RESUMO
PURPOSE: Endometriosis is a common chronic gynecological disease greatly affecting women health. Prior studies have implicated that dysferlin (DYSF) aberration might be involved in the pathogenesis of ovarian endometriosis. In the present study, we explore the potential presence of DYSF mutations in a total of 152 Han Chinese samples with ovarian endometriosis. METHODS: We analyze the potential presence of DYSF mutations by direct DNA sequencing. RESULTS: A total of seven rare variants/mutations in the DYSF gene in 10 out of 152 samples (6.6%) were identified, including 5 rare variants and 2 novel mutations. For the 5 rare variants, p.R334W and p.G941S existed in 2 samples, p.R865W, p.R1173H and p.G1531S existed in single sample, respectively; for the two novel mutations, p.W352* and p.I1642F, they were identified in three patients. These rare variants/mutations were absent or existed at extremely low frequency either in our 1006 local control women without endometriosis, or in the China Metabolic Analytics Project (ChinaMAP) and Genome Aggregation Database (gnomAD) databases. Evolutionary conservation analysis results suggested that all of these rare variants/mutations were evolutionarily conserved among 11 vertebrate species from Human to Fox. Furthermore, in silico analysis results suggested these rare variants/mutations were disease-causing. Nevertheless, we find no significant association between DYSF rare variants/mutations and the clinical features in our patients. To our knowledge, this is the first report revealing frequent DYSF mutations in ovarian endometriosis. CONCLUSION: We identified a high frequency of DYSF rare variants/mutations in ovarian endometriosis for the first time. This study suggests a new correlation between DYSF rare variants/mutations and ovarian endometriosis, implicating DYSF rare variants/mutations might be positively involved in the pathogenesis of ovarian endometriosis.
Assuntos
Disferlina/genética , Endometriose/genética , Doenças Ovarianas/genética , Adulto , Povo Asiático/genética , China/epidemiologia , Endometriose/etnologia , Feminino , Humanos , Mutação , Doenças Ovarianas/etnologiaRESUMO
Previous studies have proven that paired immunoglobulin-like receptor B (PirB) plays a crucial suppressant role in neurite outgrowth and neuronal plasticity after central nervous system injury. However, the role of PirB in neuronal survival after cerebral ischemic injury and its mechanisms remains unclear. In the present study, the role of PirB is investigated in the survival and apoptosis of cerebral cortical neurons in cultured primary after oxygen and glucose deprivation (OGD)-induced injury. The results have shown that rebarbative PirB exacerbates early neuron apoptosis and survival. PirB gene silencing remarkably decreases early apoptosis and promotes neuronal survival after OGD. The expression of bcl-2 markedly increased and the expression of bax significantly decreased in PirB RNAi-treated neurons, as compared with the control- and control RNAi-treated ones. Further, phosphorylated TrkB and mTOR levels are significantly downregulated in the damaged neurons. However, the PirB silencing markedly upregulates phosphorylated TrkB and mTOR levels in the neurons after the OGD. Taken together, the overexpression of PirB inhibits the neuronal survival through increased neuron apoptosis. Importantly, the inhibition of the phosphorylation of TrkB and mTOR may be one of its mechanisms.
