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.

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.)

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)

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

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

Bovine epizootic encephalomyelitis caused by Akabane virus in southern Japan

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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

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...

THE ROLE OF CONTARST ENHANCEMENT IN VISUALIZATION OF ACUTE DISSEMINATED ENCEPHALOMYELITIS

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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.

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.

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)

CT findings in acute small bowel diverticulitis; Computertomographie bei akuter Duenndarmdivertikulitis

Energy Technology Data Exchange (ETDEWEB)

Ferstl, F.J.; Obert, R. [Radiologisch-Nuklearmedizinisches Zentrum (RNZ) am St. Theresienkrankenhaus Nuernberg (Germany)

2004-02-01

Small bowel diverticulitis is a rare cause of an acute abdomen. Originating from acquired diverticula of the jejunum, less often of the ileum, or Meckel diverticulum, the symptoms are non-specific, simulating other acute inflammatory disorders, such as appendicitis, cholecystitis or colonic diverticulitis. The diagnosis of small bowel diverticulitis is solely based on radiologic findings, with computed tomography (CT) regarded as the method of choice. In recent years, a number of case reports have described the spectrum of the CT features in acute small bowel diverticulitis and its dependence on the severity of the inflammatory process. Typical findings are an inflamed diverticulum, inflammatory mesenteric infiltration, extraluminal gas collection and mural edema of adjacent small bowel loops with resultant separation of bowel loops. An enterolith is rarely found in an inflamed diverticulum. Complications include abscesses, fistulae, small bowel obstruction and free perforation with peritonitis. Small bowel diverticulitis can be a diagnostic problem if it involves the terminal ileum or Meckel's diverticulum. For preoperative confirmation of the presumed diagnosis of small bowel diverticulitis on CT, an enteroclysis for acquired diverticula or a technetium scan for Meckel's diverticulum should be performed. We present the CT findings in three patients of acute small bowel diverticulitis, two affecting the jejunum and one a Meckel's diverticulum. (orig.) [German] Die akute Duenndarmdivertikulitis ist eine seltene Ursache eines akuten Abdomens. Ausgehend von den erworbenen Divertikeln des Jejunums, seltener des Ileums, oder von einem Meckel-Divertikel, manifestiert sich die Divertikulitis klinisch durch eine unspezifische Symptomatik, die zuerst an die haeufigeren, akutentzuendlichen Erkrankungen des Abdomens wie z. B. Appendizitis, Cholezystitis oder Kolondivertikulitis denken laesst. Die Duenndarmdivertikulitis kann praeoperativ nur durch

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.

Akut myeloid lösemi hastasında kronik dissemine kandidiyazisin başarılı tedavisi

OpenAIRE

K, Ozturk E; N, Soyer; S, Bayraktaroglu; M, Hekimgil; M, Tobu; B, Arda

2014-01-01

Kronik dissemine kandidiyazis (KDK) sistemik yaygın bir kandida enfeksiyonu çeşididir ve nötropenik hastaları etkiler. Bu vaka sunumunda remisyon indüksiyon kemoterapisi sırasında KDK tanısı alan ve sırasıyla amfoterisin B ve flukonazol ile tedavi edilen bir akut myeloid lösemi olgusu sunulmuştur. Kemoterapi sonrası geniş spektrumlu antibiyotiklere yanıtsız ateş ortaya çıktı. Lipozomal amfoterisin B (Lip-Amf-B) tedavisi başlandı. Serum galaktomannan (GM) testi ve kan kültürleri negatifti. Yük...

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.

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)

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

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.

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

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

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...

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...

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.

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.

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)

AKUT: a process for the separation of aerosols, krypton, and tritium from burner off-gas in HTR-fuel reprocessing

International Nuclear Information System (INIS)

Laser, M.; Barnert-Wiemer, H.; Beaujean, H.; Merz, E.; Vygen, H.

1975-01-01

The AKUT process consists of the following process steps: (1) aerosol retention by an electrostatic separator followed by HEPA filters, (2) oxidation of CO with O 2 or reaction of excess O 2 with CO, respectively, (3) compression, (4) scrubbing and/or liquefaction, (5) separation of krypton by distillation, and (6) separation of tritiated water and iodine by adsorption or chemical reaction. Liquefied off-gas with low permanent gas content resulting from graphite burning with oxygen may be distilled at ambient temperature. Off-gas with higher permanent gas content from burning with oxygen enriched air must be processed at lower temperature. The ambient temperature flow sheet is preferable from an economic as well as safety point of view. (U.S.)

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.

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....

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...

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

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)

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

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.

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

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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.

Hubungan Kadar Gula Darah saat Masuk Rumah Sakit dengan Jenis Sindroma Koroner Akut di RS Dr. M. Djamil Padang

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Willy Valerian

2015-05-01

Full Text Available AbstrakSindrom Koroner Akut (SKA merupakan spektrum dari penyakit arteri koroner yang tidak stabil, mulai dari angina pektoris tidak stabil sampai infark miokardium. SKA terbagi atas Unstable Angina Pectoris (UAP, ST elevation myocardial infarction (STEMI, Non-ST elevation myocardial infarction (NSTEMI. Tujuan penelitian ini adalah untuk menentukan hubungan antara kadar gula darah saat masuk rumah sakit dan jenis SKA. Metode penelitian yang digunakan adalah cross sectional. Penelitian dilakukan di Instalasi Rekam Medik RS Dr. M. Djamil Padang dengan mengambil data pasien SKA dari Januari 2012 sampai Desember 2012. Hasil penelitian ini didapatkan jenis SKA dengan gula darah yang tidak normal dari 60 sampel, yaitu: UAP 25%, NSTEMI 35%, STEMI 40%. Hasil pengolahan data dapat dilihat bahwa nilai p = 0,592 yang artinya tidak terdapat hubungan yang bermakna antara kadar gula darah saat masuk rumah sakit dengan jenis SKA. Hal ini terjadi mungkin karena terlalu sedikitnya sampel dan banyak sampel kriteria ekslusi dalam pencarian data. Sebaiknya dalam penelitian yang akan datang dapat memperbanyak sampel.Kata kunci: sindrom koroner akut, kadar gula darah, hubungan kadar gula darah dengan SKA AbstractAcute Coronary Syndrome (ACS is a spectrum of coronary artery disease that is not stable, ranging from unstable angina to myocardial infarction. Acute Coronary Syndrome is divided into Unstable Angina Pectoris (UAP, ST elevation myocardial infarction (STEMI, non-ST elevation myocardial infarction (NSTEMI. The objective of this study was to determine the relationship between blood sugar levels when admitted to hospital and Acute Coronary Syndrome type by using cross sectional study. The study was conducted at the Medical Records RS Dr. M. Djamil Padang. The ACS data collected from January 2012 until December 2012. The results of this study was found the SKA with abnormal blood sugar of 60 samples, i.e. UAP25%, NSTEMI35%, 40% STEMI. On the results of data

Amelioration of ongoing experimental autoimmune encephalomyelitis with fluoxetine.

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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.

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.)

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.)

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.)

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

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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.

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

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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

Acute disseminated encephalomyelitis in dengue viral infection.

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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.

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.

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.)

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.)

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

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.)

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.).

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.

Hubungan Kadar Glukosa Darah Saat Masuk Rumah Sakit Dengan Lama Hari Rawat Pasien Sindrom Koroner Akut (SKA Di RSUP Dr. M. Djamil Padang

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Rosi Oktarina

2013-05-01

Full Text Available AbstrakHiperglikemia masih menjadi topik penelitian yang sering dihubungkan dengan kejadian sindrom koroner akut (SKA di dunia, terutama hiperglikemia saat masuk rumah sakit. Hal ini didasari oleh beberapa pengaruh kadar glukosa darah yang tinggi terhadap sistem kardiovaskuler seperti gangguan fungsi ventrikel kiri, stroke volume yang menurun, regurgitasi katup mitral berulang, gangguan pada waktu pengisian diastolik hingga risiko tinggi untuk arritmia, serta hubungannya dengan peningkatan risiko trombosis. Sehingga semakin memperjelas pengaruh hiperglikemia yang tidak hanya dapat meningkatkan risiko terjadinya SKA, melainkan juga dapat memperburuk kondisi pasien SKA sendiri. Penelitian ini bertujuan mengidentifikasi hubungan kadar glukosa darah sewaktu dengan lama hari rawat pasien Sindrom Koroner Akut (SKA. Jenis penelitian yang digunakan adalah penelitian analitik dengan menggunakan desain penelitian Cross Sectional Study. Penelitian ini menggunakan data sekunder yang diambil di Instalasi Rekam Medik (Medical Record, yakni data rekam medik pasien yang didiagnosis sebagai Sindrom Koroner Akut (SKA yang dirawat inap di Rumah Sakit Umum Pusat DR. M. Djamil Padang Periode Januari–Desember 2011. Ditemukan sebagian besar pasien SKA masuk rumah sakit dengan kadar Glukosa Darah Sewaktu (GDS sebesar ≥ 200 mg/dl (40% dan lama hari rawat sebesar ≥ 7 hari (52%. Dari hasil analisa bivariat dengan menggunakan uji korelasi Spearman ditemukan adanya hubungan searah antara kadar glukosa darah saat masuk rumah sakit dengan lama hari rawat pasien SKA dengan kekuatan hubungan yang sedang, r = +0,492, p = 0, 000 (p<0,05. Pemantauan terhadap kadar GDS yang diperiksa saat pasien masuk rumah sakit perlu dilakukan dan untuk penelitian yang akan datang diharapkan dapat diteliti lebih lanjut faktor-faktor lain yang mempengaruhi lama hari rawat pasien SKA.Kata kunci: Kadar glukosa darah saat masuk RS, lama hari rawatAbstractHyperglicemia is still become a research

MRI findings of acute disseminated encephalomyelitis

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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.

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....

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...

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

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...

Persistent pseudobulbar affect secondary to acute disseminated encephalomyelitis

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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.

Gambaran Profil Lipid pada Pasien Infark Miokard Akut di RSUP M. Djamil Padang Periode 1 Januari 2011 - 31 Desember 2012

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Lamuna Fathila

2015-05-01

Full Text Available AbstrakInfark Miokard Akut (IMA merupakan nekrosis otot jantung akibat terganggunya kebutuhan dan suplai oksigen ke jantung secara mendadak. Faktor risikonya adalah perubahan profil lipid yaitu Kolesterol total, Kolesterol LDL. Kolesterol HDL, dan trigliserida yang dikaitkan dengan pembentukan plak aterosklerosis. Manfaat penelitian ini untuk mengetahui gambaran profil lipid pada pasien IMA. Tujuan penelitian ini untuk mengetahui gambaran profil lipid pada pasien IMA di RSUP M. Djamil Padang periode 1 Januari 2011-31 Desember 2012. Penelitian dilakukan dengan metode deskriptif dengan desain cross sectional study di bagian Rekam Medik RSUP M. Djamil Padang. Hasil penelitian menunjukkan umur terbanyak pasien IMA 45-59 tahun, Jenis kelamin terbanyak pasien IMA adalah laki-laki, perbandingannya adalah 2,7 : 1, Pasien IMA yang memiliki kadar kolesterol total tinggi 79 orang (38,92% dan normal 124 orang (61,08%, Pasien IMA yang memiliki kadar kolesterol LDL tinggi 76 orang (37,44% dan normal 127 orang (62,56%, Pasien IMA yang memiliki kadar kolesterol HDL rendah 145 orang (71,43% dan normal 58 orang (28,57%, dan Pasien IMA yang memiliki kadar trigliserida tinggi 44 orang (21,67% dan normal 159 orang (78,33%.Kata kunci: infark miokard akut, kolesterol total, kolesterol LDL, Kolesterol HDL, trigliserida AbstractAcute Myocardial Infarction (AMI is a muscle necrosis of the heart through disruption of demand and supply of oxygen to the heart suddenly. Risk factors of AMI is a change of lipid profile (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, and Triglycerides associated with the formation of atherosclerotic plaque. The benefit of this research is to reveal the lipid profile in patients with AMI. The objective of this study was to determine the description of lipid profile in patients with AMI at RSUP M. Djamil Padang period January 1st, 2011-December 31th, 2012. The study was conducted with descriptive methods to the design of cross sectional

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

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

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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

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....

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...

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

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...

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...

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.

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.

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....

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

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

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.)

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

Acute abdomen. Clinical background and demands on imaging; Akutes Abdomen. Klinische Begriffsbestimmung und Anforderungen an die Bildgebung

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Graeb, C.; Jauch, K.W. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Klinik und Poliklinik fuer Chirurgie, Muenchen (Germany); Reiser, M.; Graser, A. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany)

2010-03-15

The term ''acute abdomen'' does not describe a specific disease entity but is more a critical clinical state which incorporates very heterogeneous clinical presentations. The prognosis of any disease depends on the time frame from the onset of symptoms to the initiation of a specific therapy. For this reason there are special expectations by clinicians regarding the diagnostic assessment provided by radiology which is expected to deliver an immediate diagnosis supporting further therapeutic decisions. Along with the patient's clinical history, physical examination and blood tests, radiological diagnostics are essential for enabling a specific treatment. From a surgical point of view the radiologist is expected to help in differentiating between cases with indications for emergency surgery and cases eligible for elective surgery or conservative treatment. (orig.) [German] Der Begriff ''akutes Abdomen'' stellt keine eigenstaendige Erkrankung dar, sondern beschreibt einen kritischen klinischen Zustand, unter dessen Oberbegriff sich die unterschiedlichsten Krankheitsbilder subsumieren lassen. Das Zeitintervall zwischen dem Auftreten der ersten Symptome bis zur Einleitung einer gezielten Therapie ist fuer die Prognose der Patienten der entscheidende Faktor. Aus diesem Grund bestehen besondere Anforderungen an die bildgebende Diagnostik, die dazu beitragen soll, innerhalb kuerzester Zeit eine moeglichst genaue Diagnose zu stellen. Neben Anamnese, klinischer Untersuchung und Labordiagnostik stellt die radiologische Untersuchung einen wesentlichen Baustein vor der Therapieeinleitung dar. Aus chirurgischer Sicht muessen Krankheitsbilder, die eine sofortige Notfalloperation erforderlich machen, von Erkrankungen differenziert werden, die eine elektive Chirurgie oder ein konservatives Vorgehen indizieren. (orig.)

"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.

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...

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.

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.

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...

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.

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)

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.

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...

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.)

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.

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

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

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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.

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

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

R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice.

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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.

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....

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

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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.

Acute pancreatitis: a case report

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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

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

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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.

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

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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.

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

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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.

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

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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.

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....

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/...

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...

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...

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...

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...

Chondroitin 6-O-sulfate ameliorates experimental autoimmune encephalomyelitis.

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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.

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

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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.

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

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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

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

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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

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.

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

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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

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

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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.

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

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

Diagnostics of vascular diseases as a cause for acute abdomen; Diagnostik vaskulaerer Erkrankungen als Ursache fuer das akute Abdomen

Energy Technology Data Exchange (ETDEWEB)

Juchems, M.S. [Universitaetsklinikum Ulm, Klinik fuer Diagnostische und Interventionelle Radiologie, Ulm (Germany); Aschoff, A.J. [Klinikum Kempten-Oberallgaeu, Abteilung fuer Radiologie, Kempten (Germany)

2010-03-15

Vascular pathologies are rare causes of an acute abdomen. If the cause is a vascular disease a rapid diagnosis is desired as vascular pathologies are associated with high mortality. A differentiation must be made between arterial and venous diseases. An occlusion of the superior mesenteric artery is the most common reason for acute mesenteric ischemia but intra-abdominal arterial bleeding is also of great importance. Venous pathologies include thrombotic occlusion of the portal vein, the mesenteric vein and the vena cava. Multi-detector computed tomography (MDCT) is predestined for the diagnostics of vascular diseases of the abdomen. Using multiphasic contrast protocols enables reliable imaging of the arterial and venous vessel tree and detection of disorders with high sensitivity and specificity. Although conventional angiography has been almost completely replaced by MDCT as a diagnostic tool, it is still of high importance for minimally invasive interventions, for example in the management of gastrointestinal bleeding. (orig.) [German] Vaskulaere Pathologien sind seltene Ursachen fuer den klinischen Zustand eines akuten Abdomens. Liegt eine vaskulaere Erkrankung vor, ist jedoch aufgrund der hohen Mortalitaet eine zuegige Diagnostik von grosser Wichtigkeit. Bei den Erkrankungen der abdominellen Gefaesse sind arterielle von venoesen Ursachen zu unterscheiden. Ein Verschluss der A. mesenterica superior ist die haeufigste Ursache fuer die akute Mesenterialischaemie, daneben sind Blutungen in den abdominellen Gefaessprovinzen des arteriellen Gefaessbaums von Bedeutung. Venoese Pathologien betreffen thrombotische Verschluesse der Pfortader, der V. mesenterica und der V. cava. Die Multidetektor-CT (MDCT) ist zur Diagnostik vaskulaerer Erkrankungen des Abdominalraums praedestiniert. Mit mehrphasigen Untersuchungsprotokollen gelingt es, den arteriellen und venoesen Gefaessbaum zuverlaessig darzustellen und Erkrankungen mit hoher Sensitivitaet und Spezifitaet zu

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...

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.

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.

IL-12p35 Inhibits Neuroinflammation and Ameliorates Autoimmune Encephalomyelitis

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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.

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.)

Cerebral blood flow autoregulation in patients with acute bacterial meningitis

DEFF Research Database (Denmark)

Møller, Kirsten

2001-01-01

Ph.d. afhandlingen omhandler sammenhængen mellem hjernens blodtilførsel (CBF) og middelarterietrykket (MAP) hos patienter med akut bakteriel meningitis. Hos raske er CBF uafhængig af MAP, hvilket kaldes CBF autoregulation. Svækket autoregulation antages at øge risikoen for cerebral hypoperfusion og...... iskæmi under episoder med lavt MAP, og for cerebral hyperperfusion og vasogent ødem ved højt MAP. CBF autoregulationen undersøgtes hos tyve voksne patienter med akut bakteriel meningitis i den tidlige sygdomsfase (... meningitis, men retableres ved klinisk restitution. Autoregulationen kan endvidere delvis retableres ved akut hyperventilation. Fundene har potentiel betydning for valg af supportiv terapi hos patienter med meningitis....

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.

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.

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.

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...

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

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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.

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.

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

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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.

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

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.)

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...

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...

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

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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.

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...

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.

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

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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.

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

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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.

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

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...

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

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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.

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

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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...

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

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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

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

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

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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.

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

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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

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

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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/.

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

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

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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.

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

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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.

SAP Suppresses the Development of Experimental Autoimmune Encephalomyelitis in C57BL6 Mice

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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

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.

