Leigh's syndrome
Female; Humans; Disease Progression; Autopsy; Severity of Illness Index; Risk Assessment; Biopsy; Magnetic Resonance Imaging; Fatal Outcome; infant; Q3 Literature Search; Needle; Basal Ganglia/pathology; Immunohistochemistry; Leigh Disease/diagnosis/physiopathology/therapy
A 15-month-old female child presented with sudden onset cough and hyperventilation along with evidence of metabolic acidosis. She had past history of recurrent vomiting, episodes of abnormal posturing, difficulty in deglutition and regression of milestones since 12 months of age. CT scan of the brain revealed hypodense lesions in bilateral basal ganglia and on MRI there were T2 hyperintensities in bilateral lentiform nuclei, caudate nuclei, thalamus, red nuclei and dentate nuclei. Biochemical examination revealed persistently elevated serum lactate levels with high lactate/pyruvate ratio. Resuscitative measures were of no avail and the child succumbed to the illness on the second day of admission. Neuropathological examination at autopsy demonstrated marked spongiosis, focal necrosis, endothelial proliferation, reactive astrogliosis and extensive demyelination involving bilateral basal ganglia, midbrain and spinal cord which were typical of Leigh's sub acute necrotizing encephalomyelopathy.
2004
Mannan AA; Sharma MC; Shrivastava P; Ralte AM; Gupta V; Behari M; Sarkar C
Indian Journal Of Pediatrics
2004
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Journal Article
<a href="http://doi.org/10.1007/bf02828121" target="_blank" rel="noreferrer">10.1007/bf02828121</a>
Immunohistochemical localization of endomorphin-1 and endomorphin-2 in immune cells and spinal cord in a model of inflammatory pain
Male; Animals; Rats; Biomarkers of Pain; Immunohistochemistry; Freund's Adjuvant; Hindlimb; Wistar; Lymph Nodes/cytology; Lymphocytes/chemistry; Macrophages/chemistry; Monocytes/chemistry; Oligopeptides/analysis; Pain/chemically induced/immunology; Posterior Horn Cells/chemistry; Skin/chemistry/immunology/innervation
Recently, two novel highly selective mu-opioid receptor (MOR) agonists, endomorphin-1 and endomorphin-2, have been isolated from bovine as well as human brains and were proposed to be the endogenous ligand for MOR. Later, endomorphin-1 and endomorphin-2 have been detected in the immune system of rats and humans using radioimmunoassay in combination with reverse-high-phase-liquid chromatography. In the present study, we analyzed the expression of endomorphin-1, endomorphin-2 and MOR by immunohistochemistry in a model of Freund's complete adjuvant (FCA)-induced painful inflammation. While MOR was upregulated on peripheral and central nerve terminals, inflammation did not alter endomorphin-2 expression in nerve fibers either in the dorsal horn of the spinal cord or in subcutaneous tissue. Endomorphin-1 and endomorphin-2 were expressed in immune cells (macrophage/monocytes) in the medullary region of the popliteal lymph nodes. The proportion of immunocytes (macrophage/monocytes, lymphocytes) containing endomorphin-1 and endomorphin-2 was increased in inflamed lymph nodes and subcutaneous paw tissue of animals with local inflammatory pain. Taken together, the upregulation of MOR and of its endogenous ligands endomorphin-1 and endomorphin-2 in immunocytes suggests an involvement of these opioid peptides in the peripheral control of inflammatory pain.
