canonical Wnt–β-catenin signaling has been reported in multiple sclerosis (MS, although the results are controversial. The present study aimed to examine the role of the Wnt–β-catenin pathway in experimental MS and also to test moringin (4-[α-L-rhamnopyranosyloxy]-benzyl isothiocyanate, resulting from exogenous myrosinase hydrolysis of the natural phytochemical glucomoringin 4(α-L-rhamnosyloxy-benzyl glucosinolate as a modulator of neuroinflammation via the β-catenin–PPARγ axis. Experimental autoimmune encephalomyelitis (EAE, the most common model of MS, was induced in C57BL/6 mice by immunization with MOG35–55. Released moringin (10 mg/kg glucomoringin +5 µL myrosinase/mouse was administered daily for 1 week before EAE induction and continued until mice were killed on day 28 after EAE induction. Our results clearly showed that the Wnt–β-catenin pathway was downregulated in the EAE model, whereas moringin pretreatment was able to avert this. Moringin pretreatment normalizes the aberrant Wnt–β-catenin pathway, resulting in GSK3β inhibition and β-catenin upregulation, which regulates T-cell activation (CD4 and FoxP3, suppresses the main inflammatory mediators (IL-1β, IL-6, and COX2, through activation of PPARγ. In addition, moringin attenuates apoptosis by reducing the expression of the Fas ligand and cleaved caspase 9, and in parallel increases antioxidant Nrf2 expression in EAE mice. Taken together, our results provide an interesting discovery in identifying moringin as a modulator of the Wnt–β-catenin signaling cascade and as a new potential therapeutic target for MS treatment. Keywords: Wnt

    9. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing--remitting experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Rasmussen, Stine; Wang, Yue; Kivisäkk, Pia

      2007-01-01

      callosal projecting neurons. There was significant impairment of retrograde labeling of NeuN-positive callosal projecting neurons and reduction in the labelling of their transcallosal axons. These data demonstrate a novel paradigm of cortical and callosal neuropathology in a mouse model of MS, perpetuated......Cortical pathology, callosal atrophy and axonal loss are substrates of progression in multiple sclerosis (MS). Here we describe cortical, periventricular subcortical lesions and callosal demyelination in relapsing-remitting experimental autoimmune encephalomyelitis in SJL mice that are similar...... to lesions found in MS. Unlike the T-cell infiltrates that peak during acute disease, we found that microglia activation persists through the chronic disease phase. Microglia activation correlated with abnormal phosphorylation of neurofilaments in the cortex and stripping of synaptic proteins in cortical...

    10. Enhanced response to antigen within lymph nodes of SJL/J mice that were protected against experimental allergic encephalomyelitis by T cell vaccination

      DEFF Research Database (Denmark)

      Zeine, R; Heath, D; Owens, T

      1993-01-01

      The effects of T cell vaccination on peripheral immune responsiveness are not yet fully understood. We have induced resistance to rat spinal cord homogenate (RSCH)-induced experimental allergic encephalomyelitis (EAE) in SJL/J mice by vaccination with four T cell lines (RZ8, RZ15, RZ16, and A51......) which were reactive to myelin basic protein (MBP) but not to proteolipid protein (PLP). The effect was relatively neuroantigen-specific since vaccination with ovalbumin (OVA)-reactive and alloantigen-specific cells did not prevent EAE induction. Alloantigen-reactive cells reduced the rate of relapse....... The number of central nervous system (CNS) infiltrates and mean clinical EAE scores were significantly reduced. This is the first report demonstrating T cell vaccination in the SJL/J mouse, a strain in which PLP is the predominant encephalitogen in RSCH. The vaccinating cells were of the memory/effector (CD...

    11. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Vowinckel, E; Reutens, D; Becher, B

      1997-01-01

      Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We...... examined the utility of using in vitro and in vivo ligand binding to the PBR as a measure of lesion activity in autoimmune CNS demyelinating diseases. Applying a combined autoradiography and immunohistochemical approach to spinal cord and brain tissues from mice with EAE, we found a correlation at sites...... of inflammatory lesions between [3H]-PK11195 binding and immunoreactivity for the activated microglial/macrophage marker Mac-1/CD11b. In MS tissues, [3H]-PK11195 binding correlated with sites of immunoreactivity for the microglial/macrophage marker CD68, at the edges of chronic active plaques. Positron emission...

    12. Simultaneous presentation of acute disseminated encephalomyelitis (ADEM) and systemic lupus erythematosus (SLE) after enteroviral infection: can ADEM present as the first manifestation of SLE?

      Science.gov (United States)

      Kim, J-M; Son, C-N; Chang, H W; Kim, S-H

      2015-05-01

      Central Nervous System (CNS) involvement of Systemic Lupus Erythematosus (SLE) includes a broad range of neuropsychiatric syndromes. Acute Disseminated Encephalomyelitis (ADEM) is a demyelinating CNS disorder characterized by encephalopathy and multifocal lesions predominantly involving the white matter on brain magnetic resonance imaging. ADEM associated with SLE has been only rarely reported. We report an unusual case of a 17-year-old girl who developed ADEM after enteroviral infection as the first manifestation of SLE. The authors emphasize that the patient's illness was preceded by enteroviral infection and that ADEM occurred before any other symptoms of SLE, which makes this case unique. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

    13. IL-4/IL-13 Heteroreceptor Influences Th17 Cell Conversion and Sensitivity to Regulatory T Cell Suppression To Restrain Experimental Allergic Encephalomyelitis.

      Science.gov (United States)

      Barik, Subhasis; Ellis, Jason S; Cascio, Jason A; Miller, Mindy M; Ukah, Tobechukwu K; Cattin-Roy, Alexis N; Zaghouani, Habib

      2017-10-01

      IL-4 and IL-13 have been defined as anti-inflammatory cytokines that can counter myelin-reactive T cells and modulate experimental allergic encephalomyelitis. However, it is not known whether endogenous IL-4 and IL-13 contribute to the maintenance of peripheral tolerance and whether their function is coordinated with T regulatory cells (Tregs). In this study, we used mice in which the common cytokine receptor for IL-4 and IL-13, namely the IL-4Rα/IL-13Rα1 (13R) heteroreceptor (HR), is compromised and determined whether the lack of signaling by endogenous IL-4 and IL-13 through the HR influences the function of effector Th1 and Th17 cells in a Treg-dependent fashion. The findings indicate that mice-deficient for the HR (13R -/- ) are more susceptible to experimental allergic encephalomyelitis than mice sufficient for the HR (13R +/+ ) and develop early onset and more severe disease. Moreover, Th17 cells from 13R -/- mice had reduced ability to convert to Th1 cells and displayed reduced sensitivity to suppression by Tregs relative to Th17 effectors from 13R +/+ mice. These observations suggest that IL-4 and IL-13 likely operate through the HR and influence Th17 cells to convert to Th1 cells and to acquire increased sensitivity to suppression, leading to control of immune-mediated CNS inflammation. These previously unrecognized findings shed light on the intricacies underlying the contribution of cytokines to peripheral tolerance and control of autoimmunity. Copyright © 2017 by The American Association of Immunologists, Inc.

    14. Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM): Design and Implementation of a Prospective/Retrospective Rolling Cohort Study.

      Science.gov (United States)

      Unger, Elizabeth R; Lin, Jin-Mann S; Tian, Hao; Natelson, Benjamin H; Lange, Gudrun; Vu, Diana; Blate, Michelle; Klimas, Nancy G; Balbin, Elizabeth G; Bateman, Lucinda; Allen, Ali; Lapp, Charles W; Springs, Wendy; Kogelnik, Andreas M; Phan, Catrina C; Danver, Joan; Podell, Richard N; Fitzpatrick, Trisha; Peterson, Daniel L; Gottschalk, C Gunnar; Rajeevan, Mangalathu S

      2017-04-15

      In the Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM), we relied on expert clinician diagnoses to enroll patients from 7 specialty clinics in the United States in order to perform a systematic collection of data on measures of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Healthy persons and those with other illnesses that share some features with ME/CFS were enrolled in comparison groups. The major objectives were to: 1) use standardized questionnaires to measure illness domains of ME/CFS and to evaluate patient heterogeneity overall and between clinics; 2) describe the course of illness, identify the measures that best correlate with meaningful clinical differences, and assess the performances of questionnaires as patient/person-reported outcome measures; 3) describe prescribed medications, orders for laboratory and other tests, and management tools used by expert clinicians to care for persons with ME/CFS; 4) collect biospecimens for future hypothesis testing and for evaluation of morning cortisol profiles; and 5) identify measures that best distinguish persons with ME/CFS from those in the comparison groups and detect subgroups of persons with ME/CFS who may have different underlying causes. Enrollment began in 2012 and is planned to continue in multiple stages through 2017. We present the MCAM methods in detail, along with an initial description of the 471 patients with ME/CFS who were enrolled in stage 1. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

    15. Progressive Encephalomyelitis with Rigidity and Myoclonus Associated With Anti-GlyR Antibodies and Hodgkin’s Lymphoma: A Case Report

      Directory of Open Access Journals (Sweden)

      Linda Borellini

      2017-08-01

      Full Text Available IntroductionA 60-year-old man presented with a 6-month history of low back pain and progressive rigidity of the trunk and lower limbs, followed by pruritus, dysphonia, hyperhydrosis, and urinary retention. Brain and spinal imaging were normal. EMG showed involuntary motor unit hyperactivity. Onconeural, antiglutamic acid decarboxylase (anti-GAD, voltage-gated potassium channel, and dipeptidyl peptidase-like protein 6 (DPPX autoantibodies were negative. CSF was negative. Symptoms were partially responsive to baclofen, gabapentin, and clonazepam, but he eventually developed severe dysphagia. Antiglycine receptor (anti-GlyR antibodies turned out positive on both serum and CSF. A plasmapheresis cycle was completed with good clinical response. A PET scan highlighted an isolated metabolically active axillary lymphnode that turned out to be a classic type Hodgkin lymphoma (HL, in the absence of bone marrow infiltration nor B symptoms. Polychemotherapy with ABVD protocol was completed with good clinical response and at 1-year follow-up the neurological examination is normal.BackgroundProgressive encephalomyelitis with rigidity and myoclonus (PERM is a rare and severe neurological syndrome characterized by muscular rigidity and spasms as well as brain stem and autonomic dysfunction. It can be associated with anti-GAD, GlyR, and DPPX antibodies. All of these autoantibodies may be variably associated with malignant tumors and their response to immunotherapy, as well as to tumor removal, is not easily predictable.ConclusionProgressive encephalomyelitis with rigidity and myoclonus has already been described in association with HL, but this is the first case report of a HL manifesting as anti-GlyR antibodies related PERM. Our report highlights the importance of malignancy screening in autoimmune syndromes of suspected paraneoplastic origin.

    16. A SELDI mass spectrometry study of experimental autoimmune encephalomyelitis: sample preparation, reproducibility, and differential protein expression patterns.

      Science.gov (United States)

      Azzam, Sausan; Broadwater, Laurie; Li, Shuo; Freeman, Ernest J; McDonough, Jennifer; Gregory, Roger B

      2013-05-01

      Experimental autoimmune encephalomyelitis (EAE) is an autoimmune, inflammatory disease of the central nervous system that is widely used as a model of multiple sclerosis (MS). Mitochondrial dysfunction appears to play a role in the development of neuropathology in MS and may also play a role in disease pathology in EAE. Here, surface enhanced laser desorption ionization mass spectrometry (SELDI-MS) has been employed to obtain protein expression profiles from mitochondrially enriched fractions derived from EAE and control mouse brain. To gain insight into experimental variation, the reproducibility of sub-cellular fractionation, anion exchange fractionation as well as spot-to-spot and chip-to-chip variation using pooled samples from brain tissue was examined. Variability of SELDI mass spectral peak intensities indicates a coefficient of variation (CV) of 15.6% and 17.6% between spots on a given chip and between different chips, respectively. Thinly slicing tissue prior to homogenization with a rotor homogenizer showed better reproducibility (CV = 17.0%) than homogenization of blocks of brain tissue with a Teflon® pestle (CV = 27.0%). Fractionation of proteins with anion exchange beads prior to SELDI-MS analysis gave overall CV values from 16.1% to 18.6%. SELDI mass spectra of mitochondrial fractions obtained from brain tissue from EAE mice and controls displayed 39 differentially expressed proteins (p≤ 0.05) out of a total of 241 protein peaks observed in anion exchange fractions. Hierarchical clustering analysis showed that protein fractions from EAE animals with severe disability clearly segregated from controls. Several components of electron transport chain complexes (cytochrome c oxidase subunit 6b1, subunit 6C, and subunit 4; NADH dehydrogenase flavoprotein 3, alpha subcomplex subunit 2, Fe-S protein 4, and Fe-S protein 6; and ATP synthase subunit e) were identified as possible differentially expressed proteins. Myelin Basic Protein isoform 8 (MBP8) (14.2 k

    17. Thyroid Malignancy Association with Cortical and Subcortical Brain SPECT Changes In Patients Presenting with a Myalgic Encephalomyelitis / Chronic Fatigue Syndrome

      International Nuclear Information System (INIS)

      Hyde, Byron; Leveille, Jean; Vaudrey, Sheila; Green, Tracy

      2007-01-01

      Thyroid malignancy in ME/CFS patients greatly exceeds the normal incidence of thyroid malignancy in any known subgroup. The thyroid malignancy incidence in the ME/CFS group may exceed 6,000 / 100,000. As part of their investigation, Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) patients should be examined by thyroid ultrasound for evidence of thyroid pathology and malignancy. Thyroid pathology may be missed in this group of patients if investigation relies only upon serum testing for TSH, FT3, FT4, microsomal and thyroglobulin antibodies, which are usually normal. Thyroid uptake scans tend also to be normal and may also miss malignant lesions. A newly recognized syndrome may exist in ME/CFS patients characterized by: (a) thyroid malignancy, (b) persistent abnormal cortical and subcortical SPECT brain scans (NeuroSPECT), (c) failure of thyroidectomy surgery and hormone replacement to correct the fatigue syndrome, and (d) an unusual high incidence of cervical vertebrae osteoarthritic changes. ME/CFS patients with treated non-malignant thyroid disease and abnormal NeuroSPECT scans may also fail to improve despite adequate thyroid hormone replacement. A brief summary of the differences between ME and CFS is discussed. Lee, Hur and Ahn [1] stated that thyroid malignancy is said to be an infrequent occurrence found in 0.5 to 3 patients per 100,000 in the general population. They noted that in a subgroup of patients booked for mammography, a thyroid ultrasound was also performed. In this group, they found thyroid malignancy frequency was as high as 3 per 100,000. It is not known if their subgroup was at a higher risk for malignancy. Mittelstaedt [2] in the Globe and Mail states that thyroid malignancy was 15 per 100,000. In the past 100 patients whom I have investigated for (ME/CFS)[3], with or without associated Fibromyalgia Syndrome (FS), I have found that 6% of these patients had thyroid malignancy. In each of these patients the diagnosis was made by

    18. Comparing specialist medical care with specialist medical care plus the Lightning Process® for chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME): study protocol for a randomised controlled trial (SMILE Trial)

      OpenAIRE

      Crawley, Esther; Mills, Nicola; Hollingworth, Will; Deans, Zuzana; Sterne, Jonathan A; Donovan, Jenny L; Beasant, Lucy; Montgomery, Alan

      2013-01-01

      Background Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and potentially serious condition with a limited evidence base for treatment. Specialist treatment for paediatric CFS/ME uses interventions recommended by National Institute for Health and Clinical Excellence (NICE) including cognitive behavioural therapy, graded exercise therapy and activity management. The Lightning Process® (LP) is a trademarked intervention derived from osteopathy, life-coachi...

    19. Anxiety and depression in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): Examining the incidence of health anxiety in CFS/ME.

      Science.gov (United States)

      Daniels, Jo; Brigden, Amberly; Kacorova, Adela

      2017-09-01

      There is a lack of research examining the incidence of health anxiety in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), despite this being an important research area with potentially significant clinical implications. This preliminary study aimed to determine the incidence of anxiety and depression, more specifically health anxiety, in a sample of CFS/ME patients over a 3-month period. The research was a cross-sectional questionnaire-based study, using a consecutive sample of patients who were assessed in a CFS/ME service. Data were taken from the Short Health Anxiety Inventory and the Hospital Anxiety and Depression Scale to identify incidence of anxiety, depression, and health anxiety. Data were collected from 45 CFS/ME patients over the sampling period. Thirty-one patients (68.9%) scored above the normal range but within the subclinical range of health anxiety, and 19 patients (42.2%) scored within the clinically significant health anxiety range. Anxiety and depression were common, with prevalence rates of 42.2% and 33.3% respectively, which is comparable to data found in a recent large-scale trial. Health anxiety in CFS/ME patients is likely to be common and warrants further investigation to provide a better insight into how this may influence treatment and symptom management. Anxiety and depression were common in a sample of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients, with a high proportion meeting criteria for severe health anxiety. While CFS/ME and health anxiety are distinct and separate conditions, it is unsurprising that patients with CFS/ME, who commonly report feeling 'delegitimized', may experience high levels of anxiety relating to their physical symptoms. Clinicians should consider screening for health anxiety due to the possible clinical implications for treatment; mutual maintenance may negatively influence treatment success in a complex condition such as CFS/ME. Health anxiety has been found to be common

    20. Evaluation of Possible Prognostic Factors of Fulminant Acute Disseminated Encephalomyelitis (ADEM) on Magnetic Resonance Imaging with Fluid-Attenuated Inversion Recovery (FLAIR) and Diffusion-Weighted Imaging

      Energy Technology Data Exchange (ETDEWEB)

      Donmez, F.Y.; Aslan, H.; Coskun, M. (Dept. of Radiology, Faculty of Medicine, Baskent Univ., Ankara (Turkey))

      2009-04-15

      Background: Acute disseminated encephalomyelitis (ADEM) may be a rapidly progressive disease with different clinical outcomes. Purpose: To investigate the radiological findings of fulminant ADEM on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) images, and to correlate these findings with clinical outcome. Material and Methods: Initial and follow-up magnetic resonance imaging (MRI) scans in eight patients were retrospectively evaluated for distribution of lesions on FLAIR images and presence of hemorrhage or contrast enhancement. DWI of the patients was evaluated as to cytotoxic versus vasogenic edema. The clinical records were analyzed, and MRI results and clinical outcome were correlated. Results: Four of the eight patients died, three had full recovery, and one had residual cortical blindness. The distribution of the hyperintense lesions on FLAIR sequence was as follows: frontal (37.5%), parietal (50%), temporal (37.5%), occipital (62.5%), basal ganglia (50%), pons (37.5%), mesencephalon (37.5%), and cerebellum (50%). Three of the patients who died had brainstem involvement. Two patients had a cytotoxic edema, one of whom died, and the other developed cortical blindness. Six patients had vasogenic edema: three of these patients had a rapid progression to coma and died; three of them recovered. Conclusion: DWI is not always helpful for evaluating the evolution or predicting the outcome of ADEM. However, extension of the lesions, particularly brainstem involvement, may have an influence on the prognosis.

    1. BJ-1108, a 6-Amino-2,4,5-trimethylpyridin-3-ol analogue, regulates differentiation of Th1 and Th17 cells to ameliorate experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Kang, Youra; Timilshina, Maheshwor; Nam, Tae-Gyu; Jeong, Byeong-Seon; Chang, Jae-Hoon

      2017-02-28

      CD4 + T cells play an important role in the initiation of an immune response by providing help to other cells. Among the helper T subsets, interferon-γ (IFN-γ)-secreting T helper 1 (Th1) and IL-17-secreting T helper 17 (Th17) cells are indispensable for clearance of intracellular as well as extracellular pathogens. However, Th1 and Th17 cells are also associated with pathogenesis and contribute to the progression of multiple inflammatory conditions and autoimmune diseases. In the current study, we found that BJ-1108, a 6-aminopyridin-3-ol analogue, significantly inhibited Th1 and Th17 differentiation in vitro in a concentration-dependent manner, with no effect on proliferation or apoptosis of activated T cells. Moreover, BJ-1108 inhibited differentiation of Th1 and Th17 cells in ovalbumin (OVA)-specific OT II mice. A complete Freund's adjuvant (CFA)/OVA-induced inflammatory model revealed that BJ-1108 can reduce generation of proinflammatory Th1 and Th17 cells. Furthermore, in vivo studies showed that BJ-1108 delayed onset of disease and suppressed experimental autoimmune encephalomyelitis (EAE) disease progression by inhibiting differentiation of Th1 and Th17 cells. BJ-1108 treatment ameliorates inflammation and EAE by inhibiting Th1 and Th17 cells differentiation. Our findings suggest that BJ-1108 is a promising novel therapeutic agent for the treatment of inflammation and autoimmune disease.

    2. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Symptom Severity: Stress Management Skills are Related to Lower Illness Burden.

      Science.gov (United States)

      Lattie, Emily G; Antoni, Michael H; Fletcher, Mary Ann; Czaja, Sara; Perdomo, Dolores; Sala, Andreina; Nair, Sankaran; Fu, Shih Hua; Penedo, Frank J; Klimas, Nancy

      2013-01-01

      The onset of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) typically involves reductions in activities of daily living and social interactions (jointly referred to as "illness burden"). Emotional distress has been linked to increased reported symptoms, and stress management skills have been related to lower fatigue severity in CFS patients. Symptom severity and illness burden are highly correlated. The ability to manage stress may attenuate this relationship, allowing individuals to feel less burdened by the illness independent of the severity of their symptoms. This study aimed to evaluate if perceived stress management skills affect illness burden via emotional distress, independent of ME/CFS symptom severity. A total of 117 adults with ME/CFS completed measures of perceived stress management skills, emotional distress, ME/CFS symptom severity and illness burden. Regression analyses revealed that greater perceived stress management skills related to less social and fatigue-related illness burden, via lower emotional distress. This relationship existed independent of the association of symptom severity on illness burden, and was stronger among those not currently employed. Ability to manage stress is associated with a lower illness burden for individuals with ME/CFS. Future studies should evaluate the efficacy of psychosocial interventions in lowering illness burden by targeting stress management skills.

    3. Extensive vascular remodeling in the spinal cord of pre-symptomatic experimental autoimmune encephalomyelitis mice; increased vessel expression of fibronectin and the α5β1 integrin

      Science.gov (United States)

      Boroujerdi, Amin; Welser-Alves, Jennifer V.; Milner, Richard

      2013-01-01

      Alterations in vascular structure and function are a central component of demyelinating disease. In addition to blood-brain barrier (BBB) breakdown, which occurs early in the course of disease, recent studies have described angiogenic remodeling, both in multiple sclerosis tissue and in the mouse demyelinating model, experimental autoimmune encephalomyelitis (EAE). As the precise timing of vascular remodeling in demyelinating disease has yet to be fully defined, the purpose of the current study was to define the time-course of these events in the MOG35-55 EAE model. Quantification of endothelial cell proliferation and vessel density revealed that a large part of angiogenic remodeling in cervical spinal cord white matter occurs during the pre-symptomatic phase of EAE. At the height of vascular remodeling, blood vessels in the cervical spinal cord showed strong transient upregulation of fibronectin and the α5β1 integrin. In vitro experiments revealed that α5 integrin inhibition reduced brain endothelial cell proliferation under inflammatory conditions. Interestingly, loss of vascular integrity was evident in all vessels during the first 4–7 days post-immunization, but after 14 days, was localized predominantly to venules. Taken together, our data demonstrate that extensive vascular remodeling occurs during the pre-symptomatic phase of EAE and point to a potential role for the fibronectin-α5β1 integrin interaction in promoting vascular remodeling during demyelinating disease. PMID:24056042

    4. Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis

      Directory of Open Access Journals (Sweden)

      Alessia ePiermattei

      2016-05-01

      Full Text Available Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll like receptor 2 (Tlr2, by exploiting a previously characterized Tlr2 variant (Met82Ile. Tlr2 82ile promoted self-specific pro-inflammatory polarization as well as expansion of ag-specific FoxP3+ Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 pro-inflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participate directly to a putative binding pocket for sugars and Cadherins. The distinct pro- and anti-inflammatory actions impacted on severity, extent of remission and distribution of the lesions within the Central Nervous System of Experimental Autoimmune Encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.

    5. Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal Model

      Science.gov (United States)

      Al-Ghobashy, Medhat A.; Elmeshad, Aliaa N.; Abdelsalam, Rania M.; Nooh, Mohammed M.; Al-Shorbagy, Muhammad; Laible, Götz

      2017-04-01

      Recombinant human myelin basic protein (rhMBP) was previously produced in the milk of transgenic cows. Differences in molecular recognition of either hMBP or rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This indicated differences in immunological response between rhMBP and hMBP. Here, the activity of free and controlled release rhMBP poly(ɛ-caprolactone) nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model. Following optimization of nanoformulation, discrete spherical, rough-surfaced rhMBP NPs with high entrapment efficiency and controlled release pattern were obtained. Results indicated that rhMBP was loaded into and electrostatically adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP NPs before EAE-induction reduced the average behavioral score in EAE mice and showed only mild histological alterations and preservation of myelin sheath, with rhMBP NPs showing increased protection. Moreover, analysis of inflammatory cytokines (IFN-γ and IL-10) in mice brains revealed that pretreatment with free or rhMBP NPs significantly protected against induced inflammation. In conclusion: i) rhMBP ameliorated EAE symptoms in EAE animal model, ii) nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine and iii) clinical investigations are required to demonstrate the activity of rhMBP NPs as a therapeutic vaccine for MS.

    6. A Comparison of Neuroimaging Abnormalities in Multiple Sclerosis, Major Depression and Chronic Fatigue Syndrome (Myalgic Encephalomyelitis): is There a Common Cause?

      Science.gov (United States)

      Morris, Gerwyn; Berk, Michael; Puri, Basant K

      2018-04-01

      There is copious evidence of abnormalities in resting-state functional network connectivity states, grey and white matter pathology and impaired cerebral perfusion in patients afforded a diagnosis of multiple sclerosis, major depression or chronic fatigue syndrome (CFS) (myalgic encephalomyelitis). Systemic inflammation may well be a major element explaining such findings. Inter-patient and inter-illness variations in neuroimaging findings may arise at least in part from regional genetic, epigenetic and environmental variations in the functions of microglia and astrocytes. Regional differences in neuronal resistance to oxidative and inflammatory insults and in the performance of antioxidant defences in the central nervous system may also play a role. Importantly, replicated experimental findings suggest that the use of high-resolution SPECT imaging may have the capacity to differentiate patients afforded a diagnosis of CFS from those with a diagnosis of depression. Further research involving this form of neuroimaging appears warranted in an attempt to overcome the problem of aetiologically heterogeneous cohorts which probably explain conflicting findings produced by investigative teams active in this field. However, the ionising radiation and relative lack of sensitivity involved probably preclude its use as a routine diagnostic tool.

    7. Mechanisms Explaining Muscle Fatigue and Muscle Pain in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a Review of Recent Findings.

      Science.gov (United States)

      Gerwyn, Morris; Maes, Michael

      2017-01-01

      Here, we review potential causes of muscle dysfunction seen in many patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) such as the effects of oxidative and nitrosative stress (O&NS) and mitochondrial impairments together with reduced heat shock protein production and a range of metabolic abnormalities. Several studies published in the last few years have highlighted the existence of chronic O&NS, inflammation, impaired mitochondrial function and reduced heat shock protein production in many patients with ME/CFS. These studies have also highlighted the detrimental effects of chronically elevated O&NS on muscle functions such as reducing the time to muscle fatigue during exercise and impairing muscle contractility. Mechanisms have also been revealed by which chronic O&NS and or impaired heat shock production may impair muscle repair following exercise and indeed the adaptive responses in the striated muscle to acute and chronic increases in physical activity. The presence of chronic O&NS, low-grade inflammation and impaired heat shock protein production may well explain the objective findings of increased muscle fatigue, impaired contractility and multiple dimensions of exercise intolerance in many patients with ME/CFS.

    8. Myalgic Encephalomyelitis (ME and Chronic Fatigue Syndrome (CFS: The essence of objective assessment, accurate diagnosis, and acknowledging biological and clinical subgroups.

      Directory of Open Access Journals (Sweden)

      Frank N.M. Twisk

      2014-03-01

      Full Text Available Myalgic Encephalomyelitis (ME was identified as a new clinical entity in 1959 and has been acknowledged as a disease of the central nervous system/neurological disease by the World Health Organisation since 1969. Cognitive impairment, (muscle weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after minor exertion, are distinctive symptoms of ME.Chronic Fatigue Syndrome (CFS was introduced in 1988 and was redefined into clinically evaluated, unexplained (persistent or relapsing chronic fatigue, accompanied by at least four out of a list of eight symptoms, e.g. headaches and unrefreshing sleep, in 1994.Although the labels are used interchangeably, ME and CFS define distinct diagnostic entities. Post-exertional malaise and cognitive deficits e.g. are not mandatory for the diagnosis CFS, while obligatory for the diagnosis ME. Fatigue is not obligatory for the diagnosis ME.Since fatigue and other symptoms are subjective and ambiguous, research has been hampered. Despite this and other methodological issues, research has observed specific abnormalities in ME/CFS repetitively, e.g. immunological abnormalities, oxidative and nitrosative

    9. A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior.

      Science.gov (United States)

      Morris, Gerwyn; Anderson, George; Galecki, Piotr; Berk, Michael; Maes, Michael

      2013-03-08

      It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions.

    10. Treatment with NAD(+) inhibited experimental autoimmune encephalomyelitis by activating AMPK/SIRT1 signaling pathway and modulating Th1/Th17 immune responses in mice.

      Science.gov (United States)

      Wang, Jueqiong; Zhao, Congying; Kong, Peng; Sun, Huanhuan; Sun, Zhe; Bian, Guanyun; Sun, Yafei; Guo, Li

      2016-10-01

      Nicotinamide adenine dinucleotide (NAD(+)) plays vital roles in mitochondrial functions, cellular energy metabolism and calcium homeostasis. In this study, we investigated the effect of NAD(+) administration for the treatment of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. EAE, a classical animal model of multiple sclerosis (MS), was induced by subcutaneous injection of myelin oligodendrocyteglycoprotein (MOG). The mice were treated with 250mg/kg (body weight) NAD(+) in PBS administered intraperitoneally once daily. We observed that NAD(+) treatment could lessen the severity of EAE. Additionally, NAD(+) treatment attenuated pathological injuries of EAE mice. We also found that the AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1(SIRT1) pathway was activated in the NAD(+)-treated mice and NAD(+) treatment suppressed pro-inflammatory T cell responses. Our findings demonstrated that NAD(+) could be an effective and promising agent to treat multiple sclerosis and its effects on other autoimmune diseases should be explored. Copyright © 2016 Elsevier B.V. All rights reserved.

    11. Anti-inflammatory mechanisms of IFN-γ studied in experimental autoimmune encephalomyelitis reveal neutrophils as a potential target in multiple sclerosis

      Directory of Open Access Journals (Sweden)

      Nichole M Miller

      2015-08-01

      Full Text Available Multiple sclerosis (MS is an autoimmune disease of the central nervous system (CNS mediated by T helper (h1 and/or Th17 CD4 T cells that drive inflammatory lesion development along with demyelination and neuronal damage. Defects in immune regulatory mechanisms are thought to play a role in the pathogenesis of MS. While an early clinical trial indicated that IFN-γ administration was detrimental to MS, studies in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE, indicated that IFN-γ exhibits a number of anti-inflammatory properties within the CNS. These mechanisms include inhibition of IL-17 production, induction of regulatory T cells, T cell apoptosis and regulation of chemokine production. Mice deficient in IFN-γ or its receptor were instrumental in deciphering the anti-inflammatory properties of IFN-γ in the CNS. In particular, they revealed that IFN-γ is a major regulator of neutrophil recruitment into the CNS, which by a variety of mechanisms including disruption of the blood-brain-barrier (BBB and production of reactive oxygen species are thought to contribute to the onset and progression of EAE. Neutrophils were also shown to be instrumental in EAE relapses. To date neutrophils have not been appreciated as a driver of MS, but more recently based largely on the strong EAE data this view is being reevaluated by some investigators in the field.