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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.

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.

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.

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

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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.

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

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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.

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

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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...

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

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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.

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...

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.

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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.

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

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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.

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

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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.

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

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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.

Akutô

DEFF Research Database (Denmark)

Oxenbøll, Morten

2009-01-01

establishing rebels or other opponents as criminals and bandits has often legitimized cruel oppression of them. Felons have sometimes been accused of specific crimes in order to legitimize interrogation techniques and punishments, which would otherwise have been deemed too harsh and brutal. Allusions...... the importance of the term as a rhetorical device in legal disputes and chronicles. The appearance of akuto in sources from this period does therefore not suggest growing ‘unlawfulness' in the provinces in this period, but rather a result of a growing application of central authority and law to local disputes...

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

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

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.

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

Acute pain treatment on postoperative and medical non-surgical wards [Akutschmerztherapie auf operativen und konservativen Stationen

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Korczak, Dieter

2013-05-01

Full Text Available [english] The effectiveness of acute pain treatment in hospitals is examined. An efficient therapy of acute pain is efficient and cost-effective. Although every patient is entitled for the relief of pain, many hospitals do not treat acute pain in an optimal manner.[german] Es wird die Effektivität der Akutschmerztherapie in Krankenhäusern untersucht. Eine effiziente Behandlung akuter Schmerzen ist wirksam und spart Kosten. Obwohl jeder Patient Anspruch auf Linderung seiner Schmerzen hat, behandeln viele Krankenhäuser akute Schmerzen noch nicht optimal.

Myocardial Infarction and Risk of Suicide

DEFF Research Database (Denmark)

Larsen, Karen Kjær; Agerbo, Esben; Christensen, Bo

2010-01-01

Akut myokardieinfarkt og risikoen for selvmord: Et populationsbaseret case-control studie Baggrund Akut myokardieinfarkt (MI) er associeret med øget risiko for angst, depression, nedsat livskvalitet og mortalitet af alle årsager. Det er uvist om MI er associeret med øget risiko for selvmord. Vi...... at være høj mindst 5 år efter MI. Konklusion MI følges af en øget risiko for selvmord for patienter med eller uden psykiatrisk sygdom. Vores resultater indikerer vigtigheden af at screene patienter med MI for depression og selvmordstanker. Udgivelsesdato: December 7...

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...

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...

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.

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.

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

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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.

Impact of the Swedish National Stroke Campaign on stroke awareness.

Science.gov (United States)

Nordanstig, A; Asplund, K; Norrving, B; Wahlgren, N; Wester, P; Rosengren, L

2017-10-01

Time delay from stroke onset to arrival in hospital is an important obstacle to widespread reperfusion therapy. To increase knowledge about stroke, and potentially decrease this delay, a 27-month national public information campaign was carried out in Sweden. To assess the effects of a national stroke campaign in Sweden. The variables used to measure campaign effects were knowledge of the AKUT test [a Swedish equivalent of the FAST (Face-Arm-Speech-Time)] test and intent to call 112 (emergency telephone number) . Telephone interviews were carried out with 1500 randomly selected people in Sweden at eight points in time: before, three times during, immediately after, and nine, 13 and 21 months after the campaign. Before the campaign, 4% could recall the meaning of some or all keywords in the AKUT test, compared with 23% during and directly after the campaign, and 14% 21 months later. Corresponding figures were 15%, 51%, and 50% for those remembering the term AKUT and 65%, 76%, and 73% for intent to call 112 when observing or experiencing stroke symptoms. During the course of the campaign, improvement of stroke knowledge was similar among men and women, but the absolute level of knowledge for both items was higher for women at all time points. The nationwide campaign substantially increased knowledge about the AKUT test and intention to call 112 when experiencing or observing stroke symptoms, but knowledge declined post-intervention. Repeated public information therefore appears essential to sustain knowledge gains. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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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

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.

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

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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.

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.

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

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

Science.gov (United States)

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.

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.

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.

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.

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

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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.

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

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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.

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

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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

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

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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.

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.

UJI TOKSISITAS AKUT FRAKSI ETIL ASETAT BATANG DAN DAUN PACAR AIR (Impatiens balsamina Linn TERHADAP TIKUS PUTIH BETINA GALUR SPRAGUE DAWLEY

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Nia Anzini

2014-06-01

,05, tidak ada perbedaan yang signifikan pada konsumsi minum harian antara kelompok perlakuan dengan kontrol aquadest  (p>0,05 dan terdapat perbedaan signifikan antara tikus kontrol CMC dan perlakuan (p<0,05. Berdasarkan hasil scoring kerusakan hati dan ginjal menunjukkan fraksi etil asetat batang dan daun pacar air secara histologi merusak organ hati, namun tidak menyebabkan kerusakan ginjal hewan uji Kata kunci:    toksisitas akut, fraksi etil asetat, Impatiens balsamina Linn, OECD 425

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

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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.

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

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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

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

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

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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

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

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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

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

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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.

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

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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.

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

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.

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

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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

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

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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.

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

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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.

Perawatan Kandidiasis Pseuodomembran Akut dan Mukositis Oral pada Penderita Kanker Nasofaring yang Menerima Khemoterapi dan Radioterapi

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S. Supriatno

2016-10-01

Full Text Available Latar belakang: Terapi radiasi merupakan metode primer perawatan pasien kanker leher dan kepala. Perubahan funsional dan kerusakan jaringan oral menyebabkan timbulnya mukositia oral yang diikuti dengan kandidiasis oral. Tujuan: Melaporkan efek samping perawatan khemoterapi dan radioterapi pada pasien kanker nasofaring yang terjadi di rongga mulut berupa kandidiasis pseudomembran akut dan mukositis oral serta penatalaksanaannya. Kasus: Seorang laki-laki, 69 tahun, datang ke Bagian Gigi dan Mulut RSUP Dr. Sardjito, atas rujukan dari instalasi Penyakit Dalam., RSUP Dr. Sardjito, dengan keluhan sakit untuk menelan makanan dan mulutnya banyak bercak-bercak putih. Keluhan dirasakan satu minggu setelah dilakukan khemoterapi ke-3 dan radioterapi ke-9. Pasien didiagnosa kanker nasofaring (NPC dengan klasifikasi T2N3M0. Pemeriksaan klinik menunjukkan adanya lapisan putih pada mukosa lidah, pipi, palatum, dan mukosa bibir. Seluruh mukosa mulut berwarna merah tua dan terdapat anguler cheilitis di kedua sudut bibir. Pasien diklasifikasikan menderita mukositis oral derajat 1. Penatalaksanaan: Menghilangkan jaringan nekrotik dan debris dengan berkumur larutan perhidrol 3% dan pemberian medikasi termasuk tablet nistatin 500.000 IU, betadin kumur, dan larutan perhidrol 3% selama 1 minggu. Saat reevaluasi, pasien sudah dapat menelan dan makan yang sedikit keras tanpa ada rasa sakit lagi. Pemeriksaan klinis didapatkan bercak putih di lidah, palatum, pipi dan bibir sudah tidak ada. Warna mukosa oral telah normal, OHI dan kondisi umum baik dalam 1 minggu pasca perawatan. Kesimpulan: Perawatan kandidiasis dan mukositis oral akibat kemoradioterapi pada pasien kanker nasofaring telah berhasil dan kondisi oral membaik. Pasien dapat mengunyah dan menelan makanan tanpa ada rasa sakit, dan hasil pengobatan yang diberikan pada pasien sesuai dengan harapan operator.   Background: Radiation therapy remains the primary method of treatment for patients with head and neck

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

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.

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

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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.

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

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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.

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.

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

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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.

Superior Mezenter Arter Embolisinde Erken Tanı ve Embolektomi

OpenAIRE

AYDIN, İbrahim; YÜCEL, Ahmet; PERGEL, Ahmet; KARAKAYA, Ahmet; OĞULLAR, Sabri; ŞAHİN, Dursun; ÖZER, Ender

2016-01-01

Akut mezenter arter embolisi, acil girişim gerektiren, nekroz geliştiğinde yaygın ince barsak rezeksiyonu ve sonrasında gelişen kısa barsak sendromu nedeniyle yaşam kalitesini düşüren, morbidite ve mortalitesi oldukça yüksek bir hastalıktır. Multidetektör kontrastlı BT, akut mezenterik embolinin erken tanısında oldukça önemlidir. Biz burada, kontrastlı abdominal BT ile erken tanı ve sonrasında bağırsak rezeksiyonu gerekmeden yalnızca embolektomi yaparak tedavi ettiğimiz olguyu sunmayı amaçlad...

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

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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.

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

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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.

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

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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.

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

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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.

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...

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

Science.gov (United States)

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

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

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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

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.

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

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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.

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

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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.

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

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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.

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

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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.

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.

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

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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

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

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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

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

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

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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.

Trombolyse og akut myokardieinfarkt. Mindre restiskoemi ved førstegangs akut myokardieinfarkt

DEFF Research Database (Denmark)

Mickley, H F; Pless, P; Nielsen, J R

1994-01-01

% in reperfused patients versus 62% in controls. During 36-hour ambulatory ST-segment monitoring, however, the duration of myocardial ischaemia was significantly reduced in thrombolyzed patients: 322 minutes versus 1144 minutes in controls (p work capacity...... in thrombolyzed patients compared with controls: 160 +/- 41 versus 139 +/- 34 W (p reduces residual myocardial ischaemia. The reduced ischaemic burden is assumed...

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

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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

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

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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.

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

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.

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.

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

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

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

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

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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.

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

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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.

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

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

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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

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

Features of residency training and psychological distress among ...

African Journals Online (AJOL)

Features of residency training and psychological distress among residents in a Nigerian teaching hospital. O Esan, A Adeoye, P Onakoya, O Opeodu, K Owonikoko, D Olulana, M Bello, A Adeyemo, L Onigbogi, O Idowu, T Akute ...

Akut smertebehandling af stofmisbrugere

DEFF Research Database (Denmark)

Rindom, Henrik; Højsted, Jette; Brünés, Nina

2017-01-01

The challenge of managing acute pain in opioid-addicted patients is a question of fully understanding the pharmacological effects of the illegal drugs and to prevent overdosing or withdrawal symptoms. It requires a thorough knowledge of the patient's daily consumption of legal and illegal drugs...... and an understanding obtained through an accepting and empathetic communication with the patient. Substitution management aims to prevent opioid withdrawal symptoms and is not a means of managing pain. When planning the pain management the patient must receive at least 25% of the daily methadone dose, recalculated...

Akut-i-kronisk leversvigt

DEFF Research Database (Denmark)

Ørntoft, Nikolaj Worm; Thomsen, Karen Louise; Dam, Gitte

2017-01-01

Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by acute decompensation of liver cirrhosis, organ failure and high short-term mortality (20-80% at one month). The main precipitants are infections and excessive alcohol intake, and the mechanistic features include a high ...... level of systemic inflammation, macrophage activation and liver injury. The severity of ACLF is graded according to the number and extent of organ failures. Prognostic scores help predict mortality and support decisions on intensive treatment or futility....

Akut kulilteforgiftning efter vandpiberygning

DEFF Research Database (Denmark)

Paulsen, Jakob Felbo; Villads, Kasper von Rosen; Sonne, Morten

2016-01-01

Carbon monoxide poisoning is potentially lethal, and early recognition and treatment is essential. An 18-year-old man was admitted due to syncope and a carboxyhaemoglobin level of 17% after water pipe tobacco smoking. He received normo- and hyperbaric oxygen as treatment and was discharged after...

Acute abdomen. Akutes Abdomen

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Beger, H.G.; Kern, E. (eds.)

1987-01-01

The book first presents the anatomy and physiology of the abdomen and continues with chapters discussing clinical and laboratory aspects and a suitable order of diagnostic examinations with reference to the acute processes, explaining the diagnostic tools: ultrasonography, radiography including angiography and CT, tapping techniques and endoscopy together with their basic principles, examination techniques, and diagnosis. One chapter presents a complete survey of the processes involving the entire abdomen - as e.g. peritonitis, ileus, abdominal trauma, intraperitoneal hemorrage. This chapter profoundly discusses the diagnostics and therapies including emergency measures and surgery. Problems requiring consultation among varous specialists, in internal medicine, gynecology, urology, or pediatrics, are discussed in great detail. Information for the anesthetist is given for cases of emergency. More than one third of the book is devoted to organ-specific information, dicussing the pathogenesis, diagnostics, and therapy of the oesophagus, stomach, large and small intestine, bile ducts, pankreas, liver, spleen, and the abdominal vessels and the abdominal wall. (orig.) With 153 figs., 90 tabs.

Billeddiagnostik ved akut lungeemboli

DEFF Research Database (Denmark)

Hess, Søren; Madsen, Poul Henning; Jørgensen, Henrik Boel

2005-01-01

and echocardiography in acute pulmonary embolism and identified 562 articles, of which 16 original papers met our inclusion criteria. From these, we concluded that none of the modalities is applicable in every situation. Spiral computed tomography can confirm the diagnosis but cannot rule out subsegmental embolism....... With lung scintigraphy, perfusion imaging alone is probably sufficient and suited to both confirming and ruling out the diagnosis. Echocardiography should be reserved for patients with an emergent need for treatment and cannot rule out the diagnosis. Udgivelsesdato: 2005-Oct-10...

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.

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

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

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.

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.

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.

Norovirus Outbreak Investigation in Surmene District of Trabzon Province July 2010

Directory of Open Access Journals (Sweden)

Gamze Can

2011-10-01

Full Text Available Bu calismada, Temmuz 2010’da Trabzon Ilinin Surmene Ilcesinde meydana gelen norovirus salgininda yapilan incelemeleri sunmak amaclanmistir. Akut gastroenterit vakalari ilk olarak 09 Temmuz tarihinde ortaya cikmaya baslamis ve ilk gun 271 olan vaka sayisi ikinci gun 880’e ulasmistir. Ilk gunden itibaren alinan onlemlerle hizla dusen vaka sayisi norovirusun kisiden kisiye bulas ozelligi nedeniyle, 10. gun itibariyle az sayida vaka ile devam etmis ve 28 Temmuz itibariyle beklenen seviyeye inmistir. Salgin suresince 2483 akut gastroenterit vaka basvurusu olmustur. Salgina neden olarak; Daha once uygun duzeylerde seyreden klor duzeyinin tank bosalmasi sonucu bir sure sistemde dusuk duzeyde kalmasi ve ayni donemde bir aydir kullanimda olmayan bir kuyu pompasinin tamirinin bitirilip sistemden yeterince su akitilmadan devreye sokulmasi surecinin superpoze olmasi ile sistemin ana depoda kirlenmesi olarak tespit edilmistir. [TAF Prev Med Bull 2011; 10(5.000: 501-510

Dødelig venlafaxinforgiftning

DEFF Research Database (Denmark)

Pedersen, Julie Steen; Munck, Lars Kristian

2014-01-01

Venlafaxin er en serotonin- og noradrenalingenoptagelseshæmmer, der er godkendt til behandling af depressioner og angsttilstande. Symptomer ved forgiftning er serotonergt syndrom, generaliserede krampeanfald, rabdomyolyse samt akut lever-, hjerte- og nyresvigt. Der findes ingen antidot. Med afsæt i...

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

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.

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

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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.

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

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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.

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

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

Science.gov (United States)

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

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...

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)

Abscesses after appendectomy due to intraoperative loss of fecaliths; Abszesse nach Appendektomie durch intraoperativ verlorene Appendicolithen

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Hoermann, M.; Kreuzer, S. [Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria). Abt. chirurgische Faecher; Sacher, P. [UniversitaetsSpital Zuerich (Switzerland). Abt. Kinderchirurgie; Eich, G.F. [UniversitaetsSpital Zuerich (Switzerland). Inst. fuer Diagnostische Radiologie

2001-08-01

Objective: Fecaliths appear to predispose a patient to acute appendicitis, abscess formation, and perforation. The number of preoperative radiological evaluations is increasing, although children with suspected perforation still undergo surgery immediately. We report and discuss imaging findings and implications in children with acute appendicitis and fecalithis. Methods: Four children (3 girls, 1 boy; mean age 9 years) underwent surgery for acute appendicitis. Three children underwent sonography and plain radiography before surgery, 1 child was operated without radiological evaluation. After readmission, all 4 children underwent sonography and plain radiography before surgery. Results: In 3 patients a fecalith was diagnosed initially. After uneventful recovery all 4 patients had acute abdominal pain and readmission was necessary. In all 4 patients the escaped fecalith was demonstrated with sonography and plain radiography confirmed surgically. Conclusion: Discussion about the role of imaging in acute appendicitis has concentrated on the diagnostic yield of cross-section techniques. The importance of demonstrating a fecalith, prompting a more thorough intraoperative search has found little attention. The radiologist should also detect and localize a fecalith and should be aware of retained fecaliths as a cause of abscess formation after appendectomy. (orig.) [German] Ziel: Faekolithen praedisponieren Kinder zu akuter Appendizitis und fuehren vermehrt zu Perforation und Abszessen. Wir berichten und diskutieren die Bedeutung der Bildgebung bei Kindern mit Faekolithen und perforierter akuter Appendizitis. Methoden: 4 Kinder (drei Maedchen, ein Junge, Altersmeridian 9 Jahre) wurden wegen perforierter akuter Appendizitis operiert. Drei Kinder erhielten praeoperativ eine Ultraschalluntersuchung und ein Abdomen-Uebersichtsbild. Nach Neuaufnahme wurden nun bei allen Kindern eine Ultraschalluntersuchung und ein Abdomen-Uebersichtsbild angefertigt und neuerlich operiert

The Efficacy of Probiotic in Adults with Acute Infectious Diarrhea

Directory of Open Access Journals (Sweden)

Mawin Mahen

2017-04-01

Full Text Available Diarrhea is a global health problem with high morbidity and mortality. In developing countries, acute diarrhea is most commonly caused by infectious pathogens. Regardless of the cause, diarrhea is primarily treated by fluid replacement therapy to decrease the risk of dehydration and death, although it does not affect the duration of diarrhea. Probiotics are able to shorten the duration of diarrhea in children, but its efficacy in adults is unclear. This study aimed to evaluate the benefit of probiotic in reducing the duration of acute diarrhea in adults as compared to placebo. Systematic search was done using four databases: PubMed, Scopus, ProQuest, and Embase, without limit on the year of publication. Randomized clinical trials were selected as the appropriate study design to answer the clinical question and two studies were considered relevant for appraisal. In conclusion, probiotics could improve the recovery of acute infectious diarrhea in adults (level of evidence 1b however more studies should be carried out since only very few strains of probiotics have been investigated. Keywords: probiotics, treatment efficacy, acute diarrhea, adults.     Efektivitas Probiotik pada Orang Dewasa dengan Diare:  Sebuah Laporan Kasus Berbasis Bukti   Abstrak Diare merupakan masalah kesehatan global dengan angka morbiditas dan mortalitas yang tinggi. Di negara berkembang, diare akut biasanya disebabkan oleh infeksi. Terlepas dari penyebabnya, tata laksana utama diare adalah terapi rehidrasi untuk mengurangi dehidrasi dan kematian walaupun hal tersebut tidak memengaruhi durasi diare. Probiotik dapat memperpendek durasi diare pada anak-anak, namun efektivitasnya pada orang dewasa masih belum jelas. Tujuan penelitian ini adalah untuk mengevaluasi efek probiotik dalam mengurangi durasi diare akut pada orang dewasa dibandingkan plasebo. Pencarian sistematik dilakukan pada empat database: PubMed, Scopus, ProQuest, dan Embase, tanpa membatasi tahun publikasi

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.