2002
Mousa SA; Machelska H; Schafer M; Stein C
Journal Of Neuroimmunology
2002
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/s0165-5728(02)00049-8" target="_blank" rel="noreferrer">10.1016/s0165-5728(02)00049-8</a>
Modulation of peripheral endogenous opioid analgesia by central afferent blockade
Male; Analgesics; Animals; Rats; Injections; Immunohistochemistry; Spinal; Enkephalin; beta-Endorphin/metabolism; Wistar; Pain Threshold/drug effects; Neurons; Afferent/drug effects; Central Nervous System/drug effects; Endorphins/metabolism/physiology; Flow Cytometry; Foot/pathology; Inflammation/pathology; Methionine/metabolism; Morphine/administration & dosage/pharmacology; Opioid/administration & dosage/pharmacology; Peripheral Nerves/drug effects; Psychomotor Performance/drug effects
BACKGROUND: Peripheral tissue injury causes a migration of opioid peptide-containing immune cells to the inflamed site. The subsequent release and action of these peptides on opioid receptors localized on peripheral sensory nerve terminals causes endogenous analgesia. The spinal application of opioid drugs blocks the transmission of nociceptive information from peripheral injury. This study investigates the influence of exogenous spinal opioid analgesia on peripheral endogenous opioid analgesia. METHODS: Six and forty-eight hours after initiation of continuous intrathecal morphine infusion and administration of Freund's complete adjuvant into the hind paw of rats, antinociceptive and antiinflammatory effects were measured by paw pressure threshold, paw volume, and paw temperature, respectively. Inflammation and quantity of opioid-containing cells were evaluated by immunocytochemistry and flow cytometry. Cold water swim stress-induced endogenous analgesia was examined 24 h after discontinuation of intrathecal morphine administration. RESULTS: Intrathecal morphine (10 micro g/h) resulted in a significant and stable increase of paw pressure threshold ( P 0.05). At 48 but not at 6 h after Freund's complete adjuvant, the number of beta-endorphin-containing cells and cold water swim-induced antinociception were significantly reduced in intrathecal morphine-treated rats compared with those treated with intrathecal vehicle ( P< 0.05). CONCLUSIONS: These findings suggest an interplay of central and peripheral mechanisms of pain control. An effective central inhibition of pain apparently signals a reduced need for recruitment of opioid-containing immune cells to injured sites.
2003
Schmitt TK; Mousa SA; Brack A; Schmidt DK; Rittner HL; Welte M; Schafer M; Stein C
Anesthesiology
2003
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1097/00000542-200301000-00030" target="_blank" rel="noreferrer">10.1097/00000542-200301000-00030</a>
Modern approach to children with osteogenesis imperfecta
Child; Female; Humans; Male; Prognosis; Treatment Outcome; Severity of Illness Index; Risk Assessment; Biopsy; Combined Modality Therapy; Preschool; infant; Needle; Clodronate; Diphosphonates/therapeutic use; Immunohistochemistry; Bone Density/physiology; Physical Therapy Modalities; Orthopedic Fixation Devices; Orthopedic Procedures/instrumentation/methods; Osteogenesis Imperfecta/pathology/therapy
Osteogenesis Imperfecta (OI) is characterized by bone fragility. At least seven discrete types have been described ranging from mild disease to a lethal form. In a large number of cases, mutations in one of the two genes encoding type I collagen have been found. In forms recently described (types V, VI, VII), such mutations have been excluded. In two other forms, (Bruck, and osteoporosis - pseudoglioma syndromes) defects in other proteins have been characterized. In OI, bone fragility stems from: decreased bone mass, disturbed organization of bone tissue, and altered bone geometry (size and shape). Histologic studies have shown that increased bone turnover is the rule in OI bone. This justifies using bisphosphonates in order to reduce osteoclast mediated bone resorption. Initial results are encouraging. Cyclical intravenous pamidronate administration reduces bone pain and fracture incidence, and increases bone density and level of ambulation, with minimal side effects. Effects on bone include increase in size of vertebral bodies and thickening of cortical bone. These results allow for more efficacious corrective surgery using intramedullary rodding of the long bones and paravertegral instrumentation. Specific occupational and physiotherapy programs are integral parts of the treatment protocol. This multidisciplinary approach will prevail until strategies aiming at the correction of the basic defect(s) will have come to fruition.