Assuntos
Apoptose , Sobrevivência Celular/efeitos dos fármacos , Córtex Cerebral/metabolismo , Neurônios/metabolismo , Receptores Imunológicos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Glucose/metabolismo , Glicoproteínas de Membrana/metabolismo , Fármacos Neuroprotetores/farmacologia , Oxigênio/metabolismo , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Receptores Imunológicos/genética , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Our previous study indicated that coadministration of tramadol and minocycline exerted synergistic effects on spinal nerve ligation (SNL)-induced neuropathic mechanical allodynia. However, the underlying mechanisms are still unclear. Recent reports indicated that spinal proinflammatory factor interleukin-1ß (IL-1ß) contributed to the development of neuropathic pain and the positive feedback communication between neuron and glia. Therefore, the present research is to confirm whether spinal IL-1ß-related pathway response contributes to the synergistic effects of tramadol and minocycline on SNL-induced neuropathic pain. Real-time RT-PCR demonstrated IL-1ß up-expression in the ipsilateral spinal dorsal horn 3 days after lesion, which could be significantly decreased by tramadol and minocycline coadministration. Immunofluorescence and Western blot indicated that SNL-induced microglial phosphorylated p38 (p-p38) upregulation was also inhibited by tramadol and minocycline coapplication. Meanwhile, intrathecal administration of p38 inhibitor SB203580 markedly alleviated mechanical allodynia whilst reducing IL-1ß and Fos expression induced by SNL. Moreover, intrathecal neutralized antibody of IL-1ß could depress SNL-induced mechanical allodynia and Fos expression. These results suggest that depressing SNL-induced aberrant activation of the spinal dorsal horn IL-1ß-related pathway contributes to the underlying mechanism of the synergistic effects of tramadol and minocycline coadministration on SNL-induced neuropathic mechanical allodynia.
Assuntos
Analgésicos/administração & dosagem , Interleucina-1beta/metabolismo , Minociclina/administração & dosagem , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Nervos Espinhais/metabolismo , Tramadol/administração & dosagem , Animais , Anticorpos/farmacologia , Combinação de Medicamentos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Imidazóis/farmacologia , Interleucina-1beta/imunologia , Ligadura , Masculino , Microglia/metabolismo , Fosforilação , Células do Corno Posterior/metabolismo , Piridinas/farmacologia , Ratos Sprague-Dawley , Teste de Desempenho do Rota-Rod , Transdução de Sinais/efeitos dos fármacos , Nervos Espinhais/efeitos dos fármacos , Nervos Espinhais/cirurgia , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL)-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.
Assuntos
Analgésicos Opioides/uso terapêutico , Antibacterianos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Minociclina/uso terapêutico , Neuralgia/tratamento farmacológico , Traumatismos dos Nervos Periféricos/complicações , Tramadol/uso terapêutico , Analgésicos Opioides/administração & dosagem , Animais , Antibacterianos/administração & dosagem , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Minociclina/administração & dosagem , Neuralgia/etiologia , Neuralgia/metabolismo , Medição da Dor , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Teste de Desempenho do Rota-Rod , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Tramadol/administração & dosagemRESUMO
BACKGROUND: The objective of the present study was to explore the resuscitation effects of starch nanospheres solution on hemodynamics in rats with hemorrhagic shock. METHODS: A total of 20 Sprague-Dawley rats were randomly divided into 2 groups: resuscitation group 1 (infusion with Ringer's solution) and resuscitation group 2 (infusion with starch nanospheres solution) with 10 rats per group. The rats in resuscitation groups 1 and 2 were subjected to hemorrhagic shock, and resuscitation was performed with Ringer's solution and starch nanospheres solution. The changes in the hemodynamic values of the rats in both groups were observed and recorded. RESULTS: The hemodynamic values included the systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, heart rate, and respiratory rate. After resuscitation, the systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate in resuscitation group 2 had reverted back to the base values (P > 0.05). The systolic blood pressure, diastolic blood pressure, and mean arterial pressure were lower at all points in resuscitation group 1 than in resuscitation group 2 (P < 0.05). The respiratory rate was more rapid after resuscitation at 30 and 60 min in resuscitation group 1 than in resuscitation group 2 (P < 0.05). CONCLUSIONS: Starch nanospheres solution expands the circulating blood volume and improves the hemodynamics. It also increases the effective circulating blood volume and improves the shock symptoms of effective hypovolemia.