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

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.

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.

Behandling af patienter med Guillan Barré syndrom

DEFF Research Database (Denmark)

Oliel, Vibeke S.

2011-01-01

Resumè Guillain Barrés syndrom er en autoimmum sygdom karakteriseret ved motorisk, sensorisk og autonom dysfunktion. I Danmark rammes omkring 80 personer i alle aldre årligt af sygdommen. Akut inflammatorisk polyradikoloneuropati rammer de perifere nervers nerveskeder og medfører progredierende...

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.

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.

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.

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.)

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.)

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

Directory of Open Access Journals (Sweden)

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.

Designing in situ simulation in the emergency department

DEFF Research Database (Denmark)

Paltved, Charlotte; Bjerregaard, Anders Thais; Krogh, Kristian

2017-01-01

Baggrund: Dette interventionsstudie har til formål at forbedre patientsikkerheden gennem design af in situ simulation. Undersøgelsen fandt sted på en akut medicinsk stue i den centrale region i Danmark. Forskning tyder på, at mangelfuld handover kommunikation kan øge sandsynligheden for kritiske ...

Kennis en hantering van slangbyte deur algemene praktisyns op die ...

African Journals Online (AJOL)

antiserum en boomslang-antiserum. Daar is egter twee nadelige en po- tensieel ernstige komplikasies ver- bonde aan die gebruik van antise- rum, naamlik akute anafilaktiese reaksie, a.g.v. allergiese reaksie tee- noor perdeserum (waaruit poliva- lente antiserum voorberei word), en serumsiekte a.g.v. 'n vertraagde hi-.

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

Directory of Open Access Journals (Sweden)

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

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

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

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

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.

Akut pesticidforgiftning--et globalt folkesundhedsproblem

DEFF Research Database (Denmark)

Konradsen, Flemming

2006-01-01

Following the intensification of agriculture and the promotion of agro-chemicals in low and middle income countries, acute pesticide poisoning has become a major public health problem with more than 300,000 deaths each year around the world. The easy availability of highly toxic pesticides...

ETIOLOGI MIKRIBIOLOGIS PENYAKIT DIARE AKUT

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Cyrus H. Simanjuntak

2012-09-01

Full Text Available As in other developing countries, diarrhoea is a major cause of morbidity and mortality in Indo­nesia. It is estimated that at least 4-5 million deaths per year in the world are caused by acute di­arrhoea. In Indonesia, 40% of deaths in the first 2 years of life is caused by acute diarrhoea. This study is to assess the microbial agents of diarrhoea! disease, from patients of 2 hospitals in Ja­karta. Rectal swabs for bacteriological examination were collected from patients at the admission using Cary & Blair as a transport media. Stools for Rota virus examination were collected in a tube container and kept at 4- 6°C before further processing. Conventional bacteriological procedures were performed for isolation and identification of bacterial agents. Enterotoxigenic E. Coli (E T E Cj was examined by ELISA for LT and by intragastric inocula­tion of suckling mice for ST. Campylobacter was incubated at 42°C in a candle jar using desiccator as a jar. The isolation results from 1937 specimens collected were V. cholera 01 50,2%, Rota virus 31,0%, ETEC 6,8%, Campylobacter sp 4,8%, Salmonella sp 4,3%, V. parahaemolyticus 1,6%, NAG 0,9%, Shi­gella sp 0,8%, Y. enterocolytica 0,2% and mixed infection of 2 or 3 different agent 5%. Most of the V. cholera isolated were of the Ogawa sero-type (98,9%. ETEC consisted of 69,2% LT alone, 21,4% ST alone and 8,9% both LT and ST. The most prevalent among 10 Salmonella species isolated were S. oranienberg 34,9% and S. kreveld 21,7%. The most prevalent among 4 species of Shigella isolated were Sh. flexneri 43,8% and Sh. dysen-triae 31,3%. Diarrhoeal diseases were continuously found through the year with 2 peaks; one high peak in May, June and July and the other lower peak in December and January.

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

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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

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

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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

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

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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.

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

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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.

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

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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.

New-onset atrial fibrillation after acute myocardial infarction in patients with left ventricular systolic dysfunction recorded by an Implantable Cardiac Monitor - Incidence, prediction and prognosis

DEFF Research Database (Denmark)

Jøns, Christian

2010-01-01

BAGGRUND OG FORMÅL Forekomsten af atrieflimren (AF) er øget hos patienter med akut myokardieinfarkt og venstre ventrikel dysfunction (defineret som LVEF ≤ 40%), men langtidsforekomst og prognose for nyopstået AF hos denne population er ukendt. Formålet med denne afhandling er, at undersøge foreko...

Noninvasiv ventilationsbehandling i akutafdelinger

DEFF Research Database (Denmark)

Sørensen, Dorthe

2017-01-01

også gives som continuous positive airway pressure (CPAP), dvs. en ikke-cyklisk ventilation med et konstant tryk og luftflow, der svarer til en eksspiratorisk modstand, og derfor også er uden egentlig inspiratorisk støtte (2,3). NIV-behandling ved akut respirationssvigt anvendes i dag præhospitalt (4...

Couples' experiences of interacting with outside others in chronic fatigue syndrome: a qualitative study.

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Brooks, Joanna; King, Nigel; Wearden, Alison

2014-03-01

Social isolation and stigma are frequently reported by patients with chronic fatigue syndrome/myalgic encephalomyelitis and relationships in the home environment with those close to the patients (their 'significant others') may thus be particularly important. Rather little attention has yet been paid to the beliefs and experiences of 'significant others' themselves in this context. This study sought to explore in-depth the beliefs and experiences of both patients and 'significant others' in relation to chronic fatigue syndrome/myalgic encephalomyelitis. In-depth interviews using a semi-structured interview schedule designed around the core constructs of the Common-Sense Model of self-regulation were conducted with two patients with chronic fatigue syndrome/myalgic encephalomyelitis and their spouses. Interpretative Phenomenological Analysis was used to analyse interview data. Experiences of social interactions in relation to chronic fatigue syndrome/myalgic encephalomyelitis with others outside of the relationship dyad emerged as a key issue for all participants when reflecting on their experiences of living with the condition. These concerns are presented under two themes: interactions with healthcare professionals and interactions with the social world. It is evident that significant others play an important role in the lived experience of chronic fatigue syndrome/myalgic encephalomyelitis. For both patients and significant others, the wider social world and interactions with outside others may be important influences on dyadic coping in chronic fatigue syndrome/myalgic encephalomyelitis. Both future research and treatment interventions could usefully include a 'significant other' perspective.

Conformal radiation therapy of localized prostate cancer: acute tolerance and early evaluation of effectiveness; Konformierende Strahlentherapie des lokalisierten Prostatakarzinoms: Akute Toleranz und fruehe Wirksamkeit

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Zierhut, D. [Klinische Radiologie, Radiologische Universitaetsklinik Heidelberg (Germany); Flentje, M. [Klinische Radiologie, Radiologische Universitaetsklinik Heidelberg (Germany); Sroka-Perez, G. [Klinische Radiologie, Radiologische Universitaetsklinik Heidelberg (Germany); Rudat, V. [Klinische Radiologie, Radiologische Universitaetsklinik Heidelberg (Germany); Engenhart-Cabillic, R. [Klinische Radiologie, Radiologische Universitaetsklinik Heidelberg (Germany); Wannenmacher, M. [Klinische Radiologie, Radiologische Universitaetsklinik Heidelberg (Germany)

1997-02-01

Aim: In a prospective trial early effectiveness and acute toxicity of conformal 3D-planned radiotherapy for localized prostate cancer was quantified using dose-volume-histogramms and evaluated with respect of treatment technique. Results: Eleven patients (of 32) had none, 15 mild (RTOG grade 1) and 6 moderate symptoms (RTOG grade 2, mainly diarrhoea, dysuria and polyuria). Acute complications leading to treatment interruption did not occur. In 16 patients symptoms disappeared within 6 weeks after radiotherapy. Only 2 men had symptoms which lasted longer than 3 months and were endoscopically examined. Up to now no late complications were detected. Incidence and severity of toxicity was significantly (p<0,05) related to the size of treatment volume. Akute toxicity was found to depend statistically significant (p<0,05) on the proportional volume of bladder and rectum, irradiated with more than 35 Gy. In 81% of the patients with pretherapeutic elevated PSA levels normalisation of PSA was observed. Overall mean PSA levels of 15.7{+-}22.6 {mu}g/l at the beginning of radiotherapy fell to 2.1{+-}3.7 {mu}g/l 6 weeks after irradiation. Only 1 Patient relapsed locally 22 months after radiation therapy. Conclusion: We conclude that due to modern 3D-planned conformal techniques with optimization of treatment dose and improved protection of critical organs such as urinary bladder and rectum, radiotherapy allows an effective and well tolerated therapy of localized prostatic carcinoma. (orig./VHE) [Deutsch] Ziel: Quantifizierung der fruehen Wirksamkeit und akuten Toxizitaet der 3D-geplanten und konformierenden Strahlentherapie des lokalisierten Prostatakarzinoms mittels Dosis-Volumen-Histogramm sowie Untersuchung der Abhaengigkeit von der Bestrahlungstechnik in einer prospektiven Studie. Ergebnisse: Elf Patienten hatten keine, 15 leichte (RTOG Grad I) und sechs maessiggradige Nebenwirkungen (RTOG Grad II, meist Diarrhoe, Dysurie und Polyurie). Bei keinem Patienten musste die

Exercise Training in Stable Heart Transplant recipients

DEFF Research Database (Denmark)

Dall, Christian Have

Afhandlingen består af to forsøg, et randomiseret crossover forsøg der undersøger effekten af træning på hjertetransplanterede, samt et klinisk forsøg der undersøger akut blodtryksstigning ved styrketræning hos hjertetransplanterede, hjertesvigtspatienter, og patienter med iskæmisk hjertesygdom. ...

Drug prescription by telephone consultation in Danish out-of-hours primary care

DEFF Research Database (Denmark)

Moth, Grete; Huibers, Linda; Christensen, Morten Bondo

2014-01-01

De danske praktiserende læger visiterer alle patienter, der henvender sig til lægevagten med et akut helbredsproblem. Omkring 60 % af alle henvendelser afslutter lægerne selv ved en telefonkonsultation, ofte i form af rådgivning eller receptudskrivning. Alligevel er der kun begrænset viden om hyp...

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.

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.

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

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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.

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.

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.

Pancreatitis. An update; Pankreatitis. Ein Update

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Schreyer, A.G. [Universitaetsklinikum Regensburg, Institut fuer Roentgendiagnostik, Regensburg (Germany); Grenacher, L. [Diagnostik Muenchen, MVZ Radiologie, Muenchen (Germany); Juchems, M. [Klinikum Konstanz, Diagnostische und Interventionelle Radiologie, Konstanz (Germany)

2016-04-15

Acute and chronic pancreatitis are becoming increasingly more severe diseases in the western world with far-reaching consequences for the individual patient as well as the socioeconomic situation. This article gives an overview of the contribution of radiological imaging to the diagnostics and therapy of both forms of the disease. Acute pancreatitis can be subdivided into severe (20 %) and mild manifestations. The diagnostics should be performed with computed tomography (CT) or magnetic resonance imaging (MRI) for assessing necrosis or potential infections only in severe forms of pancreatitis. In chronic pancreatitis transabdominal ultrasound should initially be adequate for assessment of the pancreas. For the differential diagnosis between pancreatic carcinoma and chronic pancreatitis, MRI with magnetic resonance cholangiopancreatography (MRCP) followed by an endoscopic ultrasound-guided fine needle aspiration is the method of choice. For the primary diagnosis for acute and chronic pancreatitis ultrasound examination is the modality of first choice followed by radiological CT and MRI with MRCP examinations. (orig.) [German] Akute und chronische Pankreatitis sind in der westlichen Welt zunehmende schwere Krankheitsbilder mit tiefgreifenden Konsequenzen fuer den einzelnen Patienten sowie soziooekonomisch. Der Beitrag radiologischer Bildgebung zur Diagnostik und Therapie beider Erkrankungsformen soll im vorliegenden Uebersichtsbeitrag diskutiert werden. Die akute Pankreatitis kann in eine schwere (20 %) und milde Verlaufsform unterteilt werden. Lediglich bei den schweren Formen sollte eine CT- oder MRT-Diagnostik bzgl. der Beurteilung von Nekrosen und moeglichen Infektionen erfolgen. Bei der chronischen Pankreatitis genuegt zunaechst eine Beurteilung des Pankreas durch transabdominellen Ultraschall. Hier sind die MRT mit der Magnetresonanzcholangiopankreatikographie (MRCP) sowie die endosonographisch gesteuerte Feinnadelpunktion die Methode, um

magna (Straus, 1820.

Directory of Open Access Journals (Sweden)

Hatice Parlak

2015-12-01

Full Text Available Nif Çayi Kirletilmiş Tatli Su ve Sedimentinin Daphnia magna (Strauss, 1820 Üzerine Akut Ve Kronik Toksisitesi. Nif Çayı Endüstriyel, evsel ve tarımsal deşarjlar ile doğrudan kirlenmektedir. Çayın suyunun evsel ve endüstriyel alanlarda sulama ve yıkama suyu olarak kullanılması rahatsızlık verici boyuttadır, bu nedenle doğal populasyonlar için potansiyel toksisitesinin bilinmesi büyük öneme sahiptir. Bu çalışmanın amacı Nif Çayı su ve sediment örneklerinin su piresi Daphnia magna kullanılarak toksisitesinin belirlenmesidir. Su ve sediment örneklerinin letal toksisitesi 48-saat akut test, subletal toksisite ise 7-gün kronik test ile gerçekleştirilmiştir. D.magna kullanılarak yapılan 48 saat Akut test sonuçlarına göre LC 50 değerleri su örnekleri için 6.8 ile 12.67 µl/L arasında sediment örnekleri içn 6.826 ile 38.038 µg/L arasında bulunmuştur. Subletal konsantrasyonlara maruz bırakılarak yapılan kronik testler sonucunda tüm istasyonlardan alınan su ve sediment örneklerin canlının üremesi üzerine negatif etkisi olduğu gözlenmiştir. Elde edilen veriler ışığında bu deneme sisteminin rutin kirlilik belirleme çalışmaları için uygunluğu tespit edilmiştir

Tuberkulose forårsaget af Mycobacterium africanum

DEFF Research Database (Denmark)

Bek, Dorte; Kjeldsen, Marianne Kirstine; Hansen, Nikolaj Friis

2010-01-01

Tuberkulose (TB) forårsages af patogene arter fra Mycobacterium tuberculosis komplekset (MTBC) og har en incidens på cirka 7/100.000 i Danmark. På mistanke om TB hos en akut indlagt 40 årig afrikansk mand initieredes anti-TB behandling. Efter 13 timers indlæggelse afgik patienten ved døden. Fra...

Akutte dødsfald ved tvangsfastholdelse af svært hyperaktive personer

DEFF Research Database (Denmark)

Leth, Peter Mygind; Thomsen, Jørgen Lange

2012-01-01

må henføres til et syndrom som betegnes excited delirium syndrome (EDS), en akut indsættende tilstand karakteriseret ved en hyperaktiv og voldelig adfærd, næsten overmenneskelig styrke og immunitet for smerte. Obduktion viser ikke forandringer som kan forklare dødsfaldet. Årsagen til EDS er ukendt...

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

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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�

Drænbehandling af recidiverende otitis media hos børn

DEFF Research Database (Denmark)

Lous, Jørgen; Trankjær, Christina Ryborg; Thomsen, Janus Laust

2010-01-01

I et nyligt publiceret Cochrane-review om effekten af indsættelse af trommehindedræn hos børn med recidiverende akut otitis media (RAOM) fandt man kun to studier, som opfyldte inklusionskriterierne. De inkluderede studier påviste en absolut risikoreduktion for at få AOM på 0,34 på seks måneder. Ved...

Danske hæmatologer er foran de amerikanske. http://haematologisktidsskrift.dk/diagnostik/282-danske-haematologer-er-foran-de-amerikanske.html

DEFF Research Database (Denmark)

Hokland, Peter

2017-01-01

Amerikanske hæmatologer og hæmatopatologer har udarbejdet en ny guideline, der skal forbedre diagnosticeringen og dermed behandlingen af akut anæmi, De er på linje med, hvad de hæmatologiske afdelinger allerede gør i Danmark, hvor man arbejder tæt sammen og følger samme protokol. Og kvaliteten er...

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.

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

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

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.

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

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.

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.

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

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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.

Nitrat i drikkevandet og vores sundhed

DEFF Research Database (Denmark)

Hansen, Birgitte; Schullehner, Jörg; Sigsgaard, Torben

2014-01-01

Nitrat i drikkevandet er uønsket, da det kan påvirke vores sundhed negativt. Den øvre grænse for hvor meget nitrat der tillades i drikkevandet er fastsat i forhold til risikoen for akut forgiftning med nitrit og blå børn-syndromet. Men nitrat i drikkevandet mistænkes også for at være medvirkende...

Tingkat Pengetahuan Pasien Diabetes Melitus tentang Komplikasi Diabetes Melitus di RSUP Haji Adam Malik Medan

OpenAIRE

Siboro, Junita I.L.

2010-01-01

Diabetes melitus merupakan suatu penyakit tidak menular yang ditandai dengan peningkatan kadar gula darah yang disertai ketidaknormalan metabolisme karbohidrat. Diabetes melitus merupakan penyebab kematian keempat terbesar di dunia. Diabetes melitus juga menyebabkan komplikais akut dan kronik yang juga dapat menyebabkan kematian. Peningkatan komplikasi dipengaruhi oleh Pengetahuan, umur, obesitas dan kebiasaan hidup yang kurang sehat. Penelitian ini bertujuan untuk mengidentifikasi tingkat p...

