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591.
Opioid peptide-expressing leukocytes: identification, recruitment, and simultaneously increasing inhibition of inflammatory pain 总被引:12,自引:0,他引:12
Rittner HL Brack A Machelska H Mousa SA Bauer M Schäfer M Stein C 《Anesthesiology》2001,95(2):500-508
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. 相似文献
592.
Frances C Wright Calvin HL Law Linda D Last Neil Klar David P Ryan Andrew J Smith 《BMC health services research》2006,6(1):4-8
Background
A significant gap has been documented between best practice and the actual practice of surgery. Our group identified that colorectal cancer staging in Ontario was suboptimal and subsequently developed a knowledge translation strategy using the principles of social marketing and the influence of expert and local opinion leaders for colorectal cancer. 相似文献593.
New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome 总被引:6,自引:2,他引:6
Engel AG; Ohno K; Milone M; Wang HL; Nakano S; Bouzat C; Pruitt JN nd; Hutchinson DO; Brengman JM; Bren N; Sieb JP; Sine SM 《Human molecular genetics》1996,5(9):1217-1227
Mutations in genes encoding the epsilon, delta, beta and alpha subunits of
the end plate acetylcholine (ACh) receptor (AChR) are described and
functionally characterized in three slow-channel congenital myasthenic
syndrome patients. All three had prolonged end plate currents and AChR
channel opening episodes and an end plate myopathy with loss of AChR from
degenerating junctional folds. Genetic analysis revealed heterozygous
mutations: epsilon L269F and delta Q267E in Patient 1, beta V266M in
Patient 2, and alpha N217K in Patient 3 that were not detected in 100
normal controls. Patients 1 and 2 have no similarly affected relatives; in
Patient 3, the mutation cosegregates with the disease in three generations.
epsilon L269F, delta Q267E and beta V266M occur in the second and alpha
N217K in the first transmembrane domain of AChR subunits; all have been
postulated to contribute to the lining of the upper half of the channel
lumen and all but delta Q267E are positioned toward the channel lumen, and
introduce an enlarged side chain. Expression studies in HEK cells indicate
that all of the mutations express normal amounts of AChR. epsilon L269F,
beta V266M, and alpha N217K slow the rate of channel closure in the
presence of ACh and increase apparent affinity for ACh; epsilon L269F and
alpha N217K enhance desensitization, and epsilon L269F and beta V266M cause
pathologic channel openings in the absence of ACh, rendering the channel
leaky, delta Q267E has none of these effects and is therefore a rare
polymorphism or a benign mutation. The end plate myopathy stems from
cationic overloading of the postsynaptic region. The safety margin of
neuromuscular transmission is compromised by AChR loss from the junctional
folds and by a depolarization block owing to temporal summation of
prolonged end plate potentials at physiologic rates of stimulation.
相似文献
594.
John V. Fahy MB ChB MRCPI Jane Liu MS Hofer Wong BS Homer A. Boushey MD Dr. Fahy is supported by NRSA grant No. HL is the recipient of a traveling studentship in medicine from the National University of Ireland. 《The Journal of allergy and clinical immunology》1994,93(6)
To determine whether analysis of the constituents of induced sputum permits detection of changes provoked by aerosolized antigen challenge, we performed sputum induction (20-minute inhalation of aerosolized 3% saline solution) before and after aerosolized allergen challenge in eight subjects with asthma. Total cell counts and cell differentials of nonsquamous cells in induced sputum samples were determined after the samples were homogenized in dithiothreitol. Centrifugation of the entire homogenized sputum sample yielded supernatant that could be analyzed for biochemical constituents. We found that the median percentage of eosinophils and neutrophils in induced sputum samples was significantly higher 4 hours after allergen challenge than at baseline (12% vs 0.5%, p < 0.05; 30.5% vs 7.5%, p < 0.05) and remained high 24 hours after challenge. Median levels of eosinophil cationic protein and histamine in induced sputum supernatants were significantly higher 4 hours after challenge than at baseline (151.3 vs 39.8 ng/ml, p < 0.05; 19.4 vs 8.8 μg, p < 0.05) and remained significantly higher 24 hours after challenge. Tryptase was detectable in sputum from seven of the subjects, and in these subjects, we found a trend toward an increase in median tryptase levels 4 hours after allergen challenge (4.4 vs 2.2 U/L, p = 0.09). We conclude that analysis of induced sputum after aerosolized allergen challenge reveals changes in inflammatory cells and markers similar to those reported in bronchoalveolar lavage fluid and that sputum induction is a useful noninvasive method for studying allergic airway inflammation in asthma. (J ALLERGY CLIN IMMUNOL 1994;93:1031-9.) 相似文献
595.