Assuntos
Hemodinâmica/efeitos dos fármacos , Ressuscitação , Choque Hemorrágico/fisiopatologia , Amido/farmacologia , Animais , Masculino , Nanosferas , Ratos , Ratos Sprague-Dawley , SoluçõesRESUMO
Objective: Microorganisms have been the main cause of refractory and high recurrence of diabetic foot ulcer (DFU). This study attempted to observe the skin bacterial colony in healthy skin, diabetic skin and DFU skin. Methods: Forty-eight diabetes patients were recruited at Panyu Central Hospital from March 2021 to March 2022 and divided into DFU group (T group, n = 22), diabetes without foot ulcer group (TW group, n = 26). Besides, a healthy control group (H group, n = 10) was recruited at the same time. The swab samples of foot skin in the same position in the three groups were collected. The microorganisms obtained from the skin were analyzed by 16S rRNA gene sequencing. The composition of the skin microorganisms was determined, and the species diversity of the skin microbiota was analyzed by α and ß diversity. The species differences in the skin microbiota and the relative abundance of different operational taxonomic units (OUTs) with the most significant abundance were analyzed by linear discriminant analysis effect size (LEfSe). Results: Significant changes were found in the composition of the skin microbiota in the T and TW groups relative to the H group. However, the species diversity of the skin microbiota was significantly reduced in the T and TW groups, with the lowest one in the T group. The composition of microbial diversity in the T group was significantly different from that of the TW and H groups. Among the skin bacterial colonies, the abundance of Staphylococcus, Enhydrobacter, and Corynebacterium_1 was obviously reduced, while that of Escherichia coli and Pseudomonas was significantly increased. Conclusion: Changes in the abundance of Staphylococcus, Enhydrobacter, Corynebacterium_1, Escherichia coli and Pseudomonas in the skin bacterial colonies can be the main causative factors for DFU. This study indicates that altering the microbiota composition of wounds may help the treatment of DFU.
RESUMO
Neuropathic pain (NP) is an intractable clinical problem without satisfactory treatments. However, certain natural products have been revealed as effective therapeutic agents for the management of pain states. In this study, we used the spinal nerve ligation (SNL) pain model to investigate the antinociceptive effect of triptolide (T10), a major active component of the traditional Chinese herb Tripterygium wilfordii Hook F. Intrathecal T10 inhibited the mechanical nociceptive response induced by SNL without interfering with motor performance. Additionally, the anti-nociceptive effect of T10 was associated with the inhibition of the activation of spinal astrocytes. Furthermore, intrathecal administration of T10 attenuated SNL-induced janus kinase (JAK) signal transducers and activators of transcription 3 (STAT3) signalling pathway activation and inhibited the upregulation of proinflammatory cytokines, such as interleukin-6, interleukin-1 beta, and tumour necrosis factor-α, in dorsal horn astrocytes. Moreover, NR2B-containing spinal N-methyl D-aspartate receptor (NMDAR) was subsequently inhibited. Above all, T10 can alleviate SNL-induced NP via inhibiting the neuroinflammation in the spinal dorsal horn. The anti-inflammation effect of T10 may be related with the suppression of spinal astrocytic JAK-STAT3 activation. Our results suggest that T10 may be a promising drug for the treatment of NP.
RESUMO
BACKGROUND: We have previously reported that inhibition of astrocytic activation contributes to the analgesic effects of intrathecal ketamine on spinal nerve ligation (SNL)-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK), a member of mitogen-activated protein kinase (MAPK) family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decrease lipopolysaccharide (LPS)-induced phosphorylated JNK (pJNK) expression and could thus exert its anti-inflammatory effect. We hypothesized that inhibition of astrocytic JNK activation might be involved in the suppressive effect of ketamine on SNL-induced spinal astrocytic activation. METHODS: Immunofluorescence histochemical staining was used to detect SNL-induced spinal pJNK expression and localization. The effects of ketamine on SNL-induced mechanical allodynia were confirmed by behavioral testing. Immunofluorescence histochemistry and Western blot were used to quantify the SNL-induced spinal pJNK expression after ketamine administration. RESULTS: The present study showed that SNL induced ipsilateral pJNK up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. Intrathecal ketamine relieved SNL-induced mechanical allodynia without interfering with motor performance. Additionally, intrathecal administration of ketamine attenuated SNL-induced spinal astrocytic JNK activation in a dose-dependent manner, but not JNK protein expression. CONCLUSIONS: The present results suggest that inhibition of JNK activation may be involved in the suppressive effects of ketamine on SNL-induced spinal astrocyte activation. Therefore, inhibition of spinal JNK activation may be involved in the analgesic effects of ketamine on SNL-induced neuropathic pain.