Konsentrasi Hambat Minimum (KHM) Kadar Sampel Alang-Alang (Imperata Cylindrica) dalam Etanol melalui Metode Difusi Cakram

OpenAIRE

Mulyadi, Moh; Wuryanti, Wuryanti; Sarjono, Purbowatiningrum Ria

2017-01-01

Bakteri merupakan mikroorganisme yang berada di sekitar kita. Penelitian yang sering dilakukan untuk mencari sumber alternatif lain yang berfungsi sebagai antibakteri karena adanya beberapa bakteri yang menjadi resisten terhadap suatu antibakteri. Bahan-bahan yang dilaporkan memiliki aktifitas antibakteri diantaranya adalah alang-alang. Alang-alang berkhasiat untuk obat radang ginjal akut, antibakteri, muntah darah, kencing nanah dan mimisan. Penelitian ini bertujuan untuk memperoleh Kosentra...

Akut svimmelhed hos den neurologiske patient

DEFF Research Database (Denmark)

Bruun, Marie; Højgaard, Joan L. Sunnleyg; Kondziella, Daniel

2013-01-01

Acute vertigo of neurological origin may be caused by haemorrhages and tumours in the posterior fossa and, most frequently, by ischaemic infarction in the vertebrobasilar circulation. Urgent diagnosis is necessary to avoid further ischaemic episodes, herniation due to cerebellar oedema and/or fatal...... brainstem infarction. The history should focus on accompanying neurological symptoms. However, vertigo with cerebellar lesions may be monosymptomatic and then bedside evaluation of oculomotor function is the key to correct diagnosis. This paper discusses the pathophysiology, symptomatology and clinical...... evaluation of acute vertigo of neurological origin....

Ambulant ST-segmentmonitorering efter akut myokardieinfarkt

DEFF Research Database (Denmark)

Mickley, H; Junker, A; Friis, E V

1994-01-01

Over the last decade the concept of silent myocardial ischaemia has received considerable attention. Without doubt, the increased use of ambulatory ST-segment monitoring is the most important reason for the growing interest in this field. The prevalence of ambulatory ischaemia after myocardial...... with previous myocardial infarction, but there is considerable disagreement about how this is expressed in terms of cardiac events. Patient selection, small patient numbers, and different timing of ambulatory monitoring are proposed as important reasons for the inconsistent findings. The precise role...

Salmonella-infektion kompliceret med akut nyreinsufficiens

DEFF Research Database (Denmark)

Thøgersen, Thøger; Jensen, Jørgen Erik; Jespersen, Bente

2003-01-01

Acute renal failure is a known complication to Salmonella gastroenteritis, and patients with chronic renal failure or impaired host defence are at increased risk. In the two presented cases there had been a few days of gastroenteritis before the hospitalisation, but the only symptoms...... at the admission were fatigue and dyspnoea. In both cases severe uraemia had developed and the patients and their physicians did not expect the episode of gastroenteritis to be the only etiology of acute renal failure. Both patients had normal renal histology and Salmonella was grown in their faeces. Subsequently...

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.

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

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.

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

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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.

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

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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

NKT cells can help mediate the protective effects of 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis in mice.

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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.

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

Posisi Amerika Serikat dalam Penyelesaian Konflik Palestina-Israel 1

OpenAIRE

Paat, Vera

2013-01-01

Konflik Palestina-Israel boleh jadi merupakan konflik yang memakan waktu panjang setelah Perang Salib yang pernah terjadi antara dunia Timur dan Barat di sekitar abad keduabelas. Konflik yang telah berlangsung enam puluhan tahun ini menjadi konflik cukup akut yang menyita perhatian masyarakat dunia. Penyelesaian konflikPalestina-Israel, semakin menunjukkan bahwa perdamaian Palestina-Israel memang sulit diwujudkan. Pasalnya, akhir 2008 yang diprediksi dunia Internasional (dalam hal ini Amerika...

Fenol, Flavonoid, Dan Aktivitas Antioksidan Pada Ekstrak Kulit Batang Pulai (Alstonia Scholaris R.br)

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Zuraida, Zuraida; Sulistiyani, Sulistiyani; Sajuthi, Dondin; Suparto, Irma Herawati

2017-01-01

Pulai (Alstonia scholaris R.Br), family Apocynaceae adalah salah satu tumbuhan hutan yang berfungsi sebagai obat tradisional untuk mengobati demam, malaria, batuk berdahak, diare, kencing manis, penurun kolesterol, cacingan, rematik akut, borok, dan hipertensi. Salah satu penyebab penyakit jantung, aterosklerosis, dan kanker adalah stres oksidatif. Stres ini dapat disembuhkan atau dikurangi dengan menggunakan antioksidan. Flavonoid merupakan senyawa fenol dan termasuk salah satu metabolit sek...

TEMPUYUNG SEBAGAI ALTERNATIF PENGHANCUR BATU GINJAL

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Martuti Budiharto

2012-09-01

Full Text Available Sonchus arvensis L, atau yang lebih dikenal di Indonesia dengan sebutan tempuyung, adalah salah satu tanaman yang sudah banyak digunakan oleh masyarakat untuk penghancur batu ginjal baik dalam bentuk rebusan maupun bentuk preparat farmasi seperti kapsul ataupun serbuk biasa.Dalam makalah ini dikemukakan tentang review hasil uji toksisitas akut dan uji aktivitas farmakodinamik efek anti kalkuli tanaman Sonchus arvensiss L dari beberapa penelitian

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

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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.

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

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

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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.

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.

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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.

CEACAM3: ein neuartiger phagozytischer Rezeptor der angeborenen Immunantwort zur Erkennung human-spezifischer Pathogene

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Schmitter, Tim

2006-01-01

Eine Infektion durch das ausschließlich human-spezifische Pathogen Neisseria gonorrhoeae manifestiert sich bei einer symptomatischen Kolonisierung in der sog. Gonorrhö, einer venerischen Erkrankung, die durch akute Inflammation des befallenen Gewebes und durch die massive Infiltration von Granulozyten charakterisiert ist. Die Gonokokken können im Verlauf einer symptomatischen Infektion über ihre OpaCEA-Adhäsine mit CEACAM Proteinen unterschiedlicher Wirtszellen interagieren. In der vorliegend...

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.

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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.

INSOMNIA DAN DIAGNOSIS PSIKIATRI PADA PASIEN DI INSTALASI RAWAT DARURAT (IRD RSUP SANGLAH

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Alfa Matrika Sapta Dewanti

2015-01-01

Full Text Available Insomnia adalah suatu kesulitan dalam memulai tidur, mempertahankan tidur, atau tiduryang tidak menyegarkan selama 1 bulan atau lebih di mana keadaan sulit tidur ini harusmenyebabkan gangguan klinis yang signifikan. Insomnia dibagi menjadi insomnia primerdan sekunder. Penelitian ini merupakan penelitian deskriptif yang bertujuan untukmenjelaskan karakteristik insomnia dan diagnosis psikiatri pada pasien di Instalasi RawatDarurat (IRD RSUP Sanglah. Data penelitian ini berdasarkan register pasien IRD RSUPSanglah periode Mei-November 2013. Sampel yang memenuhi kriteria inklusi ini terdiridari 52 laki-laki (49% dan 54 perempuan (51%. Menurut tipe insomnia, 17% insomniaprimer dan 83% insomnia sekunder. Berdasarkan usia, 11% pada usia  ?20 tahun, 32%pada usia 21-30 tahun, usia 31-50 tahun  40% dan 17% pada usia>50 tahun. Pasien yangmenikah 51%, belum menikah 39%, janda 6% dan duda 4%. Pasien yang bekerja 56% dan44% tidak bekerja. Berdasarkan diagnosis psikiatri, skizofrenia 20 (22,7%, psikotik akut17 (19,3%, depresi  12 (13,6%, bipolar 7 (8%, delirium 8 (9,1%, GMO 10 (11,4% dangangguan penyesuaian 14 (15,9%. Dari keseluruhan pasien insomnia yang datang ke IRD,17% merupakan insomnia primer dan 83% insomnia sekunder. Diagnosis psikiatri pasieninsomnia terbanyak adalah pasien psikotik, yaitu skizofrenia 22,7% dan psikotik akut19,3%.

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

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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.

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/

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.

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

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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

Genamplifikation in humanen Zellen: Untersuchungen an einem Leukämiefall und an HeLa-Zellen

OpenAIRE

Bruckert, Petra

2003-01-01

Die cytogenetische Manifestation von Genamplifikation in humanen Zellen wurde in einem Fall von akuter myeloischer Leukämie (AML) sowie an der humanen Cervixcarcinomzelllinie HeLa S3 untersucht. In dem AML-Fall ergab die Karyotypisierung der Leukämiezellen neben dem Verlust eines X-Chromosoms das Vorliegen einer extrachromosomalen Genamplifikation in Form von Double Minutes. Mit Hilfe der Comparativen Genomischen Hybridisierung (CGH) und der Fluoreszenz-in situ-Hybridisierung (FISH) wurde die...

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...

Blodtryksnedsaettelse kan forvaerre symptomerne ved akut apopleksi

DEFF Research Database (Denmark)

Garde, E; Jørgensen, H S; Olsen, T S

1995-01-01

Patients with acute stroke often present with high blood pressure (BP) on hospital admission. Because hypertension is a risk factor for stroke, and because severe BP elevation may increase oedema and the risk of haemorrhage, acute antihypertensive therapy might seem reasonable. On the other hand...

Akut iskaemisk proktitis efter et epileptisk anfald

DEFF Research Database (Denmark)

Klintmann, Camille Kristine; Hillingsø, Jens; Glenthøj, Anders

2008-01-01

Acute ischemic proctitis is a rare diagnosis mainly because the rectum is supplied by an extensive arterial network. Consequently, in more than 90% of patients with ischemic colitis the rectum is spared. Previously reported cases are related to severe vascular insufficiency of the rectal circulat...... circulation caused by systemic atherosclerosis, usually following aortic or aortoiliac operations. We report one case of acute ischemic proctitis following an epileptic attack....

Akut monosymptomatisk anisokori efter skift af scopolaminplaster

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Rosenbæk, Jeppe Bakkestrøm

2017-01-01

, and neurological examinations were normal. Shortly before, she had removed a scopolamine (hyoscine) patch from a patient and had following inadvertently rubbed her eye. The symptoms remitted completely within 24 hours. Knowledge of this benign phenomenon is important in order to advise patients and caregivers when...

Akut kompartmentsyndrom efter total knæalloplastik

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Arenkiel, Bjørn; Kjærgaard, Maj; Lauritsen, Anne Øberg

2012-01-01

and fasciotomy is important. We describe a case with a patient, who had undergone a total knee arthroplasty and after a postoperative period of 5,5 hours she developed extreme pain in the limb, below the operated knee. The diagnosis was confirmed by sonography, and an acute fasciotomy was performed....

Cricoideatryk a.m. Sellick ved akut anaestesiindledning?

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Alstrøm, Henrik Bitz; Belhage, Bo

2007-01-01

Since Brian Sellick introduced the cricoid pressure in 1961, it has become standard practice for the rapid sequence intubation. The manoeuvre has a high priority and is recommended maintained even during difficult intubation. In this review the lack of evidence for the aspiration-reducing effect...

Akut kirurgisk behandling ved malignt cerebralt infarkt

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Lilja-cyron, Alexander; Eskesen, Vagn; Hansen, Klaus

2016-01-01

Malignant stroke is an intracranial herniation syndrome caused by cerebral oedema after a large hemispheric or cerebellar stroke. Malignant middle cerebral artery infarction is a devastating disease with a mortality around 80% despite intensive medical treatment. Decompressive craniectomy reduces...

Akut kirurgisk behandling ved malignt cerebralt infarkt

DEFF Research Database (Denmark)

Lilja-Cyron, Alexander; Eskesen, Vagn; Hansen, Klaus

2017-01-01

Malignant stroke is an intracranial herniation syndrome caused by cerebral oedema after a large hemispheric or cerebellar stroke. Malignant middle cerebral artery infarction is a devastating disease with a mortality around 80% despite intensive medical treatment. Decompressive craniectomy reduces...

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

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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.

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

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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.

PENERAPAN FUZZY INFERENCE SYSTEM TAKAGI-SUGENO-KANG PADA SISTEM PAKAR DIAGNOSA PENYAKIT GIGI

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Lutfi Salisa Setiawati

2016-04-01

Full Text Available Generally, expert system only show types of disease after user choose symptoms. In the study is done the addition of disease severity level. The method applied in the calculation of the severity is a method of Fuzzy Inference System Takagi-Sugeno-Kang (Method of Sugeno. This study attempts to know whether method Fuzzy Inference System Takagi-Sugeno-Kang can work for expert system in giving the diagnosis diseases of the teeth. The result of this research or severity for diseases of pulpitis reversible 38,53%, pulpitis irreversible 59,64%, periodontitis 69,62%, acute periodontitis 51,43%, gingivitis 45.5%, acute pericoronitis 53,93%, sub acute pericoronitis 52,14%, chronic pericoronitis 46,05%, caries dentist an early stage 37,61%, caries dentist toward an advanced stage 43,89%, caries dentist an advanced stage 51,76%, gangrene pulpa 42,5%, polyps pulpa 56,43%, and periostitis 58,55%. A conclusion that was obtained from the study that is a method of Fuzzy Inference System Takagi-Sugeno-Kang could be applied to expert system of the teeth. Key Word: Teeth , Expert System , Expert System Teeth , Fuzzy Logic , Fuzzy Inference System , Takagi-Sugeno-Kang , Fuzzy Sugeno Pada umumnya, istem pakar hanya menampilkan jenis penyakit setelah user memilih gejala-gejala. Pada penelitian ini dilakukan penambahan tingkat keparahan penyakit. Metode yang diterapkan dalam perhitungan tingkat keparahan ini yaitu Metode Fuzzy Inference System Takagi-Sugeno-Kang (Metode Sugeno. Penelitian ini bertujuan untuk mengetahui apakah metode Fuzzy Inference System Takagi-Sugeno-Kang dapat diterapkan pada sistem pakar dalam memberikan diagnosa penyakit gigi. Hasil dari penelitian ini didapatkan tingkat keparahan untuk penyakit Pulpitis Reversibel 38,53%, Pulpitis Irreversibel 59,64%, Periodontitis 69,62%, Periodontitis Akut 51,43%, Gingivitis 45,5%, Perikoronitis Akut 53,93%, Perikoronitis Sub Akut 52,14%, Perikoronitis Kronis 46,05%, Karies Denties Tahap Awal 37,61%, Karies

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

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

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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

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

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.

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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.

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

Observações clínicas e laboratoriais em cães com cinomose nervosa Clinical and laboratory findings in dogs with distemper encephalomyelitis

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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.

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

Beginn und Dosisanpassung einer intensivierten konventionellen Insulintherapie (ICT beim Erwachsenen

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Lohr R

2012-01-01

Full Text Available Eine intensivierte Insulintherapie (ICT ist die Behandlung der Wahl bei Diabetes mellitus Typ 1 und auch bei vielen Menschen mit insulinpflichtigem Typ-2-Diabetes. Bei Therapiebeginn müssen individuell Insuline ausgewählt und die richtige Dosierung festgelegt werden. Im weiteren Verlauf ist dann die Anpassung der Insulintherapie an besondere Alltagssituationen wie Sport oder akute Erkrankungen vorrangig. Eine gute Patientenschulung und eine gute Zusammenarbeit zwischen Betroffenem und Behandlerteam sind entscheidend, um diese komplizierte Therapie erfolgreich umzusetzen.

Hopp, hopp, hopp im Schweinsgalopp? Klauen- und Gliedmaßengesundheit beim Schwein

OpenAIRE

Leeb, Christine; Bernardi, Florian; Winckler, Christoph

2009-01-01

Immer wieder kommen aus der Praxis Anfragen, über Lahmheitbeim Schwein zu berichten, auch ein Klauenpflegekurs wurde bereits durchgeführt, um akute Probleme lösen zu können. Doch was sind die Ursachen für Lahmheiten beim Schwein? Dieser Beitrag soll nicht nur die klinischen Symptome aufzählen und rasche Lösungen vermitteln (die es selten gibt), sondern Fragen stellen und zum selbst Beobachten und Nachdenken anregen. Dazu wird vom Wildschwein ausgehend das Normalverhalten betrac...

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

The Association of Lipoprotein Changes and the Development of Plasma Leakage in Dengue Infection

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Leonard Nainggolan

2017-04-01

Full Text Available There’s interrelationship between infection and lipoprotein. This is a cohort prospective study which conducted November 2010 – February 2011. This study aimed to assess the changes of HDL-C, LDL-C, total cholesterol (TC, triglyceride (TG, in acute and critical phase of dengue infection and its association with plasma leakage. Subjects who had fever 48 hours or less and Dengue NS1 antigen test positive were admitted to Cipto Mangunkusumo Hospital Jakarta. We examined clinical and CBC daily; level of albumin, HDL-C, LDL-C, TC, TG; ultrasound to find ascites and pleural effusion. Among 51 subjects, 21 subjects (41% had plasma leakage. There were significant lower of HDL-C, LDL-C, and higher TG in critical phase than acute phase. In critical phase, subjects with plasma leakage had a significant lower HDL-C level [26.3 (8.2 vs 33.1 (12.1 mg/dL, p=0.029] but not for LDL-C, TC, and TG. They also had a significantly higher reduction in HDL-C [19.6 (9.1 vs 11.5 (5.8 mg/dL, p<0.0001] and TC [25.1 (20.0 vs 15.2 (14.5 mg/dL, 0.045] over the course of acute to critical phase. Lipoprotein changes during dengue infection were more pronounced among subjects who developed plasma leakage. The higher reduction in HDL-C is associated with the development of plasma leakage. Keywords: dengue infection, plasma leakage, cholesterol, lipoprotein, HDL   Hubungan antara Penurunan Kadar Kolesterol dengan Kejadian Kebocoran Plasma pada Infeksi Dengue   Abstrak Terdapat hubungan timbal balik antara infeksi dengan lipoprotein. Penelitian ini adalah penelitian kohort prospektif yang dilakukan November 2010 – Februari. Penelitian ini bertujuan untuk mengetahui perubahan kolesterol HDL, LDL, kolesterol total, dan trigliserid (TG pada fase akut dan kritis infeksi dengue serta hubungannya dengan kebocoran plasma. Subyek dengan demam 48 jam atau kurang dan uji Dengue NS1 antigen positif dirawat di RSUPN Cipto Mangunkusumo Jakarta. Dilakukan pemeriksaan klinis dan darah

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

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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

A feline case of isolated fourth ventricle with syringomyelia suspected to be related with feline infectious peritonitis.