Leukocytes in the regulation of pain and analgesia 总被引:3,自引:0,他引:3
When tissue is destroyed or invaded by leukocytes in inflammation, numerous mediators are delivered by the circulation and/or liberated from resident and immigrated cells at the site. Proalgesic mediators include proinflammatory cytokines, chemokines, protons, nerve growth factor, and prostaglandins, which are produced by invading leukocytes or by resident cells. Less well known is that analgesic mediators, which counteract pain, are also produced in inflamed tissues. These include anti-inflammatory cytokines and opioid peptides. Interactions between leukocyte-derived opioid peptides and opioid receptors can lead to potent, clinically relevant inhibition of pain (analgesia). Opioid receptors are present on peripheral endings of sensory neurons. Opioid peptides are synthesized in circulating leukocytes, which migrate to inflamed tissues directed by chemokines and adhesion molecules. Under stressful conditions or in response to releasing agents (e.g., corticotropin-releasing factor, cytokines, noradrenaline), leukocytes can secrete opioids. They activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of excitatory neuropeptides. This review presents discoveries that led to the concepts of pain generation by mediators secreted from leukocytes and of analgesia by immune-derived opioids. 相似文献
596.
G. E. ANDERSEN J. HERTEL C. KÜHL L. MØLSTED-PEDERSEN 《Acta paediatrica (Oslo, Norway : 1992)》1982,71(1):27-32
ABSTRACT. Changes in plasma glycerol (FG), free fatty acids (FFA) and triglyceride (TG) were studied in 24 normo- and 8 hypoglycemic infants of diabetic mothers (IDM). In both groups a normal rise in plasma FG 2 hours after birth was found indicating unimpaired lipolysis. The rise in plasma FFA, however, was only about 50% of normal in normoglycemic IDM and about 25% of normal in hypoglycemic IDM. The rise in plasma TG was normal in normoglycemic and about 70% of normal in hypoglycemic IDM. The 2 hour rise in plasma FFA correlated with the 2 hour concentration of insulin and glucose, whereas the rise in plasma FG and TG did not. Maternal plasma FFA correlated with fetal FFA retention (unbilical vein minus artery (V-A) FFA concentrations). No correlations were found between maternal plasma FFA values and birth-weights nor between umbilical V-A FFA concentrations and birth-weights. 相似文献
597.
J. HERTEL G. E. ANDERSEN N. J. BRANDT E. CHRISTENSEN C. KÜHL L. MØLSTED-PEDERSEN 《Acta paediatrica (Oslo, Norway : 1992)》1982,71(1):33-37
ABSTRACT. Plasma amino acid concentrations (AAC) were studied in 31 diabetic mothers (10 of White class A, 10 of B-C and 11 of D-F) and their 32 infants during the first 24 hours after birth. Only minor differences between the 3 groups were found at birth and 2 hours, and none at 12 and 24 hours after birth. The individual AAC in umbilical vein plasma did not correlate with birthweight. All AAC except aspartic acid, aspargine, cystine and glutamic acid were higher in umbilical venous plasma than in maternal plasma. Umbilical venousarterial differences of amino acids did not correlate with maternal or umbilical vein insulin concentrations except for threonine and valine. In general essential amino acids decreased after birth. In 8 infants with hypoglycemia and hyperinsulinism at 2 hours of age several plasma amino acids were lower than in the normoglycemic infants. 相似文献
598.
599.
M Van de Bor P Mooy D van Zoeren R Berger HH van Gelderen HL Teijema 《Archives of disease in childhood》1984,59(12):1183-1185
We describe a girl with neonatal hyperammonaemia due to carbamyl phosphate synthetase I deficiency. Treatment consisted of protein restriction from the second day of life. Sodium benzoate was given for three weeks after birth and again from 7 months of age together with sodium phenylacetate to improve protein tolerance. Growth and development are normal at 15 months of age. 相似文献
600.
A number of observations indicate that exposure to IL-4 is essential for
the priming of Th2-type effector T cells and that exposure to IL-12 is
essential for the priming of Th1-type effector T cells. However, the
initial source of IL-4 in the early immune response has not been clearly
identified. Dendritic cells (DC) are the most potent antigen- presenting
cells (APC) in priming naive T cells. In this report, we show that DC
exposed to IL-10 may play an important role in the priming of
IL-4-secreting cells in the early immune response. DC isolated from splenic
adherent cell cultures treated with rIL-10 (IL-10-DC) primed naive
ovalbumin (OVA)-TCR transgenic T cells to secrete IL-4 upon re- stimulation
with OVA and splenic APC. By contrast, DC isolated from rIL- 12, rIL-4 or
control treated cultures induced almost exclusively Th1- type effector T
cells. IL-4 secretion was detected in the primary cultures of IL-10-DC plus
naive CD4+ T cells and the priming of IL-4- secreting T cells by IL-10-DC
was dependent on endogenous IL-4 production in the priming culture since
anti-IL-4 neutralizing antibody completely abrogated the priming of
IL-4-secreting cells. Anti-B7-2 but not anti-B7-1 inhibited the ability of
IL-10-DC to prime T cells to secrete IL-4. Furthermore, the ability of
IL-10 DC to prime for IL-4- secreting T cells was closely related to the
down-regulation of CD40 ligand-mediated IL-12 p70 production by DC in the
primary cultures and was markedly reduced by adding exogenous IL-12 to the
priming cultures. Thus, our findings indicate that early immunologic events
that drive Th2 differentiation involve the effects of IL-10 on DC.
相似文献