    12. A B Cell-Driven Autoimmune Pathway Leading to Pathological Hallmarks of Progressive Multiple Sclerosis in the Marmoset Experimental Autoimmune Encephalomyelitis Model

      Directory of Open Access Journals (Sweden)

      Bert A. ’t Hart

      2017-07-01

      Full Text Available The absence of pathological hallmarks of progressive multiple sclerosis (MS in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus. The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34–56 from human myelin oligodendrocyte glycoprotein (MOG formulated with a mineral oil [incomplete Freund’s adjuvant (IFA]. Pathological aspects include demyelination of cortical gray matter with microglia activation, oxidative stress, and redistribution of iron. When the peptide is formulated in complete Freund’s adjuvant, which contains mycobacteria that relay strong activation signals to myeloid cells, oxidative damage pathways are strongly boosted leading to more intensive pathology. The proven absence of immune potentiating danger signals in the MOG34–56/IFA formulation implies that a narrow population of antigen-experienced T cells present in the monkey’s immune repertoire is activated. This novel pathway involves the interplay of lymphocryptovirus-infected B cells with MHC class Ib/Caja-E restricted CD8+ CD56+ cytotoxic T lymphocytes.

    13. Rational design and synthesis of altered peptide ligands based on human myelin oligodendrocyte glycoprotein 35-55 epitope: inhibition of chronic experimental autoimmune encephalomyelitis in mice.

      Science.gov (United States)

      Tselios, Theodore; Aggelidakis, Mihalis; Tapeinou, Anthi; Tseveleki, Vivian; Kanistras, Ioannis; Gatos, Dimitrios; Matsoukas, John

      2014-11-04

      Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). Although the etiology of MS remains unclear, there is evidence T-cell recognition of immunodominant epitopes of myelin proteins, such as the 35-55 epitope of myelin oligodendrocyte glycoprotein (MOG), plays a pathogenic role in the induction of chronic EAE. Cyclization of peptides is of great interest since the limited stability of linear peptides restricts their potential use as therapeutic agents. Herein, we have designed and synthesized a number of linear and cyclic peptides by mutating crucial T cell receptor (TCR) contact residues of the human MOG35-55 epitope. In particular, we have designed and synthesized cyclic altered peptide ligands (APLs) by mutating Arg41 with Ala or Arg41 and Arg46 with Ala. The peptides were synthesized in solid phase on 2-chlorotrityl chloride resin (CLTR-Cl) using the Fmoc/t-Bu methodology. The purity of final products was verified by RP-HPLC and their identification was achieved by ESI-MS. It was found that the substitutions of Arg at positions 41 and 46 with Ala results in peptide analogues that reduce the severity of MOG-induced EAE clinical symptoms in C57BL/6 mice when co-administered with mouse MOG35-55 peptide at the time of immunization.

    14. The nuclear IκB family protein IκBNS influences the susceptibility to experimental autoimmune encephalomyelitis in a murine model.

      Science.gov (United States)

      Kobayashi, Shuhei; Hara, Akira; Isagawa, Takayuki; Manabe, Ichiro; Takeda, Kiyoshi; MaruYama, Takashi

      2014-01-01

      The nuclear IκB family protein IκBNS is expressed in T cells and plays an important role in Interferon (IFN)-γ and Interleukin (IL)-2 production. IκB-ζ, the most similar homolog of IκBNS, plays an important role in the generation of T helper (Th)17 cells in cooperation with RORγt, a master regulator of Th17 cells. Thus, IκB-ζ deficient mice are resistant to Th17-dependent experimental autoimmune encephalomyelitis (EAE). However, IκB-ζ deficient mice develop the autoimmune-like Sjögren syndrome with aging. Here we found that IκBNS-deficient (Nfkbid-/-) mice show resistance against developing Th17-dependent EAE. We found that Nfkbid-/- T cells have decreased expression of IL-17-related genes and RORγt in response to Transforming Growth Factor (TGF)-β1 and IL-6 stimulation. Thus, IκBNS plays a pivotal role in the generation of Th17 cells and in the control of Th17-dependent EAE.

    15. Differential numbers of foci of lymphocytes within the brains of Lewis rats exposed to weak complex nocturnal magnetic fields during development of experimental allergic encephalomyelitis.

      Science.gov (United States)

      Persinger, Michael A

      2009-01-01

      To discern if specific structures of the rat brain contained more foci of lymphocytes following induction of experimental allergic encephalomyelitis and exposures to weak, amplitude-modulated magnetic fields for 6 min once per hour during the scotophase, the residuals between the observed and predicted values for the numbers of foci for 320 structures were obtained. Compared to the brains of sham-field exposed rats, the brains of rats exposed to 7-Hz 50 nT (0.5 mG) amplitude-modulated fields showed more foci within hippocampal structures and the dorsal central grey of the midbrain while those exposed to 7-Hz 500 nT (5 mG) fields showed greater densities within the hypothalamus and optic chiasm. The brains of rats exposed to either the 50 nT or 500 nT amplitude-modulated 40-Hz fields displayed greater densities of foci within the midbrain structures related to rapid eye movement. Most of the enhancements of infiltrations within the magnetic field-exposed rats occurred in structures within periventricular or periaqueductal regions and were both frequency- and intensity-dependent. The specificity and complexity of the configurations of the residuals of the numbers of infiltrated foci following exposures to the different fields suggest that the brain itself may be a "sensory organ" for the detection of these stimuli.

    16. CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis by regulating GM-CSF and IL-23 production in dendritic cells

      Science.gov (United States)

      Poppensieker, Karola; Otte, David-Marian; Schürmann, Britta; Limmer, Andreas; Dresing, Philipp; Drews, Eva; Schumak, Beatrix; Klotz, Luisa; Raasch, Jennifer; Mildner, Alexander; Waisman, Ari; Scheu, Stefanie; Knolle, Percy; Förster, Irmgard; Prinz, Marco; Maier, Wolfgang; Zimmer, Andreas; Alferink, Judith

      2012-01-01

      Dendritic cells (DCs) are pivotal for the development of experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which they control disease remain to be determined. This study demonstrates that expression of CC chemokine receptor 4 (CCR4) by DCs is required for EAE induction. CCR4−/− mice presented enhanced resistance to EAE associated with a reduction in IL-23 and GM-CSF expression in the CNS. Restoring CCR4 on myeloid cells in bone marrow chimeras or intracerebral microinjection of CCR4-competent DCs, but not macrophages, restored EAE in CCR4−/− mice, indicating that CCR4+ DCs are cellular mediators of EAE development. Mechanistically, CCR4−/− DCs were less efficient in GM-CSF and IL-23 production and also TH-17 maintenance. Intraspinal IL-23 reconstitution restored EAE in CCR4−/− mice, whereas intracerebral inoculation using IL-23−/− DCs or GM-CSF−/− DCs failed to induce disease. Thus, CCR4-dependent GM-CSF production in DCs required for IL-23 release in these cells is a major component in the development of EAE. Our study identified a unique role for CCR4 in regulating DC function in EAE, harboring therapeutic potential for the treatment of CNS autoimmunity by targeting CCR4 on this specific cell type. PMID:22355103

    17. Serial magnetic resonance imaging of acute disseminated encephalomyelitis, including evaluation of the contrast-enhancing effect on lesions by Gd-DTPA

      International Nuclear Information System (INIS)

      Tanaka, Yasunori; Matsuo, Michimasa

      1996-01-01

      Many papers on the MR features of acute disseminated encephalomyelitis (ADEM) have been published, but only a few described contrast-enhanced MRI for this disease. In this study, we analyzed serial changes in MR features and the contrast-enhancing effect on lesions in five patients (5 men, 4-19 years old) discharged with the final diagnosis of ADEM. Hyperintense lesions in brain/spinal cord were demonstrated on T2-weighted MR images in all cases, but not all lesions were enhanced by Gd-DTPA. In the follow-up study many lesions disappeared, but some lesions were enlarged and some new lesions were found. These findings suggest that, although ADEM is clinically monophasic, some cases may progress with the coexistence of reducing, vanishing, and new lesions. Some clinically acute lesions were not enhanced. This might be explained by the following reasons; lesions on various phases coexist, the damage to the blood-brain barrier in the lesions is of different degrees even if it is on the same phase, and the duration of acute phase activity is short. Additionally, some hyperintense lesions remained for a long time on T2-weighted images in spite of the absence of clinical manifestation. That hyperintense area might reflect edema caused by incomplete repair of the blood-brain barrier. From our evaluation of these five cases, MRI is not useful for the diagnosis and follow-up study of ADEM. (author)

    18. Ginger extracts influence the expression of IL-27 and IL-33 in the central nervous system in experimental autoimmune encephalomyelitis and ameliorates the clinical symptoms of disease.

      Science.gov (United States)

      Jafarzadeh, A; Mohammadi-Kordkhayli, M; Ahangar-Parvin, R; Azizi, V; Khoramdel-Azad, H; Shamsizadeh, A; Ayoobi, A; Nemati, M; Hassan, Z M; Moazeni, S M; Khaksari, M

      2014-11-15

      The immunomodulatory effects of the IL-27 and IL-33 and the anti-inflammatory effects of ginger have been reported in some studies. The aim was to evaluate the effects of the ginger extract on the expression of IL-27 and IL-33 in a model of experimental autoimmune encephalomyelitis (EAE). In PBS-treated EAE mice the expression of IL-27 P28 was significantly lower whereas the expression of IL-33 was significantly higher than unimmunized control mice. In 200 and 300 mg/kg ginger-treated EAE groups the expression of IL-27 P28 and IL-27 EBI3 was significantly higher whereas the expression of IL-33 was significantly lower than PBS-treated EAE mice. The EAE clinical symptoms and the pathological scores were significantly lower in ginger-treated EAE groups. These results showed that the ginger extract modulates the expression of the IL-27 and IL-33 in the spinal cord of EAE mice and ameliorates the clinical symptoms of disease. Copyright © 2014 Elsevier B.V. All rights reserved.

    19. Development of a duplex real-time RT-PCR for the simultaneous detection and differentiation of Theiler's murine encephalomyelitis virus and rat theilovirus.

      Science.gov (United States)

      Yuan, Wen; Wang, Jing; Xu, Fengjiao; Huang, Bihong; Lian, Yuexiao; Rao, Dan; Yin, Xueqin; Wu, Miaoli; Zhu, Yujun; Zhang, Yu; Huang, Ren; Guo, Pengju

      2016-10-01

      Theiler's murine encephalomyelitis virus (TMEV) and rat theilovirus (RTV), the member of the genus Cardiovirus, are widespread in laboratory mice and rats, and are potential contaminants of biological materials. Cardioviruses infection may cause serious complications in biomedical research. To improve the efficiency of routine screening for Cardioviruses infection, a duplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was developed for simultaneous detection and differentiation of TMEV and RTV. The duplex assay was specific for reference strains of TMEV and RTV, and no cross-reaction was found with seven other rodent viruses. The limits of detection of both TMEV and RTV were 4×10(1) copies RNA/reaction. Reproducibility was estimated using standard dilutions, with coefficients of variation duplex real-time RT-PCR and conventional RT-PCR. For 439 clinical samples,95 samples were positive for TMEV and 72 samples were positive for RTV using duplex real-time RT-PCR approach, whereas only 77 samples were positive for TMEV and 66 samples were positive for RTV when conventional RT-PCR was applied. Mixed infections were found in 20 samples when analyzed by conventional RT-PCR whereas 30 samples were found to be mixed infection when duplex real-time RT-PCR was applied. This duplex assay provides a useful tool for routine health monitoring and screening of contaminated biological materials of these two viruses. Copyright © 2016 Elsevier B.V. All rights reserved.

    20. Distribution of eastern equine encephalomyelitis viral protein and nucleic acid within central nervous tissue lesions in white-tailed deer (Odocoileus virginianus).

      Science.gov (United States)

      Kiupel, M; Fitzgerald, S D; Pennick, K E; Cooley, T M; O'Brien, D J; Bolin, S R; Maes, R K; Del Piero, F

      2013-11-01

      An outbreak of eastern equine encephalomyelitis (EEE) occurred in Michigan free-ranging white-tailed deer (Odocoileus virginianus) during late summer and fall of 2005. Brain tissue from 7 deer with EEE, as confirmed by reverse transcriptase polymerase chain reaction, was studied. Detailed microscopic examination, indirect immunohistochemistry (IHC), and in situ hybridization (ISH) were used to characterize the lesions and distribution of the EEE virus within the brain. The main lesion in all 7 deer was a polioencephalomyelitis with leptomeningitis, which was more prominent within the cerebral cortex, thalamus, hypothalamus, and brainstem. In 3 deer, multifocal microhemorrhages surrounded smaller vessels with or without perivascular cuffing, although vasculitis was not observed. Neuronal necrosis, associated with perineuronal satellitosis and neutrophilic neuronophagia, was most prominent in the thalamus and the brainstem. Positive IHC labeling was mainly observed in the perikaryon, axons, and dendrites of necrotic and intact neurons and, to a much lesser degree, in glial cells, a few neutrophils in the thalamus and the brainstem, and occasionally the cerebral cortex of the 7 deer. There was minimal IHC-based labeling in the cerebellum and hippocampus. ISH labeling was exclusively observed in the cytoplasm of neurons, with a distribution similar to IHC-positive neurons. Neurons positive by IHC and ISH were most prominent in the thalamus and brainstem. The neuropathology of EEE in deer is compared with other species. Based on our findings, EEE has to be considered a differential diagnosis for neurologic disease and meningoencephalitis in white-tailed deer.

    1. A Molecular Neurobiological Approach to Understanding the Aetiology of Chronic Fatigue Syndrome (Myalgic Encephalomyelitis or Systemic Exertion Intolerance Disease) with Treatment Implications.

      Science.gov (United States)

      Monro, Jean A; Puri, Basant K

      2018-02-06

      Currently, a psychologically based model is widely held to be the basis for the aetiology and treatment of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME)/systemic exertion intolerance disease (SEID). However, an alternative, molecular neurobiological approach is possible and in this paper evidence demonstrating a biological aetiology for CFS/ME/SEID is adduced from a study of the history of the disease and a consideration of the role of the following in this disease: nitric oxide and peroxynitrite, oxidative and nitrosative stress, the blood-brain barrier and intestinal permeability, cytokines and infections, metabolism, structural and chemical brain changes, neurophysiological changes and calcium ion mobilisation. Evidence is also detailed for biologically based potential therapeutic options, including: nutritional supplementation, for example in order to downregulate the nitric oxide-peroxynitrite cycle to prevent its perpetuation; antiviral therapy; and monoclonal antibody treatment. It is concluded that there is strong evidence of a molecular neurobiological aetiology, and so it is suggested that biologically based therapeutic interventions should constitute a focus for future research into CFS/ME/SEID.

    2. Disorders of the cerebellopontine angle; Klinik der Kleinhirnbrueckenwinkelerkrankungen

      Energy Technology Data Exchange (ETDEWEB)

      Block, F. [Helios-Kliniken Schwerin (Germany). Neurologische Klinik

      2006-03-15

      Disorders of the cerebellopontine angle may present by symptoms like vertigo, hearing problems, affection of the trigeminal or facial nerve. Ipsilateral ataxia and contralateral hemiparesis develop in case of a rather large tumor in this region and display an involvement of the cerebellum and/or brainstem. However, some of these typical symptoms are not recognized by the patient. Thus, in case of a suspicion of a disorder of the cerebellopontine angle the relevant functions have to be tested clinically. In addition, electrophysiology can confirm dysfunction of these cranial nerves. Mainstay of the therapy should be the treatment of the underlying cause. Nevertheless, not seldom it is necessary to treat symptoms like vertigo or facial pain. (orig.) [German] Schwindel, Hoerstoerungen, Affektionen des N. trigeminus oder des N. facialis stellen die wesentlichen und haeufigen Symptome bei Kleinhirnbrueckenwinkelerkrankungen dar. Ipsilaterale Gliedmassenataxie und kontralaterale Hemiparese sprechen fuer eine Mitbeteiligung von Kleinhirn und/oder Hirnstamm, die meist nur bei grossen Prozessen in dieser Region auftreten. Da einige Veraenderungen sich fuer den Patienten unbemerkt entwickeln, ist bei Verdacht eine gezielte klinische Untersuchung dieser Funktionen angezeigt, die durch elektrophysiologische Diagnostik wie z. B. akustisch evozierte Potenziale oder Blinkreflexe untermauert werden kann. Auch wenn natuerlich die kausale Therapie im Vordergrund steht, ist es gar nicht selten notwendig, eine symptomatische Behandlung durchzufuehren. Dies trifft besonders fuer Symptome wie Schwindel oder Gesichtsschmerzen zu. (orig.)

    3. Klinik, Therapie und Langzeitverlauf des hypophysären Riesenwuchses

      OpenAIRE

      Seidt, Monika, geb. Sauter

      2005-01-01

      Anhand von 24 retrospektiv analysierten Fällen mit hypophysärem Riesenwuchs aus 14 verschiedenen Kliniken innerhalb der letzten 3,5 Jahrzehnte werden die klinische Symptomatik, die endokrinologische und bildgebende Diagnostik und die gewählten Therapieansätze mit ihren Langzeitverläufen verglichen und diskutiert. Gegenwärtige Therapie der Wahl ist die selektive operative Resektion des Wachstumshormon-produzierenden Hypophysenadenomes, gegebenenfalls ergänzt durch eine medikamentöse Behandlung...

    4. Analisis dan Perancangan Electronik Customer Relationship Management Pada Klinik XYZ

      Directory of Open Access Journals (Sweden)

      Joni Suhartono

      2010-12-01

      Full Text Available This research is to foster a good connection between company and customers. For customers, e-CRM will accommodate in interation and transaction with the company. This research is done because there are still weaknesses for customer’s service. The research method used is literature, analysis method, and also designing method in identifying system needs then design one supporting system for the company. The research result is a CRM website that gives up-to-date information and suitable for customer needs. Therefore, CRM is hoped to help company giving a better service to customers.

    5. Anorektal malformasyonlu olgularda klinik deneyimimiz: 115 olgunun analizi

      Directory of Open Access Journals (Sweden)

      Mehmet Hanifi Okur

      2014-06-01

      Full Text Available Objective: In this study, we aimed to evaluate our results on children with anorectal malformations (ARM and associated anomalies. Methods: A total of 115 children who treated and followed in our clinic between 2000 and 2006 were retrospectively evaluated. Physical examination including perineal region, laboratory exams, abdominal X-ray, ultrasonography, echocardiography, and voiding cystourethrography when necessary were done to determine the type of ARM and associated anomalies. The patients were classified according to type of ARM and other pathologies. Results: Of the patients, 40.8% had high type ARM, 31.3% had low type, 17.3% had intermediate type, 9.5% had ectopic anterior located anus, and 0.86% had cloacal malformation. Associated anomalies were seen in 48.6% of patients. Associated anomalies were most commonly seen in high type of ARM patients (59.5%. Colostomy was performed in 80 patients; right transverse loop colostomy was performed in 56 (70% cases, while high sigmoid colostomy was performed in 24 remaining cases. Stoma prolapse was developed in 17.8% of patients who underwent right transverse loop colostomy. Conclusion: It is crucial to examine perineal area carefully during the first admission and follow-up to determine the type of ARM and associated anomalies. It is beneficial to perform ultrasonography, echocardiography, distal colostogram, X-ray, and voiding cystourethrography when necessary. High divergent sigmoid colostomy may decrease complication rate in ARM patients.

    6. Savant Sendromu: Klinik ve Nöropsikolojik Özellikleri

      OpenAIRE

      Durukan, İbrahim; Türkbay, Tümer

      2010-01-01

      Savant sendromu, ağır düzeyde gelişimsel ya da zihinsel yetersizliklerin yanında çoğu insanda bulunmayan sıra dışı zihinsel becerileri olan kişileri tanımlamaktadır. Kişinin genel zeka düzeyi ortalamanın altında olmasına karşın bir ya da birden fazla alanda aşırı düzeyde bilgi sahibidir. Savant sendromu olgularının yaklaşık yarısının otistik bozukluğa bağlı, kalan yarısının da diğer tip gelişimsel bozukluklar, zeka geriliği veya merkezi sinir sistemi hastalıkları ya da yaralanmalarına bağlı o...

    7. Klinik, diagnostik og behandling af Lyme-borreliose

      DEFF Research Database (Denmark)

      Ocias, Lukas Frans; Jensen, Bo Bødker; Knudtzen, Fredrikke Christie

      2017-01-01

      Lyme borreliosis is an infection caused by the Borrelia burgdorferi sensu lato complex and transmitted by Ixodes ricinus ticks in Denmark. It can manifest itself in several different forms of which erythema migrans is the most common and is diagnosed by clinical assessment of the characteristic...

    8. Dendritic cells and anergic type I NKT cells play a crucial role in sulfatide-mediated immune regulation in experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Maricic, Igor; Halder, Ramesh; Bischof, Felix; Kumar, Vipin

      2014-08-01

      CD1d-restricted NKT cells can be divided into two groups: type I NKT cells use a semi-invariant TCR, whereas type II express a relatively diverse set of TCRs. A major subset of type II NKT cells recognizes myelin-derived sulfatides and is selectively enriched in the CNS tissue during experimental autoimmune encephalomyelitis (EAE). We have shown that activation of sulfatide-reactive type II NKT cells by sulfatide prevents induction of EAE. In this article, we have addressed the mechanism of regulation, as well as whether a single immunodominant form of synthetic sulfatide can treat ongoing chronic and relapsing EAE in SJL/J mice. We have shown that the activation of sulfatide-reactive type II NKT cells leads to a significant reduction in the frequency and effector function of myelin proteolipid proteins 139-151/I-A(s)-tetramer(+) cells in lymphoid and CNS tissues. In addition, type I NKT cells and dendritic cells (DCs) in the periphery, as well as CNS-resident microglia, are inactivated after sulfatide administration, and mice deficient in type I NKT cells are not protected from disease. Moreover, tolerized DCs from sulfatide-treated animals can adoptively transfer protection into naive mice. Treatment of SJL/J mice with a synthetic cis-tetracosenoyl sulfatide, but not α-galactosylceramide, reverses ongoing chronic and relapsing EAE. Our data highlight a novel immune-regulatory pathway involving NKT subset interactions leading to inactivation of type I NKT cells, DCs, and microglial cells in suppression of autoimmunity. Because CD1 molecules are nonpolymorphic, the sulfatide-mediated immune-regulatory pathway can be targeted for development of non-HLA-dependent therapeutic approaches to T cell-mediated autoimmune diseases. Copyright © 2014 by The American Association of Immunologists, Inc.

    9. A Cyclic Altered Peptide Analogue Based on Myelin Basic Protein 87-99 Provides Lasting Prophylactic and Therapeutic Protection Against Acute Experimental Autoimmune Encephalomyelitis.

      Science.gov (United States)

      Emmanouil, Mary; Tseveleki, Vivian; Triantafyllakou, Iro; Nteli, Agathi; Tselios, Theodore; Probert, Lesley

      2018-01-31

      In this report, amide-linked cyclic peptide analogues of the 87-99 myelin basic protein (MBP) epitope, a candidate autoantigen in multiple sclerosis (MS), are tested for therapeutic efficacy in experimental autoimmune encephalomyelitis (EAE). Cyclic altered peptide analogues of MBP 87-99 with substitutions at positions 91 and/or 96 were tested for protective effects when administered using prophylactic or early therapeutic protocols in MBP 72-85 -induced EAE in Lewis rats. The Lys 91 and Pro 96 of MBP 87-99 are crucial T-cell receptor (TCR) anchors and participate in the formation of trimolecular complex between the TCR-antigen (peptide)-MHC (major histocompability complex) for the stimulation of encephalitogenic T cells that are necessary for EAE induction and are implicated in MS. The cyclic peptides were synthesized using Solid Phase Peptide Synthesis (SPPS) applied on the 9-fluorenylmethyloxycarboxyl/tert-butyl Fmoc/tBu methodology and combined with the 2-chlorotrityl chloride resin (CLTR-Cl). Cyclo(91-99)[Ala 96 ]MBP 87-99 , cyclo(87-99)[Ala 91,96 ]MBP 87-99 and cyclo(87-99)[Arg 91 , Ala 96 ]MBP 87-99 , but not wild-type linear MBP 87-99 , strongly inhibited MBP 72-85 -induced EAE in Lewis rats when administered using prophylactic and early therapeutic vaccination protocols. In particular, cyclo(87-99)[Arg 91 , Ala 96 ]MBP 87-99 was highly effective in preventing the onset and development of clinical symptoms and spinal cord pathology and providing lasting protection against EAE induction.

    10. Effects of time after infection, mosquito genotype, and infectious viral dose on the dynamics of Culex tarsalis vector competence for western equine encephalomyelitis virus.

      Science.gov (United States)

      Mahmood, Farida; Chiles, Robert E; Fang, Ying; Green, Emily N; Reisen, William K

      2006-06-01

      The vector competence of Culex tarsalis Coquillett for the BFS 1703 strain of western equine encephalomyelitis virus (WEEV) changed significantly as a function of time after infection, mosquito genotype, and infectious virus dose. After ingesting a high virus dose (5 log10 plaque-forming units [PFU]/0.1 ml), female of the susceptible high virus producer (HVP) strain rapidly amplified the virus, developed a disseminated infection, and efficiently transmitted WEEV by 4 days postinfection (dpi). The quantity of virus expectorated peaked at 4 dpi (mean 3.4 log10 PFU), and the percentage of females transmitting per os peaked at 7 dpi (80%); both measures of transmission subsequently decreased to low levels throughout the remainder of infected life. HVP females imbibing a low virus dose (3 log10 PFU/0.1 ml) were infected less frequently and took longer to amplify virus to levels recorded for the high virus dose group and did not transmit virus efficiently, thereby indicating midgut infection and escape barriers were dose and time dependent. These data emphasized the importance of elevated avian viremias in Cx. tarsalis vector competence. Females from the WEEV-resistant (WR) strain and two wild-type strains from Kern and Riverside counties were significantly less susceptible to infection at both high and low doses than was the HVP strain. Overall, females with a high virus titer more frequently had a disseminated infection, but there did not seem to be a distinct threshold demarcating this relationship. In marked contrast, all infected females transmitting virus had body titers >4.3 log10 PFU, and most had titers >4.8 log10 PFU. These data indicated that not all females with a disseminated infection transmitted virus because of the presence of one or more salivary gland barriers.

    11. 1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H17 cells to protect against experimental autoimmune encephalomyelitis.

      Directory of Open Access Journals (Sweden)

      Jae-Hoon Chang

      Full Text Available BACKGROUND: Vitamin D(3, the most physiologically relevant form of vitamin D, is an essential organic compound that has been shown to have a crucial effect on the immune responses. Vitamin D(3 ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE; however, the direct effect of vitamin D(3 on T cells is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In an in vitro system using cells from mice, the active form of vitamin D(3 (1,25-dihydroxyvitamin D(3 suppresses both interleukin (IL-17-producing T cells (T(H17 and regulatory T cells (Treg differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D(3 (1,25(OH(2D(3 to reduce the amount of IL-2 regulates the generation of Treg cells, but not T(H17 cells. Under T(H17-polarizing conditions, 1,25(OH(2D(3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH(2D(3's negative regulation of T(H17 development is still defined in the IL-10(-/- T cells. Although the STAT1 signal reciprocally affects the secretion of IL-10 and IL-17, 1,25(OH(2D(3 inhibits IL-17 production in STAT1(-/- T cells. Most interestingly, 1,25(OH(2D(3 negatively regulates CCR6 expression which might be essential for T(H17 cells to enter the central nervous system and initiate EAE. CONCLUSIONS/SIGNIFICANCE: Our present results in an experimental murine model suggest that 1,25(OH(2D(3 can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for T(H17-mediated autoimmune diseases.

    12. In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

      Science.gov (United States)

      Maes, Michael; Ringel, Karl; Kubera, Marta; Anderson, George; Morris, Gerwyn; Galecki, Piotr; Geffard, Michel

      2013-09-05

      Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation. We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale). The incidence of positive autoimmune activity against 5-HT was significantly higher (pfatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise. The results show that, in ME/CFS, increased 5-HT autoimmune activity is associated with activation of immuno-inflammatory pathways and increased bacterial translocation, factors which are known to play a role in the onset of autoimmune reactions. 5-HT autoimmune activity could play a role in the pathophysiology of ME/CFS and the onset of physio-somatic symptoms. These results provide mechanistic support for the notion that ME/CFS is a neuro-immune disorder. Copyright © 2013 Elsevier B.V. All rights reserved.

    13. The status of and future research into Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: the need of accurate diagnosis, objective assessment, and acknowledging biological and clinical subgroups

      Science.gov (United States)

      Twisk, Frank N. M.

      2014-01-01

      Although Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are used interchangeably, the diagnostic criteria define two distinct clinical entities. Cognitive impairment, (muscle) weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after a minor exertion, are distinctive symptoms of ME. This latter phenomenon separates ME, a neuro-immune illness, from chronic fatigue (syndrome), other disorders and deconditioning. The introduction of the label, but more importantly the diagnostic criteria for CFS have generated much confusion, mostly because chronic fatigue is a subjective and ambiguous notion. CFS was redefined in 1994 into unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of eight symptoms, e.g., headaches and unrefreshing sleep. Most of the research into ME and/or CFS in the last decades was based upon the multivalent CFS criteria, which define a heterogeneous patient group. Due to the fact that fatigue and other symptoms are non-discriminative, subjective experiences, research has been hampered. Various authors have questioned the physiological nature of the symptoms and qualified ME/CFS as somatization. However, various typical symptoms can be assessed objectively using standardized methods. Despite subjective and unclear criteria and measures, research has observed specific abnormalities in ME/CFS repetitively, e.g., immunological abnormalities, oxidative and nitrosative stress, neurological anomalies, circulatory deficits and mitochondrial dysfunction. However, to improve future research standards and patient care, it is crucial that patients with post-exertional malaise (ME) and patients without this odd phenomenon are acknowledged as separate clinical entities that the diagnosis of ME and CFS in research and clinical practice is based upon accurate criteria and an objective assessment of characteristic symptoms

    14. Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts.

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      Collin, Simon M; Nuevo, Roberto; van de Putte, Elise M; Nijhof, Sanne L; Crawley, Esther

      2015-10-28

      To investigate differences between young children, adolescents and adults with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Comparison of clinical cohorts from 8 paediatric and 27 adult CFS/ME services in the UK and a paediatric randomised controlled trial from the Netherlands. Outcome measures include: fatigue (the UK-Chalder Fatigue Scale); Disability (the UK-SF-36 physical function subscale; the Netherlands-CHQ-CF87); school attendance, pain, anxiety and depression (the UK-Hospital Anxiety & Depression Scale, Spence Children's Anxiety Scale; the Netherlands-Spielberger State-Trait Anxiety Inventory for Children, Children's Depression Inventory); symptoms; time-to-assessment; and body mass index. We used multinomial regression to compare younger (aged fatigue, and had been ill for longer. Younger children were less likely to have cognitive symptoms (OR 0.18 (95% CI 0.13 to 0.25)) and more likely to present with a sore throat (OR 1.42 (1.07 to 1.90). Adolescents were more likely to have headaches (81.1%, OR 1.56 (1.36% to 1.80%)) and less likely to have tender lymph nodes, palpitations, dizziness, general malaise and pain, compared to adults. Adolescents were more likely to have comorbid depression (OR 1.51 (1.33 to 1.72)) and less likely to have anxiety (OR 0.46 (0.41 to 0.53)) compared to adults. Paediatricians need to recognise that children with CFS/ME present differently from adults. Whether these differences reflect an underlying aetiopathology requires further investigation. FITNET trial registration numbers are ISRCTN59878666 and NCT00893438. This paper includes secondary (post-results) analysis of data from this trial, but are unrelated to trial outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

    15. Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data.

      Science.gov (United States)

      Maes, Michael; Twisk, Frank N M; Johnson, Cort

      2012-12-30

      There is much debate on the diagnostic classification of Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS) and chronic fatigue (CF). Post-exertional malaise (PEM) is stressed as a key feature. This study examines whether CF and CFS, with and without PEM, are distinct diagnostic categories. Fukuda's criteria were used to diagnose 144 patients with chronic fatigue and identify patients with CFS and CF, i.e. those not fulfilling the Fukuda's criteria. PEM was rated by means of a scale with defined scale steps between 0 and 6. CFS patients were divided into those with PEM lasting more than 24h (labeled: ME) and without PEM (labeled: CFS). The 12-item Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to measure severity of illness. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, and lysozyme, and serum neopterin were employed as external validating criteria. Using fatigue, a subjective feeling of infection and PEM we found that ME, CFS, and CF were distinct categories. Patients with ME had significantly higher scores on concentration difficulties and a subjective experience of infection, and higher levels of IL-1, TNFα, and neopterin than patients with CFS. These biomarkers were significantly higher in ME and CFS than in CF patients. PEM loaded highly on the first two factors subtracted from the data set, i.e. "malaise-sickness" and "malaise-hyperalgesia". Fukuda's criteria are adequate to make a distinction between ME/CFS and CF, but ME/CFS patients should be subdivided into ME (with PEM) and CFS (without PEM). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

    16. Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis

      International Nuclear Information System (INIS)

      Mattner, F.; Katsifis, A.; Ballantyne, P.; Staykova, M.; Willenborg, D.O.