Science.gov (United States)

Kitagawa, Masato; Okada, Midori; Sato, Tsuneo; Kanayama, Kiichi; Sakai, Takeo

2007-07-01

A one-year-old female cat was unable to stand. Magnetic resonance imaging was performed, and an enlargement of the lateral, third, and fourth ventricles and syringomyelia were detected. The cat was diagnosed with an isolated fourth ventricle (IFV) with syringomyelia. The serum isoantibody test for the feline infectious peritonitis (FIP) virus was 1:3,200. After the cat died, a pathological examination revealed nonsuppurative encephalomyelitis. We suspected that the IFV, detected in the cat, was associated with FIP encephalomyelitis. To our knowledge, there has been no report on IFV in veterinary medicine.

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.

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

PROFILAKSIS RABIES

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Susilawathi NM

2014-09-01

Full Text Available Rabies merupakan penyakit ensefalitis akut yang disebabkan oleh virus RNA, famili Rhabdoviridae, genus lyssavirus. Anjing adalah reservoir utama penularan rabies, puluhan ribu kematian per tahun disebabkan oleh gigitan anjing rabies. Bila seseorang menunjukkan gejala rabies, biasanya selalu fatal.  Profilaksis terhadap rabies merupakan tindakan efektif dan aman. Mencuci luka dan vaksinasi segera setelah kontak dengan hewan tersangka rabies dapat mencegah timbulnya rabies hampir 100%. Strategi yang paling efektif untuk mencegah rabies adalah mengurangi penularan rabies pada anjing melalui vaksinasi.[MEDICINA 2009;40:55-9].

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

Directory of Open Access Journals (Sweden)

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

Jejunal divertikulitis som årsag til akut abdomen

DEFF Research Database (Denmark)

Arsic, Ivan; Cuk, Pedja; Nielsen, Michael Festersen

2014-01-01

diverticular disease is intravenous fluids and antibiotics. If there is an occurrence of peritonitis as a complication of jejunal diverticulitis, laparatomy may be indicated. Both of the patients received a conservative treatment with intravenous fluids and antibiotics with good response....

Iltbehandling ved akut eksacerbation af kronisk obstruktiv lungesygdom

DEFF Research Database (Denmark)

Ringbaek, Thomas; Lange, Peter; Mogensen, Torben

2008-01-01

Acute exacerbation of COPD is a major cause of hospitalisation in Denmark. Most of the patients require supplemental oxygen in the acute phase and some patients continue oxygen therapy at home after discharge. In this paper we discuss the physiological mechanisms of respiratory failure seen...... in acute exacerbations of COPD. The principles for oxygen therapy in the acute phase are described and recommendations for oxygen therapy are suggested....

Selekteret akut indlaeggelse på en medicinsk afdeling

DEFF Research Database (Denmark)

Teglbjærg, Lars Stubbe; Teglbjaerg, Lars Larsen Stubbe

2008-01-01

INTRODUCTION: The aim of the study was to describe the pattern of admissions to a medical department and to analyse whether acute admissions can be referred to hospitals with limited access to acute medical and surgical assistance and limited access to intensive care. MATERIALS AND METHODS: All...... acute admissions to the medical department during a three-week period were registered. The medical officer in charge of the distribution of patients filled in a questionnaire at the time of telephone contact with the referring physician concerning the feasibility of referral to a medical department...... with limited access to acute assistance. RESULTS: Out of 113 patients judged suitable for referral to a hospital with limited access to acute assistance, 60% had or developed conditions judged to require hospitals with a specialised level of acute services. CONCLUSION: Contact with a medical officer...

STRES AKUT KARENA BISING SEBAGAI PENYEBAB TERJADINYA XEROSTOMIA

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Wilda Hafny Lubis

2015-08-01

Full Text Available In general annoyance of noise appears after many years of exposure. The speeds of disturbance depend on level of noise, impulsive component and duration of exposure, personal sensitivity that unknown characteristic. Noise belonging to acute stress needs short period to occur different from sorrow that takes long period. Stress will activate the regulator nerve and maintain intern environment to creates the homeostasis. Stress condition in long period will influence hormonal system, autonomic system until the exhaustion stadium and a few emotional expressive will be fixed for example dry mouth. Stress will also influence immune system so it is not effective to destroy the virus, microorganism and irregular cell that finally cause oral diseases.

Akut underernæring hos børn

DEFF Research Database (Denmark)

Rytter, Maren Johanne Heilskov; Michaelsen, Kim F.; Friis, Henrik

2017-01-01

The prevalence of malnutrition has declined significantly over the last 30 years. Despite this, malnutrition remains a major cause of illness and death among children worldwide, particularly in low- and medium-income countries. Marasmus and kwashiorkor are the most life-threatening forms...... of malnutrition. Treatment protocols enable effective treatment, but only a minority of malnourished children have access to treatment. Furthermore, treating children with complicated malnutrition requiring hospitalization remains a clinical challenge....

Otoneurologisk udredning ved akut opstået svimmelhed

DEFF Research Database (Denmark)

Hansen, Søren; Ninn-Pedersen, Mirjana; Thomasen, Per Caye

2011-01-01

Benign paroxysmal positional vertigo, vestibular neuronitis and Menière's disease cause most cases of acute vertigo. However, doctors must consider central neurological reasons to vertigo. If it is determined that a patient has oto-neurological vertigo, the next task is to determine whether...... the patient has a peripheral or a central cause of vertigo, if the condition is potentially lethal and if there is a need for acute radiological imaging and/or medical intervention. This review highlights the oto-neurological approach to the dizzy patient with particular focus on the patient's history...

Stresshyperglykaemi hos et barn med svaer akut gastroenteritis

DEFF Research Database (Denmark)

Bjerre, Jesper V.

2002-01-01

A case of a two years and ten months old girl with severe acute gastroenteritis, dehydration, and hyperglycaemia is described. Transient hyperglycaemia is a common clinical finding in children under stress. We discuss the distinction between hyperglycaemia as a prediabetic state and that as a phy......A case of a two years and ten months old girl with severe acute gastroenteritis, dehydration, and hyperglycaemia is described. Transient hyperglycaemia is a common clinical finding in children under stress. We discuss the distinction between hyperglycaemia as a prediabetic state...

Parvovirus B19-akut hepatitis hos immunkompetent patient

DEFF Research Database (Denmark)

Larsen, Lykke

2011-01-01

This article describes a case of acute hepatitis in an adult person without subsequent complications caused by parvovirus B19 (PVB19). The diagnosis was made by detection of PVB19 IgM and IgG antibody in the blood using ELISA. There was not made any affirmative polymerase chain reaction for DNA...

Akut glaukom efter endarterektomi af arteria carotis interna

DEFF Research Database (Denmark)

Lindholt, J S; Klaerke, A

2000-01-01

glaucoma was diagnosed by tonometry and gonioscopy, and treated with laser-iridectomy. The patient was discharged two days later without neurological or ophthalmological deficits. Manifest acute glaucoma postoperatively seems never to have been reported. However, the choroid is not autoregulated...

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

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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.

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

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.

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

Sähköautojen käyttäminen sähkövarastoina

OpenAIRE

Paju, Juuso

2016-01-01

Sähköautojen yleistyminen voi aiheuttaa ongelmia niiden latauksessa. Akut ovat kapasiteetiltaan aiempaa suurempia ja ne pitäisi ladata lyhyessä ajassa. 90 prosenttia sähköautojen latauksesta tulee tapahtumaan kotona, mutta pientalojen sähköjärjestelmien mitoituksissa ei aiemmin ole otettu huomioon sähköautojen latauspisteiden käyttämää suurta latausvirtaa. Tässä opinnäytetyössä oli tarkoitus tutkia sähköauton pientalossa tapahtuvan latauksen aikana esiintyviä virtoja, tehoja ja pääsulakke...

Treatment of the off-gas stream from the HTR reprocessing head-end

International Nuclear Information System (INIS)

Barnert-Wiemer, H.; Juergens, B.; Vijgen, H.

1985-01-01

The AKUT II-facility (nominal throughput 10 m 3 /h, STP) for the clean-up of the burner off-gas has been operated for 20 cold runs in parallel to the JUPITER reprocessing head-end. Two of these runs were continuous operation tests with a duration of 50 and 80 hours, respectively. The facility met or exceeded all design specifications. In a further test series the distillation column alone was run with pure CO 2 and two- and three-component gas mixtures to determine the flooding curves and the stage height (HETP)

Early hematologic changes during prostate cancer radiotherapy predictive for late urinary and bowel toxicity

Energy Technology Data Exchange (ETDEWEB)

Pinkawa, Michael; Djukic, Victoria; Klotz, Jens; Holy, Richard; Eble, Michael J. [RWTH Aachen University, Department of Radiation Oncology, Aachen (Germany); Ribbing, Carolina [RWTH Aachen University, Department of Diagnostic and Interventional Radiology, Aachen (Germany)

2015-10-15

Gruppe von 91 Patienten mit einem Prostatakarzinom, die sich zur primaeren (n = 51) oder postoperativen (n = 40) Radiotherapie (RT) vorgestellt haben, wurden Blutproben (Blutbild, Akute-Phase-Proteine und Zytokine) vor (T1), dreimal waehrend (T2-T4) und 6-8 Wochen nach RT (T5) untersucht. Vor RT (Ausgangsbefund), am letzten Tag (akute Toxizitaet), median 2 Monate und 16 Monate (Spaettoxizitaet) nach RT haben die Patienten einen validierten Fragebogen beantwortet (Expanded Prostate Cancer Index Composite). Akute Scoreaenderungen > 20 Punkte und spaete Aenderungen > 10 Punkte wurden als klinisch relevant bewertet. Die Radiotherapie fuehrte zu signifikanten Veraenderungen der haematologischen Parameter, mit dem groessten Effekt auf Lymphozyten (mittlerer Abfall von 31-45 %) und signifikanter Abhaengigkeit vom Zielvolumen. Eine Erhoehung des C-reaktiven Proteins (CRP) auf > 5 mg/l und ein Haemoglobinabfall ≥ 5 G/l zum Zeitpunkt T2 waren unabhaengig praediktiv fuer akute Miktionsbeschwerden (jeweils p < 0,01). Eine CRP-Erhoehung fand sich vorwiegend bei primaerer RT der Prostata (p = 0,02). Ein frueher Lymphozytenanstieg ≥ 0,3G/l bei T2 war protektiv gegen spaete Miktions- und Darmbeschwerden (jeweils p = 0,02). Weitere signifikante praediktive Faktoren fuer spaete Darmbeschwerden waren abfallende Haemoglobinwerte (Grenzwert ≥ 5 G/l) bei T2 (p = 0,04); Veraenderungen der TNFα- (Tumornekrosefaktor; p = 0,03) und Ferritinspiegel (p = 0,02) bei T5. Alle Patienten mit spaeten Darmbeschwerden hatten Interleukin-(IL-)6-Werte < 1,5 ng/l bei T2 (vs. 63 % ohne Darmbeschwerden; p = 0,01). Fruehe haematologische Veraenderungen waehrend der Radiotherapie beim Prostatakarzinom sind praediktiv fuer spaete Miktions- und Darmbeschwerden. (orig.)

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)

Nursing intervention for geriatric patients dischargedhome from ED

DEFF Research Database (Denmark)

Rosted, Elizabeth Emilie

2009-01-01

visitatorer i Pensions og omsorgskontoret Amager, Københavns Kommune interviewes. Data analyseres kvalitativt vha. indholdsanalyse. Resultater På baggrund af resultaterne forventes studiet at genere viden om effekten af struktureret sygeplejeintervention til geriatriske patienter på en dansk akut medicinsk...... der er uløste problemer og der udarbejdes en udskrivningsrapport med løsningsforslag, hvorefter der træffes aftale om konkret problemløsning med fx pårørende, egen læge  og/eller visitator i primærsektor. Dataindsamling: Ved baseline samt en og seks måneders opfølgning indsamles demografiske data...

Surveillance of hospital-acquired infections in women having undergone caesarean section in the County of Aarhus

DEFF Research Database (Denmark)

Leth, Rita Andersen

informationer fra både elektroniske databaser, medicinske journaler samt fra kvindernes selvudfyldte spørgeskemaer. Formålene med studierne var at undersøge: 1) kejsersnit som en risikofaktor for postpartum bakteriæmi (BSI), urinvejsinfektion (UVI) og postoperativ sårinfektion (PSI) sammenlignet med vaginal...... kejsersnit i forhold til vaginal fødsel, dels en øget infektionsrisiko efter akut kejsersnit i forhold til elektivt kejsersnit. Fedme og Type 1 diabetes er risikofaktorer for infektion efter kejsersnit og kombinationen af overvægt og diabetes øger risikoen for infektion yderligere. En elektronisk overvågning...

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.

Active induction of experimental autoimmune encephalomyelitis by MOG35-55 peptide immunization is associated with differential responses in separate compartments of the choroid plexus

Directory of Open Access Journals (Sweden)

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

Akut pancreatitis forårsaget af galdesten i barnealderen

DEFF Research Database (Denmark)

Zachariassen, G; Saffar, D F; Mortensen, J

1999-01-01

A 10 year-old girl presented with acute abdominal pain. Serum-amylase was 3959 U/l. Ultrasonography showed dilatation of both the common bile duct and the pancreatic duct and a high density area near the ampulla. Endoscopic retrograde cholangiography (ERC) verified a stone near the ampulla, which...

Cricoideatryk a.m. Sellick ved akut anæstesiindledning?

DEFF Research Database (Denmark)

Alstrøm, Henrik Bitz; Belhage, Bo

2007-01-01

Since Brian Sellick introduced the cricoid pressure in 1961, it has become standard practice for the rapid sequence intubation. The manoeuvre has a high priority and is recommended maintained even during difficult intubation. In this review the lack of evidence for the aspiration-reducing effect...

Akut fosfatnefropati som komplikation til udrensning med oral natriumfosfat

DEFF Research Database (Denmark)

Colic, Edin; Marcussen, Niels

2011-01-01

Acute phosphate nephropathy (APhN) has recently been identified as a reason for acute and subsequently chronic renal failure, following exposure to the oral sodium phosphate bowel purgatives. Renal biopsies show acute and chronic tubular injury with calcium phosphate deposits. A case of biopsy...

Cricoideatryk a.m. Sellick ved akut anæstesiindledning?

DEFF Research Database (Denmark)

Alstrøm, Henrik Bitz; Belhage, Bo

2007-01-01

of cricoid pressure is discussed. The findings suggest that it may have harmful effects in connection with intubation, laryngeal mask placement and ventilation. In conclusion, it is suggested that cricoid pressure is released in the case of intubation difficulties.......Since Brian Sellick introduced the cricoid pressure in 1961, it has become standard practice for the rapid sequence intubation. The manoeuvre has a high priority and is recommended maintained even during difficult intubation. In this review the lack of evidence for the aspiration-reducing effect...

CD31-Expression am Primärtumor und Nachweis hämatogen disseminierter Tumorzellen im Knochenmark von Brustkrebspatientinnen

OpenAIRE

Eisenmann, Petra

2005-01-01

Der Nachweis von disseminierten Tumorzellen im Knochenmark von Patientinnen mit primärem Mammakarzinom ist ein wichtiger prognostischer Parameter. In der vorliegenden Arbeit wurde der Nachweis von CD31 am Primärtumor Mammakarzinom mit dem Auftreten von Mikrometastasen im Knochenmark korreliert. Ferner wurde die prognostische Bedeutung von disseminierten Tumorzellen im Knochenmark und die prognostische Bedeutung von CD31 evaluiert. Bei 50 Patientinnen des Gesamtkollektivs von 195 (25,6%) wu...

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.

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

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.)

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.).

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.

Directory of Open Access Journals (Sweden)

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

Hepatit A'ya Bağlı Guillain-Barre Sendromu: Nadir Bir Birliktelik

OpenAIRE

Canpolat, Mehmet; Ceylan, Özgür; Çelik, İlknur; Bayram, Ayşe Kaçar; Per, Hüseyin; Doğanay, Selim; Gümüş, Hakan; Aslan, Duran; Kumandaş, Sefer

2015-01-01

Guillain Barre Sendromu (GBS), çocukluktan ileri yaşlara kadar her yaş grubunda rastlanabilen, akut başlangıçlı, simetrik ve jeneralize kas güçsüzlüğü, arefleksi ve periferik sinirlerin inflamatuvar demyelinizasyonu ile karakterize bir hastalıktır. GBS 'un patogenezi net olarak bilinmemekle birlikte otoimmun bir hastalık olduğu düşünülmektedir. Guillian-Barre Sendromu(GBS) ile enfeksiyon hastalıkları arasındaki ilişki iyi bilinmektedir. Hepatit A enfeksiyonu sırasında GBS gelişimi nadir ...

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.

