Assuntos
Traumatismos da Perna/complicações , Anormalidades Linfáticas/patologia , Anormalidades Linfáticas/cirurgia , Pele/patologia , Biópsia por Agulha , Criança , Progressão da Doença , Seguimentos , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética/métodos , Masculino , México , Resultado do TratamentoRESUMO
Coma blisters (CBs) are self-limited lesions that occur in regions of pressure during unconscious states classically induced by barbiturates. We report a case of CBs sans coma that were histologically confirmed in a 41-year-old woman who developed multiple tense abdominal bullae with surrounding erythema following a transatlantic flight. Interestingly, the patient was fully conscious and denied medication use or history of medical conditions. A clinical diagnosis of CBs was confirmed by histopathologic findings of eccrine gland necrosis, a hallmark of these bulIous lesions.
Assuntos
Vesícula/diagnóstico , Glândulas Écrinas/patologia , Eritema/patologia , Abdome , Adulto , Aeronaves , Vesícula/etiologia , Vesícula/patologia , Feminino , Seguimentos , Humanos , Necrose , ViagemRESUMO
Opioids have immunomodulatory functions and may alter susceptibility to immune disorders. Behavioral studies also indicate that chemokines, molecules expressed by immune cells, block opioid-induced analgesia in the periaqueductal grey (PAG). Bi-directional heterologous desensitization of opioid and chemokine receptors has been described in cell systems. We report the anatomical and functional interactions of chemokine receptors with the mu-opioid receptor (MOR) in the rat brain. The chemokine receptors, CXCR4 and CX3CR1, as well as their chemokine substrates, CXCL12 and CX3CL1, are widely expressed in the central nervous system (CNS). Immunohistochemical techniques were utilized to investigate MOR-CXCR4 and MOR-CX3CR1 receptor colocalization in multiple brain areas. Our results demonstrate co-expression of these receptors on individual neurons in several regions including cingulate cortex, hippocampus, and PAG, suggesting functional receptor interactions. Whole-cell patch-clamp recordings of PAG neurons in a rat brain slice preparation were used to examine morphine or chemokine (CXCL12, CX3CL1) effects alone, or in combination on neuronal membrane properties. Morphine (10 µM) hyperpolarized and reduced input resistance of PAG neurons. CXCL12 and CX3CL1 (10 nM) had no impact on either parameter. In the presence of CXCL12, morphine's electrophysiological effects were blocked in all neurons examined, whereas with CX3CL1, morphine's effects were blocked in 57% of neurons studied. The data provide electrophysiological evidence for MOR-CXCR4 and MOR-CX3CR1 heterologous desensitization in the PAG at the single-cell level. These interactions may contribute to the limited utility of opioid analgesics for inflammatory pain treatment and supports chemokines as neuromodulators.
Assuntos
Quimiocinas/fisiologia , Substância Cinzenta Periaquedutal/anatomia & histologia , Substância Cinzenta Periaquedutal/fisiologia , Receptores Opioides mu/fisiologia , Animais , Anticorpos/química , Anticorpos/imunologia , Química Encefálica/fisiologia , Receptor 1 de Quimiocina CX3C , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Fenômenos Eletrofisiológicos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imuno-Histoquímica , Masculino , Potenciais da Membrana/fisiologia , Microscopia de Fluorescência , Neurônios/fisiologia , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Receptores CXCR4/metabolismo , Receptores de Quimiocinas/metabolismoRESUMO
The serotonin (5-hydroxytryptamine; 5-HT) system has a well-characterized role in depression. Recent reports describe comorbidities of mood-immune disorders, suggesting an immunological component may contribute to the pathogenesis of depression as well. Chemokines, immune proteins which mediate leukocyte trafficking, and their receptors are widely distributed in the brain, mediate neuronal patterning, and modulate various neuropathologies. The purpose of this study was to investigate the neuroanatomical relationship and functional impact of the chemokine stromal cell-derived factor-1alpha/CXCL12 and its receptor, CXCR4, on the serotonin dorsal raphe nucleus (DRN) system in the rat using anatomical and electrophysiological techniques. Immunohistochemical analysis indicates that over 70% of 5-HT neurons colocalize with CXCL12 and CXCR4. At a subcellular level, CXCL12 localizes throughout the cytoplasm whereas CXCR4 concentrates to the outer membrane and processes of 5-HT neurons. CXCL12 and CXCR4 also colocalize on individual DRN cells. Furthermore, electrophysiological studies demonstrate CXCL12 depolarization of 5-HT neurons indirectly via glutamate synaptic inputs. CXCL12 also enhances the frequency of spontaneous inhibitory and excitatory postsynaptic currents (sIPSC and sEPSC). CXCL12 concentration-dependently increases evoked IPSC amplitude and decreases evoked IPSC paired-pulse ratio selectively in 5-HT neurons, effects blocked by the CXCR4 antagonist AMD3100. These data indicate presynaptic enhancement of GABA and glutamate release at 5-HT DRN neurons by CXCL12. Immunohistochemical analysis further shows CXCR4 localization to DRN GABA neurons, providing an anatomical basis for CXCL12 effects on GABA release. Thus, CXCL12 indirectly modulates 5-HT neurotransmission via GABA and glutamate synaptic afferents. Future therapies targeting CXCL12 and other chemokines may treat serotonin related mood disorders, particularly depression experienced by immune-compromised individuals.