      2005-01-01

      Peripheral benzodiazepine receptors (PBRs) are upregulated on macrophages and activated microglia, and radioligands for the PBRs can be used to detect in vivo neuroinflammatory changes in a variety of neurological insults, including multiple sclerosis. Substituted 2-phenyl imidazopyridine-3-acetamides with high affinity and selectivity for PBRs have been prepared that are suitable for radiolabelling with a number of positron emission tomography and single-photon emission computed tomography (SPECT) isotopes. In this investigation, the newly developed high-affinity PBR ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo [1,2-a]pyridine-3-acetamide, or CLINDE, was radiolabelled with 123 I and its biodistribution in the central nervous system (CNS) of rats with experimental autoimmune encephalomyelitis (EAE) evaluated. EAE was induced in male Lewis rats by injection of an emulsion of myelin basic protein and incomplete Freund's adjuvant containing Mycobacterium butyricum. Biodistribution studies with 123 I-CLINDE were undertaken on EAE rats exhibiting different clinical disease severity and compared with results in controls. Disease severity was confirmed by histopathology in the spinal cord of rats. The relationship between inflammatory lesions and PBR ligand binding was investigated using ex vivo autoradiography and immunohistochemistry on rats with various clinical scores. 123 I-CLINDE uptake was enhanced in the CNS of all rats exhibiting EAE when compared to controls. Binding reflected the ascending nature of EAE inflammation, with lumbar/sacral cord > thoracic cord > cervical cord > medulla. The amount of ligand binding also reflected the clinical severity of disease. Ex vivo autoradiography and immunohistochemistry revealed a good spatial correspondence between radioligand signal and foci of inflammation and in particular ED-1 + cells representing macrophages and microglia. These results demonstrate the ability of 123 I-CLINDE to measure in vivo

    17. CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis

      Directory of Open Access Journals (Sweden)

      Roy Monica

      2012-01-01

      Full Text Available Abstract Background Granulocytes generally exert protective roles in the central nervous system (CNS, but recent studies suggest that they can be detrimental in experimental autoimmune encephalomyelitis (EAE, the most common model of multiple sclerosis. While the cytokines and adhesion molecules involved in granulocyte adhesion to the brain vasculature have started to be elucidated, the required chemokines remain undetermined. Methods CXCR2 ligand expression was examined in the CNS of mice suffering from EAE or exposed to bacterial toxins by quantitative RT-PCR and in situ hybridization. CXCL1 expression was analyzed in IL-6-treated endothelial cell cultures by quantitative RT-PCR and ELISA. Granulocytes were counted in the brain vasculature after treatment with a neutralizing anti-CXCL1 antibody using stereological techniques. Results CXCL1 was the most highly expressed ligand of the granulocyte receptor CXCR2 in the CNS of mice subjected to EAE or infused with lipopolysaccharide (LPS or pertussis toxin (PTX, the latter being commonly used to induce EAE. IL-6 upregulated CXCL1 expression in brain endothelial cells by acting transcriptionally and mediated the stimulatory effect of PTX on CXCL1 expression. The anti-CXCL1 antibody reduced granulocyte adhesion to brain capillaries in the three conditions under study. Importantly, it attenuated EAE severity when given daily for a week during the effector phase of the disease. Conclusions This study identifies CXCL1 not only as a key regulator of granulocyte recruitment into the CNS, but also as a new potential target for the treatment of neuroinflammatory diseases such as multiple sclerosis.

    18. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells.

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      Mehrnaz Nouri

      Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system with a pathogenesis involving a dysfunctional blood-brain barrier and myelin-specific, autoreactive T cells. Although the commensal microbiota seems to affect its pathogenesis, regulation of the interactions between luminal antigens and mucosal immune elements remains unclear. Herein, we investigated whether the intestinal mucosal barrier is also targeted in this disease. Experimental autoimmune encephalomyelitis (EAE, the prototypic animal model of MS, was induced either by active immunization or by adoptive transfer of autoreactive T cells isolated from these mice. We show increased intestinal permeability, overexpression of the tight junction protein zonulin and alterations in intestinal morphology (increased crypt depth and thickness of the submucosa and muscularis layers. These intestinal manifestations were seen at 7 days (i.e., preceding the onset of neurological symptoms and at 14 days (i.e., at the stage of paralysis after immunization. We also demonstrate an increased infiltration of proinflammatory Th1/Th17 cells and a reduced regulatory T cell number in the gut lamina propria, Peyer's patches and mesenteric lymph nodes. Adoptive transfer to healthy mice of encephalitogenic T cells, isolated from EAE-diseased animals, led to intestinal changes similar to those resulting from the immunization procedure. Our findings show that disruption of intestinal homeostasis is an early and immune-mediated event in EAE. We propose that this intestinal dysfunction may act to support disease progression, and thus represent a potential therapeutic target in MS. In particular, an increased understanding of the regulation of tight junctions at the blood-brain barrier and in the intestinal wall may be crucial for design of future innovative therapies.

    19. A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

      Science.gov (United States)

      Corbitt, Matthew; Campagnolo, N; Staines, D; Marshall-Gradisnik, S

      2018-02-20

      Gastrointestinal (GI) symptoms and irritable bowel (IB) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The aim of this study was to conduct a systematic review of these symptoms in CFS/ME, along with any evidence for probiotics as treatment. Pubmed, Scopus, Medline (EBSCOHost) and EMBASE databases were searched to source relevant studies for CFS/ME. The review included any studies examining GI symptoms, irritable bowel syndrome (IBS) and/or probiotic use. Studies were required to report criteria for CFS/ME and study design, intervention and outcome measures. Quality assessment was also completed to summarise the level of evidence available. A total of 3381 publications were returned using our search terms. Twenty-five studies were included in the review. Randomised control trials were the predominant study type (n = 24). Most of the studies identified examined the effect of probiotic supplementation on the improvement of IB symptoms in IBS patients, or IB symptoms in CFS/ME patients, as well as some other significant secondary outcomes (e.g. quality of life, other gastrointestinal symptoms, psychological symptoms). The level of evidence identified for the use of probiotics in IBS was excellent in quality; however, the evidence available for the use of probiotic interventions in CFS/ME was poor and limited. There is currently insufficient evidence for the use of probiotics in CFS/ME patients, despite probiotic interventions being useful in IBS. The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall. Standardisation of protocols and methodology in these studies is required.

    20. Loss of the receptor tyrosine kinase Axl leads to enhanced inflammation in the CNS and delayed removal of myelin debris during Experimental Autoimmune Encephalomyelitis

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      Prieto Anne L

      2011-05-01

      Full Text Available Abstract Background Axl, together with Tyro3 and Mer, constitute the TAM family of receptor tyrosine kinases. In the nervous system, Axl and its ligand Growth-arrest-specific protein 6 (Gas6 are expressed on multiple cell types. Axl functions in dampening the immune response, regulating cytokine secretion, clearing apoptotic cells and debris, and maintaining cell survival. Axl is upregulated in various disease states, such as in the cuprizone toxicity-induced model of demyelination and in multiple sclerosis (MS lesions, suggesting that it plays a role in disease pathogenesis. To test for this, we studied the susceptibility of Axl-/- mice to experimental autoimmune encephalomyelitis (EAE, an animal model for multiple sclerosis. Methods WT and Axl-/- mice were immunized with myelin oligodendrocyte glycoprotein (MOG35-55 peptide emulsified in complete Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Mice were monitored daily for clinical signs of disease and analyzed for pathology during the acute phase of disease. Immunological responses were monitored by flow cytometry, cytokine analysis and proliferation assays. Results Axl-/- mice had a significantly more severe acute phase of EAE than WT mice. Axl-/- mice had more spinal cord lesions with larger inflammatory cuffs, more demyelination, and more axonal damage than WT mice during EAE. Strikingly, lesions in Axl-/- mice had more intense Oil-Red-O staining indicative of inefficient clearance of myelin debris. Fewer activated microglia/macrophages (Iba1+ were found in and/or surrounding lesions in Axl-/- mice relative to WT mice. In contrast, no significant differences were noted in immune cell responses between naïve and sensitized animals. Conclusions These data show that Axl alleviates EAE disease progression and suggests that in EAE Axl functions in the recruitment of microglia/macrophages and in the clearance of debris following demyelination. In addition, these data

    1. ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile.

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      Rie Yamamoto

      Full Text Available Sphingosine-1-phosphate (S1P is a biologically active sphingolipid that acts through the members of a family of five G protein-coupled receptors (S1P1-S1P5. S1P1 is a major regulator of lymphocyte trafficking, and fingolimod, whose active metabolite fingolimod phosphate acts as a nonselective S1P receptor agonist, exerts its immunomodulatory effect, at least in part, by regulating the lymphocyte trafficking by inducing down regulation of lymphocyte S1P1. Here, we detail the pharmacological profile of 5-{5-[3-(trifluoromethyl-4-{[(2S-1,1,1-trifluoropropan-2-yl]oxy}phenyl]-1,2,4-oxadiazol-3-yl}-1H-benzimidazole (ASP4058, a novel next-generation S1P receptor agonist selective for S1P1 and S1P5. ASP4058 preferentially activates S1P1 and S1P5 compared with S1P2, 3, 4 in GTPγS binding assays in vitro. Oral administration of ASP4058 reduced the number of peripheral lymphocytes and inhibited the development of experimental autoimmune encephalomyelitis (EAE in Lewis rats. Further, ASP4058 prevented relapse of disease in a mouse model of relapsing-remitting EAE. Although these immunomodulatory effects were comparable to those of fingolimod, ASP4058 showed a wider safety margin than fingolimod for bradycardia and bronchoconstriction in rodents. These observations suggest that ASP4058 represents a new therapeutic option for treating multiple sclerosis that is safer than nonselective S1P receptor agonists such as fingolimod.

    2. Astrocyte matricellular proteins that control excitatory synaptogenesis are regulated by inflammatory cytokines and correlate with paralysis severity during experimental autoimmune encephalomyelitis

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      Pennelope K. Blakely

      2015-10-01

      Full Text Available The matricellular proteins, secreted protein acidic and rich in cysteine (SPARC and SPARC-like 1 (SPARCL1, are produced by astrocytes and control excitatory synaptogenesis in the central nervous system. While SPARCL1 directly promotes excitatory synapse formation in vitro and in the developing nervous system in vivo, SPARC specifically antagonizes the synaptogenic actions of SPARCL1. We hypothesized these proteins also help maintain existing excitatory synapses in adult hosts, and that local inflammation in the spinal cord alters their production in a way that dynamically modulates motor synapses and impacts the severity of paralysis during experimental autoimmune encephalomyelitis (EAE in mice. Using a spontaneously remitting EAE model, paralysis severity correlated inversely with both expression of synaptic proteins and the number of synapses in direct contact with the perikarya of motor neurons in spinal grey matter. In both remitting and non-remitting EAE models, paralysis severity also correlated inversely with sparcl1:sparc transcript and SPARCL1:SPARC protein ratios directly in lumbar spinal cord tissue. In vitro, astrocyte production of both SPARCL1 and SPARC was regulated by T cell-derived cytokines, causing dynamic modulation of the SPARCL1:SPARC expression ratio. Taken together, these data support a model whereby proinflammatory cytokines inhibit SPARCL1 and/or augment SPARC expression by astrocytes in spinal grey matter that, in turn, cause either transient or sustained synaptic retraction from lumbar spinal motor neurons thereby regulating hind limb paralysis during EAE. Ongoing studies seek ways to alter this SPARCL1:SPARC expression ratio in favor of synapse reformation/maintenance and thus help to modulate neurologic deficits during times of inflammation. This could identify new astrocyte-targeted therapies for diseases such as multiple sclerosis.

    3. Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4⁺ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis.

      Science.gov (United States)

      Takemiya, Takako; Takeuchi, Chisen; Kawakami, Marumi

      2017-12-19

      Microsomal prostaglandin synthetase-1 (mPGES-1) is an inducible terminal enzyme that produces prostaglandin E₂ (PGE₂). In our previous study, we investigated the role of mPGES-1 in the inflammation and demyelination observed in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, using mPGES - 1 -deficient ( mPGES-1 -/- ) and wild-type (wt) mice. We found that mPGES-1 facilitated inflammation, demyelination, and paralysis and was induced in vascular endothelial cells and macrophages and microglia around inflammatory foci. Here, we investigated the role of interleukin-1β (IL-1β) in the intercellular mechanism stimulated by mPGES-1 in EAE spinal cords in the presence of inflammation. We found that the area invaded by CD4-positive (CD4⁺) T cells was extensive, and that PGE₂ receptors EP1-4 were more induced in activated CD4⁺ T cells of wt mice than in those of mPGES - 1 -/- mice. Moreover, IL-1β and IL-1 receptor 1 (IL-1r1) were produced by 65% and 48% of CD4⁺ T cells in wt mice and by 44% and 27% of CD4⁺ T cells in mPGES-1 -/- mice. Furthermore, interleukin-17 (IL-17) was released from the activated CD4⁺ T cells. Therefore, mPGES-1 stimulates an intercellular interaction between CD4⁺ T cells by upregulating the autocrine function of IL-1β in activated CD4⁺ T cells, which release IL-17 to facilitate axonal and myelin damage in EAE mice.

    4. In Vivo Quantification of Inflammation in Experimental Autoimmune Encephalomyelitis Rats Using Fluorine-19 Magnetic Resonance Imaging Reveals Immune Cell Recruitment outside the Nervous System.

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      Jia Zhong

      Full Text Available Progress in identifying new therapies for multiple sclerosis (MS can be accelerated by using imaging biomarkers of disease progression or abatement in model systems. In this study, we evaluate the ability to noninvasively image and quantitate disease pathology using emerging "hot-spot" 19F MRI methods in an experimental autoimmune encephalomyelitis (EAE rat, a model of MS. Rats with clinical symptoms of EAE were compared to control rats without EAE, as well as to EAE rats that received daily prophylactic treatments with cyclophosphamide. Perfluorocarbon (PFC nanoemulsion was injected intravenously, which labels predominately monocytes and macrophages in situ. Analysis of the spin-density weighted 19F MRI data enabled quantification of the apparent macrophage burden in the central nervous system and other tissues. The in vivo MRI results were confirmed by extremely high-resolution 19F/1H magnetic resonance microscopy in excised tissue samples and histopathologic analyses. Additionally, 19F nuclear magnetic resonance spectroscopy of intact tissue samples was used to assay the PFC biodistribution in EAE and control rats. In vivo hot-spot 19F signals were detected predominantly in the EAE spinal cord, consistent with the presence of inflammatory infiltrates. Surprising, prominent 19F hot-spots were observed in bone-marrow cavities adjacent to spinal cord lesions; these were not observed in control animals. Quantitative evaluation of cohorts receiving cyclophosphamide treatment displayed significant reduction in 19F signal within the spinal cord and bone marrow of EAE rats. Overall, 19F MRI can be used to quantitatively monitored EAE disease burden, discover unexpected sites of inflammatory activity, and may serve as a sensitive biomarker for the discovery and preclinical assessment of novel MS therapeutic interventions.

    5. Intestinal Barrier Dysfunction Develops at the Onset of Experimental Autoimmune Encephalomyelitis, and Can Be Induced by Adoptive Transfer of Auto-Reactive T Cells

      Science.gov (United States)

      Nouri, Mehrnaz; Bredberg, Anders; Weström, Björn; Lavasani, Shahram

      2014-01-01

      Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a pathogenesis involving a dysfunctional blood-brain barrier and myelin-specific, autoreactive T cells. Although the commensal microbiota seems to affect its pathogenesis, regulation of the interactions between luminal antigens and mucosal immune elements remains unclear. Herein, we investigated whether the intestinal mucosal barrier is also targeted in this disease. Experimental autoimmune encephalomyelitis (EAE), the prototypic animal model of MS, was induced either by active immunization or by adoptive transfer of autoreactive T cells isolated from these mice. We show increased intestinal permeability, overexpression of the tight junction protein zonulin and alterations in intestinal morphology (increased crypt depth and thickness of the submucosa and muscularis layers). These intestinal manifestations were seen at 7 days (i.e., preceding the onset of neurological symptoms) and at 14 days (i.e., at the stage of paralysis) after immunization. We also demonstrate an increased infiltration of proinflammatory Th1/Th17 cells and a reduced regulatory T cell number in the gut lamina propria, Peyer's patches and mesenteric lymph nodes. Adoptive transfer to healthy mice of encephalitogenic T cells, isolated from EAE-diseased animals, led to intestinal changes similar to those resulting from the immunization procedure. Our findings show that disruption of intestinal homeostasis is an early and immune-mediated event in EAE. We propose that this intestinal dysfunction may act to support disease progression, and thus represent a potential therapeutic target in MS. In particular, an increased understanding of the regulation of tight junctions at the blood-brain barrier and in the intestinal wall may be crucial for design of future innovative therapies. PMID:25184418

    6. Multivalent Soluble Antigen Arrays Exhibit High Avidity Binding and Modulation of B Cell Receptor-Mediated Signaling to Drive Efficacy against Experimental Autoimmune Encephalomyelitis.

      Science.gov (United States)

      Hartwell, Brittany L; Pickens, Chad J; Leon, Martin; Berkland, Cory

      2017-06-12

      A pressing need exists for antigen-specific immunotherapies (ASIT) that induce selective tolerance in autoimmune disease while avoiding deleterious global immunosuppression. Multivalent soluble antigen arrays (SAgA PLP:LABL ), consisting of a hyaluronic acid (HA) linear polymer backbone cografted with multiple copies of autoantigen (PLP) and cell adhesion inhibitor (LABL) peptides, are designed to induce tolerance to a specific multiple sclerosis (MS) autoantigen. Previous studies established that hydrolyzable SAgA PLP:LABL , employing a degradable linker to codeliver PLP and LABL, was therapeutic in experimental autoimmune encephalomyelitis (EAE) in vivo and exhibited antigen-specific binding with B cells, targeted the B cell receptor (BCR), and dampened BCR-mediated signaling in vitro. Our results pointed to sustained BCR engagement as the SAgA PLP:LABL therapeutic mechanism, so we developed a new version of the SAgA molecule using nonhydrolyzable conjugation chemistry, hypothesizing it would enhance and maintain the molecule's action at the cell surface to improve efficacy. "Click SAgA" (cSAgA PLP:LABL ) uses hydrolytically stable covalent conjugation chemistry (Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC)) rather than a hydrolyzable oxime bond to attach PLP and LABL to HA. We explored cSAgA PLP:LABL B cell engagement and modulation of BCR-mediated signaling in vitro through flow cytometry binding and calcium flux signaling assays. Indeed, cSAgA PLP:LABL exhibited higher avidity B cell binding and greater dampening of BCR-mediated signaling than hydrolyzable SAgA PLP:LABL . Furthermore, cSAgA PLP:LABL exhibited significantly enhanced in vivo efficacy compared to hydrolyzable SAgA PLP:LABL , achieving equivalent efficacy at one-quarter of the dose. These results indicate that nonhydrolyzable conjugation increased the avidity of cSAgA PLP:LABL to drive in vivo efficacy through modulated BCR-mediated signaling.

    7. An under-active or over-active internal world? An exploration of parallel dynamics within psyche and soma, and the difficulty of internal regulation, in patients with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

      Science.gov (United States)

      Driver, Christine

      2005-04-01

      This paper explores the dynamics brought into analytic work when there is a symmetric fusion between psyche and soma within the patient. It will consider how such a fusion may emerge from reverberations between physical constitution and a lack of maternal attunement, containment and reflective function. I will describe the work with a patient, Jane, who was diagnosed with Myalgic Encephalomyelitis (ME) during the course of her analysis. The dynamic of her physical symptoms within the analytic work, and the impact of her internal affects and internal 'objects' within the transference and countertransference, indicated a difficulty in finding an homeostatic balance resulting in overactivity and underactivity at both somatic and psychological levels. Using the clinical work with Jane this paper will also examine the interrelationship between mother-infant attachment, an inadequate internalized maternal reflective function, affect dysregulation, unconscious fusion, the lack of psyche-soma differentiation and the impact of the latter in relation to internal regulation systems, or lack of, in patients with Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME). I will draw on similar work carried out by Holland (1997), Simpson (1997) and Simpson et al. (1997). The paper will also employ the concept of the reflective function (Fonagy 2001; Knox 2003), and consider Matte-Blanco's (1999) concepts of generalization and unconscious symmetry in relation to the patient's internal world. I go on to consider how analysis provides a point outside the 'fusion' that can enable the 'deadlock' to be broken.

    8. Observações clínicas e laboratoriais em cães com cinomose nervosa Clinical and laboratory findings in dogs with distemper encephalomyelitis

      Directory of Open Access Journals (Sweden)

      Eduardo Alberto Tudury

      1997-06-01

      Full Text Available Em 81 cães com sinais clínicos, lesões histológicas e corpúsculos de inclusão no sistema nervoso central característicos de cinomose nervosa foi constatada ocorrência freqüente de: alteração das reações posturais (87,65%, diminuição da secreção lacrimal (83,95%, presença de mioclonias (75,30%, paresias (69,12%, conjuntivite (56,79%, corioretinite/ hiperqueratose naso-digital (51,85%, linfopenia (51,85%, anemia (48,05%, principalmente microcítica hipocrômica, e discretas alterações liquóricas caracterizadas por aumento de proteínas totais (77,33% e pleocitose linfocítica (50,72%. A presença de corpúsculos de Lenz em tecidos extraneurais oscilou entre 30 e 45 %, com maior freqüência em linfonodos. Enquanto outras anormalidades clínicas, neurológicas e laboratoriais não tiveram freqüência expressiva para dar apoio ao diagnóstico, o incorreto programa de vacina��ão foi uma constante.Eighty-one dogs with clinical signs and histological lesions characteristic of distemper encephalomyelitis were evaluated. Only dogs with Lenz inclusion bodies in the central nervous system were included in the study. High prevalent findings included: changes in postural reactions (87.65%, decreased tear production (83.95%, myoclonus (75.30%, paresis (69.12%, conjunctivitis (56.79%, chorioretinitis/digital and nasal hyperkeratosis (51.85%. Anemia (48.05%, lymphopenia (51.95%, and mild changes in the cerebrospinal fluid characterized by increase in total protein (77.33% and lymphocytic pleocytosis (50.72% were common laboratorial findings. Presence of Lenz inclusions bodies in tissues other than nervous system varied from 30 to 45%, with a higher frequence in the limph nodes. Other abnormalities in physical, neurological and laboratorial examinations were not helpful in establishing the diagnosis. Most animals examined were not properly vaccinated.

    9. IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci

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      Lee Eunyoung

      2012-01-01

      Full Text Available Abstract Background Murine experimental autoimmune encephalomyelitis (EAE, a model for multiple sclerosis, presents typically as ascending paralysis. However, in mice in which interferon-gamma (IFNγ signaling is disrupted by genetic deletion, limb paralysis is accompanied by atypical deficits, including head tilt, postural imbalance, and circling, consistent with cerebellar/vestibular dysfunction. This was previously attributed to intense cerebellar and brainstem infiltration by peripheral immune cells and formation of neutrophil-rich foci within the CNS. However, the exact mechanism by which IFNγ signaling prohibits the development of vestibular deficits, and whether the distribution and composition of inflammatory foci within the CNS affects the course of atypical EAE remains elusive. Methods We induced EAE in IFNγ-/- mice and bone marrow chimeric mice in which IFNγR is not expressed in the CNS but is intact in the periphery (IFNγRCNSKO and vice versa (IFNγRperiKO. Blood-brain barrier permeability was determined by Evans blue intravenous administration at disease onset. Populations of immune cell subsets in the periphery and the CNS were quantified by flow cytometry. CNS tissues isolated at various time points after EAE induction, were analyzed by immunohistochemistry for composition of inflammatory foci and patterns of axonal degeneration. Results Incidence and severity of atypical EAE were more pronounced in IFNγRCNSKO as compared to IFNγRperiKO mice. Contrary to what we anticipated, cerebella/brainstems of IFNγRCNSKO mice were only minimally infiltrated, while the same areas of IFNγRperiKO mice were extensively populated by peripheral immune cells. Furthermore, the CNS of IFNγRperiKO mice was characterized by persistent neutrophil-rich foci as compared to IFNγRCNSKO. Immunohistochemical analysis of the CNS of IFNγ-/- and IFNγR chimeric mice revealed that IFNγ protective actions are exerted through microglial STAT1

    10. NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice.

      Science.gov (United States)

      Waddell, Amanda; Zhao, Jun; Cantorna, Margherita T

      2015-05-01

      Active vitamin D [1,25-dihydroxyvitamin D3 (1,25D3)] blocks the development of experimental autoimmune diseases. However, the molecular and immunobiological mechanisms underlying 1,25D3's anti-inflammatory properties are not fully understood. We employed a murine model of experimental autoimmune encephalomyelitis (EAE) in order to determine the role of NKT cells in 1,25D3-mediated protection from EAE. Wild-type (WT) mice or mice lacking all NKT cells (CD1d(-/-)) or invariant NKT cells (Jα18(-/-)) were fed control or 1,25D3-supplemented diets. All mice fed with the control diet developed severe EAE. 1,25D3 treatment of WT mice protected them from developing EAE. CD1d(-/-) and Jα18(-/-) mice treated with 1,25D3 were not protected to the same extent as WT mice. Myelin oligodendrocyte glycoprotein-specific IL-17 and IFN-γ production was significantly reduced in 1,25D3 WT mice compared with WT but was not decreased in 1,25D3 CD1d(-/-) mice compared with CD1d(-/-) mice. IL-4(-/-) mice were utilized to determine how IL-4 deficiency affects susceptibility to EAE. IL-4(-/-) mice were not protected from developing EAE by α-galactosylceramide (α-GalCer) or 1,25D3 treatment. Furthermore, 1,25D3 treatment of splenocytes in vitro decreased α-GalCer-induced IL-17 and increased IL-4, IL-5 and IL-10 production. 1,25D3 alters the cytokine profile of invariant NKT cells in vitro. These studies demonstrate that NKT cells are important mediators of 1,25D3-induced protection from EAE in mice and NKT cell-derived IL-4 may be an important factor in providing this protection. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

    11. Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor in experimental autoimmune encephalomyelitis models of multiple sclerosis.

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      Sofia Sisay

      Full Text Available Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1 receptor and the orphan G protein receptor fifty-five (GPR55. Studies using C57BL/10 and C57BL/6 (Cnr2 (tm1Zim CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 (Dgen receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2 (tm1Zim mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational

    12. Children's experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review and meta-ethnography of qualitative studies.

      Science.gov (United States)

      Parslow, Roxanne M; Harris, Sarah; Broughton, Jessica; Alattas, Adla; Crawley, Esther; Haywood, Kirstie; Shaw, Alison

      2017-01-13

      To synthesis the qualitative studies of children's experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Systematic review and meta-ethnography. CFS/ME is an important disabling illness, with uncertain cause and prognosis. As a result, children with CFS/ME can find themselves living with greater uncertainty and stigma, exacerbating the impact of the condition. There is a growing body of qualitative research in CFS/ME, yet there has been no attempt to systematically synthesis the studies involving children. Studies exploring the experiences of children diagnosed with CFS/ME, published or unpublished, using qualitative methods were eligible. MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched as well as grey literature, reference lists and contacting authors. Quality assessment was done independently using the Critical Appraisal Skills Programme (CASP) checklist. Studies were synthesised using techniques of meta-ethnography. Ten studies involving 82 children with CFS/ME aged 8-18 were included. Our synthesis describes four third-order constructs within children's experiences: (1) disruption and loss: physical, social and the self; (2) barriers to coping: suspension in uncertainty, problems with diagnosis and disbelief; (3) facilitators to coping: reducing uncertainty, credible illness narratives, diagnosis and supportive relationships and (4) hope, personal growth and recovery. CFS/ME introduces profound biographical disruption through its effects on children's ability to socialise, perform school and therefore how they see their future. Unfamiliarity of the condition, problems with diagnosis and felt stigma prevent children from forming a new illness identity. Children adopt coping strategies such as building credible explanations for their illness. Physical, social, emotional and self-dimensions of life should be included when treating and measuring outcomes from healthcare in paediatric CFS/ME. There is a need for greater recognition

    13. Exacerbation of experimental autoimmune encephalomyelitis in prion protein (PrPc-null mice: evidence for a critical role of the central nervous system

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      Gourdain Pauline

      2012-01-01

      Full Text Available Abstract Background The cellular prion protein (PrPc is a host-encoded glycoprotein whose transconformation into PrP scrapie (PrPSc initiates prion diseases. The role of PrPc in health is still obscure, but many candidate functions have been attributed to the protein, both in the immune and the nervous systems. Recent data show that experimental autoimmune encephalomyelitis (EAE is worsened in mice lacking PrPc. Disease exacerbation has been attributed to T cells that would differentiate into more aggressive effectors when deprived of PrPc. However, alternative interpretations such as reduced resistance of neurons to autoimmune insult and exacerbated gliosis leading to neuronal deficits were not considered. Method To better discriminate the contribution of immune cells versus neural cells, reciprocal bone marrow chimeras with differential expression of PrPc in the lymphoid or in the central nervous system (CNS were generated. Mice were subsequently challenged with MOG35-55 peptide and clinical disease as well as histopathology were compared in both groups. Furthermore, to test directly the T cell hypothesis, we compared the encephalitogenicity of adoptively transferred PrPc-deficient versus PrPc-sufficient, anti-MOG T cells. Results First, EAE exacerbation in PrPc-deficient mice was confirmed. Irradiation exacerbated EAE in all the chimeras and controls, but disease was more severe in mice with a PrPc-deleted CNS and a normal immune system than in the reciprocal construction. Moreover, there was no indication that anti-MOG responses were different in PrPc-sufficient and PrPc-deficient mice. Paradoxically, PrPc-deficient anti-MOG 2D2 T cells were less pathogenic than PrPc-expressing 2D2 T cells. Conclusions In view of the present data, it can be concluded that the origin of EAE exacerbation in PrPc-ablated mice resides in the absence of the prion protein in the CNS. Furthermore, the absence of PrPc on both neural and immune cells does not

    14. Association of biomarkers with health-related quality of life and history of stressors in myalgic encephalomyelitis/chronic fatigue syndrome patients.

      Science.gov (United States)

      Fenouillet, Emmanuel; Vigouroux, Aude; Steinberg, Jean Guillaume; Chagvardieff, Alexandre; Retornaz, Frédérique; Guieu, Regis; Jammes, Yves

      2016-08-31

      Myalgic encephalomyelitis chronic fatigue syndrome (ME/CFS) is a common debilitating disorder associated with an intense fatigue, a reduced physical activity, and an impaired quality of life. There are no established biological markerof the syndrome. The etiology is unknown and its pathogenesis appears to be multifactorial. Various stressors, including intense physical activity, severe infection, and emotional stress are reported in the medical history of ME/CFS patients which raises the question whether any physiological and biological abnormalities usually found in these patients could be indicative of the etiology and/or the quality-of-life impairment. Thirty-six patients and 11 age-matched healthy controls were recruited. The following variables that appear to address common symptoms of ME/CFS were studied here: (1) muscle fatigue during exercise has been investigated by monitoring the compound muscle action potential (M-wave); (2) the excessive oxidative stress response to exercise was measured via two plasma markers (thiobarbituric acid reactive substances: TBARS; reduced ascorbic-acid: RAA); (3) a potential inflammatory component was addressed via expression of CD26 on peripheral blood mononuclear cells; (4) quality-of-life impairment was assessed using the London Handicap Scale (LHS) and the Medical Outcome Study Short Form-36 (SF-36). The medical history of each patient, including the presence of stressors such as intense sports practice, severe acute infection and/or severe emotional stress was documented. We observed that: (1) there were striking differences between cases and controls with regard to three biological variables: post-exercise M-wave, TBARS variations and CD26-expression at rest; (2) each of these three variables correlated with the other two; (3) abnormalities in the biomarkers associated with health-related quality of life: the LHS score was negatively correlated with the exercise-induced TBARS increase and positively correlated with CD26

    15. Single nucleotide polymorphisms and genotypes of transient receptor potential ion channel and acetylcholine receptor genes from isolated B lymphocytes in myalgic encephalomyelitis/chronic fatigue syndrome patients.