2003
Zeitlin L; Fassier F; Glorieux FH
Journal Of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society Of North America
2003
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1097/01.bpb.0000049567.52224.fa" target="_blank" rel="noreferrer">10.1097/01.bpb.0000049567.52224.fa</a>
Subcellular pathways of beta-endorphin synthesis, processing, and release from immunocytes in inflammatory pain
Male; Animals; Rats; Biomarkers of Pain; Microscopy; Immunohistochemistry; Wistar; beta-Endorphin/biosynthesis; Carboxypeptidase H/metabolism; Extremities; Immunoelectron; Inflammation/immunology/metabolism; Leukocytes/drug effects/metabolism/ultrastructure; Norepinephrine/pharmacology; Pain/immunology/metabolism; Pro-Opiomelanocortin/metabolism; Proprotein Convertase 1/metabolism; Proprotein Convertase 2/metabolism; Secretory Vesicles/metabolism/ultrastructure; Sympathomimetics/pharmacology
The opioid peptide beta-endorphin (END) as well as mRNA for its precursor proopiomelanocortin (POMC) are found not only in the pituitary gland, but also within various types of immune cells infiltrating inflamed sc tissue. During stressful stimuli END is released and interacts with peripheral opioid receptors to inhibit pain. However, the subcellular pathways of POMC processing and END release have not yet been delineated in inflammatory cells. The aim of the present study was to examine the presence of POMC, carboxypeptidase E, the prohormone convertases 1 (PC1), and 2 (PC2), PC2-binding protein 7B2, and the release of END from inflammatory cells in rats. Using immunohistochemistry we detected END and POMC alone or colocalized with PC1, PC2, carboxypeptidase E, and 7B2 in macrophages/monocytes, granulocytes, and lymphocytes of the blood and within inflamed sc paw tissue. Immunoelectron microscopy revealed that END is localized within secretory granules packed in membranous structures in macrophages, monocytes, granulocytes, and lymphocytes. Finally, END is released by noradrenaline from immune cells in vitro. Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules.
2004
Mousa SA; Shakibaei M; Sitte N; Schafer M; Stein C
Endocrinology
2004
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Journal Article
<a href="http://doi.org/10.1210/en.2003-1287" target="_blank" rel="noreferrer">10.1210/en.2003-1287</a>
Local analgesic effect of endogenous opioid peptides
Humans; Pain; Adult; Aged; Middle Aged; Double-Blind Method; Biomarkers of Pain; Injections; Intravenous; Receptors; Opioid/drug effects; Immunohistochemistry; Enkephalin; Arthroscopy; beta-Endorphin/analysis/physiology; Dynorphins/analysis/physiology; Endorphins/analysis/physiology; Intra-Articular; Knee Joint/surgery; Methionine/analysis/physiology; Naloxone/administration & dosage/pharmacology; Postoperative/etiology; Synovial Membrane/chemistry; Synovitis/metabolism
Opioids produce analgesia by interacting with local opioid receptors in peripheral inflamed tissue. This study investigated whether endogenous ligands of these receptors are present in synovia and whether such opioid peptides can inhibit pain by activation of intra-articular opioid receptors. Samples of synovium from 8 patients undergoing arthroscopic knee surgery were examined by immunohistochemistry for the presence of beta-endorphin, met-enkephalin, and dynorphin. All tissue samples showed synovitis. Inflammatory cells stained strongly for beta-endorphin and met-enkephalin but not for dynorphin. To find out whether blockade of intra-articular opioid receptors affected pain, we randomly assigned 22 patients undergoing arthroscopic knee surgery to receive naloxone (0.04 mg) intra-articularly (n = 10) or intravenously (n = 12); each patient received a placebo injection into the other site. Postoperative pain was assessed by visual analogue scale, a numerical rating scale, the McGill pain questionnaire, and supplementary analgesic consumption during the next 24 h. All pain scores were higher in the intra-articular naloxone group than in the intravenous naloxone group. The differences were significant (p < 0.05) during the first 4 h. Supplementary analgesic consumption was significantly higher in the intra-articular group (52.5 [14.0] vs 15.6 [8.0] mg diclofenac, p < 0.05). Opioid peptides are present in inflamed synovial tissue and can inhibit pain after knee surgery through an action specific to intra-articular opioid receptors. These findings expand the gate control theory of pain and suggest new approaches such as the development of peripherally acting opioid analgesics without central side-effects.