Total-body irradiation before bone marrow transplantation for acute leukemia in first or second complete remission. Results and prognostic factors in 326 consecutive patients

Energy Technology Data Exchange (ETDEWEB)

Belkacemi, Y.; Pene, F.; Touboul, E.; Laugier, A.; Gemici, C.; Housset, M.; Ozsahin, M. [Hopital Tenon, Paris (France). Dept. of Radiation Oncology; Rio, B. [Dept. of Hematology, Hotel-Dieu, Paris (France); Leblond, V. [Groupe Hospitalier Petie-Salpetriere, Paris (France); Gorin, N.C. [Hopital Saint-Antoine, Paris (France)

1998-02-01

Between 1980 and 1993, 326 patients with acute non-lymphoblastic leukemia (ANLL, n=182) and acute lymphoblastic leukemia (ALL, n=144) in complete remission underwent TBI either in single dose (190 patients: 10 Gy administered to the midplane, and 8 Gy to the lungs [STBI]) or in 6 fractions (136 patients: 12 Gy on 3 consecutive days, and 9 Gy to the lungs [FTBI]) before BMT. The patients were analyzed according to 3 instantaneous dose rate groups: 118 patients in the LOW group ({<=}0.048 Gy/min), 188 in the MEDIUM group (>0.048 and {<=}0.09 Gy/min), and 20 in the HIGH group (>0.09 cGy/min). Conditioning chemotherapy consisted of cyclophosphamide (CY) alone in 250 patients, CY and other drugs in 54, and 22 patients were conditioned using combinations without CY. Following TBI, allogeneic and autologous BMT were realized respectively in 118 and 208 patients. Multivariate analyses revealed that the best factors influencing the survival were 1st CR, age {<=}40 years, and BMT after 1985. The RI was influenced independently only by the remission status. On the other hand, the TRM rate was lower in patients who did not experience graft-vs.-host disease (GvHD), and in those treated after 1985 (p=0.0005). GvHD was the only independent factor involved in the development of IP. When considering the cataract incidence, the only independent factor was the instantaneous dose rate. The outcome of BMT patients conditioned with TBI for acute leukemia was not significantly influenced by the TBI technique, and TRM seemed to be lower in patients treated after 1985. On the other hand, cataract incidence was significantly influenced by the instantaneous dose rate. (orig./MG) [Deutsch] Um den Einfluss der Ganzkoerperbestrahlung (TBI) auf die Prognose und die Inzidenz von Komplikationen bei Knochenmarktransplantationen (BMT) zu evaluieren, haben wir retrospektiv unser Patientengut, das bei akuter Leukaemie vor der BMT mit der TBI behandelt wurde, analysiert. Von 1980 bis 1993 wurden 326

Long-term results of total body irradiation in adults with acute lymphoblastic leukemia

Energy Technology Data Exchange (ETDEWEB)

Marnitz, Simone; Zich, Alexander; Budach, Volker; Jahn, Ulrich; Neumann, Oliver [Charite University Medicine, Department of Radiation Oncology, Berlin (Germany); Martus, Peter [University Tuebingen, Institute of Clinical Epidemiology and Applied Biostatistics, Tuebingen (Germany); Arnold, Renate [Charite University Medicine, Campus CVK, Department of Hematology and Oncology, Bone Marrow Transplant Unit, Berlin (Germany)

2014-05-15

breadth. (orig.) [German] Ziel der Arbeit war die Auswertung der Akut- und Spaettoxizitaet sowie der Therapieergebnisse erwachsener Patienten mit akuter lymphatischer Leukaemie (ALL) nach Ganzkoerperbestrahlung (''total body irradiation'', TBI) als Teil des Therapiekonzepts. Im Rahmen einer retrospektiven Auswertung von 110 erwachsenen Patienten (34 ± 12 Jahre) mit ALL, die eine TBI (6-mal 2 Gy-12 Gy) vor Transplantation erhalten hatten, werden therapiebedingte Akut- und Spaettoxizitaet, Mortalitaet und Therapieergebnisse dargestellt. Die mittlere Nachbeobachtungszeit betrug 70 Monate. Die leukaemiefreien 2- und 5-Jahres-Ueberlebensraten betragen 78 bzw. 72 %. Nach im Median 7 Monaten erlitten 29 % (32/110) der Patienten ein medullaeres Rezidiv. Das Geschlecht war der einzige statistisch signifikante Faktor bezueglich des Gesamtueberlebens zugunsten der weiblichen Patienten. Die therapiebedingte Mortalitaets- und die Gesamtueberlebensraten nach 2 und 5 Jahren waren 16 und 22 %, bzw. 60 und 52,7 %. Die chronische ''Graft-versus-host''-Erkrankung (cGVHD) der Haut war die haeufigste Spaetreaktion (n = 33, 30 %), gefolgt von 15,5 % (17/110) pulmonaler cGVHD. Eine Lungenfibroseentwickelten 6 Patienten. Ophthalmologische Symptome berichteten 28 % (31/110); 11 % der Patienten (12/110) entwickelten eine symptomatische Osteoporose, 5/110 (4,5 %) eine Hypothyreose und 2 Patienten einen Diabetes mellitus. Von den maennlichen Patienten litten 11 % unter erektiler Dysfunktion oder Libidoverlust nach Therapie. Wegen menopausaler Beschwerden benoetigten 2/36 Frauen nach einer mittleren Zeit von 28 Monaten nach Therapie eine Hormonersatztherapie. Keine Patientin wurde nach Therapie schwanger. Es wurde weder eine akute noch eine spaete kardiale Toxizitaet dokumentiert, ebenso kein Sekundaermalignom. Obwohl das Therapieergebnis des vorliegenden Kollektivs im oberen Bereich der Literatur einzuordnen ist, bleiben sowohl die therapiebedingte

Are stamina and fatigue polar opposites? A case study.

Science.gov (United States)

So, Suzanna; Evans, Meredyth; Jason, Leonard A; Brown, Abigail

2015-01-01

Most individuals with Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) (Carruthers et al., 2003 ), Myalgic Encephalomyelitis (ME) (Carruthers et al., 2011 ), and chronic fatigue syndrome (CFS) (Fukuda et al., 1994 ) indicate that they experience fatigue and sharp decreases in energy levels, which hinder the ability to engage in physical activities (Friedberg & Jason, 1998 ). However, there are some individuals who reduce activity engagement in order to avoid a worsening of symptoms; thus these individuals may endorse lower levels of fatigue. Accordingly, those with low levels of fatigue but low endurance/stamina might be inadvertently excluded from some criteria based on the fatigue requirement. The current study serves as an exploration of the relationship between fatigue and stamina and the effects of these constructs on illness symptomology and their implications for assessment and diagnosis.

Anstrengelsesinduceret ST-segmentdepression efter akut myokardieinfarkt. Forekomst og prognostisk betydning

DEFF Research Database (Denmark)

Mickley, H; Pless, P; May, O

1989-01-01

On the basis of a review of 20 investigations (3,587 patients), the prevalence of significant ST-segment-depression (ST-depr) in patients performing an exercise test 9-30 days after acute myocardial infarction (AMI) was found to be 33% (3-70%). The reason for the considerable variation is due...... to a combination of several factors: 1) different and frequently incomplete definition of significant ST-depr; 2) heterogenically composed patient groups (first vs subsequent AMI, different prevalence of infarct types and localization, consecutive vs selected patients, +/- cardioactive drugs during the exercise...

Acute injury of the ankle joint; Akutes Trauma des Sprunggelenks

Energy Technology Data Exchange (ETDEWEB)

Breitenseher, M.J. [Univ. Klinik fuer Radiodiagnostik, Abt. fuer Osteologie und Besondere Klinische Einrichtung Magnet Resonanz, AKH, Wien (Austria)]|[Ludwig-Boltzmann-Institut fuer Radiologisch-Physikalische Tumordiagnostik, Vienna (Austria)

1999-01-01

The diagnosis of lateral collateral ankle ligament trauma is based on patient history, clinical examination, and clinical stress tests. If the clinical stress test is positive, stress radiography could be performed. There is no consensus about the usefulness of stress radiography in acute ankle sprain, particularly about the cut-off talar tilt angle beyond which a two-ligament rupture would be certain, ranging from 5 to 30 . Today MRI is not used for this indication, although it allows, with controlled positioning of the foot and with defined sections, visualization of injured lateral collateral ankle ligaments. In ankle injuries, plain radiographs form the established basis of diagnostic imaging and can provide definitive answers in most cases. CT is used in complex fractures for complete visualization. MRI is the method of choice for several diagnostic problem cases, including occult fractures and post-traumatic avascular necrosis. In tendon injuries, MRI is important if ultrasound is not diagnostic. Generally, for the evaluation of acute ankle injuries, MRI is the most important second-step procedure when radiographs are nondiagnostic. (orig.) [Deutsch] Die Diagnose einer lateralen Bandverletzung beim frischen Sprunggelenkstrauma fusst auf der Anamnese, der klinischen Untersuchung und klinischen Stresstests. Bei positiven klinischen Stresstests kann eine Stressradiographie durchgefuehrt werden. Es gibt keine Uebereinstimmung fuer den Wert der Stressradiographie beim frischen Supinationstrauma des Sprunggelenks, insbesonders fuer den Winkel der Aufklappbarkeit bei einer Zweibandverletzung, der von 5 -30 reicht. Die MRT wird zur Zeit bei dieser Indikation nur in Einzelfaellen benutzt, obwohl sie mit definierter Fusspositionierung und Ausrichtung der Untersuchungsebene eine ausgezeichnete Beurteilung der Sprunggelenksbaende erlaubt. Bei knoecherner Sprunggelenksverletzungen ist die Verwendung des konventionellen Roentgen die etablierte Methode und meist diagnostisch. Die CT kommt bei komplexen Frakturen zum Einsatz, um das gesamte Frakturausmass darzustellen. Die MRT ist die Methode der Wahl bei verschiedenen Problemfaellen wie okkulter Fraktur oder posttraumatischer Osteonekrose. Bei Sehnenverletzungen ist die MRT wichtig, falls eine Ultraschalluntersuchung nicht zur Diagnose fuehrt. Allgemein entwickelt sich bei der Untersuchung der frischen Sprunggelenksverletzung die MRT zur zweitwichtigsten bildgebenden Methode, falls das konventionelle Roentgen zu keiner ausreichenden Diagnose kommt. (orig.)

POLA PERESEPAN ANTIBIOTIK PADA MANAJEMEN FARINGITIS AKUT DEWASA DI PUSKEMAS

Directory of Open Access Journals (Sweden)

Dewi Puspita Apsari

2017-10-01

Full Text Available Acute pharyngitis is one of the most common diseases in primary health care, Bali. However, the best management to control the number of antibiotics prescribing in acute pharyngitis is not known. This study aims to determine the best management to control antibiotics prescribing in adult who has acute pharyngitis. This prospective cohort study involved 93 patients aged 12-45 years who had been diagnosed with acute pharyngitis by a physician. Measurements were made on the number of drugs per prescription, frequency antibiotic, quantity antibiotic and DDD antibiotics. Centor Criteria and RADT can reduce the number of antibiotic prescriptions than empirical management in primary health care district X, Bali. Decrease occurred on the the number of drugs per prescription, frequency antibiotic, quantity antibiotic and DDD antibiotics. Management centor criteria and RADT are the best strategies to reduce antibiotic prescription in primary health care distict X, Bali. 

Neurologiske symptomer og akut hepatitis associeret til parvovirus B19

DEFF Research Database (Denmark)

Giørtz-Carlsen, Birgitte; Rittig, Søren; Thelle, Thomas

2007-01-01

The spectrum of symptoms correlated to parvovirus B19 infections has expanded greatly during the past years. We report a case of anaemia, encephalitis-like symptoms and acute hepatitis in a 15-months-old Danish girl associated with parvovirus B19, verified by positive serum IgM og IgG antibodies....... She presented with non-febrile seizures and decreased level of consciousness. Later she developed signs of acute hepatitis. The course was benign. Udgivelsesdato: 2007-Nov-19...

Vellykket implementering af farmaceutisk intervention på Akut Modtage Afdeling

DEFF Research Database (Denmark)

Grønkjær, Louise Smed; Jensen, Mia Lolk; Madsen, Hanne

2011-01-01

We document the process of implementing a clinical pharmacist service at the acute medical admission unit at Odense University Hospital. During the period December 2009 through April 2010 we reviewed 915 medication lists, which resulted in 628 interventions with generic substitution as the most...

Valproatinduceret akut interstitiel nefritis med et alvorligt forløb

DEFF Research Database (Denmark)

Martuseviciene, Giedre; Kamper, Anne-Lise; Horn, Thomas

2006-01-01

A case of acute interstitial nephritis caused by sodium valproate is reported. The sodium valproate treatment was continued after initial diagnosis and the patient developed end-stage renal failure. After transplantation, interstitial nephritis was demonstrated in the renal graft....

Statiner ved akut koronart syndrom--en gennemgang af et Cochranereview

DEFF Research Database (Denmark)

Linde, Jesper James; Jensen, Gorm Boje

2012-01-01

infarction and stroke, but at four-month follow-up the incidence of unstable angina pectoris was significantly reduced. Despite the lack of evidence for an additional effect of early statin administrations on hard clinical end points, we find good reasons to maintain statins in the early treatment of ACS....

Erhvervsprognosen 18 måneder efter et streptokinasebehandlet akut myokardieinfarkt

DEFF Research Database (Denmark)

Christensen, Jeppe Hagstrup; Ravn, Lene; Rasmussen, Søren Elkjaer

1996-01-01

had continuous chest pain of less than six hours prior to admission and electrocardiographic changes consistent with acute myocardial infarction. The two groups were comparable with respect to medical variables related to their myocardial infarction and to educational level. A total of 17 patients (53......In order to assess the impact of thrombolytic therapy on return to work 18 months after a first myocardial infarction 32 patients treated with streptokinase were compared to 30 patients not treated with streptokinase. The study was designed as a historical cohort study. The patients in both groups......%) in the streptokinase group and 16 (53%) among controls had stopped working 18 months after their MI. An association between the treatment and the working status could not be found (relative risk = 1.0) nor could it be found if the figures were corrected for deaths and retirements because of age. In conclusion...

CUCI TANGAN SEBELUM MAKAN MENURUNKAN RISIKO KEJADIAN HEPATITIS AKUT KLINIS

Directory of Open Access Journals (Sweden)

Umar Firdous

2012-09-01

Full Text Available In the area of Hepatitis A outbreak, washing hand before handling food is very important, because most of the cases do not wash their hand before breakfast, lunch or dinner and they eat without spoon. This study is to find out relation between washing hand before handling food with clinical acute hepatitis cases in the area of Hepatitis A outbreak. This study used a case control design, analysing secondary data of Hepatitis A outbreak investigation from November 2001 to January 2002. The population is a the community which living in Calincing housing in Cogreg Village, Parungsub district of Bogor, aged between 15 to 55 years old. Sixty cases and 120 controls have been analysed. Result of this study found that there is a significant relation (p=0.000 between washing hand before handling food with clinical acute hepatitis case, OR=3.442 (95% CI: 1.638- 7.235. Education is a confounding variable to this relation.

Generel anæstesi anvendes for hyppigt ved akut sectio

DEFF Research Database (Denmark)

Frydshou, Andreas; Mitchell, Anja U; Møller, Ann

2012-01-01

As general anaesthesia (GA) for caesarean section (CS) compared to regional anaesthesia (RA) can increase maternal risks, it has been suggested that 85% of all acute CS should be performed in RA. We observed whether anaesthesiologists at a Danish university hospital over a 4,5 year-period fulfill...

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)

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 ...

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...

DESENDAN SEYİRLİ BİR GUİLLAİN BARRE SENDROMU OLGUSU

OpenAIRE

Başarslan, Fatmagül; Yılmaz, Cahide; Tutanç, Murat; Arıca, Vefik; Üstün, Nilgün; Davarcı, Işıl

2011-01-01

ÖZETGuillain Barre Sendromu (GBS), sıklıkla simetrik güçsüzlük ve arefleksi ile karakterize akut inflamatuar polinöropatidir. Geçirilmiş bakteriyel veya viral enfeksiyonların tetiklediği otoimmün bir hastalık olduğu kabul edilmektedir. Çocukluk çağı GBS'de mortalite %1-2 oranındadır ve genellikle solunum yetersizliğine bağlı olarak gelişir. Burada 14 yaşında viral enfeksiyon sonrası GBS gelişen bir erkek çocuk sunularak bu sendromun klinik özellikleri gözden geçirildi.Anahtar kelimeler: ...

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...

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...

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

Case Report

African Journals Online (AJOL)

other abnormalities detected (Figure 1). The radiological differential diagnoses included RPLS, vasculitis, acute demyelinating encephalomyelitis and infective encephalitis. Cerebro-spinal fluid examination obtained by lumber puncture was not diagnostic. Vasculitic screen showed a positive ANA titer of 1/320 with speckled.

Relapsing-Remitting MS (RRMS)

Medline Plus

Full Text Available ... Multiple Sclerosis and Your Emotions (.pdf) Download Brochure Disease Modifying Therapies Overview (.pdf) Download Document Pediatric MS Learn More Transverse Myelitis Learn More Neuromyelitis Optica (NMO) Learn More HTLV-I ... Learn More Acute Disseminated Encephalomyelitis (ADEM) Learn More ...

DoD Global Emerging Infections Surveillance and Response System -- Partnering in the Fight Against Emerging Infections, Fiscal Year 2006

Science.gov (United States)

2007-02-01

Cairo), nutritional surveys in Honduras (through NMRCD in Lima), malaria research on the Burmese border (through AFRIMS in Bangkok), and brucel - losis...collected specimens of from cases of cutaneous anthrax, bubonic plague, brucel - losis, Venezuelan equine encephalomyelitis, and Hantavirus. These

UniProt search blastx result: AK289029 [KOME

Lifescience Database Archive (English)

Full Text Available protein 3' (nsP3'); RNA-directed RNA polymerase nsP4 (EC 2.7.7.48) (Non-structural protein 4) (nsP4)] - Eastern equine... encephalitis virus (strain PE-0.0155) (EEEV) (Eastern equine encephalomyelitis virus) 0 ...

UniProt search blastx result: AK289029 [KOME

Lifescience Database Archive (English)

Full Text Available protein 3' (nsP3'); RNA-directed RNA polymerase nsP4 (EC 2.7.7.48) (Non-structural protein 4) (nsP4)] - Eastern equine... encephalitis virus (strain PE-3.0815) (EEEV) (Eastern equine encephalomyelitis virus) 0 ...

Why does multiple sclerosis only affect human primates?

NARCIS (Netherlands)

't Hart, Bert A.

Background: Multiple sclerosis (MS) develops exclusively in humans. Non-human primates are resistant against MS, although they are highly susceptible to the MS animal model, experimental autoimmune encephalomyelitis (EAE). Unravelling of the cause(s) underlying this discrepancy is highly relevant as

Relapsing-Remitting MS (RRMS)

Medline Plus

Full Text Available ... ADEM) Balo’s Disease HTLV-I Associated Myelopathy (HAM) Neuromyelitis Optica (NMO) Schilder's Disease Transverse Myelitis d Symptoms & Diagnosis ... Other Conditions to Rule Out Lyme Disease Lupus Neuromyelitis Optica Acute Disseminated Encephalomyelitis (ADEM) d For Clinicians d ...

MOG extracellular domain (p1-125) triggers elevated frequency of CXCR3+ CD4+ Th1 cells in the CNS of mice and induces greater incidence of severe EAE

DEFF Research Database (Denmark)

Thyagabhavan Mony, Jyothi; Khorooshi, Reza; Owens, Trevor

2014-01-01

Myelin-specific T cells are implicated in multiple sclerosis (MS) and drive experimental autoimmune encephalomyelitis (EAE). EAE is commonly induced with short peptides, whereas in MS, whole myelin proteins are available for immune response. We asked whether immunization with the immunoglobulin-l...

Hypersensitivity Responses in the Central Nervous System

DEFF Research Database (Denmark)

Khorooshi, Reza; Asgari, Nasrin; Mørch, Marlene Thorsen

2015-01-01

of pathology in neuromyelitis optica (NMO), a central nervous system (CNS) demyelinating disease where activated neutrophils infiltrate, unlike in MS. The most widely used model for MS, experimental autoimmune encephalomyelitis, is an autoantigen-immunized disease that can be transferred to naive animals...