      Science.gov (United States)

      Marshall-Gradisnik, Sonya; Johnston, Samantha; Chacko, Anu; Nguyen, Thao; Smith, Peter; Staines, Donald

      2016-12-01

      Objective The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown; however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca 2+ ) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients. Methods A total of 11 CFS/ME patients (aged 31.82 ± 5.50 years) and 11 non-fatigued controls (aged 33.91 ± 5.06 years) were included. Flow cytometric protocols were used to determine B cell purity, followed by SNP and genotype analysis for 21 mammalian TRP ion channel genes and nine mammalian ACh receptor genes. SNP association and genotyping analysis were performed using ANOVA and PLINK analysis software. Results Seventy-eight SNPs were identified in nicotinic and muscarinic acetylcholine receptor genes in the CFS/ME group, of which 35 were in mAChM3. The remaining SNPs were identified in nAChR delta (n = 12), nAChR alpha 9 (n = 5), TRPV2 (n = 7), TRPM3 (n = 4), TRPM4 (n = 1) mAChRM3 2 (n = 2), and mAChRM5 (n = 3) genes. Nine genotypes were identified from SNPs in TRPM3 (n = 1), TRPC6 (n = 1), mAChRM3 (n = 2), nAChR alpha 4 (n = 1), and nAChR beta 1 (n = 4) genes, and were located in introns and 3' untranslated regions. Odds ratios for these specific genotypes ranged between 7.11 and 26.67 for CFS/ME compared with the non-fatigued control group. Conclusion This preliminary investigation identified a number of SNPs and genotypes in genes encoding TRP ion channels and AChRs from B cells in patients with CFS/ME. These may be involved in B cell functional changes, and suggest a role for Ca 2+ dysregulation in AChR and TRP ion channel signalling in the pathomechanism of CFS/ME.

    16. Prevalence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS in three regions of England: a repeated cross-sectional study in primary care

      Directory of Open Access Journals (Sweden)

      Fayyaz Shagufta

      2011-07-01

      Full Text Available Abstract Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS or chronic fatigue syndrome (CFS has been used to name a range of chronic conditions characterized by extreme fatigue and other disabling symptoms. Attempts to estimate the burden of disease have been limited by selection bias, and by lack of diagnostic biomarkers and of agreed reproducible case definitions. We estimated the prevalence and incidence of ME/CFS in three regions in England, and discussed the implications of frequency statistics and the use of different case definitions for health and social care planning and for research. Methods We compared the clinical presentation, prevalence and incidence of ME/CFS based on a sample of 143,000 individuals aged 18 to 64 years, covered by primary care services in three regions of England. Case ascertainment involved: 1 electronic search for chronic fatigue cases; 2 direct questioning of general practitioners (GPs on cases not previously identified by the search; and 3 clinical review of identified cases according to CDC-1994, Canadian and Epidemiological Case (ECD Definitions. This enabled the identification of cases with high validity. Results The estimated minimum prevalence rate of ME/CFS was 0.2% for cases meeting any of the study case definitions, 0.19% for the CDC-1994 definition, 0.11% for the Canadian definition and 0.03% for the ECD. The overall estimated minimal yearly incidence was 0.015%. The highest rates were found in London and the lowest in East Yorkshire. All but one of the cases conforming to the Canadian criteria also met the CDC-1994 criteria, however presented higher prevalence and severity of symptoms. Conclusions ME/CFS is not uncommon in England and represents a significant burden to patients and society. The number of people with chronic fatigue who do not meet specific criteria for ME/CFS is higher still. Both groups have high levels of need for service provision, including health and social

    17. Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis

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      de Carvalho Leite Jose C

      2011-11-01

      Full Text Available Abstract Background Needs-based resource allocation is fundamental to equitable care provision, which can meet the often-complex, fluctuating needs of people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME. This has posed challenges both for those providing and those seeking support providers, in building shared understanding of the condition and of actions to address it. This qualitative study reports on needs for equity in health and social care expressed by adults living with CFS/ME. Methods The participants were 35 adults with CFS/ME in England, purposively selected to provide variation in clinical presentations, social backgrounds and illness experiences. Accounts of experienced needs and needs-related encounters with health and social services were obtained through a focus group (n = 6 and semi-structured interviews (n = 35. These were transcribed and needs related topics identified through data-led thematic analysis. Findings Participants emphasised needs for personalised, timely and sustained support to alleviate CFS/ME impacts and regain life control, in three thematic areas: (1 Illness symptoms, functional limitations and illness management; (2 practical support and social care; (3 financial support. Access of people with CFS/ME to support from health and social services was seen to be constrained by barriers stemming from social, cultural, organisational and professional norms and practices, further heightened for disadvantaged groups including some ethnic minorities. These reduced opportunities for their illness to be explained or associated functional limitations and social disadvantages to be addressed through social support. Participants sought more understanding of bio-psycho-social aspects of CFS/ME, of felt needs of people with CFS/ME and of human rights and disability rights, for providing person-centred, equitable care. Conclusions Changes in attitudes of health practitioners, policy makers and general public

    18. Down-regulation of NTPDase2 and ADP-sensitive P2 Purinoceptors Correlate with Severity of Symptoms during Experimental Autoimmune Encephalomyelitis

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      Marija Jakovljevic

      2017-10-01

      Full Text Available The present study explores tissue and cellular distribution of ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2 and the gene and protein expression in rat spinal cord during the course of experimental autoimmune encephalomyelitis (EAE. Given that NTPDase2 hydrolyzes ATP with a transient accumulation of ADP, the expression of ADP-sensitive P2 purinoceptors was analyzed as well. The autoimmune disease was actively induced in Dark Agouti female rats and the changes were analyzed 10, 15 and 29 days after the induction. These selected time points correspond to the onset (Eo, peak (Ep and recovery (Er from EAE. In control animals, NTPDase2 was confined in the white matter, in most of the glial fibrillary acidic protein (GFAP-immunoreactive (ir astrocytes and in a considerable number of nestin-ir cells, while the other cell types were immunonegative. Immunoreactivity corresponding to NTPDase2 decreased significantly at Eo and Ep and then returned to the baseline levels at Er. The preservation of the proportion of GFAP single-labeled and GFAP/NTPDase2 double-labeled elements along the course of EAE indicated that changes in NTPDase2-ir occurred at fibrous astrocytes that typically express NTPDase2 in normal conditions. Significant downregulation of P2Y1 and P2Y12 receptor proteins at Eo and several-fold induction of P2Y12 and P2Y13 receptor proteins at Ep and/or Er were observed implying that the pathophysiological process in EAE may be linked to ADP signaling. Cell-surface expression of NTPDase2, NTPDase1/CD39 and ecto-5′-nucleotidase (eN/CD73 was analyzed in CD4+ T cells of a draining lymph node by fluorescence-activated cell sorting. The induction of EAE was associated with a transient decrease in a number of CD4+ NTPDase2+ T cells in a draining lymph node, whereas the recovery was characterized by an increase in NTPDase2+ cells in both CD4+ and CD4− cell populations. The opposite was found for NTPDase1/CD39+ and eN/CD73+ cells, which

    19. Experimental autoimmune encephalomyelitis: Association with mutual regulation of RelA (p65)/NF-κB and phospho-IκB in the CNS

      International Nuclear Information System (INIS)

      Hwang, Insun; Ha, Danbee; Ahn, Ginnae; Park, Eunjin; Joo, Haejin; Jee, Youngheun

      2011-01-01

      Highlights: → The phosphorylation of RelA's inhibitory factor IκB and subsequent RelA activation are important to the disease process of EAE. → The expression of RelA and phospho-IκB was markedly increased in the initiation and during the progression of EAE. → TPCK-treated EAE mice showed lower incidence of EAE with less severe symptoms and quicker recovery than vehicle-treated EAE mice. → TPCK significantly suppressed the MOG 35-55 -specific T cell proliferation by reducing the production of IFN-γ and IL-17 cytokines in EAE. → The NF-κB cascade's activity increased gradually with the development of symptoms and brain pathology of EAE. -- Abstract: Recently emerging evidence that the NF-κB family plays an important role in autoimmune disease has produced very broad and sometimes paradoxical conclusions. In the present study, we elucidated that the activation of RelA (p65) of NF-κB and IκB dissociation assumes a distinct role in experimental autoimmune encephalomyelitis (EAE) progression by altering IκB phosphorylation and/or degradation. In the present study of factors that govern EAE, the presence and immunoreactivity of nuclear RelA and phospho-IκB were recorded at the initiation and peak stage, and degradation of IκBα progressed rapidly at an early stage then stabilized during recovery. The immunoreactivity to RelA and phospho-IκB occurred mainly in inflammatory cells and microglial cells but only slightly in astrocytes. Subsequently, the blockade of IκB dissociation from NF-κB reduced the severity of disease by decreasing antigen-specific T cell response and production of IL-17 in EAE. Thus, blocking the dissociation of IκB from NF-κB can be utilized as a strategy to inhibit the NF-κB signal pathway thereby to reduce the initiation, progression, and severity of EAE.

    20. Active induction of experimental autoimmune encephalomyelitis by MOG35-55 peptide immunization is associated with differential responses in separate compartments of the choroid plexus

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      Murugesan Nivetha

      2012-08-01

      Full Text Available Abstract Background There is increasing awareness that, aside from producing cerebrospinal fluid, the choroid plexus (CP might be a key regulator of immune activity in the central nervous system (CNS during neuroinflammation. Specifically, the CP has recently been posited to control entry of sentinel T cells into the uninflamed CNS during the early stages of neuroinflammatory diseases, like multiple sclerosis (MS and its animal model experimental autoimmune encephalomyelitis (EAE. As the CP is compartmentalized into a stromal core containing fenestrated capillaries devoid of typical blood–brain barrier properties, surrounded by a tight junction-expressing choroidal epithelium, each of these compartments might mount unique responses that instigate the neuroinflammatory process. Methods To discern responses of the respective CP stromal capillary and choroidal epithelial tissues during evolving neuroinflammation, we investigated morphology and in situ expression of 93 immune-related genes during early stages of EAE induced by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55. Specifically, 3-D immunofluorescent imaging was employed to gauge morphological changes, and laser capture microdissection was coupled to an Immune Panel TaqMan Low Density Array to detail alterations in gene expression patterns at these separate CP sites on days 9 and 15 post-immunization (p.i.. To resolve CP effects due to autoimmunity against MOG peptide, from those due to complete Freund’s adjuvant (CFA and pertussis toxin (PTX included in the immunization, analysis was performed on MOG-CFA/PTX-treated, CFA/PTX-treated, and naïve cohorts. Results The CP became swollen and displayed significant molecular changes in response to MOG-CFA/PTX immunization. Both stromal capillary and choroidal epithelial tissues mounted vigorous, yet different, changes in expression of numerous genes over the time course analyzed - including those encoding adhesion

    1. Direct demonstration of the infiltration of murine central nervous system by Pgp-1/CD44high CD45RB(low) CD4+ T cells that induce experimental allergic encephalomyelitis

      DEFF Research Database (Denmark)

      Zeine, R; Owens, T

      1992-01-01

      -labelled CD4+ cells isolated from the CNS were responsive to MBP in vitro, whereas PKH2+ CD4+ cells from lymph nodes showed almost undetectable responses. In control experiments in which ovalbumin (OVA)-reactive T cells were transferred, a small number of fluorescent-labelled CD4+ T cells were also......In experimental allergic encephalomyelitis (EAE), autoimmune T cells infiltrate the central nervous system (CNS) and initiate demyelinating pathology. We have used flow cytometry to directly analyse the migration to the CNS of MBP-reactive CD4+ T cells labelled with a lipophilic fluorescent dye...... (PKH2), in SJL/J mice with passively transferred EAE. Labelled cells constituted about 45% of the CNS CD4+ population at the time of EAE onset. Almost all (greater than 90%) of the PKH2-labelled CD4+ T cells from EAE CNS were blasts and were alpha/beta T cell receptor (TCR)+, CD44(Pgp-1)high...

    2. Inhibition of myeloperoxidase by N-acetyl lysyltyrosylcysteine amide reduces experimental autoimmune encephalomyelitis-induced injury and promotes oligodendrocyte regeneration and neurogenesis in a murine model of progressive multiple sclerosis.

      Science.gov (United States)

      Yu, Guoliang; Zheng, Shikan; Zhang, Hao

      2018-02-07

      It is known that oxidative stress produced by proinflammatory myeloid cells plays an important role in demyelination and neuronal injury in progressive multiple sclerosis (MS). Myeloperoxidase (MPO) is a pro-oxidative enzyme released from myeloid cells during inflammation. It has been shown that MPO-dependent oxidative stress plays important roles in inducing tissue injury in many inflammatory diseases. In this report, we treated NOD experimental autoimmune encephalomyelitis (EAE) mice, a murine model of progressive MS, with N-acetyl lysyltyrosylcysteine amide (KYC), a novel specific MPO inhibitor. Our data showed that KYC treatment not only attenuated MPO-mediated oxidative stress but also reduced demyelination and axonal injury in NOD EAE mice. More importantly, we found that KYC treatment increased oligodendrocyte regeneration and neurogenesis in NOD EAE mice. Taken together, our data suggests that targeting MPO should be a good therapeutic approach for reducing oxidative injury and preserving neuronal function in progressive MS patients.

    3. MR imaging of acute disseminated encephalomyelitis, cerebellitis and myelitis in infancy: likely topographic variant of a single process; Imagen en RM de encefalomielitis aguda diseminada, cerebelitis y mielitis en la infancia: probables variantes topograficas de un mismo proceso

      Energy Technology Data Exchange (ETDEWEB)

      Fortuno, J. R.; Menor, F.; Esteban, M. J.; Pamies, J. [Hospital Universitario Infantil La Fe (Spain); Gomez-Gosalvez, F. A. [Hospital Verge dels Liris de Alcoi (Spain); Jover, J. [Hospital General de Elda (Spain)

      2003-07-01

      To describe MR images of acute disseminated encephalomyelitis (ADE) in a paediatric group, particularly focused on its likely topographic variants, cerebellitis and myelitis, its evolution, and the differential diagnosis between it an an initial outbreak of multiple sclerosis. Initial and follow-up cranial MR images were retrospectively reviewed for 14 paediatric patients diagnosed with either ADE, cerebellitis or myelitis. In 9 patients, a spinal cord monitoring was included. Three topographic variants have been considered: ADE (7 patients). In the case of ADE, the supratentorial white matter was always affected, the brain stem in five (71%) and the cerebellum in two (28,5%). Basal ganglionic lesions were detected in 5 patients (71%) and cortical lesions in one (14%). Associated spinal cord abnormality was found in five of the six cases in which this study was included (83%). ADE lesions tended to be nodular and poorly differentiated whereas in cerebellitis and myelitis the predominant pattern was one of diffuse damage. Evolution of the lesions was toward reduction/resolution. Follow-up using MR in the medium-term in 6 patients (four ADE and two cerebellitis) did not detect any new lesions. Clinical follow-up of the patients did not show any neurological recurrences in any of them. ADE, cerebillits and myelitis could be topographic variants of a single process with a common pathogeny. As the spinal cord often seems to play a role in ADE, spinal cord monitoring would be recommended, even in the absence of the above-mentioned symptoms. This spinal cord abnormality, which is usually diffuse, plus deep gray matter damage, as well as the disease of monophase course, corroborated by a sequential MR follow-up, is all helpful in the differential diagnosis with multiple sclerosis. Nonetheless, the differential diagnosis between a recurring form of ADE and an encephalomyelitis is practically impossible to make. (Author) 33 refs.

    4. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

      Directory of Open Access Journals (Sweden)

      Win Kyaw Phyu

      Full Text Available Enterovirus A71 (EV-A71 causes self-limiting, hand-foot-and-mouth disease (HFMD that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia, acinar cells (salivary gland, lacrimal gland, lymphoid cells (lymph node, spleen, and muscle fibres (skeletal, cardiac and smooth muscles, liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

    5. Pacing, Conventional Physical Activity and Active Video Games to Increase Physical Activity for Adults with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Protocol for a Pilot Randomized Controlled Trial.

      Science.gov (United States)

      Ferrar, Katia Elizabeth; Smith, Ashleigh E; Davison, Kade

      2017-08-01

      Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious illness of biological origin characterized by profound physical and cognitive exhaustion and postexertion malaise. Pacing is a common strategy used to manage available energy and complete activities of daily living; yet little research has investigated this as a strategy to increase physical activity levels. Typically, people living with ME/CFS are faced by unique barriers to physical activity participation and are less physically active than healthy peers. As such they are at increased risk of physical inactivity-related health consequences. Active video games may be a feasible and acceptable avenue to deliver physical activity intervention by overcoming many of the reported barriers to participation. The primary objective of this pilot study is to determine the feasibility and acceptability of active video games to increase physical activity levels of people with ME/CFS. The secondary aims are to explore the preliminary effectiveness of pacing and active video gaming to pacing alone and pacing plus conventional physical activity to increase the physical activity levels of adults with ME/CFS and explore the relationship between physical activity and cumulative inflammatory load (allostatic load). This study will use a mixed method design, with a 3-arm pilot randomized controlled trial, exit interviews, and collection of feasibility and process data. A total of 30 adults with ME/CFS will be randomized to receive either (1) pacing, (2) pacing and conventional physical activity, or (3) pacing and active video gaming. The intervention duration will be 6 months, and participants will be followed up for 6 months postintervention completion. The intervention will be conducted in the participant's home, and activity intensity will be determined by continuously monitored heart rate and ratings of perceived exertion. Feasibility and acceptability and process data will be collected during and at the end

    6. Subacute encephalomyelitis following measles infection

      International Nuclear Information System (INIS)

      Manchev, L.; Manchev, I.

      2012-01-01

      Full text: A 36-years-old woman was admitted in a Clinic of Neurology due to emergency presented with acute onset of altered mental status, tonic-clonic convulsions in four extremities, bladder and bowel dysfunction. This attack lasted for 2-3 minutes.The neurological investigation showed lesion of n.facialis and n.hypoglossus on the right side from central origin, right hemiparesis, positive pathologic reflex Babinski on the right side, partial sensor and motor aphasia. An analysis of the cerebrospinal fluid (CSF) showed increased levels of protein - 2.15 g/l. A week before admission to the hospital the patient had been discharged from an Infectious ward, where Measles had been diagnosed.The diagnosis was verified also with the presence of specific IgM in serum. Magnetic resonance tomography: Supratentorial on the T2W and more visibly on the FLAIR images were seen relatively homogenous high signal foci, affecting the left putamen, partially the hind limb of the left internal capsule, the body of the left nucleus caudatis, as well as more diffuse changes, affecting the cortex and subcortex in the stroke area, the upper and partially the left medial temporal gyrus. On the T1W images the changes were low signal ones. Small-degree compression of the cella media of the left lateral ventricle was noted in the changes, affecting nucleus caudatus. Infratentorial: No signal changes, affecting the cerebral stem, the small brain structures, the pontocerebral angles and the internal auditory canals were observed. Conclusion: The finding corresponds to areas of demielinization, edema and gliosis with the localization described with possible infectious genesis (encephalitis)

    7. Myalgic encephalomyelitis / chronic fatigue syndrome

      Science.gov (United States)

      ... a person’s immune system responses to stress or illness. Mental or physical stress -- Many people with ME/CFS have been under serious mental or physical stress before becoming ill. Energy ... the illness. Genetics or environmental factors may also play a ...

    8. Multiple sclerosis or multiphasic disseminated encephalomyelitis? A new question about an old problem: case report Esclerose múltipla ou encefalomielite disseminada multifásica? Uma nova questão sobre um antigo problema: relato de caso

      Directory of Open Access Journals (Sweden)

      Pérciles A. Maranhão-Filho

      1996-09-01

      Full Text Available A 42 year-old woman developed paraplegia that resolved in six months, followed by sudden right hemiparesis and dysphasia two years later. The clinical work-up, including CT and MR scans, visual evoked potentials, CSF examination and cerebral biopsy suggested the posibility of either multiple sclerosis or multiphasic disseminated encephalomyelitis. The differential diagosis between both conditions is discussed.Relato de caso de uma mulher com 42 anos de idade, que apresentou paraplegia, com resolução em seis meses seguida por hemiparesia direita e disfasia de ínico súbito. Sua história, os aspectos da tomografia computadorizada e da ressonância magnética do crânio, os resultados do potencial evocado visual, do exame do líquido cérebroespinhal, da biópsia cerebral e da ressonância magnética de controle, sugeriram as possibilidade diagnosticas de esclerose múltipla ou encefalomielite disseminada multifásica. O diagnóstico diferencial entre ambas é discutido.

    9. Elevated Expression of Fractalkine (CX3CL1 and Fractalkine Receptor (CX3CR1 in the Dorsal Root Ganglia and Spinal Cord in Experimental Autoimmune Encephalomyelitis: Implications in Multiple Sclerosis-Induced Neuropathic Pain

      Directory of Open Access Journals (Sweden)

      Wenjun Zhu

      2013-01-01

      Full Text Available Multiple sclerosis (MS is a central nervous system (CNS disease resulting from a targeted autoimmune-mediated attack on myelin proteins in the CNS. The release of Th1 inflammatory mediators in the CNS activates macrophages, antibodies, and microglia resulting in myelin damage and the induction of neuropathic pain (NPP. Molecular signaling through fractalkine (CX3CL1, a nociceptive chemokine, via its receptor (CX3CR1 is thought to be associated with MS-induced NPP. An experimental autoimmune encephalomyelitis (EAE model of MS was utilized to assess time dependent gene and protein expression changes of CX3CL1 and CX3CR1. Results revealed significant increases in mRNA and the protein expression of CX3CL1 and CX3CR1 in the dorsal root ganglia (DRG and spinal cord (SC 12 days after EAE induction compared to controls. This increased expression correlated with behavioural thermal sensory abnormalities consistent with NPP. Furthermore, this increased expression correlated with the peak neurological disability caused by EAE induction. This is the first study to identify CX3CL1 signaling through CX3CR1 via the DRG /SC anatomical connection that represents a critical pathway involved in NPP induction in an EAE model of MS.

    10. Peripheral phosphodiesterase 4 inhibition produced by 4-[2-(3,4-Bis-difluoromethoxyphenyl)-2-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-phenyl]-ethyl]-3-methylpyridine-1-oxide (L-826,141) prevents experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Moore, Craig S.; Earl, Nathalie; Frenette, Richard

      2006-01-01

      Administration of phosphodiesterase 4 (PDE4) inhibitors suppresses the pathogenesis associated with experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). In the present study, we compared the effects of rolipram and 4-[2-(3,4-bis-difluoromethoxyphenyl)-2...... observed. Only L-826,141 at a dose of 30 mg/kg p.o. significantly decreased the clinical severity of EAE compared with vehicle controls. Immunohistochemical detection of the neuronal activity marker Fos confirmed that L-826,141 did not reach concentrations in the central nervous system sufficient...

    11. Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Harris, Nicholas; Koppel, Juraj; Zsila, Ferenc; Juhas, Stefan; Il'kova, Gabriela; Kogan, Faina Yurgenzon; Lahmy, Orly; Wildbaum, Gizi; Karin, Nathan; Zhuk, Regina; Gregor, Paul

      2016-04-01

      Elucidate the mechanism of action of the small molecule inhibitor of protein binding to glycosaminoglycans, RX-111 and assay its anti-inflammatory activity in animal models of inflammatory disease. The glycosaminoglycan, heparin, was used in the mechanism of action study of RX-111. Human T lymphocytes and umbilical vein endothelial cells were used to assay the in vitro activity of RX-111. Mouse and rat models of disease were used to assay the anti-inflammatory activity of RX-111 in vivo. Circular dichroism and UV/Vis absorption spectroscopy were used to study the binding of RX-111 to the glycosaminoglycan, heparin. T lymphocyte rolling on endothelial cells under shear flow was used to assay RX-111 activity in vitro. Delayed-type hypersensitivity (DTH) and tri-nitrobenzene sulfonic acid (TNBS)-induced colitis in mice and experimental autoimmune encephalomyelitis (EAE) in rats were used to assay anti-inflammatory activity of RX-111 in vivo. RX-111 was shown to bind directly to heparin. It inhibited leukocyte rolling on endothelial cells under shear flow and reduced inflammation in the mouse model of DTH. RX-111 was efficacious in the mouse model of inflammatory bowel disease, TNBS-induced colitis and the rat model of multiple sclerosis, EAE. RX-111 exercises its broad spectrum anti-inflammatory activity by a singular mechanism of action, inhibition of protein binding to the cell surface GAG, heparan sulfate. RX-111 and related thieno[2,3-c]pyridine derivatives are potential therapeutics for the treatment of inflammatory and autoimmune diseases.

    12. Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women.

      Science.gov (United States)

      Milrad, Sara F; Hall, Daniel L; Jutagir, Devika R; Lattie, Emily G; Ironson, Gail H; Wohlgemuth, William; Nunez, Maria Vera; Garcia, Lina; Czaja, Sara J; Perdomo, Dolores M; Fletcher, Mary Ann; Klimas, Nancy; Antoni, Michael H

      2017-02-15

      Poor sleep quality has been linked to inflammatory processes and worse disease outcomes in the context of many chronic illnesses, but less is known in conditions such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms. Sixty women diagnosed with CFS/ME were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Symptom Inventory (FSI) and Center for Disease Control and Prevention (CDC)-based CFS/ME symptom questionnaires. Circulating plasma pro-inflammatory cytokine levels were measured by ELISA. Multiple regression analyses examined associations between sleep, cytokines and symptoms, controlling for age, education, and body mass index. Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β) (β=0.258, p=0.043), IL-6 (β=0.281, p=0.033), and tumor necrosis factor-alpha (TNF-α) (β=0.263, p=0.044). Worse sleep quality related to greater fatigue severity (β=0.395, p=0.003) and fatigue-related interference with daily activities (β=0.464, p<0.001), and more severe and frequent CDC-defined core CFS/ME symptoms (β=0.499, p<0.001, and β=0.556, p<0.001, respectively). Results underscore the importance of managing sleep-related difficulties in this patient population. Further research is needed to identify the etiology of sleep disruptions in CFS/ME and mechanistic factors linking sleep quality to symptom severity and inflammatory processes. Copyright © 2016 Elsevier B.V. All rights reserved.

    13. Zuo-Gui and You-Gui pills, two traditional Chinese herbal formulas, downregulated the expression of NogoA, NgR, and RhoA in rats with experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Kou, Shuang; Zheng, Qi; Wang, Yizhou; Zhao, Hui; Zhang, Qiuxia; Li, Ming; Qi, Fang; Fang, Ling; Liu, Lei; Ouyang, Junyao; Zhao, Haiyu; Wang, Lei

      2014-12-02

      Zuo-Gui pills (ZGPs) and You-Gui pills (YGPs) are 2 traditional Chinese herbal formulas used for treating multiple sclerosis (MS) in the clinical setting and have been shown to have neuroprotective effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The aim of this study was to explore the mechanisms underlying the neuroprotective functions of ZGPs and YGPs. Female Lewis rats were randomly divided into normal control, EAE model, 2g/kg ZGP-treated EAE, 3g/kg YGP-treated EAE, and prednisone acetate-treated groups. EAE model was induced by subcutaneous injection of MBP68-86 antigen. The neurological function scores were estimated. Histological structures of the brains and spinal cords were observed, and myelinated and axons imaged. NogoA, Nogo receptor (NgR), and RhoA transcript and protein levels were measured by real-time quantitative RT-PCR and western blotting on postimmunization (PI) days 14 (acute stage) and 28 (remission stage). ZGPs and YGPs significantly reduced neurological functions scores and abrogated inflammatory infiltrates, demyelination, and axonal damage. Furthermore, treatment with ZGPs and YGPs inhibited NogoA, NgR, and RhoA mRNA and protein expression in rats at both the acute and remission stages. ZGPs exhibited stronger effects on NogoA and RhoA expressions, as well as neurological function, during the acute stage of EAE, while YGPs caused greater reductions in NogoA expression during the remission stage. Our findings suggested that ZGPs and YGPs exerted neuroprotective effects by downregulation of NogoA, NgR, and RhoA pathways, with differences in response times and targets observed between ZGPs and YGPs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

    14. Encefalomielite disseminada aguda e vacinação antimeningocócica A e C: relato de caso Acute disseminated encephalomyelitis: association with meningococcal A and C vaccine: case report

      Directory of Open Access Journals (Sweden)

      Marco O. Py

      1997-09-01

      Full Text Available Os autores descrevem o caso clínico de paciente do sexo feminino, de 25 anos, que desenvolveu encefalomielite aguda disseminada (EDA iniciando-se cinco dias após vacinação para meningococcus A e C (Pasteur-Meríeux na campanha de vacinação realizada em dezembro de 1995 na cidade do Rio de Janeiro. Houve excelente resposta clínica e neurorradiológica após tratamento com corticosteróides em altas doses (pulsoterapia. Não foram encontrados relatos sobre a associação entre a vacina antimeningocócica e a EDA. A associação entre EDA e leptospirose ou infecções por Mycoplasma sugerem porém que a síndrome pode ser precipitada não só por viroses ou vacinação antiviral como também pela exposição do organismo a proteínas e polissacarídeos de bactérias.A 25-year-old woman developed acute disseminated post-vaccinal encephalomyelitis (ADEM following vaccination with A plus C meningococcal vaccine (Pasteur-Merieux. Fast disappearance of symptoms and gradual resolution of MR1 demyelinating lesions occurred after steroid treatment with high doses of intravenous methylprednisolone. To our knowledge, ADEM has not been previously described in association with meningococcal vaccine. Although most cases of ADEM occur following viral infections and vaccination, the syndrome has previously been related to leptospirosis and Mycoplasma pneumoniae infections. This suggests that it may also be related to exposure to polysaccharide-protein vaccines such as the Group A plus Group C meningococcal vaccine.

    15. Interleukin-27 Gene Therapy Prevents the Development of Autoimmune Encephalomyelitis but Fails to Attenuate Established Inflammation due to the Expansion of CD11b+Gr-1+ Myeloid Cells

      Directory of Open Access Journals (Sweden)

      Jianmin Zhu

      2018-04-01

      Full Text Available Interleukin-27 (IL-27 and its subunit P28 (also known as IL-30 have been shown to inhibit autoimmunity and have been suggested as potential immunotherapeutic for autoimmune diseases such as multiple sclerosis (MS. However, the potential of IL-27 and IL-30 as immunotherapeutic, and their mechanisms of action have not been fully understood. In this study, we evaluated the efficacy of adeno-associated viral vector (AAV-delivered IL-27 (AAV-IL-27 and IL-30 (AAV-IL-30 in a murine model of MS. We found that one single administration of AAV-IL-27, but not AAV-IL-30 completely blocked the development of experimental autoimmune encephalomyelitis (EAE. AAV-IL-27 administration reduced the frequencies of Th17, Treg, and GM-CSF-producing CD4+ T cells and induced T cell expression of IFN-γ, IL-10, and PD-L1. However, experiments involving IL-10-deficient mice and PD-1 blockade revealed that AAV-IL-27-induced IL-10 and PD-L1 expression were not required for the prevention of EAE development. Surprisingly, neither AAV-IL-27 nor AAV-IL-30 treatment inhibited EAE development and Th17 responses when given at disease onset. We found that mice with established EAE had significant expansion of CD11b+Gr-1+ cells, and AAV-IL-27 treatment further expanded these cells and induced their expression of Th17-promoting cytokines such as IL-6. Adoptive transfer of AAV-IL-27-expanded CD11b+Gr-1+ cells enhanced EAE development. Thus, expansion of CD11b+Gr-1+ cells provides an explanation for the resistance to IL-27 therapy in mice with established disease.