1993
Stein C; Hassan AH; Lehrberger K; Giefing J; Yassouridis A
Lancet
1993
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/0140-6736(93)91471-w" target="_blank" rel="noreferrer">10.1016/0140-6736(93)91471-w</a>
Pain killers of the immune system
Animals; Rats; Biomarkers of Pain; RNA; Immunohistochemistry; Radioimmunoassay; beta-Endorphin/biosynthesis/physiology; Inflammation/pathology/physiopathology; Messenger/genetics; Pain/pathology/physiopathology; Pro-Opiomelanocortin/genetics; T-Lymphocytes/metabolism
1997
Sharp B; Yaksh T
Nature Medicine
1997
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1038/nm0897-831" target="_blank" rel="noreferrer">10.1038/nm0897-831</a>
Opioid peptide-expressing leukocytes: identification, recruitment, and simultaneously increasing inhibition of inflammatory pain
Male; Pain Measurement; Analgesia; Animals; Rats; beta-Endorphin/blood; Biomarkers of Pain; Pain/physiopathology; Immunohistochemistry; Radioimmunoassay; Biomarkers Reference List; Wistar; Antibodies; Antigens; CD45/isolation & purification; Fluorescent Dyes; Hematopoietic Stem Cells/immunology; Immunomagnetic Separation; Inflammation/chemically induced/metabolism/pathology; Leukocytes/metabolism; Lymphocytes/immunology; Monoclonal/pharmacology; Opioid Peptides/biosynthesis
BACKGROUND: Inflammatory pain can be effectively controlled by an interaction of opioid receptors on peripheral sensory nerve terminals with opioid peptides released from immune cells upon stressful stimulation. To define the source of opioid peptide production, we sought to identify and quantify populations of opioid-containing cells during the course of Freund's complete adjuvant-induced hind paw inflammation in the rat. In parallel, we examined the development of stress-induced local analgesia in the paw. METHODS: At 2, 6, and 96 h after Freund's complete adjuvant inoculation, cells were characterized by flow cytometry using a monoclonal pan-opioid antibody (3E7) and antibodies against cell surface antigens and by immunohistochemistry using a polyclonal antibody to beta-endorphin. After magnetic cell sorting, the beta-endorphin content was quantified by radioimmunoassay. Pain responses before and after cold water swim stress were evaluated by paw pressure thresholds. RESULTS: In early inflammation, 66% of opioid peptide-producing (3E7+) leukocytes were HIS48+ granulocytes. In contrast, at later stages (96 h), the majority of 3E7+ immune cells were ED1+ monocytes or macrophages (73%). During the 4 days after Freund's complete adjuvant inoculation, the number of 3E7+ cells increased 5.6-fold (P < 0.001, Kruskal-Wallis test) and the beta-endorphin content in the paw multiplied 3.9-fold (P < 0.05, Kruskal-Wallis test). In parallel, cold water swim stress-induced analgesia increased by 160% (P < 0.01, analysis of variance). CONCLUSIONS: The degree of endogenous pain inhibition is proportional to the number of opioid peptide-producing cells, and distinct leukocyte lineages contribute to this function at different stages of inflammation. These mechanisms may be important for understanding pain in immunosuppressed states such as cancer, diabetes, or AIDS and for the design of novel therapeutic strategies in inflammatory diseases.
2001
Rittner HL; Brack A; Machelska H; Mousa SA; Bauer M; Schafer M; Stein C
Anesthesiology
2001
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1097/00000542-200108000-00036" target="_blank" rel="noreferrer">10.1097/00000542-200108000-00036</a>