Chemokines and chemokine receptors in inflammation of the nervous system

DEFF Research Database (Denmark)

Huang, D; Han, Yong-Chang; Rani, M R

2000-01-01

This article focuses on the production of chemokines by resident glial cells of the nervous system. We describe studies in two distinct categories of inflammation within the nervous system: immune-mediated inflammation as seen in experimental autoimmune encephalomyelitis (EAE) or multiple sclerosis...

Status of diagnostic approaches to AQP4-IgG seronegative NMO and NMO/MS overlap syndromes

DEFF Research Database (Denmark)

Juryńczyk, Maciej; Weinshenker, Brian; Akman-Demir, Gulsen

2016-01-01

: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM...

Endogenous interferon-β-inducible gene expression and interferon-β-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis

DEFF Research Database (Denmark)

Börnsen, Lars; Christensen, Jeppe Romme; Ratzer, Rikke

2015-01-01

Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used for......-induced CD4+ T-cell autoreactivity in interferon-β-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.......Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used...... for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels...

Socio-economic modelling of rabies control in Flores Island, Indonesia

NARCIS (Netherlands)

Wera, Ewaldus

2017-01-01

Rabies is a zoonotic viral disease that can cause encephalomyelitis both in animals and humans. Since its introduction in Flores Island, Indonesia in 1997, it has been a serious public health threat with significant economic consequences. To control the disease, annual dog vaccination campaigns

Global and 3D Spatial Assessment of Neuroinflammation in Rodent Models of Multiple Sclerosis

DEFF Research Database (Denmark)

Gupta, Shashank; Utoft, Regine Egeholm; Hasseldam, Henrik

2013-01-01

Multiple Sclerosis (MS) is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS). T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE) animal models for the disease. A te...

Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells

DEFF Research Database (Denmark)

Blomqvist, Maria; Rhost, Sara; Teneberg, Susann

2009-01-01

The glycosphingolipid sulfatide (SO(3)-3Galbeta1Cer) is a demonstrated ligand for a subset of CD1d-restricted NKT cells, which could regulate experimental autoimmune encephalomyelitis, a murine model for multiple sclerosis, as well as tumor immunity and experimental hepatitis. Native sulfatide...

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429)

DEFF Research Database (Denmark)

EFSA Panel on Animal Health and Welfare; More, Simon J.; Bøtner, Anette

2017-01-01

. The animal species to be listed for equine encephalomyelitis (Eastern and Western) according to Article 8(3) criteria are several species of mammals, birds, reptiles and amphibians as susceptible species; rodents, lagomorphs and several bird species as reservoirs and at least four mosquito species (family...

Korelasi dan Penyebaran Kejadian Rabies pada Anjing dan Manusia di Kabupaten Klungkung Bali Tahun 2010-2014

Directory of Open Access Journals (Sweden)

Rendi Tegar Pratama

2016-06-01

Full Text Available Rabies atau penyakit anjing gila merupakan penyakit virus yang disebabkan oleh genus Lyssavirus dari famili Rhabdoviridae bersifat akut serta sangat berbahaya dan mengakibatkan kematian karena mampu menginfeksi sistem saraf pusat yakni otak dan sumsum tulang belakang. Penelitian ini bertujuan untuk mengetahui kawasan rabies, penyebaran rabies dan korelasi antara kejadian rabies pada anjing dan manusia di Kabupaten Klungkung tahun 2010-2014. Metode yang digunakan dalam penelitian ini adalah analisis deskriptif. Untuk mengetahui hubungan kejadian rabies pada anjing dan manusia dilakukan uji korelasi Rank Spearman. Berdasarkan uji korelasi Spearman diperoleh hasil bahwa terdapat hubungan yang searah antara kejadian rabies pada anjing dan manusia. Dari uji Spearman yang dilakukan nilai koefisiensi yang diperoleh adalah 0,468 dengan nilai signifikansi 0,037.

Telemedicinsk praehospital diagnostik og visitation af en patient med akut lungeemboli

DEFF Research Database (Denmark)

Terkelsen, Astrid J.; Nielsen-Kudsk, Jens Erik; Andersen, Henning Rud

2008-01-01

Mortality in untreated pulmonary embolism is high and short-term outcome depends on a timely diagnosis. In this case telemedicine involving 12-lead ECG and GSM-based communication between the patient in the ambulance and the telemedical staff resulted in remote pre-hospital suspicion of acute...

Behandling af højt blodtryk hos patienter med akut apopleksi

DEFF Research Database (Denmark)

Olsen, T S; Jørgensen, H S; Garde, E

1995-01-01

The study was performed to investigate how often reduction of high blood pressure (> or = 220 mmHg systolic and or > or = 120 mmHg diastolic) was attempted in patients with acute stroke or transient ischemic attacks (TIA). Of 1351 consecutive patients with acute stroke or TIA 119 had high blood...... encephalopathy. It is concluded that reduction of high blood pressure in patients with stroke or TIA is attempted too often. As autoregulation is commonly impaired in acute stroke, reduction of systemic blood pressure may enhance ischaemic tissue damage. Reduction of blood pressure in acute stroke should...... pressure on admission. In 15 patients the stroke was so severe that treatment was not considered. In the remaining 104 patients reduction of the blood pressure was attempted in 28 (27%); in 23 patients immediately following admission. None of the patients had symptoms or signs of hypertensive...

Svær akut underernæring hos børn

DEFF Research Database (Denmark)

Fabiansen, Christian; Christensen, Vibeke Brix; Eklund, Martin

2010-01-01

Severe acute malnutrition (SAM) affects approx. 19 million children below five years of age in low and middle income countries. Both shortage and low quality of foods are important determinants of SAM. With the development of special ready-to-use foods and by using simple treatment protocols......, it is now possible to treat SAM successfully outside hospitals and treatment centers thereby reducing the case-fatality rate. However, only a small percentage of children with SAM have access to correct treatment....

Svær akut underernæring hos børn

DEFF Research Database (Denmark)

Fabiansen, Christian; Christensen, Vibeke Brix; Eklund, Martin

2010-01-01

Severe acute malnutrition (SAM) affects approx. 19 million children below five years of age in low and middle income countries. Both shortage and low quality of foods are important determinants of SAM. With the development of special ready-to-use foods and by using simple treatment protocols...

Ruptur af fri venstre ventrikelvaeg, septum og papillaermuskler ved akut myokardieinfarkt

DEFF Research Database (Denmark)

Kjeld, Thomas; Hassager, Christian; Hjortdal, Vibeke E.

2009-01-01

. This risk of MCA can be reduced by sufficient revascularisation, but these rare differential diagnoses to cardiogenic shock remain important. Echocardiography is the diagnostic gold standard. First line treatment is medical and often mechanical stabilization, but this should not delay quick surgical...

Sparsom viden om patientrapporterede outcomes efter større akut abdominalkirurgi

DEFF Research Database (Denmark)

Oreskov, Jakob Ohm; Ekeløf, Sarah; Burcharth, Jakob

2017-01-01

Little is known about patient-reported outcomes after major emergency abdominal surgery. Studies on patients undergoing major elective abdominal surgery and patients in the intensive care unit report significant challenges with chronic pain, functional impairment, quality of life, depression and ...

Incidence and economic impact of rabies in the cattle population of Ethiopia

NARCIS (Netherlands)

Jibat, Tariku; Mourits, Monique C.M.; Hogeveen, Henk

2016-01-01

Rabies is a viral disease that can cause fatal encephalomyelitis both in animals and humans. Although incidences of the disease in cattle have been reported, insight in the economic impact of the disease in livestock remains limited. By affecting cattle in subsistence systems, rabies may have

Vom work Book Journal 2010 5

African Journals Online (AJOL)

USER

INTRODUCTION. Rabies is a viral zoonosis characterised by encephalomyelitis. It a disease of great public health concern because the case. SUMMARY. Out of the seven recognized and four putative genotypes of lyssaviruses, genotypes 1-3 comprising namely the classical rabies virus (RABV), Lagos bat virus (LBV) and.

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 ...

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 ...

Green tea epigallocatechin-3-gallate modulates differentiation of naive CD4+ T cells into specific lineage effector cells

Science.gov (United States)

CD4+ T helper (Th) subsets Th1, Th9, and Th17 cells are implicated in inducing autoimmunity whereas regulatory T cells (Treg) have a protective effect. We previously showed that epigallocatechin-3-gallate (EGCG) attenuated experimental autoimmune encephalomyelitis (EAE) and altered CD4+ T cell subpo...

Metallothionein-I+II in neuroprotection

DEFF Research Database (Denmark)

Pedersen, Mie Ø; Jensen, Rikke; Pedersen, Dan S

2009-01-01

-I+II decrease inflammation and secondary tissue damage (oxidative stress, neurodegeneration, and apoptosis) and promote post-injury repair and regeneration (angiogenesis, neurogenesis, neuronal sprouting and tissue remodelling). Intracellularly the molecular MT-I+II actions involve metal ion control...... encephalomyelitis. (c) 2009 International Union of Biochemistry and Molecular Biology, Inc....

Role of Th1 and Th2 cells in autoimmune demyelinating disease

NARCIS (Netherlands)

Nagelkerken, L.

1998-01-01

Evidence is accumulating that Th1 cells play an important role in the development of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), whereas Th2 cells contribute to recovery from disease. A maj or determinant in the development of Th1 and Th2 cells is the type of

OPTIMALISASI MRP PARAMATER PADA COMMON MATERIAL UNTUK MEMBERI NILAI TAMBAH PADA PROSES KANBAN DI PT UNELEC INDONESIA (UNINDO DENGAN SIMULASI PART-VARIABLE TOOLS

Directory of Open Access Journals (Sweden)

Budi Susatyo

2016-02-01

Full Text Available Part-Variable Tools merupakan  aplikasi kecil yang dibuat dengan Ms. Excel, untuk melakukan perhitungan dan usulan MRP parameter dengan mempergunakan data transaksi bahan baku paling sedikit 1 tahun kebelakang.”Common Material” adalah tipe bahan baku yang ada di PT UNINDO yang harus selalu tersedia dalam kotak (bin di Gudang Persediaan dan sumber kebutuhan akan bahan baku ini diminta oleh karyawan Gudang. Permintaan jumlah kuantitinya berdasarkan jumlah akutal yang ada dibandingkan dengan nilai level permintaan kembali (ROP yang tertera pada KARTU KANBAN. Nilai ROP tersebut merupakan parameter MRP yang digunakan dalam perhitungan kebutuhan material.Perhitungan MRP dibutuhkan untuk meningkatkan kualitas, produktifitas, dan efisiensi, perbaikan komunikasi, dan menurunkan biaya-biaya dan hal hal yang tidak diperlukan serta mendekati keinginan konsumen dengan meminimalkan waktu tunggu ( Kootaneel, 2013  

PROFIL RESIDU PESTISIDA DITIOKARBAMAT DALAM TOMAT DAN SELADA PADA TINGKAT KONSUMEN DI DKI JAKARTA

Directory of Open Access Journals (Sweden)

D. Mutiatikum

2012-10-01

Full Text Available Penggunaan pestisida untuk meningkatkan produksi hasil pertanian menunjukkan adanya residu pestisida dalam komoditi pertanian. Pemaparan pestisida pada manusia dapat menimbulkan keracunan, baik akut maupun kronis bergantung pada lamanya pemaparan. Tomat dan selada adalah sayuran yang biasa dikonsumsi langsung tanpa dimasak lebih dahulu sebagai makanan, seperti lalaban, burger. salad. juice dan sebagainya Monitoring terhadap makanan tersebut dilakukan dengan cara sampling ke pasar-pasar yang berada di Jakarta. Kemudian, ditentukan kadar residu pestisida dengan menggunakan kromatografi gas (GC. Hasil analisis residu pestisida ditiokarbamat dalam tomat, terdeteksi pada semua contoh makanan dengan kadar antara 0,66- 22,27 mg/kg. Sedangkan pada selada antara 0,43- 18,57 mg/kg (BMR tomat 3 dan selada 5. 41,67% dari yang disampling melebihi BMR baik tomat maupun selada.   Kata Kunci  : Ditiokarbamat (Pestisida

Kanser hastalarında kemoterapinin C-reaktif protein düzeyine ve yaşam kalitesine olan etkileri

OpenAIRE

Gürler, Mehmet Yavuz

2011-01-01

Giriş ve Amaç: Bir inflamasyon belirteci ve akut faz reaktanı olan C-reaktif protein, karaciğer ve yağ dokusunda üretilen bir beta globulindir. Günümüz pratiğinde pek çok hastalığın tanısını desteklerken bazı hastalıkların ise takibinde ve alevlenmesinde güvenilir bir belirteçtir. Son yıllarda yapılan çalışmalar göstermiş ki kanser hastalarında bakılan serum CRP düzeyi hastalığın yaygınlığı, hastanın yaşam kalitesi, prognozu ve kemoterapiye yanıtı değerlendirmede kullanılabilme...

Rapid Intravenous Rehydration to Correct Dehydration and Resolve Vomiting in Children with Acute Gastroenteritis

Directory of Open Access Journals (Sweden)

Anoush AZARFAR

2014-09-01

Full Text Available SUMMARY: Objectives: The objective of this study is to evaluate the effect of rapid intravenous rehydration to resolve vomiting in children with acute gastroenteritis. Methods: This randomized control trial was conducted in the pediatric emergency department in a tertiary care center in Tabriz, North-West of Iran. The study participants' were 150 children with acute gastroenteritis and vomiting who were moderately dehydrated, had not responded to oral rehydration therapy and without any electrolyte abnormalities. 20–30 cc/kg of a crystalloid solution was given intravenously over 2 hours and the control group was admitted in the emergency department (ED for a standard 24 hour hydration. Effectiveness of rapid intravenous rehydration in the resolution of vomiting in children with acute gastroenteritis was evaluated. Results: In 63 children of the intervention group (out of 75 vomiting was resolved after rapid IV rehydration and they were discharged. Among them, 12 that did not tolerate oral fluids were admitted. In the control group, 62 patients' vomiting was resolved in the first 4 hours after admission, and there was no significant difference between the two groups regarding resolution of vomiting. Conclusions: Rapid intravenous rehydration in children with moderate dehydration and vomiting due to gastroenteritis is effective in reducing admission rates in the ED. ÖZET: Amaç: Bu çalışmanın amacı, akut gastroenteritli çocuklarda, hızlı intravenöz rehidratasyon tedavisinin kusma üzerine etkisini değerlendirmektir. Gereç ve Yöntem: Bu randomize kontrollü çalışma İran'ın Kuzeybatısındaki Tebriz ilinde üçüncü basamak çocuk acil servisinde gerçekleştirildi. Çalışmaya orta derecede dehidrate, elektrolit anormalliği olmayan ve oral rehidrasyon tedavisine yanıt vermemiş akut gastroenteritli 150 çocuk katıldı. İki saat içinde intravenöz yolla 20–30 cc/kg kristaloid çözelti verildi ve kontrol grubu standart

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.

Anticorpos neutralizantes para a amostra leste do virus de encefalomielite equina em equídeos no Brasil

Directory of Open Access Journals (Sweden)

Edwin H. Lennette

1943-01-01

Full Text Available Resume-se a literatura sobre encefalomielite equina no Brasil. Dos vários agentes infecciosos isolados de epizootias dessa doença somente um foi identificado com certeza e era o virus da raiva (Cunha. Exames feitos neste Laboratório com soros de equídeos que haviam passado por uma epizootia de encefalomielite no município de Peçanha, Minas Gerais, durante o fim de 1940 e princípio de 1941 revelaram que a maioria possuia anticorpos neutralizantes para o virus de encefalomielite equina de leste. Estes achados indicam que esse virus ocorre tambem no Brasil não sendo, portanto, restrito à América do Norte.The literature on equine encephalomyelitis in Brazil is very briefly sumarized. It is shown that of the several infectious agents isolated from epizootics of this disease, only one has been identified with certainty and has been found to be rabies virus (Cunha. During late 1940 and early 1941 an epizootic of encephalomyelitis occurred in the Municipio (County of Peçanha, which is located in the east central part of the State of Minas Gerais. Sera were collected from eighteen horses and mules which had passed through the epizootic, and tested for neutralizing antibodies to the St. Louis encephalitis virus and to the eastern and western strains of equine encephlomyelitis virus. None of the sera contained demonstrable antibodies to the St. Louis or western equine encephalomyelitis viruses; fourteen of the eighteen sera, however, possessed antibodies to the eastern strain. Only one of the twenty control sera, obtained from adjacent areas, was found to contain antibodies for the eastern strain, and this one also came from the Municipio of Peçanha. It is concluded that the eastern strain of equine encephlomyelitis virus occurs also in Brazil and is not confined to North America.

Validiteten af diagnosen akut myokardieinfarkt i to registre: Hjerteregistret sammenlignet med Landspatientregisteret

DEFF Research Database (Denmark)

Madsen, Mette; Balling, H; Eriksen, L S

1990-01-01

in the National Patient Register only appear to explain a lesser fraction of the disagreements as the diagnoses which were summed up in the upper part of the summaries showed reasonably good agreement with the diagnoses in the National Patient Register. Re-assessment of the diagnoses revealed that approximately...... 90% of the admissions with AMI could be verified, without modification, by reviewing the text of the summaries.(ABSTRACT TRUNCATED AT 250 WORDS) Udgivelsesdato: 1990-Jan-29...

İmmunkompetan Bir Ce rrahta Gelişen Akut Cytomegalovi rus Hepatiti

Directory of Open Access Journals (Sweden)

Esra Tanyel

2018-03-01

Full Text Available Cytomegalovirus (CMV infection in theimmunocompetentindividual is asymptomaticormanifested as a mononucleosis-likesyndrome, and severe organ damage is rarelyreported.CMV is transmittedthroughblood, body fluids, sexualandplacental transfer, andtransplantedorgans.Here, wedescribe a previouslyhealthymalepatient of acute CMV hepatitis in whomthediagnosiswasestablishedbypolymerasechainreaction (PCR CMV-DNA. A 28-year-old malesurgeonwasadmittedtoouroutpatientclinicwithcomplaints of feverforthreeweeks. Uponadmissionthepatientpresented body temperaturewas 380C andphysicalexaminationrevealed normal findingsotherthanhepatomegaly.Laboratorydatarevealed a slightlyincreasedwhitebloodcell (10000/mm3withatypicallymphocytes(>10% in peripheralbloodsmear. His liverenzymeconcentrationswereelevatedandan extensiveserologicalscreeningto identify anyviralcause of hepatitis.TheCMV IgMwaspositive, andIgGwasnegative. PCR of his bloodwaselevatedforCMV DNA(1150 copies/mL; normal range<150copies/mL.Treatmentwithganciclovirwasinitiated, afterwhich his liverfunctionbegantoimproveand her general conditionrecovered.Intheliterature, severalimmunocompetentcaseswith CMV hepatitishavebeenreported. Inaddition, patientsmaydevelopcholestatichepatitis, granulomatoushepatitis, orfulminanthepaticfailurerequiringlivertransplantationdueto CMV infection. Viralculture, serology, CMV antigenemia, histopathologicalexamination, and PCR can be used in thediagnosis of CMV infections. Anti-CMV immunoglobulinshavelowspecificityandsensitivityduringacuteinfection. Thegoldstandard in thediagnosis is CMV-DNA levelmeasured in thebloodusing PCR, andquantitativemeasurement is particularlyimportantforfollow-up. Thepresentcasereport is noteworthyforreminding CMV as an etiologicalfactorforclinicalpresentationwithfever, hepatomegaly, andelevatedliverenzymes, whenotherfactorsareexcluded.