    16. Imaging micro-glial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by Positron Emission Tomography using the mitochondrial 18 kDa translocator protein radioligand [18F]DPA-714

      International Nuclear Information System (INIS)

      Abourbeh, Galith; Theze, Benoit; Dubois, Albertine; Tavitian, Bertrand; Boisgard, Raphael; Maroy, Renaud; Brulon, Vincent; Fontyn, Yoann; Dolle, Frederic

      2012-01-01

      Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated micro-glia/macrophages play a key role in the immuno-pathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Micro-glia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of micro-glial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuro-inflammatory processes. EAE was induced in rats using a fragment of myelin basic protein, yielding acute clinical disease that reflects extensive spinal cord inflammation. Enhanced TSPO expression in spinal cords of EAE rats versus those of controls was confirmed by Western blot and immunohistochemistry. Biodistribution studies in control and EAE rats were performed using the TSPO radioligand [ 18 F]DPA-714 [N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5- a]pyrimidin-3-yl)acetamide]. At 1 h after injection, almost fivefold higher levels of [ 18 F]DPA-714 were measured in spinal cords of EAE rats versus controls. The specific binding of [ 18 F]DPA-714 to TSPO in spinal cords was confirmed in competition studies, using unlabeled (R,S)-PK11195 [(R,S)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl) - isoquinoline-3-carboxamide)] or DPA-714 in excess. MicroPET studies affirm that this differential radioactivity uptake in spinal cords of EAE versus control rats could be detected and quantified. Using [ 18 F]DPA-714, neuro-inflammation in spinal cords of EAE-induced rats could be visualized by PET, offering a sensitive technique for monitoring neuro-inflammatory lesions in the CNS and particularly in the spinal cord. In addition to current MRI protocols, this approach could provide molecular images of neuro-inflammation for detection, monitoring, and research in MS. (authors)

    17. MicroRNA-129-5p inhibits the development of autoimmune encephalomyelitis-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway.

      Science.gov (United States)

      Liu, Ai-Hua; Wu, Ya-Ting; Wang, Yu-Ping

      2017-06-01

      The study aimed to explore the effects of microRNA-129-5p (miR-129-5p) on the development of autoimmune encephalomyelitis (AE)-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway in a rat model. AE-related epilepsy models were established. Sprague-Dawley (SD) rats were randomly divided into control, model, miR-129-5p mimics, miR-129-5p inhibitor, HMGB1 shRNA, TLR4/NF-kB (TLR4/NF-kB signaling pathway was inhibited) and miR-129-5p mimics+HMGB1 shRNA groups respectively. Latency to a first epilepsy seizure attack was recorded. Neuronal injuries in the hippocampus regions were detected using HE, Nissl and FJB staining methods 24h following model establishment. Microglial cells were detected by OX-42 immunohistochemistry. Expressions of miR-129-5p, HMGB1 and TLR4/NF-kB signaling pathway-related proteins were detected by qRT-PCR. Protein expressions of HMGB1 and TLR4/NF-kB signaling pathway-related proteins were detected by Western blotting. Dual luciferase reporter gene assay showed that miR-129-5p was negatively targeting HMGB1. Neurons of hippocampal tissues in rats were heavily injured by an injection of lithium chloride. Compared with the model and control groups, neuronal injury of the hippocampus and AE-related epilepsy decreased and microglial cells increased in the miR-129-5p mimics, HMGB1 shRNA and TLR4/NF-kB groups; however, in the miR-129-5p inhibitor group, miR-129-5p expression decreased, HMGB1 expression increased, TLR4/NF-kB signaling pathway was activated, latency to a first epilepsy seizure attack was shortened, and neuronal injury increased. This study provides evidence that miR-129-5p inhibits the development of AE-related epilepsy by suppressing HMGB1 expression and inhibiting TLR4/NF-kB signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

    18. Asociación de encefalomielitis diseminada aguda y síndrome de Guillain-Barré en un adulto Association between acute disseminated encephalomyelitis and Guillain Barré syndrome in an adult

      Directory of Open Access Journals (Sweden)

      Miguel A. Pagano

      2011-06-01

      Full Text Available La encefalomielitis diseminada aguda (EMDA y el síndrome de Guillain-Barré (SGB son reconocidas como entidades distintas, que afectan diferentes sectores del sistema nervioso, pero que comparten varias características tales como la patogenia autoinmune, el impacto sobre la mielina y el antecedente de infección viral o vacunación una a cuatro semanas previas al cuadro clínico. Se presenta un paciente varón de 41 años de edad que consultó por presentar fiebre, debilidad en miembros inferiores y somnolencia dos semanas posteriores a episodio agudo de gastroenteritis. Al ingreso se constató deterioro del sensorio (obnubilación hiperreflexia patelar, Babinski bilateral y vejiga neurogénica. Veinticuatro horas después desarrolló paraplejía flácida y arreflexia generalizada, requiriendo asistencia respiratoria mecánica por insuficiencia respiratoria. El líquido cefalorraquídeo mostró pleocitosis mononuclear e hiperproteinorraquia. El estudio electrofisiológico evidenció importante disminución de las velocidades de conducción en ambos nervios ciáticos poplíteos externos, compatible con polineuropatía desmielinizante. La resonancia magnética nuclear mostró imágenes compatibles con desmielinización en cerebro, protuberancia y segmentos medulares dorsales. Se realizó diagnóstico de ASEMDA-SGB e inició tratamiento con metilprednisolona e inmunoglobulina intravenosa. Evolucionó favorablemente, recuperando las funciones motoras, vesical y la sensibilidad, siendo capaz de deambular luego de seis meses. La asociación de EMDA y SGB (ASEMDA-SGB es una condición infrecuente, generalmente señalada como de mal pronóstico, en la cual un diagnóstico precoz y un rápido y enérgico tratamiento pueden mejorar substancialmente la evolución.Acute disseminated encephalomyelitis (ADEM and Guillain-Barré Syndrome (GBS are commonly recognized as separated entities involving different parts of the nervous system. However, they share

    19. Experimental Autoimmune Encephalomyelitis (EAE-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1: Implications in Multiple Sclerosis (MS-Induced Neurological Disability and Associated Myelin Damage

      Directory of Open Access Journals (Sweden)

      Tina Khorshid Ahmad

      2017-06-01

      Full Text Available Multiple sclerosis (MS is a chronic neurological disease characterized by the destruction of central nervous system (CNS myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2 called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC and active control (AC animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC. The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG. Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC

    20. Experimental Autoimmune Encephalomyelitis (EAE)-Induced Elevated Expression of the E1 Isoform of Methyl CpG Binding Protein 2 (MeCP2E1): Implications in Multiple Sclerosis (MS)-Induced Neurological Disability and Associated Myelin Damage.

      Science.gov (United States)

      Khorshid Ahmad, Tina; Zhou, Ting; AlTaweel, Khaled; Cortes, Claudia; Lillico, Ryan; Lakowski, Ted Martin; Gozda, Kiana; Namaka, Michael Peter

      2017-06-12

      Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression. Using an EAE model of MS, we identify the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF. The expression changes of these key biological targets were then correlated with the temporal changes in neurological disability scores (NDS) over the entire disease course. Our results indicate that MeCP2E1 mRNA levels are elevated in EAE animals relative to naïve control (NC) and active control (AC) animals during all time points of disease progression. Our results suggest that the EAE-induced elevations in MeCP2E1 expression contribute to the repressed BDNF production in the spinal cord (SC). The sub-optimal levels of BDNF result in sustained NDS and associated myelin damage throughout the entire disease course. Conversely, we observed no significant differences in the expression patterns displayed for the MeCP2E2 isoform amongst our experimental groups. However, our results demonstrate that baseline protein expression ratios between the MeCP2E1 versus MeCP2E2 isoforms in the SC are higher than those identified within the dorsal root ganglia (DRG). Thus, the DRG represents a more conducive environment than that of the SC for BDNF production and transport to the CNS to assist in myelin repair. Henceforth, the sub-optimal BDNF levels we report in the SC may arise

    1. Diferensiasi Asma Atopik dengan Nonatopik pada Pasien Rawat Jalan di Klinik Paru-Asma

      Directory of Open Access Journals (Sweden)

      Prayudi Santoso

      2013-06-01

      Full Text Available There is a difficulty in asthma management regarding to unclear mechanism of asthma, and a variety of asthma phenotypes that individually require individual therapy and approach. The asthmatic phenotype atopic and nonatopic was clinically difficult to distinguish. The study was analytical descriptive with cross-sectional design. The study aim was to explore the differences of atopic and non-atopic asthmatic characteristics. The study subjects were newly asthmatic patients who were out-patients of An-Nur Lung-Asthmatic Clinic, Bandung, in 2007–2008. In patients examined total IgE, spirometry and skin prick test. There were 198 asthmatic patients comprising 149 (75.3% atopic and 40 (24.7% non-atopic asthma. The median of the non-atopic age was 39 years, while the atopic was 34 years (p=0.039. There was a significant difference between atopic (68.5% and non-atopic (44.9% in complaint of short breath (p=0.003, but non significant in spirometric examination. The history of atopy were present in atopic asthma group (p=0.011, with significance in rhinitis (81.2 vs 61.2 OR=2.7 and urticaria (14.8 vs 4.1 OR=4.0. Non-atopic asthma was not more severe that atopic asthma was known from examination of forced expiratory volume first second (FEV1. Rhinitis patient, having urticaria, have greater risk for atopic asthma. There were no difference in skin prick test results between both groups. The clinical symptoms of atopic group were in line with the positivenes results of IgE examination. Clinical condition of rhinitis and urticaria direct to the diagnosed towards atopic asthma compared than other clinical features or spirometric result.

    2. Pengendalian Mutu Laboratorium Kimia Klinik Dilihat dari Aspek Mutu Hasil Analisis Laboratorium

      OpenAIRE

      -, Riyono

      2007-01-01

      This study was aimed at learning the quality of laboratory analysis result, accuracy and precision of laboratory analysis and how the relationship of analytical internal quality control with accuracy and precision of laboratory analysis result. The measurement tools were questionnaires and gold standard. The analysis used t-test, Variance Index Score (VIS) and Spearman's Rank Correlation. Data collected from 30 respondents and 360 sample (precinorm ‘U) on 9 laboratory hospital of Sub-Province...

    3. Klinik Oncesi Yillardaki Tip Ogrencilerinin Anksiyete ve Depresyon Duzeyleri ve Etkili Olabilecek Faktorler

      Directory of Open Access Journals (Sweden)

      Nazan Karaoglu

      2011-06-01

      Full Text Available AIM: While training knowledgeable, competent and professional physicians for the patients health medical education distresses and sicken medical students. The aim of this study was to describe the general features of the preclinical years’ students and the affect of these features on the anxiety and depression level of them. METHOD: In this descriptive and cross-sectional study an anonymous and voluntary questionnaire consisting of socio-demographic variables, questions related to medical education and Hospital Anxiety and Depression Scale (HADS was applied to the first three years’ students of medical faculty. For the analyses of the data Student-t test, One-way ANOVA and chi-square tests were used. RESULTS: The mean age of the students in the study group was 19.49±1.54 years and 272 of them (56.1% were male. The anxiety and depression levels of the students from rural parts of the country and whose parents’ education levels were primary school or below were high (p<0.05. According to questions related to medical education there was a difference in anxiety levels of year one and two students who selected medical education in between first three choice (p=0.01 and between year two and three students who chose medicine because of occupation guarantee (p=0.00. There was a significant difference between students who noted family-intimates as the reason of their choice and liking medicine (p=0.00. The anxiety levels of the students who were absolutely unpleased with their choice were the highest (p<0.05. The mean anxiety and depression levels were 7.45±3.79 and 5.60±3.74 points and 87 students (17.9% anxiety level, 136 students’ (28.0% depression level were above the cut of levels in the whole group. CONCLUSION: The results of this study points to the importance of voluntary and informed selection of medical education. [TAF Prev Med Bull 2011; 10(3.000: 303-312

    4. Kepatuhan 5 Momen Hand Hygiene Pada Petugas di Laboratorium Klinik Cito Yogyakarta

      Directory of Open Access Journals (Sweden)

      Pangisti Dwi Ananingsih

      2016-01-01

      Full Text Available Hospital Associated Infection (HAIs is still a problem through out the world and in Indonesia. Health officials have a major role in the transmission of these infections. However, the low level of compliance of five moments of hand hygiene among health care workers is still one of the factors that cause a high spread of HAIs. To hand let his, it is necessary to counseling about the importance of 5 moments of hand hygiene for health worker towards patient health. Counseling can be done in various models, such as posters, training, and simulation. The study is a qualitative research with action research. Conducted in September 2015 inwards in Clinical Laboratory “Cito” Yogyakarta, the population as well as samples in this study were all health care workers in first floor of the Clinical Laboratory Cito Yogyakarta that consisting of nurses, analysts, doctors, radiographers, customer service, and cleaning service. 5 moments of hand hygiene compliance of the workers increasing after the poster socialitation, training, and simulation. The management is expected to give more attention in improving of 5 moments of hand hygiene for health worker in Clinical Laboratory Cito Yogyakarta.

    5. Dirençli epilepsi olgusunda mozaik ring kromozom 6 ve klinik önemi

      OpenAIRE

      Ocak, Zeynep; Göksügür, Sevil Bilir; Kocaman, Ertuğrul Mevlüt

      2014-01-01

      To the Editor Epilepsy is a neurologic disease occuring as a result of sudden abnormal and synchronized discharges of a group of neurons in the central nervous system CNS characterized with convulsions 1 Genetic diseases with monogenic chormosomal and multi factorial inheritance are involved in the etiology in 40 of the patients with epilepsy 2 Very significant dysmorphic characteristics are present in most chromosamal disorders associated with epilepsy 3 We presented a 7 year old male patien...

    6. UJI COBA PEMULIHAN GIZI BURUK CARA KLINIK GIZI PUSLITBANG GIZI DI POSYANDU

      Directory of Open Access Journals (Sweden)

      Djoko Kartono

      2012-11-01

      Full Text Available Trial The Management of Severe Malnourished Children of Nutrition Clinic Method, The Nutrition Research and Development Centre at Village Level.Background: Managerrent of severe malnutrition recommended by WHO should be in hospital. For family with severe malnourished child, generally poor, hospitalization means spend a lot of money. The alternative method is the out patient management developed by Nutrition Clinic of the Nutrition Research ard Development Centre.Objectives: To study the effectiveneess of management for severe malnourished of Nutrition Clinic method in village level (posyandu by village cadre.Methods: The study was carried out at 4 sub-districts in Bogor and Sukabumi, West Java. Sixty under-five children for group 1 and 60 for group 2 were selected. Three to five posyandu's cadres were selected in each village. Visit schedule to posyandu for group 1 was similar to that Nutrition Clinic while group 2 was every 1 week. Nutrition package for group 1 and 2 was same. Data collection included body measurements, morbiddity and food consumption. Observation to the cadres performance include ownership and he use of guidance book.Results: Seven percent of children aged 6-11 months, 20% aged 12-17 months, 60% aged 18-35 months and 13% aged > 36 months. Around 30% of children had been grven fruit and porridge on the age 1-4 months old. Nutritional status improved variously depended on the nutritional indices. Energy consumption was low but protein consumption had reached the recommended allowance. Compliance to come to posyandu and nutrition package was high.Conclusions: Around 10% of cchildren had changed from under-weight to well-nourished, but most of severe malnourished children remained severe in 3 months. Stunted was over 75% and remained stunted in 3 months. Wasted was 50% and began to decline in 3 months. The average of weight increment in 3 months was 0,6 kg. Cadre could give simple education to mothers using the available guidance book.Recommendations: To use wasted as an indicator in the evaluation of management of severe malnutrition. Active role of health Centre is needed to have maximum effect of the implementation of Nutrition Clinic method at village level.Key words: management, severe malnutrition, nutrition clinic, out-patient, village cadre.

    7. Pembuatan "Primary Crown" pada Perawatan dengan Restorasi Jembatan Konvensional (Laporan Kasus Klinik

      Directory of Open Access Journals (Sweden)

      Suhandi Sidjaya

      2015-10-01

      Full Text Available Secondaire caries was considered as an important contributor to the complication in fixed prosthodontic (crown & bridgework. One factor that is improper cervical margin of the restoration could lead to desementation and further to secondair caries occurance. Tensile stress as leverage at long span bridge could open the cervical margin of the retainer. Metal coping as primary coping could protect the abutment teeth of long span bridge of this possibility. This article reported two cases treated with long span conventional bridge on primary metal coping at its abutment.

    8. TINGKAT RISIKO PEMAKAIAN ALAT PELINDUNG DIRI DAN HIGINE PETUGAS DI LABORATORIUM KLINIK RSPUN CIPTOMANGUNKUSUMO, JAKARTA

      Directory of Open Access Journals (Sweden)

      Dian Perwitasari

      2012-11-01

      Full Text Available Level of Risk Used Material Safety and Hygiene Laboratory Employee In Clinical Laboratory Ciptomangunkusumo Hospital, Jakarta.The study on the description of personal protective equipment (PPE and personal hygiene for laboratorian were undertaken, in relation to high risk factor being infected with diseases including HIV/AIDS, in cl inical laboratory Ciptomangunkusumo Hospital, Jakarta, in 2001. The number of samplesis 48 personnel who work in laboratories (24 hour, emergency installation, hematology, and child laboratory, and the study design is cross-sectional. The risk level is being scored in several criteria. There are 56.8% laboratorian who did not use PPE. Based on risks, the high risk group is those who work inchild laboratory (100% and hematological laboratory (75%. Based on personal hygiene habit after handling specimen, such as handwashing, 45.4% personnel had bad personal hygiene, thus the high riskgroup in child laboratory and hematological laboratory are both 75%.Keywords: clinical laboratory, level of risk, personal hygiene

    9. Gambaran Komponen Senyum Pasien Sebelum Perawatan Ortodonti (Kajian Foto Frontal di Klinik Ortodonti RSGMP FKG UI

      Directory of Open Access Journals (Sweden)

      Yuri Analia

      2013-07-01

      Full Text Available Smile is a non-verbal communication to express spontaneous feelings and emotions. Most patients that come to have orthodontic treatments want to have an attractive smile, but before the treatment smile has not yet been studied. There are eight components to make ideal frontal smile: lip line, smile arc, upper lip curve, buccal corridor, symmetry of smile, occlusal plane, dental and gingival components. This study was descriptive in design, in order to obtain frontal smile description before orthodontic treatment of RSGMP FKG UI patients that were grouped according to facial form, age, and gender. The results of the study show that patient smile before orthodontic treatment frequently exhibits medium lip line and the mean of incisor display at 75% of clinical crown. Most subjects show gingival display of 2 mm or less. On the smile arc, the most common features are straight smile and consonant smile. Equally common smile arc positions are those touching and not touching lower lip. The average buccal corridor is in medium smile, and thus most subjects have straight upper lip curves and symmetric smiles.DOI: 10.14693/jdi.v15i1.80

    10. Gambaran Komponen Senyum Pasien Sebelum Perawatan Ortodonti (Kajian Foto Frontal di Klinik Ortodonti RSGMP FKG UI)

      OpenAIRE

      Yuri Analia; Nia Ayu Ismaniati; Maria Purbiati

      2013-01-01

      Smile is a non-verbal communication to express spontaneous feelings and emotions. Most patients that come to have orthodontic treatments want to have an attractive smile, but before the treatment smile has not yet been studied. There are eight components to make ideal frontal smile: lip line, smile arc, upper lip curve, buccal corridor, symmetry of smile, occlusal plane, dental and gingival components. This study was descriptive in design, in order to obtain frontal smile description before o...

    11. Behandlung von Essstörungen bei Jugendlichen aus Sicht der kinder- und jugendpsychiatrischen Klinik

      OpenAIRE

      Pfeiffer, Ernst; Hansen, Berit; Korte, Alexander; Lehmkuhl, Ulrike

      2005-01-01

      Der Beitrag stellt - im Sinne klinischer Leitlinien - die aktuelle Praxis einer auf die Behandlung von Essstörungen spezialisierten Universitätsklinik für Kinder- und Jugendpsychiatrie dar. Die Notwendigkeit eines multimodalen Therapiekonzeptes wird betont, bestehend aus Maßnahmen zur Normalisierung von Gewicht und Essverhalten, Heilpädagogik, einzel-, gruppen- und familienbezogener Psychotherapie, ergänzt durch Körper-, Kunst- und Musiktherapie und ggf. Psychopharmakotherapie. Abschlie...

    12. Pencapaian Brand Corporate Melalui Brand Activation Pendekatan Experiential Marketing (Studi Kasus Laboratorium Klinik)

      OpenAIRE

      Lubis, Mahdalena; Ganiem, Leila Mona

      2017-01-01

      Brand activation is a corporation's endeavor to look deeper into what's in the brand, strategy and position of the brand. A new approach to brand activation by maximizing the range of relevant assets through product and service, employees, identity and communication combined with experiential marketing through sense, feel, think, act, relate, is considered highly effective in achieving corporate brand because it emphasizes the differentiation of competitors. This study aimed to find out how t...

    13. Hubungan Tingkat Maturitas Vertebra Servikalis Dan Kalsifikasi Gigi Pada Pasien Di Klinik Ortodonti RSGMP FKG USU

      OpenAIRE

      Bahirrah, Siti

      2011-01-01

      Introduction : The aim of this study was to know the relationship between the stages of calcification of teeth and the cervical vertebral maturity stage. Methods : A retrospective cross sectional study was designed. The final study population consisted of 70 subjects (mean age chronologis 10,63 + 1,83 years). Statistical analysis of the data was performed with SPSS windows 98. Spearman rank order test correlation coefficients were used to assess the relationship between cervical vertebral and...

    14. Persepsi Mahasiswa, Dosen dan Bidan Pembimbing tentang Model Pembelajaran Klinik Kebidanan yang Ideal

      OpenAIRE

      Yanti, Yanti; Emilia, Ova; Claramita, Mora

      2017-01-01

      Background: A large number graduates of midwife even now accompanied with low competency isues in associated with quality of clinical learning. Now implementation of clinical learning with caseload model has problems. Clinical learning model in clinical practice that student, teacher and clinical midwife experienced provide greater insight to develop an effective clinical teaching strategy in midwifery education. The main objective of this study was to investigate student midwife, teacher and...

    15. Clinical appearance and treatment of malignant pleural mesothelioma; Klinik und Therapie des malignen Pleuramesothelioms

      Energy Technology Data Exchange (ETDEWEB)

      Schiebe, M. [Tuebingen Univ. (Germany). Abt. fuer Strahlentherapie; Hoffmann, W. [Tuebingen Univ. (Germany). Abt. fuer Strahlentherapie; Kortmann, R.D. [Tuebingen Univ. (Germany). Abt. fuer Strahlentherapie; Bamberg, M. [Tuebingen Univ. (Germany). Abt. fuer Strahlentherapie

      1994-11-01

      We report about 7 of our own cases, treated with surgery and radiotherapy (4) or with a combination of surgery, radiotherapy and chemotherapy (3) and discuss the clinical aspects, diagnosis and the different ways of treatment of malignant pleural mesothelioma and its influence on survival. (orig.) [Deutsch] Wir berichten ueber sieben Patienten, die operiert und bestrahlt (vier) oder durch eine Kombination von operativen Massnahmen, Strahlen- und Chemotherapie behandelt wurden (drei). Klinische und diagnostische Aspekte sowie verschiedene Therapiemodalitaeten in der Behandlung des malignen Pleuramesothelioms werden im Ueberblick dargestellt. (orig.)

    16. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Symptoms

      Science.gov (United States)

      ... may also have: Tender lymph nodes in the neck or armpits A sore throat that happens often Digestive issues, like irritable bowel syndrome Chills and night sweats Allergies and sensitivities to ...

    17. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Treatment

      Science.gov (United States)

      ... practitioner, might help with pain for some patients. Depression, Stress, and Anxiety Adjusting to a chronic, debilitating ... Consequence Pathogens and Pathology (DHCPP) Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

    18. Radiology findings in adult patients with vocal fold paralysis

      Energy Technology Data Exchange (ETDEWEB)

      Robinson, S. [Helsinki Medical Imaging Centre, University of Helsinki, Haartmaninkatu, Helsinki (Finland)]. E-mail: s.robinson@dzu.at; Pitkaeranta, A. [Department of Otorhinolaryngology, Haartmaninkatu, Helsinki (Finland)

      2006-10-15

      Aim: To compile imaging findings in patients with vocal fold paralysis. Materials and methods: A retrospective analysis of the medical charts of 100 consecutive patients, admitted to our department with vocal fold paralysis was undertaken. After laryngoscopy, patients were referred for radiological work-up depending on their clinical history and clinical findings. Ultrasound of the neck and/or contrast-enhanced spiral computed tomography (CT) of the neck and mediastinum was performed, extending to include the whole chest if necessary. In one patient, CT of the brain and in two patients, magnetic resonance angiography was undertaken. Analysis of the clinical and radiological data was performed to assess the most frequent causes for vocal fold paralysis. Results: In 66% of patients, the paralysis was related to previous surgery. Thirty-four percent of cases were labelled idiopathic after clinical examination. After imaging and follow-up, only 8% remained unexplained. Nine patients suffered from neoplasms, four from vascular disease, and 12 from infections. One patient developed encephalomyelitis disseminata on follow-up. Conclusion: Thorough radiological work-up helps to reduce the amount of idiopathic cases of vocal fold paralysis and guides appropriate therapy.

    19. Radiology findings in adult patients with vocal fold paralysis

      International Nuclear Information System (INIS)

      Robinson, S.; Pitkaeranta, A.

      2006-01-01

      Aim: To compile imaging findings in patients with vocal fold paralysis. Materials and methods: A retrospective analysis of the medical charts of 100 consecutive patients, admitted to our department with vocal fold paralysis was undertaken. After laryngoscopy, patients were referred for radiological work-up depending on their clinical history and clinical findings. Ultrasound of the neck and/or contrast-enhanced spiral computed tomography (CT) of the neck and mediastinum was performed, extending to include the whole chest if necessary. In one patient, CT of the brain and in two patients, magnetic resonance angiography was undertaken. Analysis of the clinical and radiological data was performed to assess the most frequent causes for vocal fold paralysis. Results: In 66% of patients, the paralysis was related to previous surgery. Thirty-four percent of cases were labelled idiopathic after clinical examination. After imaging and follow-up, only 8% remained unexplained. Nine patients suffered from neoplasms, four from vascular disease, and 12 from infections. One patient developed encephalomyelitis disseminata on follow-up. Conclusion: Thorough radiological work-up helps to reduce the amount of idiopathic cases of vocal fold paralysis and guides appropriate therapy

    20. Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to Activity Management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): protocol for a randomised controlled trial.

      Science.gov (United States)

      Baos, Sarah; Brigden, Amberly; Anderson, Emma; Hollingworth, William; Price, Simon; Mills, Nicola; Beasant, Lucy; Gaunt, Daisy; Garfield, Kirsty; Metcalfe, Chris; Parslow, Roxanne; Downing, Harriet; Kessler, David; Macleod, John; Stallard, Paul; Knoop, Hans; Van de Putte, Elise; Nijhof, Sanne; Bleijenberg, Gijs; Crawley, Esther

      2018-02-22

      Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and disabling condition. The National Institute for Health and Clinical Excellence (NICE) recommends Cognitive Behavioural Therapy (CBT) as a treatment option for paediatric CFS/ME because there is good evidence that it is effective. Despite this, most young people in the UK are unable to access local specialist CBT for CFS/ME. A randomised controlled trial (RCT) showed FITNET was effective in the Netherlands but we do not know if it is effective in the National Health Service (NHS) or if it is cost-effective. This trial will investigate whether FITNET-NHS is clinically effective and cost-effective in the NHS. Seven hundred and thirty-four paediatric patients (aged 11-17 years) with CFS/ ME will be randomised (1:1) to receive either FITNET-NHS (online CBT) or Activity Management (delivered via video call). The internal pilot study will use integrated qualitative methods to examine the feasibility of recruitment and the acceptability of treatment. The full trial will assess whether FITNET-NHS is clinically effective and cost-effective. The primary outcome is disability at 6 months, measured using the SF-36-PFS (Physical Function Scale) questionnaire. Cost-effectiveness is measured via cost-utility analysis from an NHS perspective. Secondary subgroup analysis will investigate the effectiveness of FITNET-NHS in those with co-morbid mood disorders. If FITNET-NHS is found to be feasible and acceptable (internal pilot) and effective and cost-effective (full trial), its provision by the NHS has the potential to deliver substantial health gains for the large number of young people suffering from CFS/ME but unable to access treatment because there is no local specialist service. This trial will provide further evidence evaluating the delivery of online CBT to young people with chronic conditions. ISRCTN registry, registration number: ISRCTN18020851 . Registered on 4 August 2016.

    1. Reduktion af stress og sygefravær blandt patienter med arbejdsrelaterede belastnings- og tilpasningsreaktioner henvist til Arbejdsmedicinsk klinik

      DEFF Research Database (Denmark)

      Glasscock, David John; Carstensen, Ole; Dalgaard, Vita Ligaya Ponce

      is plagued by a number of methodological limitations. The definition of study populations is often unclear and there is a lack of studies with patients that have a clinically documented need for treatment. There is also a lack of research that evaluates interventions aimed at both the individual patient...... and his or her place of work. In the present study, patients referred by general practitioners to a department of occupational medicine for an evaluation of the role of work stress in the development of their symptoms were examined according to protocol. When it was assessed that symptoms reflected...... functioning. Four months after baseline we found a significant treatment effect on two measures, - 3 - perceived stress and mental health. The intervention group experienced less stress and fewer symptoms compared to the control group. There was also a non-significant trend in the same direction concerning...

    2. Pengaruh Kepuasan Konsumen Terhadap Loyalitas Merek Dengan Word Of Mouth Sebagai Variabel Mediasi (Studi Pada Klinik Kecantikan Di Kota Medan)

      OpenAIRE

      Nuraini

      2017-01-01

      This research is aim to investigate the influence of customer satisfaction and word of mouth as the mediating variable towards brand loyalty. The number of sample on this research was 105 respondents from consumer of certain beauty clinic with using purposive sampling. Data collected through customer satisfaction scale, word of mouth scale, and brand loyalty scale. The result showed there was influence of customer satisfaction towards brand loyalty, also customer satisfactio...

    3. EFEKTIVITAS HYPNOTERAPI TEKNIK ANCHOR TERHADAP PERUBAHAN PERILAKU MEROKOK REMAJA Studi Pada Klien di Klinik Maulana Center of Hypnotherapy Palembang

      Directory of Open Access Journals (Sweden)

      Budiman Budiman

      2017-02-01

      Full Text Available Adolescent smoking behavior is one of the behaviors that are formed through the influence of  the  environment  and  the  curiosity  of a  teenager  on  the  enjoyment  of  cigarettes  by  a  teenager. Smoking is also not only occurs in adolescent boys by the results of the study found  that smoking behavior  also  applies  to  young  women  as  well  as  children  who  are  still  in  primary  school.  This study  examines  the  effectiveness  Anchor  Techniques  of  Hypnoterapy  toward  Adolescent  Smoking Behavior Change. Study for Client in The Clinic Maulana Center of Hypnotherapy Palembang. The hypothesis  of  this  study  is  there  Effect  of  Anchor  Techniques  of  Hypnoterapy  smoke  Adolescent Behavior Change. Research for Clients in The Clinic Maulana Center of Hypnotherapy Palembang. This  study  included  a  quantitative  study  in  which  research  methods  used  was  Quasi  Experiment design with pretest and posttest with non-control group design, a design study aimed at testing the causal  relationship  (Polit  &  Beck,  2006.  This  study  will  be  conducted  at  the  Clinic  Maulana Center  of  Hypnotherapy  Palembang  on  March-June  2015.  The  Clinic  is  located  at  street  Kebun Bunga  complex  BNI  Block  B  4  Sukarami  Palembang  and  sampling  techniques  using  purposive sampling with 15 respondens and using t-test data analysis and MANOVA. The results of this study stated  that  there  Effect  Anchor  Techniues  of  Hypnotherapy toward  Adolescent  Smoking  Behavior Change. The changes meant is leading to better behavior and that, of 15 people treated with anchor techniques of hypnotherapy 11 people stop smoking while two people can reduce the intensity and frequency of smoking to 78% while the two others are only able to be able to reduce the intensity of smoking 56, 3%. It is advisable to adolescents to be more selective in choosing friends relations, peer  groups,  and  the  utilization  of  spare  time  with  positive  activities.  Trying  to  avoid  and  try smoking, improve self-control and self-regulation to the development of technology and information in order to avoid negative environment.