Magnetic resonance imaging in acute intractional tuberculosis; Magnetresonanztomographie bei akuter intrakranieller Tuberkulose

Energy Technology Data Exchange (ETDEWEB)

Venz, S. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Sander, B. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Benndorf, G. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Terstegge, K. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Podrabsky, P. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Cordes, M. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Felix, R. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany)

1994-12-31

We reported three cases of acute intracranial tuberculosis including miliary tuberculosis, basal meningitis, tuberculomas and neuritis of cranial nerves. All patients had native and contrast enhanced CT and MRI scans. MRI revealed more granulomas and a better imaging contrast in the detection of basal meningitis. Neuritis was diagnosed only with the MRI. MRI scans should be prefered as the imaging procedure in clinically presumed intracranial tuberculosis. (orig.) [Deutsch] Die Befunde von drei Patienten mit intrakranieller Tuberkulose (intrakranielle Miliartuberkulose, Meningitis tuberculosa, Neuritis und Tuberkulome) in der Magnetresonanztomographie (MRT) wurden mit der Computertomographie (CT) verglichen. Sowohl die MRT als auch die CT wurden nativ und nach Kontrastmittelgabe durchgefuehrt. Die MRT zeigte sich im Nachweis von Granulomen insbesondere im Bereich des Hirnstamms ueberlegen. Ebenso wurde ein hoeherer Bildkontrast bei der Darstellung der Meningitis beobachtet. Eine Neuritis der Hirnnerven war nur mit der MRT nachweisbar. Die kontrastmittelunterstuetzte MRT sollte in der bildgebenden Diagnostik einer intrakraniellen Turberkulose primaer zum Einsatz gelangen. (orig.)

Plasmaferese ved akut pankreatitis associeret med svær hypertriglyceridæmi

DEFF Research Database (Denmark)

Jørgensen, Anders Bech; Schmidt, Palle Nordblad; Damholt, Mette Brimnes

2016-01-01

Acute pancreatitis can be caused by hypertriglyceridaemia. The treatment includes lowering of the blood triglyceride levels. We present a case of a 40-year-old woman who was admitted in this condition. She was treated with plasmapheresis, which led to a rapid decline of the blood triglyceride...... levels. The national Danish guidelines on treatment of acute pancreatitis do not mention plasmapheresis as a method of lowering elevated triglyceride levels. We suggest that the guidelines should be revised with attention to this treatment option....

Akut koronarangiografi er indiceret ved ST-elevation efter hjertestop uden for hospital

DEFF Research Database (Denmark)

Kjærgaard, Jesper; Bro-Jeppesen, John; Møller, Jacob Eifer

2013-01-01

be offered to patients with a high likelihood of thrombotic coronary lesions, i.e. patients with ST-segment elevation in electrocardiogram (ECG) following resuscitation. This article suggests a triage and referral based on electronic transmission of ECG and teleconference with specialized centres in all...

Virusinfektioner spiller en vigtig rolle ved akut forværring af astma

DEFF Research Database (Denmark)

Bjerregaard, Asger; Backer, Vibeke; Porsbjerg, Celeste

2014-01-01

Upper respiratory tract infections with common virusses is the most frequent cause of asthma exacerbations. Numerous defects in both epithelial function, pathogen recognition and innate immune signalling has been demonstrated in patients with asthma. The subject of this review is these recent...

Akut pankreatitis hos en 16-årig dreng efter indtag af ibuprofen

DEFF Research Database (Denmark)

Bruusgaard-Mouritsen, Mads Emil; Leerhøy, Bonna; Hansen, Mark Berner

2015-01-01

This is a case report of a 16-year-old boy with possible drug-induced pancreatitis (DIP) caused by ibuprofen. The patient had a history of psychiatric, but no somatic, disease, and he was admitted with a clinical presentation consistent with acute pancreatitis after a bolus ingestion of 10 g...... of ibuprofen in a suicidal attempt. No evidence of other causality for acute pancreatitis was identified. The patient was treated with a standard pancreatitis treatment regime and was discharged against medical advice after four days. The case represents a possible causality between ibuprofen and DIP....

Virusinfektioner spiller en vigtig rolle ved akut forværring af astma

DEFF Research Database (Denmark)

Bjerregaard, Asger; Backer, Vibeke; Porsbjerg, Celeste

2014-01-01

Upper respiratory tract infections with common virusses is the most frequent cause of asthma exacerbations. Numerous defects in both epithelial function, pathogen recognition and innate immune signalling has been demonstrated in patients with asthma. The subject of this review is these recent fin...

Effekt af psykosocial rehabilitering efter akut myokardieinfarkt. En randomiseret undersøgelse

DEFF Research Database (Denmark)

Johansen, Susanne Margrete Bølling; Baumbach, Lars A; Jørgensen, Torben

2003-01-01

INTRODUCTION: The aim of the study was to examine the effect of group based psychosocial rehabilitation following discharge compared to usual care. MATERIAL AND METHODS: A randomised clinical trial was performed in the setting of a coronary unit at Herlev University Hospital. The study sample......: The intervention did not significantly affect coping strategies, general health or physical function. The readmission rate was significantly lower in the intervention group compared to the control group. The mortality rate in the intervention group was lower after four months, one year and four years. DISCUSSION...

Perforeret akut akalkuløs kolecystitis forårsaget af hepatitis A

DEFF Research Database (Denmark)

Cuk, Pedja; Iqbal, Mozammil; Lykke, Jakob

2014-01-01

Acute acalculous cholecystitis is a rare condition associated with a high risk of gangrene, empyema and perforation of the gallbladder. In this case report it is described how hepatitis A infection leads to a fulminant perforated acalculous chole-cystitis, which is described sporadically in the l......Acute acalculous cholecystitis is a rare condition associated with a high risk of gangrene, empyema and perforation of the gallbladder. In this case report it is described how hepatitis A infection leads to a fulminant perforated acalculous chole-cystitis, which is described sporadically...

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

Two different nervous system complications of mycoplasma pneumoniae

OpenAIRE

Faruk İncecik; M. Özlem Hergüner; Şakir Altunbaşak

2010-01-01

Mycoplasma pneumoniae is an important agent of the lower and upper respiratory system infections. It may resultin some complications and clinical conditions other than infections. Meningoencephalitis, encephalitis, transversemyelitis, acute disseminated encephalomyelitis, cerebral infarction and Gullian-Barre syndrome are major neurological complications.We present here two cases with meningoencephalitis and Gullian-Barre syndrome secondary to Mycoplasma pneumoniaeinfection.

Two different nervous system complications of mycoplasma pneumoniae

Directory of Open Access Journals (Sweden)

Faruk İncecik

2010-06-01

Full Text Available Mycoplasma pneumoniae is an important agent of the lower and upper respiratory system infections. It may resultin some complications and clinical conditions other than infections. Meningoencephalitis, encephalitis, transversemyelitis, acute disseminated encephalomyelitis, cerebral infarction and Gullian-Barre syndrome are major neurological complications.We present here two cases with meningoencephalitis and Gullian-Barre syndrome secondary to Mycoplasma pneumoniaeinfection.

Geriatric Medicine, Sarkopenia, Frailty, dan Kualitas Hidup Pasien Usia Lanjut: Tantangan Masa Depan Pendidikan, Penelitian dan Pelayanan Kedokteran di Indonesia

Directory of Open Access Journals (Sweden)

Siti Setiati

2014-04-01

Full Text Available Geriatri adalah cabang ilmu kedokteran dengan fokus pada penuaan dini dan tatalaksana penyakit terkaitusia lanjut. Proses menua mengakibatkan penurunan fungsi sistem organ seperti sistem sensorik, sarafpusat, pencernaan, kardiovaskular, dan sistem respirasi. Selain itu terjadi pula perubahan komposisitubuh, yaitu penurunan massa otot, peningkatan massa dan sentralisasi lemak, serta peningkatanlemak intramuscular. Masalah yang sering dijumpai pada pasien geriatri adalah sindrom geriatri yangmeliputi: imobilisasi, instabilitas, inkontinensia, insomnia, depresi, infeksi, defisiensi imun, gangguanpendengaran dan penglihatan, gangguan intelektual, kolon irritable, impecunity, dan impotensi. Dimasa yang akan datang diperlukan tempat rawat jalan terpadu dan perawatan kasus akut geriatri dirumah sakit di seluruh Indonesia. Program lainnya adalah nutrisi usia lanjut, tempat istirahat sementara,layanan psiko-geriatri dan dementia care, dukungan care giver, pencegahan penyakit kronis dankonseling, serta menyiapkan moda transportasi yang sesuai.Kata kunci: geriatri, kedokteran, penurunan fungsi, sindrom geriatri.

MRI of pulmonary perfusion; MRT der Lungenperfusion

Energy Technology Data Exchange (ETDEWEB)

Fink, C. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen (Germany). Institut fuer Klinische Radiologie; Deutsches Krebsforschungszentrum (DKFZ), Abteilung Radiologie, Heidelberg (Germany); Risse, F.; Semmler, W. [Deutsches Krebsforschungszentrum (DKFZ), Abteilung Medizinische Physik in der Radiologie, Heidelberg (Germany); Schoenberg, S.O.; Reiser, M.F. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen (Germany). Institut fuer Klinische Radiologie; Kauczor, H.-U. [Deutsches Krebsforschungszentrum (DKFZ), Abteilung Radiologie, Heidelberg (Germany)

2006-04-15

Lung perfusion is a crucial prerequisite for effective gas exchange. Quantification of pulmonary perfusion is important for diagnostic considerations and treatment planning in various diseases of the lungs. Besides disorders of pulmonary vessels such as acute pulmonary embolism and pulmonary hypertension, these also include diseases of the respiratory tract and lung tissue as well as pulmonary tumors. This contribution presents the possibilities and technical requirements of MRI for diagnostic work-up of pulmonary perfusion. (orig.) [German] Die Perfusion der Lunge ist eine entscheidende Voraussetzung fuer einen effektiven Gasaustausch. Die Bestimmung der Lungenperfusion ist bei verschiedenen Erkrankungen der Lunge fuer Diagnostik und Therapieplanung bedeutsam. Hierzu zaehlen neben Erkrankungen der Lungengefaesse wie akute Lungenembolie und pulmonale Hypertension ebenso Erkrankungen der Atemwege, des Lungengeruests und Lungentumoren. In diesem Beitrag werden die Moeglichkeiten und technischen Voraussetzungen der MRT zur Diagnostik der Lungenperfusion dargestellt. (orig.)

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...

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 ...

The incidence of radioepidermitis and the dose-response relationship in parotid gland cancer patients treated with 125I seed brachytherapy. Incidence of radioepidermitis and the dose-response relationship

Energy Technology Data Exchange (ETDEWEB)

Mao, Ming-Hui; Zheng, Lei; Gao, Hong; Zhang, Jie; Liu, Shu-ming; Huang, Ming-wei; Shi, Yan [Peking University School and Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Beijing (China); Zhang, Jian-Guo [Peking University School and Hospital of Stomatology, Department of Oral and Maxillofacial Surgery, Beijing (China); Fujian Provincial Hospital, Fujian (China)

2014-09-09

wurden 100 Patienten mit Ohrspeicheldruesenkrebs postoperativ mit [{sup 125}I]-Seed-Brachytherapie behandelt. Die angeglichene periphere Dosis (MPD) betrug 80-140 Gy und die Aktivitaet der [{sup 125}I]-Seed war 0,7-0,8 mCi. Die durchschnittliche Dosis, die auf die Haut gebracht wurde, wurde beim postimplantologischen CT am Tag 0 nach der Implantation kalkuliert. Die Grade von akuter und verspaeteter Dermatitis wurden nach 2, 6, 12 und 18 Monaten postimplantologisch ausgewertet. Die meisten Patienten erlebten akute und verspaetete Nebenwirkungen (86 % bzw. 97 %) auf der Haut vom Grad 0-2, obwohl eine kleine Untergruppe schwere Komplikationen entwickelte. Die meisten Grad-1- bis Grad-3-Wirkungen hatten sich innerhalb von 6 Monaten nach der Implantation aufgeloest, obwohl einige der Grad-3- bis Grad-4-Wirkungen und alle Grad-4-Wirkungen waehrend des 18-monatigen Nachfolgezeitraums unveraendert geblieben sind. Die Grad-3- bis Grad-4-Wirkungen waren am bedeutendsten (75 % bzw. 25 %) mit der Dosis von 110-140 Gy; eine Dosis hoeher als 140 Gy erzeugte nur Grad-4-Wirkungen. Die [{sup 125}I]-Seed-Brachytherapie erzeugt akzeptable Ebenen von akuter und verspaeteter Radioepidermitis mit einem guten klinischen Ergebnis. Eine durchschnittliche Dosis unter 100 Gy, die auf die Haut aufgebracht wurde, war sicher, obwohl Dosen von 110-140 Gy mit Vorsicht und zusaetzlicher Ueberwachung gegeben werden sollten; Dosen hoeher als 140 Gy sind gefaehrlich und werden wahrscheinlich Grad-4-Wirkungen erzeugen. (orig.)

Vitamin D Supplementation in Submariners

Science.gov (United States)

2008-12-02

including diabetes mellitus type 1, rheumatoid arthritis , experimental autoimmune encephalomyelitis, inflammatory bowel disease, and systemic lupus...the safety and effectiveness of monthly ergocalciferol in hemodialysis patients . Nephron Clin Pract 2007;105(3):132-8 91. Goldzieher JW, Zerwekh...D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 2003;78:1463-1470. 31. Glerup H, Mikkelsen K, Poulsen L, et al

Normal Development and Function of T Cells in Proline Rich 7 (Prr7) Deficient Mice

Czech Academy of Sciences Publication Activity Database

Hrdinka, M.; Sudan, K.; Just, S.; Drobek, Aleš; Štěpánek, Ondřej; Schlueter, D.; Reinhold, D.; Jordan, B.A.; Gintschel, P.; Schraven, B.; Kreutz, M.R.

2016-01-01

Roč. 11, č. 9 (2016), č. článku e0162863. E-ISSN 1932-6203 R&D Projects: GA ČR GJ16-09208Y Institutional support: RVO:68378050 Keywords : transmembrane adapter proteins * experimental autoimmune encephalomyelitis * multiple-sclerosis * listeria - monocytogenes * lymphocyte development * negative regulation * activation * receptor * neurodegeneration * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.806, year: 2016

Ankara Üniversitesi Kriz Merkezine başvuran yas olguları üzerine bir çalışma

OpenAIRE

ŞENELMİŞ, Halil

2006-01-01

Ankara Üniversitesi Kriz Merkezi'ne BaşvuranYas Olguları Üzerine Bir ÇalışmaSosyal bir varlık olan insan yaşam süreci içerisinde zorlayıcı, yıpratıcı, tehdit edicibirçok olay ve sorunla karşılaşır. Her zaman sorunlar karşısında kullandığı çözüm yollarınınişe yaramadığını gören kişi, kendisini çaresiz hisseder. Bu yaşanan bir kriz durumudur. Krizçeşitli duygusal zorlanmalar sonunda meydana gelen akut ve süresi sınırlı bir dengebozukluğudur.Kişinin yaşamı boyunca karşılaştı...

KEJADIAN KOLONI JAMUR PADA PENDERITA OTORE DENGAN BERBAGAI PENYEBAB DI POLIKLINIK THT RUMAH SAKIT PENDIDIKAN UNHAS

Directory of Open Access Journals (Sweden)

Sedjawidada R

2014-09-01

Full Text Available Telah dilakukan penelitian survey dengan pendekatan deskriptif tentang Kejadian Koloni Jamur pada Penderita Otore dengan Berbagai Penyebab di Poliklinik THT Rumah Sakit Pendidikan Unhas. Sampel yang diteliti adalah eksudat yang diambil dari liang telinga luar setiap telinga yang menderita Otitis eksterna superfisialis basah, Otitis media supuratif akut perforasi, Otitis media supuratif kronik benigna aktif. Dari total sampel sejumlah 103 yang dipilih secara consecutive sampling didapatkan adanya koloni jamur pada otitis eksterna superfisialis basah sebesar 57,8% dengan jenis jamur Aspergillus niger 17,9%, Candida albicans 13,3% dan Aspergillus fumigatus 8,9%. Koloni jamur pada OMSA perforasi sebesar 44,4% dengan jenis jamur Aspergillus fumigatus 11,1%, Candida albicans 11,1% dan Aspergillus niger 5,6%. Koloni jamur pada OMSK benigna aktif sebesar 25% dengan jenis jamur Apergillus fumigatus 17,5%, Aspergillus niger 2,5% dan Candida albicans 2,5%.[MEDICINA 2009;40:21-6].

Epobis is a Nonerythropoietic and Neuroprotective Agonist of the Erythropoietin Receptor with Anti-Inflammatory and Memory Enhancing Effects

DEFF Research Database (Denmark)

Dmytriyeva, Oksana; Pankratova, Stanislava; Korshunova, Irina

2016-01-01

, but systemic administration of Epobis in rats delays the clinical signs of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, and the peptide has long-term, but not short-term, effects on working memory, detected as an improved social memory 3 days after administration....... These data reveal Epobis to be a nonerythropoietic and neuroprotective EPO receptor agonist with anti-inflammatory and memory enhancing properties....

Identification of Aminopeptidase N as a Cellular Receptor for Human Coronavirus-229E

Science.gov (United States)

1992-05-12

hemagglutinating encephalomyelitis virus (HEV), canine coronavirus (CCV), cat FIPV and feline enteric corona virus (FECV), human CVLPs, mouse...While the cat , dog and pig serve as natural hosts for the other coronavirus group 1 viruses , feline infectious peritonitis virus (FIPV), canine...3 2 . Virus Receptors ••••••••.••••••.....•................ 20 3. Viruses Which Cause Common Colds