    4. Terapi Bekam dan Akupunktur Terhadap Penurunan Tekanan Darah pada Penderita Hipertensi Primer (Esensial di Klinik Herbal El Zahra Kota Tarakan

      Directory of Open Access Journals (Sweden)

      Yumira Ria Santi

      2014-11-01

      Full Text Available Hypertension is health problems are often happens in society, both of urban and rural community. Prevalence in Indonesia reached was 75.8% quite high, the long term medical treatment make it more difficult to handled properly. Alternative treatment like cupping and acupuncture are patients hypertension efforts to be free from side effects inflicted by chemical medicines. The purpose of this study was to determine the effect of cupping and acupuncture therapy effectiveness in blood pressure reduction among patients with primary hypertension. Study design used in this study was pre experimental designs with pretest–posttest, used statistics of paired t-test and independent t-test. The Results of paired test showed that value of p were 0.003 for systole blood pressure of cupping and 0.000 for systole blood pressure of acupuncture while diastole blood pressure of cupping obtained by value of p were 0.065 and 0.775 for diastole blood pressure of acupuncture, it means that cupping and acupuncture only had an affect on systole blood pressure reduction. Analysis results of independent t-test showed that value of p were 0.051 for systole blood pressure and 0.511 for diastole blood pressure, it means that there was no differences between cupping and acupuncture therapy. Based on average of blood pleasure reduction, acupuncture can reduce of 17 mmHg of systole blood pressure while cupping only 10 mmHg, in acupuncture also reduce of 16 mmHg diastole blood pressure while cupping canl 19 mmHg.

    5. Kondisi Periodontal Akibat Pemakaian Piranti Ortodonti Cekat Pada Pasien Di Klinik Ortodonti Rsgm Fakultas Kedokteran Gigi, Universitas Sumatera Utara

      OpenAIRE

      Yahya, Nur Adila Binti

      2015-01-01

      Evaluation on correlation of fixed orthodontic appliance with periodontal conditions on patients in Orthodontic clinic (RSGM) of Dentistry Faculty, University of North Sumatera. IX + 38 pages Fixed orthodontic appliance is an appliance that is fixed on teeth that cannot be opened by patients. Fixed orthodontic appliance may cause many oral complications due to the difficulities in maintaining good oral hygiene. Plaque is formed with the appliance of fixed orthodontic appliance which o...

    6. Klinik Mastitli Köpeklerden Alınan Süt Örneklerinde Aerobik Bakteri Muayenesi

      OpenAIRE

      TOYDEMIR, Tuğba; BAĞCIGİL, Arzu; TEKELI ÖZGÜR, N.; Kırşan, İsmail

      2015-01-01

      Canine mastitis occurs primarily during the postpartum period and may also occur during pseudopregnancy, as well as after early weaning of puppies. Clinical and bacteriological examinations of mammary secretion were performed in 17 bitches and results of the bacteriological examination of milk samples were evaluated. Staphylococcus intermedius (n=11) was the predominant isolate from the canine milk while the other microorganisms were Escherichia coli, Pseudomonas aeruginosa, S. aureus, Citrob...

    7. UPAYA KOMUNIKASI PEMASARAN INTERAKTIF PADA KLINIK SPESIALIS TERPADU RUMAH SAKIT GIGI DAN MULUT (RSGM FAKULTAS KEDOKTERAN GIGI UNAIR SURABAYA

      Directory of Open Access Journals (Sweden)

      Made Asri Budisuari

      2012-11-01

      Full Text Available Integrated Marketing Communications (IMC constitute of internal marketing, interactive and external communications. This research only addresses Interactive marketing communications. The specialized Dental Clinic (Integrated VIP Specialist has been under utilized. The problem exists presumably due to lack of interactive communications. The objective of this research is to formulate an IMC improvement effort for the Specialized Dental Clinic.This was an observational study conducted at the Specialized Dental Clinic from February up to Desember 2003. Observed variables were patient and organization of the clinic. Customers who visited the Specialized Dental Clinic were observed from the initial services the exit interview using questionnaire was collected by researche. The respondens were providers and customers (patientsThe result showed that the variable of customer service center and servicescapes were not well organized while personal selling relatively good.It is suggested that market survey should be done by the Specialized Dental Clinic, to actuate interactive marketing communication and to establish the utilization targets.

    8. Çocuklarda Dehidratasyonun Klinik ve Laboratuar Bulgularının Değerlendirilmesi

      OpenAIRE

      Aydın, Ahmet; Adal, Erdal

      2014-01-01

      SummaryDiarrheal dehydration is one of the leading causes of death in children in developing countries The assessment of the severiy of dehydration is the first step in successful fluid administration In this article physical signs and laboratory findings of dehydration will be reviewed Key words: Dehydration Children

    9. FAKTOR-FAKTOR YANG BERPENGARUH PADA LOYALITAS PELANGGAN KLINIK SARAF RUMAH SAKIT JIWA DAERAH Dr R.M. SOEDJARWADI

      Directory of Open Access Journals (Sweden)

      Rima Hayu Sri Widadi

      2016-07-01

      variable for the relationship between service quality and customer loyalty, while for the relationship between the image of the hospital with customer loyalty can not be termed as intermediate variable (intervening.

    10. Computerized tomography of the head. Technical fundamentals - interpretation - clinical aspects. Computertomographie des Kopfes. Technische Grundlagen - Interpretation - Klinik

      Energy Technology Data Exchange (ETDEWEB)

      Radue, E W; Kendall, B E; Moseley, I F

      1980-01-01

      To begin with, an outline is given of the physical fundamentals, the data processing procedure, and the structure of the various scanning systems. The authors give only general information on these as detailed descriptions are offered by the producers. Practical hints are given on positioning of patients and on data documentation which have been tried with good results at the authors' institutions. As regards the description of normal anatomical structures, only one planigraphic angle is described as there are atlases presenting all possible planigraphic planes and angles. However, the changes in shape of anatomical structures are described for different angles. The chapter on interpretation is based on the information to be recognized on the pictures. Considerations for differential diagnoses are listed for every single parameter. A diagnosis of probability ought to be possible merely on the basis of the data, without any clincial information. Anamnesis and clinical findings are required to increase diagnostic reliability. In the last chapter, the CT pictures of intraeranial, neurological diseases are presented. Besides typical pictures, also non-typical and infrequent findings are given.

    11. FAKTOR-FAKTOR YANG BERPENGARUH PADA LOYALITAS PELANGGAN KLINIK SARAF RUMAH SAKIT JIWA DAERAH Dr R.M. SOEDJARWADI

      OpenAIRE

      Rima Hayu Sri Widadi; Farid Wadji

      2016-01-01

      The Customer loyalty is absolutely necessary in this era of increasingly fierce competition, including in the health care business . Because of the absence of customer loyalty, the hospital will not grow well even be left by customers. The purpose of this study was to analyze the factors that affect customer loyalty in Clinical of Neurology RSJD Dr. RM Soedjarwadi .The total sample of 139 respondents in there with purposive sampling. Based on SEM analysis concluded that the impact of service ...

    12. METODE KONVENSIONAL, KINESIOTAPING, DAN MOTOR RELEARNING PROGRAMME BERBEDA EFEKTIVITAS DALAM MENINGKATKAN POLA JALAN PASIEN POST STROKE DI KLINIK ONTOSENO MALANG

      Directory of Open Access Journals (Sweden)

      Dimas Sondang Irawan

      2014-03-01

      Full Text Available Stroke patient would have impaired activities of daily living. One-sided weakness of extremities, poor body control, and gait instability. Rehabilitation in stroke patient, effective and can improve the function of the impaired limb. Exercise can provide the functional activity of learning and apply the basic premise that the capacity of the brain is able to reorganize and adaptable so with targeted exercises it can be improved. This study aimed to compare the efficiacy of conventional methods, applications kinesiotaping, and MRP method in improving the gait pattern of stroke patients. The study has pre and post test with control group design using 3 groups. There are 10 people in each group. The first group was given conventional intervention methods, group II given Kinesiotaping application, and the third group was given the intervention using the MRP  with duration of exercise 3 times a week with a time of 60 minutes for 4 weeks. Data in the form of pre-test and post-test patterns of stroke patients analized by using Wisconsin Gait Scale. Samples were 30 divided into 3 groups. In the conventional group had a mean age of 62.3 years with a number of men 5 men and 5 women. At Kinesiotaping group had a mean age of 65.1 years with a number 6 men and 4 women. While the MRP group had a mean age of 62.6 years with a number 6 men and 4 women. Results of hypothesis testing using Anova showed a significant difference between the (average of the WGS scores after intevention of the three groups, with value of p<0,05. The comparison on each method showed that the Kinesiotaping application and MRP have significant difference, but the Kinesiotaping application showed no significally difference with MRP. The conclusions in this study that the conventional methods, Kinesiotaping application and MRP has different efficacy on improfing gait pattern of stroke patient.

    13. GAMBARAN KLINIK DAN LATAR BELAKANG PASIEN DENGAN DIAGNOSIS KLNIK SEBAGAI LICHEN PLANUS DI POLI PENYAKIT MULUT RSCM DAN RSGM

      Directory of Open Access Journals (Sweden)

      Sri Tjahjani Sumantri

      2015-08-01

      Full Text Available Lichen planys is disorder of the skin and mucous membrane that presenting pruritic, purple and polygonal papules. Oral lesions may persist for years and with clinical appearance that sometimes very ocnfusing. In most cases, oral lesions are present as white, reticulated or natelike areas involving the mucosa. These lesions are characteristic and called Wickham's striae. This paper presented some cases with lesions that resembled oral lichen planus.

    14. Interferon-gamma regulates oxidative stress during experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Espejo, Carmen; Penkowa, Milena; Sáez-Torres, Irene

      2002-01-01

      disease eliciting secretion of proinflammatory cytokines like IFN-gamma or TNF-alpha, and it has been suggested that cytokine-induced oxidative stress could have a role in EAE neuropathology. However, the individual roles of these and other cytokines in the pathogenesis of the disease are still uncertain....... Here we analyze the role of IFN-gamma during EAE by using both IFN-gamma receptor-knockout (IFN-gamma R(-/-)) and wild-type mice, both strains immunized with peptide 40-55 from rat myelin oligodendrocyte glycoprotein. The levels of oxidative stress were determined through the analysis...... of immunoreactivity for inducible NO synthase, nitrotyrosine, and malondialdehyde, as well as through the expression of the tissue-protective antioxidant factors metallothionein I+II (MT-I+II). We also examined the number of cells undergoing apoptosis as judged by using the TUNEL technique. The levels of oxidative...

    15. Interferon regulatory factor-7 modulates experimental autoimmune encephalomyelitis in mice

      DEFF Research Database (Denmark)

      Salem, Mohammad; Mony, Jyothi T; Lobner, Morten

      2011-01-01

      . Furthermore, IRF7-deficient mice developed more severe disease. Flow cytometric analysis showed that the extent of leukocyte infiltration into the CNS was higher in IRF7-deficient mice with significantly higher number of infiltrating macrophages and T cells, and the distribution of infiltrates within......ABSTRACT: BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) with unknown etiology. Interferon-beta (IFN-beta), a member of the type I IFN family, is used as a therapeutic for MS and the IFN signaling pathway is implicated in MS susceptibility...... of MS-like disease in mice. Methods The role of IRF7 in development of EAE was studied by immunizing IRF7-KO and C57BL/6 (WT) mice with myelin oligodendrocyte glycoprotein using a standard protocol for the induction of EAE. We measured leukocyte infiltration and localization in the CNS using flow...

    16. Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Koch, Marcus W; Zabad, Rana; Giuliani, Fabrizio; Hader, Walter; Lewkonia, Ray; Metz, Luanne; Wee Yong, V

      2015-11-15

      Microglial activation is thought to be a key pathophysiological mechanism underlying disease activity in all forms of MS. Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory properties that is widely used in the treatment of rheumatological diseases. In this series of experiments, we explore the effect of HCQ on human microglial activation in vitro and on the development of experimental autoimmune encephalitis (EAE) in vivo. We activated human microglia with lipopolysaccharide (LPS), and measured concentrations of several pro- and anti-inflammatory cytokines in untreated and HCQ pretreated cultures. We investigated the effect of HCQ pretreatment at two doses on the development of EAE and spinal cord histology. HCQ pretreatment reduced the production of pro-inflammatory (TNF-alpha, IL-6, and IL-12) and anti-inflammatory (IL-10 and IL-1 receptor antagonist) cytokines in LPS-stimulated human microglia. HCQ pretreatment delayed the onset of EAE, and reduced the number of Iba-1 positive microglia/macrophages and signs of demyelination in the spinal cords of HCQ treated animals. HCQ treatment reduces the activation of human microglia in vitro, delays the onset of EAE, and decreases the representation of activated macrophages/microglia and demyelination in the spinal cord of treated mice. HCQ is a plausible candidate for further clinical studies in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

    17. 9 CFR 113.325 - Avian Encephalomyelitis Vaccine.

      Science.gov (United States)

      2010-01-01

      ... samples of completed product shall be tested for virus titer using the titration method used in paragraph... more chickens shall be used as vaccinates for each method of administration recommended on the label... predetermined quantity of vaccine virus. Five replicate virus titrations shall be conducted on an aliquot of the...

    18. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Possible Causes

      Science.gov (United States)

      ... change in the person’s immune system and the way it responds to infection or stress. ME/CFS shares some features of autoimmune illnesses ( ... reside on top of the kidneys). The glands release various hormones, like ... called “the stress hormone,” helps to lower inflammation and calm down ...

    19. Feeding different levels of vitamin E and selenium has no effect on serum immunoglobulin Y (IgY production by layers vaccinated against Escherichia coli and avian encephalomyelitis virus Alimentação com diferentes níveis de vitamina E e selênio não influencia a produção de imunoglobulina Y (IgY no soro de poedeiras leves vacinadas contra Escherichia coli e encefalomielite aviária

      Directory of Open Access Journals (Sweden)

      Giselle Kindlein

      2007-10-01

      Full Text Available The effects of vitamin E and selenium (Se supplementation on the immunity of hens vaccinated against a mixture of six swine-pathogenic Escherichia coli (EC and avian encephalomyelitis virus (AEV were studied. Antibody production (AbP was evaluated in ninety 49 to 57-week-old H&N Nick Chick hens fed diets containing 14IU Vitamin E kg-1 (basal diet, 27, 59, 111, or 111IU vitamin E kg-1 + 0.56ppm Se supplementation. At 51 wks of age, half of the hens were vaccinated against EC, and all birds were vaccinated against AEV. At 53-weeks of age, the birds received a second dose of EC vaccine. Blood samples were collected weekly and serum was analyzed by ELISA for anti-EC IgY and was expressed as optical density (OD. Vaccinated hens had higher serum OD than the non-vaccinated hens (P£0.05. Vaccinated hens fed 27 and 59IU of vitamin E/kg had a higher (POs efeitos da suplementação de vitamina E e Selênio (Se na imunidade de galinhas vacinadas contra uma mistura de 6 sorotipos patogênicos de Escherichia coli (EC e o vírus da encefalomielite aviária (VEA foram estudados. A produção de anticorpos foi avaliada em galinhas H&N Nick Chick durante a 49a e 57a semanas de vida. As aves foram alimentadas com dietas contendo 14UI de Vitamina E kg-1 (dieta basal, 27, 59, 111 e 111UI de Vitamina E kg-1 + 0,56ppm Se suplementar. Às 51 semanas de idade, metade das galinhas foi vacinada contra EC, e todas as aves foram vacinadas contra VEA. Às 53 semanas, as aves receberam a segunda vacina contra EC. Amostras de sangue foram coletadas semanalmente e o soro foi analisado por ELISA para anti-EC IgY e expresso como densidade óptica (DO. Galinhas vacinadas tiveram maior DO do que as não-vacinadas (P<0,05. Aves vacinadas que receberam 27 e 59 UI de vitamina E/kg tiveram maior DO do soro (P<0,05 do que as alimentadas com 111 UI + Se. Os antígenos utilizados mostraram não ser modelos satisfatórios para estudar a influência de micronutrientes na resposta imune de

    20. Nigerian Medical Journal - Vol 53, No 3 (2012)

      African Journals Online (AJOL)

      The role of doppler ultrasound in high risk pregnancy: A comparative study · EMAIL ... Does any relationship exist between self reported gingival bleeding, oral health ... Leiomyomatosis peritonealis disseminata in a Nigerian woman · EMAIL ...

    1. Tropical Journal of Obstetrics and Gynaecology - Vol 22 (2005)

      African Journals Online (AJOL)

      Association between absence of vaginal lactobacilli PCR products and nugent ... Bacterial vaginosis, Candida albicans and Trichomonas vaginalis infection in .... Progressive leiomyomatosis peritonalis disseminata (LPD): a case report and ...

    2. Hubungan Pengetahuan dan Sikap Penderita Diabetes Melitus (DM) dengan Pemanfaatan Klinik Diabetes Melitus di Puskesmas Sering Kecamatan Medan Tembung Tahun 2010

      OpenAIRE

      Harahap, Erwina Rafni

      2010-01-01

      Diabetes melitus dikenal sebagai non communicable disease adalah penyakit yang sering diderita di Indonesia saat ini. Penyakit diabetes melitus semakin hari semakin meningkat, dapat dilihat dari meningkatnya frekuensi kejadian penyakit tersebut. Berdasarkan data dari Puskesmas Sering ada 105 pasien diabetes melitus. Dari data tersebut terlihat bahwa penderita diabetes melitus di Sumatera Utara masih sangat tinggi. Untuk menanggulangi masalah tersebut, sejak tahun 2007 Puskesmas Sering telah m...

    3. Kraujo perpylimas praktika tarp medicinos gydytojų, dirbančių Kauno klinikų ligoninėje

      OpenAIRE

      Zindrou, Sengin Lezan

      2017-01-01

      Author: Sengin Lézan Zindrou Title: Blood transfusion practice among medical physicians working at Kauno Klinkos Hospital. Aim: To review the clinical practice of blood transfusion in different clinical settings, to evaluate the threshold of blood transfusion as well as the units of blood used. Objectives:1. To assess blood transfusion threshold among physicians according clinical practice (different medical specialties). 2. To determine and compare the threshold for blood transfusion between...

    4. Pediatric cardiology. Clinical and practical experiences with heart diseases of children, juveniles and young adults; Kinderkardiologie. Klinik und Praxis der Herzerkrankungen bei Kindern, Jugendlichen und jungen Erwachsenen

      Energy Technology Data Exchange (ETDEWEB)

      Haas, Nikolaus A. [Herz- und Diabeteszentrum NRW, Bad Oeynhausen (Germany). Klinik fuer angeborene Herzfehler; Kleideiter, Ulrich [Klinik fuer Kinder- und Jugendmedizin, Coesfeld (Germany)

      2011-07-01

      The book on pediatric cardiology covers the following chapters: (I) Fundamentals and diagnostics: pediatric cardiologic anamnesis, electrocardiograms, thorax X-radiography, MRT and CT of the heart, nuclear medical diagnostics, exercise tests, heart catheter examination, electrophysiological tests. (II) Leading symptoms: Cyanosis, cardiac murmur, thorax pain, palpitation, syncopes. (III) Disease pictures: congenital heart defects, acquired heart defects, cardiomyopathies, heart rhythm disturbances, heart insufficiency, arterial hypertension, pulmonary hypertension, other heart involving syndromes. (IV) Therapy: Catheter interventional therapy, post-surgical pediatric cardiac therapy, surgery involving the life-support machine, mechanical cardiovascular support systems, initial treatment of newborns with critical heart defects, heart transplantation, vaccination of children with heart diseases, medicinal therapy.

    5. Quality management systems in radiology. Implementation in hospital and radiology practice; Qualitaetsmanagementsysteme in der Radiologie. Umsetzung in der Klinik und Praxis

      Energy Technology Data Exchange (ETDEWEB)

      Teichgraeber, U.; Bucourt, M. de [Charite Universitaetsmedizin Berlin (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie

      2010-11-15

      The concept of quality and the principle of continuous quality improvement are implemented by quality management systems. Quality management systems surpass mere quality control. These systems account for patient and employee needs, the management style and the structure of an enterprise. Many of these quality management systems are used in the health care industry. Some of these systems and their form of application in radiology are introduced here. (orig.)

    6. Epstein-Barr Virus Infektionen. Neue Aspekte zur Pathogenese und Klinik ( = Epstein-Barr virus infections. New pathogenic and clinical aspects)

      OpenAIRE

      Wilmes, E.; Wolf, Hans J.

      1989-01-01

      The Epstein-Barr virus (EBV) is among the most widespread of human viruses. It causes several different diseases, such as acute infectious mononucleosis (IM), chronic active EBV-infection (cEBV), the x-linked lymphoproliferative syndrome (XLP), polyclonal and oligoclonal lymphomae in connection with immunologic disorders, as well as African Burkitt's lymphoma and nasopharyngeal carcinoma. Pathogenesis, clinical features and diagnosis are discussed. In this connection, special tests on the lat...

    7. SOSIALISASI DAN KONSULTASI HUKUM BISNIS, HUKUM KEWARGANEGARAAN, HUKUM PIDANA DAN HUKUM ADAT & MASYARAKAT DI KLINIK HUKUM INTERAKTIF RADIO SUARA JANGER POLDA BALI

      Directory of Open Access Journals (Sweden)

      NI KETUT SUPASTI DHARMAWAN

      2012-09-01

      Full Text Available ABSTRACT The team lecturers from Faculty of Law socialized Business law, Nationality law, Criminal law and Adat law at the Legal Clinic Radio Polda “SUARA JANGER” on July 2007. This community services used interactive method by using telephone, SMS and e-mail. The all session of interactive legal consultation were well done and got positive response from the communities as proven by the receipt of 4 to 5 calls within a one hour interactive duration conducted once a week. Through this services community and legal consultation several legal issues such as industrial design, children’s protection who were born from mix marriage, good governance, money laundering, terrorism, and polygamy were discussed and the further legal solutions were advised by the team advisors refer to the Act No. 31 year 2000, the Act No. 12 year 2006, and the Act No.15 year 2003.

    8. Güncel bir cam iyonomer restoratif sistemin 36-aylık klinik performansının değerlendirilmesi

      OpenAIRE

      Kütük, Zeynep Bilge; Gürgan, Sevil; Yalçın Çakır, Filiz; Ergin, Esra; Öztaş, Sema Seval

      2014-01-01

      Objectives: To evaluate the 36 month clinical performance of a current glass-ionomer restorative system by comparing with a micro-filled resin composite, on Class II cavities.Materials and Methods: Sixty cavities in 26 patients were randomly divided into two groups according to the restorative systems used (n=30); the cavities in Group 1 were restored with a glass-ionomer restorative system (EQUIA/GC); packable glass-ionomer (Fuji IX GP EXTRA/GC)+self-adhesive nano-filled coating (G-Coat PLUS...

    9. STRATEGI PENGEMBANGAN INSTITUSI PELAYANAN KESEHATAN GIGI DENGAN PENDEKATAN RISET OPERASIONAL (Suatu Kajian Terhadap Perencanaan Strategik Pengembangan Klinik Gigi Akadmeik Fakultas Kedokteran Gigi Universitas Trisakti Tahun 2000 - 2004

      Directory of Open Access Journals (Sweden)

      Tri Erri Astoeti

      2015-08-01

      Full Text Available The purpose of this study was to determine the best strategy to develop dental health institution. This study used operational research method with qualitative and quantitative analysis and aided by forecasting technique such as Time Series Forecasting from QSB+ at Academic Dental Clinic (KGA FKG Usakti. The research was done in 3 (three stages. Stage 1 (input stage covered the external and internal analysis of KGS FKG Usakti through a Consensus Decision Making Group (CDMG. In stage II (matching stage the result of stage I was analyzed using Internal-External (IE and SWOT matrix. The best strategy priorities was determined in the last stage (decision stage using the QPSM matrix. In the matching stage, CDMG agreed that KGA FKG Usakti is at Grow and Build position which consisted of intensive strategies (market penetration, market development, product development, and integrative strategies (forward, backward, horizontal integration. As conclusion, KGA FKG Usakti has a significant market potential and relatively strong internal capability, in a competitive atmosphere. The position of grow and build indicates that a quality improvement is still needed. All selected strategies shall be operated and reorganized following three different structures of increasing sales/marketing, operations and performances, and supporting infrastructure.

    10. Post-operative X-ray morphology: Joints. Handbook and atlas for clinical and practical use. Postoperative Roentgenmorphologie: Gelenke. Handbuch und Atlas fuer Klinik und Praxis

      Energy Technology Data Exchange (ETDEWEB)

      Vogel, H.

      1987-01-01

      The description of X-ray findings after operations with the object of implanting protheses in joints makes up most of the contents of this book. The reconstruction of joints after trauma is only marginally dealt with. Among the various indications for implanting protheses, the replacement of joints destroyed by wear and trauma is the most important. Also considered were X-ray examinations after hallux-valgus operations and plastic surgery on hands and feet, as well as X-ray findings following operations on the lumbar part of the vertebral column (disc surgery).

    11. Glutamate metabolism is down-regulated in astrocytes during experimental allergic encephalomyelitis

      DEFF Research Database (Denmark)

      Hardin-Pouzet, H; Krakowski, M; Bourbonnière, L

      1997-01-01

      dehydrogenase (GDH) expression were dramatically reduced. These two astrocytic enzymes are responsible for degradation of glutamate, the most abundant excitatory neurotransmitter in the brain. Since elevated levels of glutamate may be neurotoxic, we propose that the decreased capacity of astrocytes...... to metabolize glutamate may contribute to EAE pathology....

    12. Bibliography on Venezuelan Equine Encephalomyelitis (VEE). Supplement 7, 1247-1300.

      Science.gov (United States)

      1982-05-01

      1979. 1287. Scherer, W. F., J. Madalengoitia, 0. Meneses, and M. Acosta. Estudio de los virus EV y aislamiento de los arbovirus ESL, EE, grupo C, y grupo...Meneses, 0. 1288 Menshikh, L. K. 120, 121, 465, 502, 863, 865, 926, 968, 969, 1065 Mercado -Sanchez, S. 698, 712, 1198 Mergenhagen, S. E. 212 Metcalf, H. E

    13. Effect of live attenuated vaccines on the course of experimental allergic encephalomyelitis. A pilot study.

      Science.gov (United States)

      Caspary, E A

      1977-01-01

      The clinical severity of EAE is enhanced by pre-treatment with distemper, measles and BCG vaccine, measles vaccine gives a more severe onset of disease. Rubella vaccine and TAB leads to mild disease which recurs on re-treatment with the appropriate vaccine. These findings and their possible significance in MS are briefly discussed.

    14. Cannabinoid treatment renders neurons less vulnerable than oligodendrocytes in experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Hasseldam, Henrik; Johansen, Flemming Fryd

      2011-01-01

      and demyelination. Furthermore, the cytokines IL-2, IL-6, IL-10, RANTES, and TGF-ß were significantly reduced as were the cellular infiltration with regulatory T cells. We suggest that cannabinoids in low doses are neuroprotective through a reduction in calpain 1 expression. Our study implies that long-term low...

    15. Role of passive T-cell death in chronic experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Issazadeh-Navikas, Shohreh; Abdallah, K; Chitnis, T

      2000-01-01

      central nervous system (CNS) compared with controls. There was also a decreased number of apoptotic cells in the CNS of Bcl-x(L) transgenic mice when compared with littermates at all time points tested. This is the first report of an autoimmune disease model in Bcl-x(L) transgenic mice. Our data indicate...

    16. Immunomodulatory effects of helminths and protozoa in multiple sclerosis and experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Hasseldam, Henrik; Hansen, C S; Johansen, F F

      2013-01-01

      hygiene standards that exist in the western world, with reduced exposure to various pathogens, including parasites, as a consequence. Parasites are known to employ various immunomodulatory and anti-inflammatory strategies, which enable them to evade destruction by the immune system. This is most likely...... one of the reasons for the disease-dampening effects, reported in numerous studies investigating parasite infections and autoimmunity. This review will focus on recent advances in the field of parasites as beneficial immunomodulators, in multiple sclerosis and the animal model experimental autoimmune...

    17. Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis : a quantitative MRI study

      NARCIS (Netherlands)

      Floris, S.; Blezer, E.L.A.; Schreibelt, Gerty; Dopp, E.; Pol, van der S.M.A.; Schadee-Eestermans, I.L.; Nicolaij, K.; Dijkstra, C.D.; Vries, de H.E.

      2004-01-01

      Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood–brain barrier

    18. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: What is ME/CFS?

      Science.gov (United States)

      ... became ill. ME/CFS changes people’s ability to do daily tasks, like taking a shower or preparing a meal. ME/CFS often makes it hard to keep a job, go to school, and take part in family and social life. ME/CFS ...

    19. Bone marrow-derived versus parenchymal sources of inducible nitric oxide synthase in experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Zehntner, Simone P; Bourbonniere, Lyne; Hassan-Zahraee, Mina

      2004-01-01

      . These discrepancies may reflect balance between immunoregulatory and neurocytopathologic roles for NO. We investigated selective effects of bone marrow-derived versus CNS parenchymal sources of iNOS in EAE in chimeric mice. Chimeras that selectively expressed or ablated iNOS in leukocytes both showed significant...

    20. A Case Definition for Children with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

      OpenAIRE

      Leonard A. Jason; Nicole Porter; Elizabeth Shelleby; David S. Bell; Charles W. Lapp; Kathy Rowe; Kenny De Meirleir

      2008-01-01

      The case definition for chronic fatigue syndrome was developed for adults (Fukuda et al. 1994), and this case definition may not be appropriate for use with children and adolescents. The lack of application of a consistent pediatric definition for this illness and the lack of a reliable instrument to assess it might lead to studies which lack sensitivity and specificity. In this article, a case definition is presented that has been endorsed by the International Association of ME/CFS.

    1. The immunology of multiple sclerosis and its animal model, experimental allergic encephalomyelitis

      DEFF Research Database (Denmark)

      Owens, T; Sriram, S

      1995-01-01

      Two questions were posed at the beginning of this article. Is EAE a good model for MS? And, is MS an autoimmune disease? The first question is easier to address than the second. EAE is the best available model for the inflammatory processes that occur in MS, and for the disease process. The latter...... depends somewhat on study of chronic relapsing EAE, rather than early or mono-episodic EAE, which, although of great immunological interest, is of less relevance to the established disease that presents as MS. The second question asks whether MS fulfills Koch's postulates as an autoimmune disease. MS has...

    2. CD1-dependent regulation of chronic central nervous system inflammation in experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Teige, Anna; Teige, Ingrid; Lavasani, Shahram

      2004-01-01

      (s). When immunized with CFA before T cell transfer, the CD1-/- mice again developed an augmented EAE compared with CD1+/+ mice. We suggest that CD1 exerts its function during CFA-mediated activation, regulating development of EAE both through enhancing TGF-beta1 production and through limiting autoreactive...

    3. Experimental allergic encephalomyelitis: peculiarities of pain-relieving therapy and place of anticonvulsants as analgetics

      Directory of Open Access Journals (Sweden)

      Nefyodov O.O.

      2015-11-01

      Full Text Available Multiple sclerosis (MS is the most common demyelinating disease affecting mainly young people of the working age (16-45 years and quickly leading to disability. Available data constitute that up to 80% of MS patients suffer from pain at different disease periods. Pain management and the analgesic drug choice in MS patients may be difficult. Anticonvulsant drugs possess an analgesic activity and are widely used in patients presenting painful neuropathic symptoms. Based on that, we aimed to investigate the nociceptive potential changes as well as the research-oriented behavior using the "open field" test in rat. An experimental animal equivalent of multiple sclerosis has been modeled, based on the methylprednisolone (M administration. Animals were also administered anticonvulsants (carbamazepine, topiramate, sodium volproat, pregabalin and gabapentin. The stu­dy showed advantages of gabapentin and pregabalin use in simulated disease treatment. This statement is based on the "open field" test results, where the motor-oriented rats’ behavior was evaluated. Administration of M+gabapentin and M+pregabalin showed positive dynamics of the motor activity: the number of squares crossed increased by 80.86% (p<0.05 and 81.73% (р<0.05 respectively. Maximum recovery of the research activity (peeking in "mink" was re­gis­tered in animals administered M+pregabalin: the increase rate was 300% (r<0.05 comparing with the 12th day of ex­periment. It was shown, that 5-days administration of M+gabapentin and M+pregabalin caused muscle tone impro­ve­ment by 190% (p<0.05 and 200% (p<0.05 respectively, comparing with animals with untreated multiple sclerosis. A sig­ni­fi­cant increase of analgesic activity of M+pregabalin and M+gabapentin combinations used together with me­thyl­pred­nisolone by 4.1 (p<0.05 and 3.6 (p<0.05 times was registered comparing with the initial methylprednisolone background.

    4. Paediatric Australian bat lyssavirus encephalomyelitis - sequential MRI appearances from symptom onset to death.

      Science.gov (United States)

      Shetty, Umesh; Phillips, Mark; Francis, Joshua R; Walsh, Mark

      2015-10-01

      Human infection with Australian bat lyssavirus is extremely rare. Here we present the craniospinal findings in a fatal case of Australian bat lyssavirus infection in an 8-year-old child. MRI plays a very important role, not only in the diagnostic work-up of Australian bat lyssavirus infection but also in the prognostic assessment.

    5. Paediatric Australian bat lyssavirus encephalomyelitis - sequential MRI appearances from symptom onset to death

      International Nuclear Information System (INIS)

      Shetty, Umesh; Phillips, Mark; Walsh, Mark; Francis, Joshua R.

      2015-01-01

      Human infection with Australian bat lyssavirus is extremely rare. Here we present the craniospinal findings in a fatal case of Australian bat lyssavirus infection in an 8-year-old child. MRI plays a very important role, not only in the diagnostic work-up of Australian bat lyssavirus infection but also in the prognostic assessment. (orig.)

    6. Continued administration of ciliary neurotrophic factor protects mice from inflammatory pathology in experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Kuhlmann, Tanja; Remington, Leah; Cognet, Isabelle

      2006-01-01

      Multiple sclerosis is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. We show that daily administration (days 8 to 24) of murine ciliary neurotrophic factor (CNTF), a neurotrophic factor that has been described as a surv......Multiple sclerosis is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. We show that daily administration (days 8 to 24) of murine ciliary neurotrophic factor (CNTF), a neurotrophic factor that has been described...... it was withdrawn. After cessation of CNTF treatment, inflammation and symptoms returned to control levels. However, slight but significantly higher numbers of oligodendrocytes, NG2-positive cells, axons, and neurons were observed in mice that had been treated with high concentrations of CNTF. Our results show...

    7. In Acute Experimental Autoimmune Encephalomyelitis, Infiltrating Macrophages Are Immune Activated, Whereas Microglia Remain Immune Suppressed

      NARCIS (Netherlands)

      Vainchtein, I. D.; Vinet, J.; Brouwer, N.; Brendecke, S.; Biagini, G.; Biber, K.; Boddeke, H. W. G. M.; Eggen, B. J. L.

      2014-01-01

      Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of

    8. Granulomatous encephalomyelitis and intestinal ganglionitis in a spectacled Amazon parrot (Amazona albifrons) infected with Mycobacterium genavense.

      Science.gov (United States)

      Gomez, G; Saggese, M D; Weeks, B R; Hoppes, S M; Porter, B F

      2011-01-01

      An approximately 30-year-old male spectacled Amazon parrot (Amazona albifrons) was presented with a 2-week history of ataxia, head shaking, weight loss and seizures. Gross findings on necropsy examination included atrophy of the musculature, ruffled feathers and minimal epicardial and abdominal fat. Microscopically, there were perivascular cuffs of macrophages with fewer lymphocytes in the grey and white matter of the brain and spinal cord. These lesions were accompanied by gliosis and mild vacuolation of the white matter. In the small intestine, up to 70% of the intestinal ganglia were effaced by infiltrates of macrophages and fewer lymphocytes. The intestinal lamina propria contained multiple inflammatory aggregates of a similar nature. Ziehl-Neelsen staining revealed the presence of numerous bacilli within the cytoplasm of macrophages in the central nervous system (CNS) and enteric ganglia. Amplification of the DNAJ gene confirmed a mycobacterial infection and subsequent polymerase chain reaction (PCR) using a species-specific primer confirmed the aetiology as Mycobacterium genavense. Infection of the CNS with Mycobacterium spp. is uncommon and has not been previously reported in a parrot. This case is unusual in that the organism exhibited tropism for neural tissue. Copyright © 2010 Elsevier Ltd. All rights reserved.

    9. IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils

      Directory of Open Access Journals (Sweden)

      Savarin Carine

      2012-05-01

      Full Text Available Abstract Background The interplay between IFN-γ, IL-17 and neutrophils during CNS inflammatory disease is complex due to cross-regulatory factors affecting both positive and negative feedback loops. These interactions have hindered the ability to distinguish the relative contributions of neutrophils, Th1 and Th17 cell-derived effector molecules from secondary mediators to tissue damage and morbidity. Methods Encephalitis induced by a gliatropic murine coronavirus was used as a model to assess the direct contributions of neutrophils, IFN-γ and IL-17 to virus-induced mortality. CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT or IFN-γ deficient (GKO memory CD4+ T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade. Results Transfer of GKO memory CD4+ T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4+ T cells, despite similar virus control and demyelination. In contrast to recipients of WT CD4+ T cells, extensive neutrophil infiltration and IL-17 expression within the CNS in recipients of GKO CD4+ T cells provided a model to directly assess their contribution(s to disease. Recipients of WT CD4+ T cells depleted of IFN-γ did not express IL-17 and were spared from mortality despite abundant CNS neutrophil infiltration, indicating that mortality was not mediated by excessive CNS neutrophil accumulation. By contrast, IL-17 depletion rescued recipients of GKO CD4+ T cells from rapid mortality without diminishing neutrophils or reducing GM-CSF, associated with pathogenic Th17 cells in CNS autoimmune models. Furthermore, co-transfer of WT and GKO CD4+ T cells prolonged survival in an IFN-γ dependent manner, although IL-17 transcription was not reduced. Conclusions These data demonstrate that IL-17 mediates detrimental clinical consequences in an IFN-γ-deprived environment, independent of extensive neutrophil accumulation or GM-CSF upregulation. The results also suggest that IFN-γ overrides the detrimental IL-17 effector responses via a mechanism downstream of transcriptional regulation.

    10. Experimental allergic encephalomyelitis in rhesus monkeys: MR spectroscopy comparison with histopathology and ultrastructure

      International Nuclear Information System (INIS)

      Cao Qian; Wang Lianqing; Wu Jing; Zhao Huadong; Zhai Jinping; Guo Xue; Liu Lianxiang; Wu Yujin

      2002-01-01

      Objective: To study the relationships between changes of rhesus monkeys with EAE in MRS and those in histopathology and ultrastructure. Methods: Nine rhesus monkeys were sensitized by the intradermal injection of homologous myelin basic protein or purified bovine MBP in complete Freund's adjuvant. The ratio of Cho/Cr and NAA/Cr was measured in EAE over course and compared with that before attack. Finally, the histologic characters of the disease was confirmed by light microscope and transmission electron microscope. Results: The lesions of acute and chronic form of EAE was extensive. The lesions of chronic form of EAE observed on MRI were multiple and limited, with mild inflammation. The ratios of NAA/Cr in acute and chronic form were decreased (t = 68.66, 5.69, separately, P < 0.05). A lot of vacuolation, hydropic degeneration, and lipofuscin in the axis-cylinders could be observed in both phases. The ratio of Cho/Cr in chronic EAE was increased (t = 3.48, P < 0.05). In acute form of EAE, severe inflammation, necrosis, and destruction of axons were observed in histopathology. However, chronic form of EAE showed marked demyelination. Conclusion: The ratios of Cho/Cr and NAA/Cr by MRS quantitative analysis can be used to determine different stages of the lesion and predict the histopathological feature in EAE in rhesus monkeys

    11. Paediatric Australian bat lyssavirus encephalomyelitis - sequential MRI appearances from symptom onset to death

      Energy Technology Data Exchange (ETDEWEB)

      Shetty, Umesh; Phillips, Mark; Walsh, Mark [Mater Hospital and Lady Cilento Children' s Hospital Medical Imaging Department, Brisbane, QLD (Australia); Francis, Joshua R. [Royal Darwin Hospital, Department of Paediatrics, Darwin (Australia)

      2015-10-15

      Human infection with Australian bat lyssavirus is extremely rare. Here we present the craniospinal findings in a fatal case of Australian bat lyssavirus infection in an 8-year-old child. MRI plays a very important role, not only in the diagnostic work-up of Australian bat lyssavirus infection but also in the prognostic assessment. (orig.)

    12. Clinical Criteria Versus a Possible Research Case Definition in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

      Science.gov (United States)

      Jason, Leonard A; McManimen, Stephanie; Sunnquist, Madison; Newton, Julia L; Strand, Elin Bolle

      2017-01-01

      The Institute of Medicine (IOM) recently developed clinical criteria for what had been known as chronic fatigue syndrome (CFS). Given the broad nature of the clinical IOM criteria, there is a need for a research definition that would select a more homogenous and impaired group of patients than the IOM clinical criteria. At the present time, it is unclear what will serve as the research definition. The current study focused on a research definition which selected homebound individuals who met the four IOM criteria, excluding medical and psychiatric co-morbidities. Our research criteria were compared to those participants meeting the IOM criteria. Those not meeting either of these criteria sets were placed in a separate group defined by 6 or more months of fatigue. Data analyzed were from the DePaul Symptom Questionnaire and the SF-36. Due to unequal sample sizes and variances, Welch's F tests and Games-Howell post hoc tests were conducted. Using a large database of over 1,000 patients from several countries, we found that those meeting a more restrictive research definition were even more impaired and more symptomatic than those meeting criteria for the other two groups. Deciding on a particular research case definition would allow researchers to select more comparable patient samples across settings, and this would represent one of the most significant methodologic advances for this field of study.

    13. Characterization of murine hepatitis virus (JHM) RNA from rats with experimental encephalomyelitis.

      Science.gov (United States)

      Jackson, D P; Percy, D H; Morris, V L

      1984-09-01

      When Wistar Furth rats are inoculated intracerebrally with the murine hepatitis virus JHM they often develop a demyelinating disease with resulting hind leg paralysis. Using an RNA transfer procedure and hybridization kinetic analysis, the virus-specific RNA in these rats was characterized. The pattern of JHM-specific RNA varied with individual infections of Wistar Furth rats. However, two species of JHM-specific RNA, the nucleocapsid and a 2.1-2.4 X 10(6)-Da RNA species were generally present. A general decrease in JHM-specific RNA in brains and spinal cord samples taken later than 20 days postinoculation was observed; however, JHM-specific RNA persisted in the spinal cord longer than in the brain of these rats.

    14. Green tea EGCG, T-cell function, and T-cell-mediated autoimmune encephalomyelitis

      Science.gov (United States)

      Autoimmune diseases are common, disabling immune disorders affecting millions of people. Recent studies indicate that dysregulated balance of different CD4+ T-cell subpopulations plays a key role in immune pathogenesis of several major autoimmune diseases. Green tea and its active ingredient, epigal...

    15. Neuroprotection without immunomodulation is not sufficient to reduce first relapse severity in experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Hasseldam, Henrik; Johansen, Flemming Fryd

      2010-01-01

      at high doses, most likely due to differences in receptor affinities. In order to investigate the effects of neuroprotection and immunomodulation in an animal model of multiple sclerosis, we examined the impact of increasing concentrations of R(+)WIN55,212-2 on the inflammatory profile in CNS during first...

    16. Faktor pendorong motivasi orang tua merawatkan gigi anak di klinik Fakultas Kedokteran Gigi Unair (Stimulating factor of parents' motivation to take their children's dental health for treatment in the Faculty of Dentistry Airlangga University)

      OpenAIRE

      Anggriana, Dita; Musyrifah, Musyrifah

      2006-01-01

      Children dental health is very beneficial for children's growth Parent’s motivation for taking their children dental for treatment before more serious dental damage can help to decrease the prevalence of children's dental damage, especially for patients who came to pedodontia clinic in the faculty of Dentistry Airlangga University. This study aimed to know the parents' motivation to take their children dental for treatment in Pedodontia clinic in the faculty of Dentistry Airlangga University ...

    17. Faktor pendorong motivasi orang tua merawatkan gigi anak di klinik Fakultas Kedokteran Gigi Unair (Stimulating factor of parents' motivation to take their children's dental health for treatment in the Faculty of Dentistry Airlangga University

      Directory of Open Access Journals (Sweden)

      Dita Anggriana

      2006-03-01

      Full Text Available Children dental health is very beneficial for children's growth Parent’s motivation for taking their children dental for treatment before more serious dental damage can help to decrease the prevalence of children's dental damage, especially for patients who came to pedodontia clinic in the faculty of Dentistry Airlangga University. This study aimed to know the parents' motivation to take their children dental for treatment in Pedodontia clinic in the faculty of Dentistry Airlangga University by giving questionnaire to 42 patient’s parents. The result of this study suggested that clinic’s facilities (scored: 2.86 as the stimulating factor had the biggest influence in motivating patient’s parents.

    18. Whole brain irradiation in case of brain metastases in from 2005 to 2011 in the clinic for nuclear medicine of the university hospital Freiburg; Ganzhirnbestrahlung bei Hirnmetastasen von 2005 bis 2011 in der Klinik fuer Strahlenheilkunde des Universitaetsklinikums Freiburg

      Energy Technology Data Exchange (ETDEWEB)

      Hintz, Mandy

      2017-10-01

      Brain metastases are the largest group of brain tumors. Their occurrence influences the overall survival and the quality of life. The retrospective study deals with the overall survival, the local tumor control and the prognostic factors of patients treated with whole brain irradiation. The data were evaluated using multivariate analysis. Whole brain irradiation has shown to be an efficient therapy option for patients with brain metastases and has the possibility to improve the overall progress-free survival and the symptom control.

    19. Gastrointestinal stromal tümörler (GİST) - Patoloji ve yeni moleküler gelişimlerin klinik uygulamaları - Bir perspektif yorum

      OpenAIRE

      Dudani, Sharmila; Kalhan, Shivani; Sharma, Sonia; Gupta, Anshu

      2014-01-01

       Gastrointestinal stromal tumours ( GISTs) are the most common  mesenchymal tumours of the GI tract. They occur most frequently in stomach (60-70%), or small intestine(SI) ( 25-30%). Rare sites include colon, rectum, appendix and esophagus (<10%). On histology their appearance varies from cellular spindle cell tumours to epithelioid to pleomorphic tumours. Traditionally, three criteria have been used to determine malignancy, which include site of origin (SI and rectal tumours  are more...

    20. Broadcasting studios Radio Bremen becomes residence rehabilitation clinic. Energy efficient retrofitting with economic building services technology; Funkhaus Radio Bremen wird Residenz Reha-Klinik. Energieeffiziente Sanierung mit wirtschaftlicher Gebaeudetechnik

      Energy Technology Data Exchange (ETDEWEB)

      Hinz, Thomas [Siemens AG, Bremen (Germany). Building Technologies Div.

      2012-07-01

      Hardly any building project is as sustainable as the rededication of a building. A recent example: The former site of Radio Bremen in the district Schwachhausen with approximately 10,000 square meters of studios, production facilities and offices were committed to the residence rehabilitation clinic with 200 beds and 100 outpatient rehab places. In order to support the economic efficiency of this measure, the existing infrastructure of the heating technology, ventilation technology and air conditioning technology was adopted and modernized.

    1. Investigations into shaking mink syndrome: an encephalomyelitis of unknown cause in farmed mink (Mustela vison) kits in Scandinavia

      DEFF Research Database (Denmark)

      Gavier-Widen, Dolores; Brojer, Caroline; Dietz, Hans Henrik

      2004-01-01

      diseases (canine distemper, Borna disease, Louping ill, West Nile virus infection, tick-borne encephalitis, Aleutian disease), tests for protozoa (Toxoplasma gondii, Neospora caninum, Encephalitozoon cuniculi), bacteria (general culture, listeria, Clamydophila psittaci), and intracerebral inoculation...

    2. Effect of Cordyceps sinensis on the Treatment of Experimental Autoimmune Encephalomyelitis: A Pilot Study on Mice Model

      Directory of Open Access Journals (Sweden)

      Shan-Shan Zhong

      2017-01-01

      Conclusions: Our preliminary study demonstrated that CS efficiently alleviated EAE severity and EAE-related pathology damage and decreased the number of Th1s in the periphery, indicating its effectiveness in the treatment of murine EAE. Thus, our findings strongly support the therapeutic potential of this agent as a new traditional Chinese medicine approach in MS treatment.

    3. Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Khorooshi, Reza; Mørch, Marlene Thorsen; Holm, Thomas Hellesøe

      2015-01-01

      show elevated levels of Type I IFNs in the central nervous system (CNS), suggesting a role for endogenous Type I IFN during inflammation. However, the therapeutic benefit of Type I IFN produced in the CNS remains to be established. The aim of this study was to examine whether experimentally induced CNS......-endogenous Type I IFN influences EAE. Using IFN-β reporter mice, we showed that direct administration of polyinosinic-polycytidylic acid (poly I:C), a potent inducer of IFN-β, into the cerebrospinal fluid induced increased leukocyte numbers and transient upregulation of IFN-β in CD45/CD11b-positive cells located...... in the meninges and choroid plexus, as well as enhanced IFN-β expression by parenchymal microglial cells. Intrathecal injection of poly I:C to mice showing first symptoms of EAE substantially increased the normal disease-associated expression of IFN-α, IFN-β, interferon regulatory factor-7 and IL-10 in CNS...

    4. Metallothionein treatment reduces proinflammatory cytokines IL-6 and TNF-alpha and apoptotic cell death during experimental autoimmune encephalomyelitis (EAE)

      DEFF Research Database (Denmark)

      Penkowa, M; Hidalgo, J

      2001-01-01

      cytokines and apoptosis during EAE could contribute to the reported diminution of clinical symptoms and mortality in EAE-immunized rats receiving Zn-MT-II treatment. Our results demonstrate that MT-II reduces the CNS expression of proinflammatory cytokines and the number of apoptotic neurons during EAE......, which is characterized by significant inflammation and neuroglial damage. We have recently shown that the exogenous administration of the antioxidant protein zinc-metallothionein-II (Zn-MT-II) significantly decreased the clinical symptoms, mortality, and leukocyte infiltration of the CNS during EAE....... However, it is not known how EAE progression is regulated nor how cytokine production and cell death can be reduced. We herewith demonstrate that treatment with Zn-MT-II significantly decreased the CNS expression of IL-6 and TNF-alpha during EAE. Zn-MT-II treatment could also significantly reduce...

    5. Longitudinal in vivo magnetic resonance imaging studies in experimental allergic encephalomyelitis : effect of a neurotrophic treatment on cortical lesion development

      NARCIS (Netherlands)

      Duckers, H.J.; Muller, H J; Verhaagen, J; Nicolay, K; Gispen, Willem Hendrik

      Proton magnetic resonance imaging enables non-invasive monitoring of lesion formation in multiple sclerosis and has an important role in assessing the potential effects of therapy. T2-weighted and short tau inversion recovery magnetic resonance imaging were used to assess the effect of a

    6. Consulting patients in setting priorities in Myalgic Encephalomyelitis (M.E.) research: findings from a national on-line survey.

      Science.gov (United States)

      Childs, Nicola; Robinson, Lisa; Chowdhury, Sonya; Ogden, Clare; Newton, Julia L

      2015-01-01

      Myalgic encephalitis (M.E.) is a common condition, the cause of which is not known and there are no treatments available. In this study the national patient support group Action for M.E. sought the opinions of their members via an online survey as to what they felt should be future priorities for M.E. Respondents were asked what they considered first, second and third research priorities to be from a list of 13 pre-defined options. Individuals were invited to provide additional free text comments about Action for M.E.'s research priorities in general. Of the 1144 respondents: 822 had M.E.; 94 were a supporting a member of Action for M.E. ; 66 were carers for someone with M.E.; 26 were professionals with an interest in M.E.; 136 had a family member or colleague with M.E. Individuals selected more than one category as applicable. The top five research priorities identified were: disease processes to achieve a better understanding of the causes of M.E.; more effective treatments; faster and more accurate diagnosis; clinical course of M.E.; outcomes and natural history; and severely affected patients. Least popular priorities were: sleep; economic research towards identifying the cost of ME; and psychological aspects. Much of the free text comments emphasised the importance of funding biomedical research into disease processes to achieve a better understanding of the causes of M.E. Three themes were identified in relation to this topic: accurate diagnosis and awareness; risk factors and causes; drug development and curative therapies. In conclusion; individuals affected by M.E. have clear views regarding priorities for research investment. These have informed Action for M.E.'s ongoing research strategy and ultimately will inform national and international research priorities.

    7. Acute onset of encephalomyelitis with atypical lesions associated with dual infection of Sarcocystis neurona and Toxoplasma gondii in a dog.

      Science.gov (United States)

      Gerhold, Richard; Newman, Shelley J; Grunenwald, Caroline M; Crews, Amanda; Hodshon, Amy; Su, Chunlei

      2014-10-15

      A two-year-old male, neutered, basset hound-beagle mix with progressive neurological impairment was examined postmortem. Grossly, the dog had multiple raised masses on the spinal cord between nerve roots. Microscopically, the dog had protozoal myeloencephalitis. Toxoplasma gondii and Sarcocystis neurona were detected in the CNS by immunohistochemistry and polymerase chain reaction (PCR). Sarcocysts in formalin-fixed muscle were negative for Sarcocystis by PCR. Banked serum was negative for T. gondii using the modified agglutination test, suggesting an acute case of T. gondii infection or immunosuppression; however, no predisposing immunosuppressive diseases, including canine distemper, were found. To the authors' knowledge, this is the first report of dual T. gondii and S. neurona infection in a dog. Published by Elsevier B.V.

    8. Time-course expression of CNS inflammatory, neurodegenerative tissue repair markers and metallothioneins during experimental autoimmune encephalomyelitis

      DEFF Research Database (Denmark)

      Espejo, C; Penkowa, M; Demestre, M

      2005-01-01

      -inflammatory, neuroprotective, antioxidant proteins expressed during EAE and MS, in which they might play a protective role. The present study aimed to describe the expression profile of a group of inflammatory, neurodegenerative and tissue repair markers as well as metallothioneins during proteolipid protein-induced EAE...

    9. Induction of glial L-CCR mRNA expression in spinal cord and brain in experimental autoimmune encephalomyelitis

      NARCIS (Netherlands)

      Brouwer, N; Zuurman, MW; Wei, T; Ransohoff, RM; Boddeke, HWGM; Biber, K

      2004-01-01

      Chemokines and chemokine receptors are important regulators of leukocyte trafficking and immune response. It is well established that chemokines and their receptors are also expressed in the central nervous system (CNS), where their expression has been associated with various neuroinflammatory

    10. Altered expression of IGF-I system in neurons of the inflamed spinal cord during acute experimental autoimmune encephalomyelitis.

      Science.gov (United States)

      Parvaneh Tafreshi, Azita; Talebi, Farideh; Ghorbani, Samira; Bernard, Claude; Noorbakhsh, Farshid

      2017-10-01

      There is growing evidence that the impaired IGF-I system contributes to neurodegeneration. In this study, we examined the spinal cords of the EAE, the animal model of multiple sclerosis, to see if the expression of the IGF-I system is altered. To induce EAE, C57/BL6 mice were immunized with the Hooke lab MOG kit, sacrificed at the peak of the disease and their spinal cords were examined for the immunoreactivities (ir) of the IGF-I, IGF binding protein-1 (IGFBP-1) and glycogen synthase kinase 3β (GSK3β), as one major downstream molecule in the IGF-I signaling. Although neurons in the non EAE spinal cords did not show the IGF-I immunoreactivity, they were numerously positive for the IGFBP-1. In the inflamed EAE spinal cord however, the patterns of expressions were reversed, that is, a significant increased number of IGF-I expressing neurons versus a reduced number of IGFBP-1 positive neurons. Moreover, while nearly all IGF-I-ir neurons expressed GSK3β, some expressed it more intensely. Considering our previous finding where we showed a significant reduced number of the inactive (phosphorylated) but not that of the total GSK3β expressing neurons in the EAE spinal cord, it is conceivable that the intense total GSK3β expression in the IGF-I-ir neurons belongs to the active form of GSK3β known to exert neuroinflammatory effects. We therefore suggest that the altered expression of the IGF-I system including GSK3β in spinal cord neurons might involve in pathophysiological events during the EAE. © 2017 Wiley Periodicals, Inc.

    11. Loss rather than downregulation of CD4+ T cells as a mechanism for remission from experimental allergic encephalomyelitis

      DEFF Research Database (Denmark)

      Zeine, R; Owens, T

      1993-01-01

      reduction in the number of CNS CD4+ T cells in remitted mice 10 days following the initial attack. More than 60% of CNS CD4+ cells were of a CD44high, CD45RBlow memory/effector phenotype both in active EAE, peak EAE and in remission, in contrast to lymph nodes where this phenotype never constituted more...... than 17%. The proportion of CD8+ T cells was not increased in remitted mice, and we detected no TCR gamma delta+ cells within the CNS. Our findings demonstrate an overt loss of CD4+ T cells from the CNS and the maintenance of an activated state by T cells within the CNS and during remission from EAE...... infiltrating the central nervous system (CNS) in symptomatic and remitted mice. We isolated mononuclear cells from the CNS at various time points during the course of EAE and used flow cytometry to describe the kinetics of CNS infiltration by CD45+, CD2+, CD3+, TCR alpha beta+, CD4+ cells. There was a 30-fold...

    12. Treatment with anti-interferon-δ monoclonal antibodies modifies experimental autoimmune encephalomyelitis in interferon-δ receptor knockout mice

      DEFF Research Database (Denmark)

      Espejo, C.; Penkowa, Milena; Saez-Torres, I.

      2001-01-01

      Neuroinflammation, neuronal degeneration, regeneration, monoclonal antibodies, multiple schlerosis......Neuroinflammation, neuronal degeneration, regeneration, monoclonal antibodies, multiple schlerosis...

    13. Beneficial effect of modified peptide inhibitor of alpha4 integrins on experimental allergic encephalomyelitis in Lewis rats

      NARCIS (Netherlands)

      van der Laan, Luc J. W.; van der Goes, Annette; Wauben, Marca H. M.; Ruuls, Sigrid R.; Döpp, Ed A.; de Groot, Corline J. A.; Kuijpers, Taco W.; Elices, Mariano J.; Dijkstra, Christine D.

      2002-01-01

      An important event in the pathogenesis of the autoimmune disease multiple sclerosis (MS) is the recruitment of lymphocytes and inflammatory macrophages to the central nervous system (CNS). Recruitment requires adhesive interactions between the leukocytes and the microvascular endothelium,

    14. SISTEM ANTREAN PELAYANAN MEDIS PRAKTIK DOKTER BERSAMA BERBASIS WEB

      Directory of Open Access Journals (Sweden)

      Imelda Rizky Purba

      2016-11-01

      Full Text Available Klinik merupakan bagian lembaga kesehatan yang menjadi tempat untuk berobat atau berkonsultasi mengenai kesehatan. Pelayanan klinik masih kurang efektif diantaranya proses antrean administrasi klinik cenderung dilakukan manual, mulai dari pendaftaran pada resepsionis, keluhan, dokter yang dituju, rekam medis dan sebagainya. Kondisi ini mendasari pengembangan sistem antrean pelayanan medis berbasis web. Sistem antrean dibuat menggunakan sistem pemilihan FIFO yaitu pasien dengan nomor antrean lebih awal mendapatkan pelayanan medis terlebih dahulu. Sistem dirancang memiliki tiga user yaitu pasien, dokter dan admin. Pengintegrasian sistem antrean yang dihasilkan mempermudah sistem administrasi termasuk mengurangi kesalahan penginputan data. Pasien dapat melakukan registrasi dan mendapatkan nomor antrean secara langsung dari sistem, dokter memberi status final pada sistem apabila telah selesai melakukan pemeriksaan dan admin tidak perlu lagi mendaftarkan pasien secara manual. Kata Kunci : Sistem Antrean, Web, Klinik, FIFO, Medis

    15. Gömülü 20 yaş dişi cerrahisinde kemik dokusuna yapılan müdahalelerde kullanılan Er:YAG lazer, piezocerrahi ve konvansiyonel frez yöntemlerinin birbirleriyle klinik olarak karşılaştırılmalı incelenmesi

      OpenAIRE

      ÇELEBİOĞLU, Bedriye Gizem

      2011-01-01

      Gömülü 20 yaş dişi çekimleri oral ve maksillofasiyal cerrahide en sık yapılan uygulamalardır. Cerrahi işlemlerin tamamında amaç doku hasarını minimalize ederek az komplikasyon yaratmak ve postoperatif iyleşme periodunda hastalara daha az ağrı ve daha fazla rahatlık sağlamaktır.Çalışmamız Pell-Gregory Sınıflaması'na göre klas 2, pozisyon B vertikal pozisyonda bilateral alt gömülü yirmi yaş dişi bulunan 30 hasta üzerinde gerçekleştirmiştir. Hastalar rastgele 2 gruba ayrıldı...

    16. Identification of brain antigens recognized by autoantibodies in experimental autoimmune encephalomyelitis-induced animals treated with etomoxir or interferon-β

      DEFF Research Database (Denmark)

      Mørkholt, Anne Skøttrup; Kastaniegaard, Kenneth; Trabjerg, Michael Sloth

      2018-01-01

      Multiple sclerosis (MS) is a neurodegenerative autoimmune disease, where chronic inflammation plays an essential role in its pathology. A feature of MS is the production of autoantibodies stimulated by an altered-peptide-ligand response and epitope spreading, resulting in loss of tolerance for self...

    17. Induction of experimental autoimmune encephalomyelitis in C57BL/6 mice deficient in either the chemokine macrophage inflammatory protein-1alpha or its CCR5 receptor

      DEFF Research Database (Denmark)

      Tran, E H; Kuziel, W A; Owens, T

      2000-01-01

      -type mice in Th1 cytokine gene expression, the kinetics and severity of disease, and infiltration of the central nervous system by lymphocytes, macrophages and granulocytes. RNase protection assays showed comparable accumulation of mRNA for the chemokines interferon-inducible protein-10, RANTES, macrophage...... and its CCR5 receptor in the induction of EAE by immunizing C57BL / 6 mice deficient in either MIP-1alpha or CCR5 with myelin oligodendrocyte glycoprotein (MOG). We found that MIP-1alpha-deficient mice were fully susceptible to MOG-induced EAE. These knockout animals were indistinguishable from wild...... chemoattractant protein-1, MIP-1beta, MIP-2, lymphotactin and T cell activation gene-3 during the course of the disease. CCR5-deficient mice were also susceptible to disease induction by MOG. The dispensability of MIP-1alpha and CCR5 for MOG-induced EAE in C57BL / 6 mice supports the idea that differential...

    18. Antagonizing the alpha(4)beta(1) Integrin, but Not alpha(4)beta(7), Inhibits Leukocytic Infiltration of the Central Nervous System in Rhesus Monkey Experimental Autoimmune Encephalomyelitis

      NARCIS (Netherlands)

      Haanstra, Krista G.; Hofman, Sam O.; Estevao, Dave M. Lopes; Blezer, Erwin L. A.; Bauer, Jan; Yang, Li-Li; Wyant, Tim; Csizmadia, Vilmos; 't Hart, Bert A.; Fedyk, Eric R.

      2013-01-01

      The immune system is characterized by the preferential migration of lymphocytes through specific tissues (i.e., tissue tropism). Tissue tropism is mediated, in part, by the alpha(4) integrins expressed by T lymphocytes. The alpha(4)beta(1) integrin mediates migration of memory T lymphocytes into the

    19. Effect of vitamin D3 on leukocyte infiltration into the brain of C57/BL6 mice with experimental autoimmune encephalomyelitis

      Directory of Open Access Journals (Sweden)

      ghasem Mosayebi

      2006-11-01

      Material and methods: Male C57BL/6 mice were divided into two therapeutic groups (n=8 per group with age and weight-matched as follow: Vitamin D3-treated EAE mice (5μg/kg/every two days of vitamin D3 given i.p. from day -3 until day +19 after disease induction. Non-treated EAE mice (EAE control received vehicle alone with same schedule. In addition, 5 age and weight-matched male C57BL/6 mice served as normal (non-EAE controls. Results: Vitamin D3-treated mice had significantly less clinical score of EAE (3.2±0.8 than non-treated mice (5.3±0.44, (p<0.001. Also, there was a significant difference between vitamin D3-trated and non treated mice (p<0.01 in relation to the number of the infiltrating cells in the brain. Conclusion: These results indicate that vitamin D3 treatment reduces infiltration of leukocytes into the brain of EAE mice, and ameliorate the disease. Thus, vitamin D3 treatment may be of therapeutic value against inflammatory disease processes associated with infiltration of activated mononuclear cells into the tissue.

    20. Ctla-4 modulates the differentiation of inducible Foxp3+ Treg cells but IL-10 mediates their function in experimental autoimmune encephalomyelitis.

      Directory of Open Access Journals (Sweden)

      Johan Verhagen

      Full Text Available In vitro induced Foxp3+ T regulatory (iTreg cells form a novel and promising target for therapeutic tolerance induction. However, the potential of these cells as a target for the treatment of various immune diseases, as well as the factors involved in their development and function, remain debated. Here, we demonstrate in a myelin basic protein (MBP-specific murine model of CNS autoimmune disease that adoptive transfer of antigen-specific iTreg cells ameliorates disease progression. Moreover, we show that the co-stimulatory molecule CTLA-4 mediates in vitro differentiation of iTreg cells. Finally, we demonstrate that the secreted, immunosuppressive cytokine IL-10 controls the ability of antigen-specific iTreg cells to suppress autoimmune disease. Overall, we conclude that antigen-specific iTreg cells, which depend on various immune regulatory molecules for their differentiation and function, represent a major target for effective immunotherapy of autoimmune disease.

    1. DP IV/CD26, APN/CD13 and related enzymes as regulators of T cell immunity: implications for experimental encephalomyelitis and multiple sclerosis.

      Science.gov (United States)

      Reinhold, Dirk; Bank, Ute; Täger, Michael; Ansorge, Siegfried; Wrenger, Sabine; Thielitz, Anja; Lendeckel, Uwe; Faust, Jürgen; Neubert, Klaus; Brocke, Stefan

      2008-01-01

      Multiple sclerosis (MS) is the most frequent demyelinating disease of the central nervous system. Peptidases like dipeptidyl peptidase IV (DP IV, CD26) and aminopeptidase N (APN, CD13) play a regulatory role in T cell activation and represent potential targets for the treatment of inflammatory disorders. Synthetic inhibitors of DP IV and/or APN enzymatic activity induce production of the immunosuppressive cytokine TGF-beta1 and subsequently suppress DNA synthesis and Th1 cytokine production of activated human T cells. Compelling evidence has demonstrated that IL-17-producing CD4 cells (Th17) are a major contributor to the pathogenesis of autoimmune inflammation. Here, we report that inhibitors of DP IV-like activity as well as of APN activity inhibit IL-17 production in activated human and mouse T cells. Combining inhibitors of DP IV and APN increases the suppressive effect on T cell specific IL-17 production in vitro compared to a single peptidase inhibitor. In the following, we summarize the evidence for the role of both ectoenzymes in T cell activation in vitro and in vivo and provide a rationale for the use of combined or dual ectopeptidase inhibitors to treat autoimmune diseases like MS.

    2. Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system

      DEFF Research Database (Denmark)

      Taupin, V; Renno, T; Bourbonnière, L

      1997-01-01

      are a target of immune attack. TNF-alpha also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-alpha at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal...

    3. Vitamin D3 influence the Th1/Th2 ratio in C57BL/6 induced model of experimental autoimmune encephalomyelitis

      Directory of Open Access Journals (Sweden)

      Maryam Soleimani

      2014-10-01

      Results: By using ELISA and RT-PCR the brain level of TNF-α, IL-10, IL-4 and IL-12 determined. Significant decrease of clinical symptoms in trial group which received vitamin D was seen comparing to control animals (P

    4. Allogeneic Adipose-Derived Mesenchymal Stromal Cells Ameliorate Experimental Autoimmune Encephalomyelitis by Regulating Self-Reactive T Cell Responses and Dendritic Cell Function

      Directory of Open Access Journals (Sweden)

      Per Anderson

      2017-01-01

      Full Text Available Multipotent mesenchymal stromal cells (MSCs have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS. Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS and cyclooxygenase- (COX- 1/2 activities. mASCs also prevented the lipopolysaccharide- (LPS- induced maturation of dendritic cells (DCs in vitro. The addition of the COX-1/2 inhibitor indomethacin, but not the iNOS inhibitor L-NAME, reversed the block in DC maturation implicating prostaglandin (PG E2 in this process. In vivo, early administration of murine and human ASCs (hASCs ameliorated myelin oligodendrocyte protein- (MOG35-55- induced EAE in C57Bl/6 mice. Mechanistic studies showed that mASCs suppressed the function of autoantigen-specific T cells and also decreased the frequency of activated (CD11c+CD40high and CD11c+TNF-α+ DCs in draining lymph nodes (DLNs. In summary, these data suggest that mASCs reduce EAE severity, in part, through the impairment of DC and T cell function.

    5. Immune modulation by a tolerogenic myelin oligodendrocyte glycoprotein (MOG)10-60 containing fusion protein in the marmoset experimental autoimmune encephalomyelitis model

      NARCIS (Netherlands)

      Y.S. Kap (Yolanda); N. van Driel (Nikki); R. Arends (Roel); G. Rouwendal; M. Verolin; E. Blezer (Erwin); N. Lycke; B.A. 't Hart (Bert)

      2015-01-01

      textabstractSummary: Current therapies for multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease, mostly target general cell populations or immune molecules, which may lead to a compromised immune system. A more directed strategy would be to re-enforce tolerance of the

    6. Immune modulation by a tolerogenic myelin oligodendrocyte glycoprotein (MOG)10-60 containing fusion protein in the marmoset experimental autoimmune encephalomyelitis model

      NARCIS (Netherlands)

      Kap, Y. S.; van Driel, N.; Arends, R.; Rouwendal, G.; Verolin, M.; Blezer, E.; Lycke, N.; 't Hart, Bert A.

      Current therapies for multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease, mostly target general cell populations or immune molecules, which may lead to a compromised immune system. A more directed strategy would be to re-enforce tolerance of the autoaggressive T cells that drive

    7. Immune modulation by a tolerogenic myelin oligodendrocyte glycoprotein (MOG)10-60 containing fusion protein in the marmoset experimental autoimmune encephalomyelitis model

      NARCIS (Netherlands)

      Kap, Y. S.; van Driel, N.; Arends, R.; Rouwendal, G.; Verolin, M.; Blezer, E.; Lycke, N.; 't Hart, B. A.

      2015-01-01

      Summary: Current therapies for multiple sclerosis (MS), a chronic autoimmune neuroinflammatory disease, mostly target general cell populations or immune molecules, which may lead to a compromised immune system. A more directed strategy would be to re-enforce tolerance of the autoaggressive T cells

    8. Acute pancreatitis: a case report

      Directory of Open Access Journals (Sweden)

      Nafia Ozlem Kazanci

      2013-06-01

      Full Text Available Akut pankreatit cocukluk caginda heterojen ve ozgul olmayan klinik bulgularla seyreden, genellikle travma, yapisal anomaliler, ilaclar ve kronik sistemik hastalik zeminde gelisen nadir gorulen bir hastaliktir.Bu olgu sunumunda daha once saglikli oldugu bilinen, karin agrisi yakinmasi ile basvuran ve akut pankreatit tanisi konulan 4 yasinda kiz hastaya yer verildi.Akut pankreatitin idiopatik olarak gelisebildigi ve ozgul olmayan klinik bulgulari nedeniyle tanida yasanabilecek guclukler goz onunde bulundurulmalidir. [J Contemp Med 2013; 3(2.000: 129-132

    9. Description of Sanitation Clinic Implementation in Primary Health Care Services in Bukittinggi

      Directory of Open Access Journals (Sweden)

      Vini Jamarin

      2016-01-01

      Full Text Available AbstrakSanitasi yang buruk dapat menjadi media transmisi agen penyakit berbasis lingkungan. Salah satu program puskesmas yang menelaah penyakit berbasis lingkungan adalah klinik sanitasi. Bukittinggi sudah menjalankan klinik sanitasi sejak tahun 2009. Tujuan penelitian ini adalah untuk mengetahui gambaran pelaksanaan program klinik sanitasi puskesmas di Kota Bukittinggi. Penelitian ini menggunakan metode deskriptif. Sampel diambil seluruhnya (total sampling, yaitu tujuh puskesmas di Bukittinggi dari September sampai Oktober 2013. Berdasarkan hasil kuesioner, dari tujuh puskesmas, seluruh petugas telah memiliki pendidikan yang baik, dua petugas telah mendapatkan pelatihan klinik sanitasi, satu puskesmas memiliki ruangan khusus klinik sanitasi, enam puskesmas memiliki poster dan leaflet, tiga puskesmas memiliki dana khusus, dan enam puskesmas memiliki seluruh buku pedoman. Berdasarkan data sekunder, jumlah penyakit berbasis lingkungan bervariasi dan fluktuatif dan jumlah klien yang datang masih sedikit dan jauh dari harapan. Penelitian ini menilai empat kegiatan klinik sanitasi, yaitu kunjungan ke rumah warga, kerjasama lintas program, kerjasama lintas sektor, dan evaluasi. Jumlah kunjungan ke rumah warga masih kurang dari harapan, kerjasama lintas program klinik sanitasi sudah berjalan di seluruh puskesmas, kerjasama lintas sektor sudah berjalan hampir di seluruh puskesmas, dan evaluasi sudah berjalan dengan jangka waktu yang bervariasi. Seluruh klinik sanitasi puskesmas kota Bukittinggi dinilai baik dengan nilai bervariasi antara 50-100%.Kata kunci: klinik sanitasi, puskesmas AbstractPoor sanitation could be the transmission media for environment-based diseases’ agents. The program of Primary Health Care Service (PHCS which deals with environment-based disease is sanitation clinic. This program has been running in Bukittinggi since 2009. The objective of this study was to see how this program has been going on in PHCS in Bukittinggi. This

    10. Switch in the expression of mGlu1 and mGlu5 metabotropic glutamate receptors in the cerebellum of mice developing experimental autoimmune encephalomyelitis and in autoptic cerebellar samples from patients with multiple sclerosis

      NARCIS (Netherlands)

      Fazio, F.; Notartomaso, S.; Aronica, E.; Storto, M.; Battaglia, G.; Vieira, E.; Gatti, S.; Bruno, V.; Biagioni, F.; Gradini, R.; Nicoletti, F.; Di Marco, R.

      2008-01-01

      Recent evidence suggests that changes in the expression of membrane receptors/ion channels in cerebellar Purkinje cells contribute to the onset of cerebellar motor symptoms in patients with multiple sclerosis (MS). We examined the expression of group-I metabotropic glutamate receptors (mGlu1 and

    11. Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells

      DEFF Research Database (Denmark)

      Issazadeh-Navikas, Shohreh; Mustafa, M; Ljungdahl, A

      1995-01-01

      , the target organ in EAE, cells expressing mRNA for IFN-gamma, first appeared at the onset of clinical signs, i.e., day 10 postimmunization (p.i.), peaked at the height of disease (day 13 p.i.) and then gradually decreased concomitant with recovery. Very few IL-4 mRNA-expressing cells appeared in the spinal...... to limit central nervous system (CNS) inflammation. In lymphoid organs, primed MBP 63-88 reactive T cells showed an interesting time-dependent evolution of their cytokine production in vitro. Thus, early after immunization there was a conspicuous MBP 63-88-induced production of both IFN-gamma and IL-4...... cord with no clear relation to clinical signs or histopathology. In contrast, expression of mRNA for TGF-beta did not increase until day 13 p.i., at height of the disease, shortly preceding recovery. These data are consistent with a disease upregulating role of IFN-gamma, while TGF-beta may act...

    12. Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor beta

      DEFF Research Database (Denmark)

      Issazadeh-Navikas, Shohreh; Ljungdahl, A; Höjeberg, B

      1995-01-01

      in cryosections of spinal cords using in situ hybridization technique with synthetic oligonucleotide probes. Three stages of cytokine mRNA expression could be distinguished: (i) interleukin (IL)-12, tumor necrosis factor (TNF)-beta (= lymphotoxin-alpha) and cytolysin appeared early and before onset of clinical...... signs of EAE; (ii) TNF-alpha peaked at height of clinical signs of EAE; (iii) IL-10 appeared increasingly at and after clinical recovery. The early expression of IL-12 prior to the expression of interferon-gamma (IFN-gamma) mRNA shown previously is consistent with a role of IL-12 in promoting...... proliferation and activation of T helper 1 (Th1) type cells producing IFN-gamma. The TNF-beta mRNA expression prior to onset of clinical signs favours a role for this cytokine in disease initiation. A pathogenic effector role of TNF-alpha was suggested from these observations that TNF-alpha mRNA expression...

    13. Mechanism of action and efficacy of RX-111, a thieno[2,3-c]pyridine derivative and small molecule inhibitor of protein interaction with glycosaminoglycans (SMIGs), in delayed-type hypersensitivity, TNBS-induced colitis and experimental autoimmune encephalomyelitis

      Czech Academy of Sciences Publication Activity Database

      Harris, N.; Koppel, J.; Zsila, F.; Juhás, Štefan; Ilková, G.; Kogan, F. Y.; Lahmy, O.; Wildbaum, G.; Karin, N.; Zhuk, R.; Gregor, P.

      2016-01-01

      Roč. 65, č. 4 (2016), s. 285-294 ISSN 1023-3830 Institutional support: RVO:67985904 Keywords : small molecule drug * glycosaminoglycan * heparin binding protein * heparan sulfate * inflammation * autoimmune disease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.659, year: 2016

    14. Julia Scher / Julia Scher ; interv. Tilman Baumgärtel

      Index Scriptorium Estoniae

      Scher, Julia

      2006-01-01

      Ameerika installatsiooni- ja tegevuskunstnikust Julia Scher'ist (sünd. 1954) ja tema loomingust, telefonivestlus kunstnikuga 15. II 2001. Installatsioonidest, milles kunstnik kasutas järelevalvesüsteemide võrgustikke, virtualsest SM-klubist elektroonilisel teadetetahvlil The Thing, New Yorgis baseeruva võrgugalerii "Adaweb" jaoks valminud võrguprojektidest "Konsent Klinik (1997) ja "Security Land" (1995) ning muust

    15. Global Health Care-seeking Discourses Facing Local Clinical Realities

      DEFF Research Database (Denmark)

      Andersen, Rikke Sand; Tørring, Marie Louise; Vedsted, Peter

      2014-01-01

      På baggrund af et længerevarende feltarbejde i danske klinikker i almen praksis undersøger denne artikel forholdet mellem forebyggelsesorienterede diskurser om lægesøgning og − hvad der betragtes som − legitime lægesøgningspraksisser på klinik-niveau. Forfatterne argumenterer for, at der i almen ...

    16. Behavioral Consequences of Kainic Acid Lesions and Fetal Transplants of the Striatum

      Science.gov (United States)

      1984-06-12

      pp. 51-56). New York: Raven Press. Bruyn, G.W., De Young, F.H., & Van Der Molen , J.H. (1972). Hiintington’s chorea and the adrenal. British...218, 347-356. Schroeder, K. (1931). Zur klinik und pathologie der Huntingtonshen krankheit, Jurnal fur Psychologie und Neurologic. 43, 183-201

    17. Musikterapi med kontakt- og kommunikationssvage børn

      DEFF Research Database (Denmark)

      Frederiksen, Britta Vinkler

      2009-01-01

      I artiklen beskrives, hvordan musikterapi er med til at støtte en målrettet udviklingsproces hos børn, med diagnoser som Asperger syndrom, autisme, opmærksomhedsforstyrrelser, ADHD o.lign. Musikkens kvaliteter beskrives og illustreres gennem vignetter fra terapiforløb, der alle er foregået i Klinik...

    18. Pneumonia Atipikal

      OpenAIRE

      Budastra I Nyoman; Siadi Purniti Putu; Subanada Ida Bagus

      2016-01-01

      Pneumonia atipikal adalah pneumonia yang disebabkan oleh mikroorganisme yang tidak dapat diidentifikasi dengan teknik diagnostik standar pneumonia pada umumnya dan tidak menunjukkan respon terhadap antibiotik b-laktam. Mikroorganisme patogen penyebab pneumonia atipikal pada umumnya adalah Mycoplasma pneumoniae, Chlamydia pneumoniae, dan Legionella pneumophila. Manifestasi klinik, pemeriksaan laboratorium dan radiologis pneumonia atipikal menunjukkan gambaran tidak spesifik. Man...

    19. Pneumonia Nosokomial

      OpenAIRE

      Keliat, E.N; Abidin, Alwinsyah; Lubis, Nursyamsiah

      2017-01-01

      Pada masa yang lalu pneumonia diklasifikasikan sebagai pneumonia tipikal yang disebabkan oleh Str. Pneumonia daan atipikal yang disebabkan kuman atipik seperti halnya M. pneumonia. Kemudian ternyata manifestasi dari patogen lain seperti H. influenza, S. aureus dan bakteri Gram negatif memberikan sindrom klinik yang identik dengan pneumonia oleh Str E.N Keliat

    20. The Implementation Word Of Mouth As Part Of Integrated Marketing Communication At Beauty Clinic Giva Skin Care Medan

      Directory of Open Access Journals (Sweden)

      Murlizar

      2017-07-01

      Full Text Available Even though it is a new comer in facial beauty parlors Klinik Kecantikan Giva Skin Care located on Jalan Sei Batanghari Medan is able to compete with the other beauty parlors. The tight competitiveness in beauty parlors has caused it to think hard to creatively attract and increase consumers from time to time. In carrying out its marketing strategy it applies Integrated Marketing Communication IMC and Transmedia Branding through varied new media which contribute ideally to develop the brand of Klinik Kecantikan Giva Skin Care to its consumers and its prospective consumers. The objective of the research was to find out and identify Word Of Mouth WOM as part of IMC and Transmedia Branding which have been consistently done by this beauty parlos in the last two years. The research used descriptive qualitativemethod and constructive paradigm the data were analyzed by conducting case study. Constructivism considered that the subject in this case Nanda as the marketing manager of Klinik Kecantikan Giva Skin Care was the central factor in the communicativeactivity and in the social relations and was functioned as the social control. The data were gathered by conducting observation in-depth interviews with the marketing manager and library study. The result of the research showed that Klinik Kecantikan Giva Skin Care applied Transmedia Brand and IMC in the form of Advertising Direct Marketing Interactive Media and Internet Selling Promotion Publicity and Personal Selling in order to maintain its survival in the midst tight competitiveness in beauty parlor business in Medan.

    1. The value of contrast media in spinal cord abnormalities

      International Nuclear Information System (INIS)

      Matsumasa Takahashi

      1995-01-01

      The contents are intramedullary tumors, inflammatry lesions, demyelinating diseases - multiple sclerosis (MS), radiation myelitis, acute disseminated encephalomyelitis (ADEM); vascular lesions - spinal cord infarct, arteriovenous malformation, cavernous haemangioma (24 refs.)

    2. Demyeliniserende sygdom hos børn med akutte neurologiske symptomer

      DEFF Research Database (Denmark)

      Olofsson, Isa Amalie; Skov, Liselotte; Miranda, Maria Jose

      2015-01-01

      Demyelinating diseases in children is a broad group of illnesses, which affect the central nervous system. Demyelinating diseases can be monophasic or chronic and comprise acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, multiple sclerosis and neuromyelitis optica...

    3. Demyeliniserende sygdom hos børn med akutte neurologiske symptomer

      DEFF Research Database (Denmark)

      Olofsson, Isa Amalie; Skov, Liselotte; Miranda, Maria Jose

      2015-01-01

      Demyelinating diseases in children is a broad group of illnesses, which affect the central nervous system. Demyelinating diseases can be monophasic or chronic and comprise acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, multiple sclerosis and neuromyelitis optica. Demye...

    4. CT and MRI 'ring sign' may be due to demyelination: diagnostic pitfall.

      LENUS (Irish Health Repository)

      Kamel, M H

      2012-02-03

      We report a case of acute demyelinating encephalomyelitis (ADEM) in which both CT and MRI showed multiple ring-enhancing lesions suggestive of abscesses or brain tumour. This is a relatively rare phenomenon.

    5. Oxidative damage and chemokine production dominate days before immune cell infiltration and EAE disease debut

      DEFF Research Database (Denmark)

      Hasseldam, Henrik; Rasmussen, Rune Skovgaard; Johansen, Flemming Fryd

      2016-01-01

      BACKGROUND: Multiple sclerosis is widely accepted as an inflammatory disease. However, studies indicate that degenerative processes in the CNS occur prior to inflammation. In the widely used animal model experimental autoimmune encephalomyelitis (EAE), we investigated the significance of degenera...

    6. The value of contrast media in spinal cord abnormalities

      Energy Technology Data Exchange (ETDEWEB)

      Takahashi, Matsumasa [Kumamoto Univ. (Japan). School of Medicine

      1996-12-31

      The contents are intramedullary tumors, inflammatry lesions, demyelinating diseases - multiple sclerosis (MS), radiation myelitis, acute disseminated encephalomyelitis (ADEM); vascular lesions - spinal cord infarct, arteriovenous malformation, cavernous haemangioma (24 refs.).

    7. Protective effect of an elastase inhibitor in a neuromyelitis optica-like disease driven by a peptide of myelin oligodendroglial glycoprotein.

      NARCIS (Netherlands)

      Herges, K.; Jong, B.A. de; Kolkowitz, I.; Dunn, C.; Mandelbaum, G.; Ko, R.M.; Maini, A.; Han, M.H.; Killestein, J.; Polman, C.; Goodyear, A.L.; Dunn, J.; Steinman, L.; Axtell, R.C.

      2012-01-01

      BACKGROUND: The pathology of neuromyelitis optica (NMO), in contrast to multiple sclerosis, comprises granulocyte infiltrates along extensive lengths of spinal cord, as well as optic nerve. Furthermore, IFN-beta treatment worsens NMO. We recently found that experimental autoimmune encephalomyelitis

    8. KÜLTÜR BALIKLARINDA Staphylococcus cohnii subsp. cohnii ENFEKSİYONU

      OpenAIRE

      AKAYLI, Tülay; ÜRKÜ, Çiğdem; BAŞARAN, Buket

      2013-01-01

      Bu çalışma ile Stafilokokkozis'in klinik bulgularını gösteren kültür gökkuşağı alabalıkları (Oncornhychus mykiss) ve sinarit (Dentex dentex) balıklarında ölümlere neden olan hastalık etkeninin saptanması amaçlanmıştır. Klinik bulgu olarak letarji, renkte koyulaşma, yüzgeç diplerinde ve gözlerde hemoraji gibi belirtiler gösteren enfekte balıklardan bakteriyolojik inceleme amacıyla TSA (Tryptic Soy Agar) ve T-TSA (%1 NaCl içeren Tryptic Soy Agar) besiyerlerine ekimler yapılmıştır. Çalışma ...

    9. The Crab Hole Mosquito Blues

      OpenAIRE

      Johnson, Karl M.; Antczak, Douglas F.; Dietz, William H.; Martin, David H.; Walton, Thomas E.

      2011-01-01

      Venezuelan equine encephalomyelitis (VEE) epizoodemics were reported at 6–10-year intervals in northern South America beginning in the 1920s. In 1937, epizootic VEE virus was isolated from infected horse brain and shown as distinct from the North American equine encephalomyelitis viruses. Subsequently, epizootic and sylvatic strains were isolated in distinct ecosystems; isolates were characterized serologically as epizootic subtype I, variants A/B and C; or sylvatic (enzootic) subtype I, vari...

    10. Determinants of medication adherence among adults with type 2 diabetes mellitus in three Malaysian public health clinics: a cross-sectional study

      OpenAIRE

      Chew BH; Hassan NH; Sherina MS

      2015-01-01

      Boon-How Chew,1 Noor-Hasliza Hassan,2 Mohd-Sidik Sherina3 1Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 2Klinik Kesihatan Dengkil, Ministry of Health, 3Department of Psychiatry, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia Abstract: Medication adherence (MA) in adults with type 2 diabetes mellitus (T2D) is associated with improved disease control (glycated hemoglobin, blood pressure, and lipid pro...

    11. Bir Buzağıda Notomeli (Notomelia) ve Pakomeli (Phocomelia) Olgusu

      OpenAIRE

      HAYAT, Ali

      2013-01-01

      Bu vaka takdiminde, 15 günlük dişi melez bir buzağıda notomeli ve pakomeli anomalisi klinik ve radyolojik olarak değerlendirildi. Notomelie ve pakomeli olgusunun buzağılarda çok nadir görülmesi ve ilginç olmasından dolayı bu vaka rapor edilmiştir.

    12. Die Entstehung einer Nachbarsegmentdekompensation nach lumbaler Spondylodese. Einfluß des sagitalen Profils

      OpenAIRE

      Noe, Stephan

      2003-01-01

      Die vorliegende Arbeit beschäftigt sich mit der Frage, ob ein Zusammenhang zwischen der frühen Dekompensation einer Nachbaretage neben einem fusioniertem Bandscheibensegment im Lendenwirbelsäulenbereich und dem sagittalen Profil der Lendenwirbelsäule besteht. Im Rahmen der Untersuchungen wurden in einer retrospektiven Untersuchung die Krankenakten und Röntgenbilder von 51 Patienten der Zentralkliniken Bad Berka (Wirbelsäulenchirurgie) und Patienten der Orthopädischen Klinik des Universitä...

    13. PERBEDAAN TINGKAT SIMTOM ANSIETAS DAN DEPRESI ANTARA PEKERJA SEKS KOMERSIAL YANG MENDERITA HIV/ AIDS DENGAN YANG TIDAK MENDERITA HIV/ AIDS

      OpenAIRE

      Rini Gusya Liza; Elmeida Effendy; Freddy Subastian

      2014-01-01

      AbstrakPenelitian ini bertujuan untuk mengetahui perbedaan tingkat simtom ansietas dan depresi antara pekerja seks komersial (PSK) yang menderita HIV/ AIDS dengan yang tidak menderita HIV/ AIDS. Penelitian potong lintang, dengan nonprobability sampling, jenis cluster sampling. Tempat penelitian adalah di lokalisasi Kabupaten Bengkalis dan di klinik VCT RSUD Kecamatan Mandau, Kabupaten Bengkalis. Subjek penelitian adalah wanita yang bekerja sebagai PSK di lokalisasi PSK, kooperatif, bersedia d...

    14. Medicinsk versus kirurgisk provokeret abort i første trimester

      DEFF Research Database (Denmark)

      Rørbye, C

      2005-01-01

      Ph.d.-afhandlingen er baseret på undersøgelser udført på Gynækologisk/Obstetrisk afdeling, H:S Hvidovre Hospital, i samarbejde med Gynækologisk/Obstetrisk Klinik, H:S Frederiksberg Hospital, i perioden 2000-2004. Formålet med studiet var at sammenligne medicinsk og kirurgisk abort med henblik på ...

    15. Ergebnissse nach arthroskopisch assistiert durchgeführter vorderer Kreuzbandplastik mit Semitendinosussehne als Triple-Implantat in Single-Incision-Technik und femoraler Endobutton-Fixation : Nachuntersuchungen über einen Zeitraum von 1 Jahr

      OpenAIRE

      Seel, Matthias

      2004-01-01

      Das Ziel dieser Arbeit ist die Überprüfung des Stabilitätsgewinnes infolge einer operativen Therapie des rupturierten vorderen Kreuzbandes mit einer ipsilateralen autogenen, femoral mit einem Endobutton fixierten, Semitendinosussehne als Dreifachschlinge bei 103 Patienten, die in der Zeit vom Juli 1993 bis zum Januar 1995 an der Orthopädischen Klinik der Justus-Liebig-Universität in Gießen operiert wurden. Des weiteren sollten im Rahmen dieser Arbeit geschlechtsspezifische Unterschiede, Unter...

    16. Evaluation der Behandlungseinheit für Tinnitus, Hör- und Sinnesstörungen (BETHS)

      OpenAIRE

      Hofmeister, Alexander A. K.

      2015-01-01

      Evaluation der Behandlungseinheit für akuten und chronischen Tinnitus an der HNO-Klinik Dr. Gärtner. Mittel der Datenerhebung waren der Tinnitus-Fragebogen (Goebel & Hiller, 1998), die Allgemeine Depressionsskala (Hauzinger & Bailer, 1993), Audiogramm und Tinnitus-Anamnese. Es wurden die Daten von 141 Patienten ausgewertet und die Veränderung der tinnitusspezifischen und depressiven Belastung sowie der Einfluss von Prädiktorvariablen untersucht. Die Ergebnisse belegen eine signifikante Redukt...

    17. Kedi ve Köpeklerde Diabetes Mellitus.

      OpenAIRE

      ŞİMŞEK, Aynur; İÇEN, Hasan

      2008-01-01

      Diabetes mellitus polidipsi, poliüri ve polifaji gibi klinik bulgularla karakterize endokrin bir hastalıktır. Bu derlemede, kedi ve köpeklerde yaygın olan hastalığın etiyoloji, patogenezis, kliniklaboratuar bulguları, tanı, ayırıcı tanı ve sağaltımına yönelik bilgilerin verilmesi amaçlanmıştır

    18. Briefwechsel 1907-1925

      OpenAIRE

      Freud, S. (Sigmund); Abraham, K. (Karl)

      2010-01-01

      Die Briefe zwischen Sigmund Freud und Karl Abraham gehören zu den wichtigsten Briefwechseln Freuds. Karl Abraham war ein wichtiges und einflussreiches Mitglied des engeren Kreises von Vertrauten rund um Freud. Als solches spielte er eine entscheidende Rolle bei der Etablierung der Disziplin der Psychoanalyse. Von Freuds Biograph Ernest Jones als einer der besten Kliniker seiner Zeit bezeichnet, trug er auch wichtige Ausarbeitungen und Weiterentwicklungen von Freuds Theorien bei. 1965 ersch...

    19. Cycles of Beauty Culture: Ethnography of Beauty Clinics Commodification

      Directory of Open Access Journals (Sweden)

      Sri Murlianti

      2014-12-01

      Full Text Available Skin care is not a completely new in beauty treatments. Previously there have been other types of cultural industry which also adopted the medical science, such as cosmetic and beauty salon industries. But, skin care beauty clinic successfully introduces the services of beauty treatments which are considered the healthiest. This paper is a summary of the research on how beauty clinic quickly became a part of everyday life of its consumers. The research focused on Natasha Skin Care, a most popular beauty clinic in Indonesia at the moment. According to Richard Johnson, the process of a culture industry reaches the society through a communication that in form a pattern cyclic communications. The stages in the pattern are interconnected but slipped, each stage is affecting others but are not specified in an uncertain manner; between the producer of culture industry with its consumers. This study is a multidiscipline research using three methods of interpretation namely ethnography, discourses analysis, and social hermeneutic study.Klinik kecantikan bukanlah budaya yang benar-benar baru dalam perawatan kecantikan. Sebelumnya telah ada jenis industri budaya lain yang juga mengadopsi ilmu kedokteran, seperti industri kosmetik dan salon kecantikan. Namun klinik kecantikan sukses menyandang predikat sebagai jasa perawatan kecantikan yang dianggap paling sehat. Tulisan ini merupakan rigkasan penelitian tentang bagaimana klinik kecantikan begitu cepat menjadi bagian hidup sehari–hari masyarakat konsumennya. Fokus penelitian ini adalah Natasha Skin Care, sebuah klinik kecantikan paling popular di Indonesia saat ini. Menurut Richard Johson proses sebuah industri budaya sampai pada masyarakat konsumennya melalui komunikasi yang timpang, membentuk pola komunikasi siklik, saling terhubung namun penuh dengan keterpelesetan, saling mewarnai namun tidak menentukan secara pasti antara produsen industri budaya dengan masyarakat konsumennya. Penelitian ini ditempuh

    20. Verletzungspotential für Kinder und Jugendliche beim Trampolinspringen

      OpenAIRE

      Kosev, I; Folz, B

      2015-01-01

      Hintergrund: 62% der Deutschen haben ein Trampolin in ihrem Garten. Die Sprunggeräte gehören inzwischen fast zur Standardspielausrüstung. Im Rahmen unserer Beobachtungen über Unfallverletzungen der Kopf-Hals-Region zeigte sich, dass das Trampolinspringen mit Verletzungen im Kopf/Hals-Bereich einhergehen kann. In der vorliegenden Arbeit handelt es sich um eine prospektive Analyse der in den letzten Jahren an unserer Klinik behandelten Patienten mit Trampolinverletzungen. Methode: In dieser Ü...