Assuntos
Analgésicos , Astrócitos/efeitos dos fármacos , Astrócitos/enzimologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Ketamina , Neuralgia/tratamento farmacológico , Medula Espinal/citologia , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Ativação Enzimática , Hiperalgesia , Injeções Espinhais , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Ketamina/farmacologia , Ketamina/uso terapêutico , Ligadura , Masculino , Atividade Motora/efeitos dos fármacos , Medição da Dor , Ratos , Ratos Sprague-Dawley , Nervos Espinhais/efeitos dos fármacos , Nervos Espinhais/fisiopatologia , Nervos Espinhais/cirurgiaRESUMO
Reports suggest that microglia play a key role in spinal nerve ligation (SNL)-induced neuropathic pain, and toll-like receptor 3 (TLR3) has a substantial role in the activation of spinal microglia and the development of tactile allodynia after nerve injury. In addition, ketamine application could suppress microglial activation in vitro, and ketamine could inhibit proinflammatory gene expression possibly by suppressing TLR-mediated signal transduction. Therefore, the present study was designed to disclose whether intrathecal ketamine could suppress SNL-induced spinal microglial activation and exert some antiallodynic effects on neuropathic pain by suppressing TLR3 activation. Behavioral results showed that intrathecal ketamine attenuated SNL-induced mechanical allodynia, as well as spinal microglial activation, in a dose-dependent manner. Furthermore, Western blot analysis displayed that ketamine application downregulated SNL-induced phosphorylated-p38 (p-p38) expression, which was specifically expressed in spinal microglia but not in astrocytes or neurons. Besides, ketamine could reverse TLR3 agonist (polyinosine-polycytidylic acid)-induced mechanical allodynia and spinal microglia activation. It was concluded that intrathecal ketamine depresses TLR3-induced spinal microglial p-p38 mitogen-activated protein kinase pathway activation after SNL, probably contributing to the antiallodynic effect of ketamine on SNL-induced neuropathic pain.
Assuntos
Analgésicos/farmacologia , Ketamina/farmacologia , Microglia/efeitos dos fármacos , Neuralgia/patologia , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/patologia , Receptor 3 Toll-Like/metabolismo , Análise de Variância , Animais , Antígeno CD11b/metabolismo , Contagem de Células/métodos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações Medicamentosas , Lateralidade Funcional , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Masculino , Microglia/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neuralgia/complicações , Medição da Dor/métodos , Poli I-C/farmacologia , Ratos , Ratos Sprague-Dawley , Sinaptofisina/metabolismoRESUMO
Spinal N-methyl d-aspartate receptor (NMDAR) plays a pivotal role in nerve injury-induced central sensitization. Recent studies suggest that NMDAR also contributes to neuron-astrocyte signaling. c-Jun N-terminal kinase (JNK) is persistently and specifically activated (indicated by phosphorylation) in spinal cord astrocytes after nerve injury and thus it is considered as a dependable indicator of pain-related astrocytic activation. NMDAR-mediated JNK activation in spinal dorsal horn might be an important form of neuron-astrocyte signaling in neuropathic pain. In the present study, we observed that intrathecal injection of MK-801, a noncompetitive NMDA receptor antagonist, or Ro25-6981 and ifenprodil, which are selective antagonists of NR2B-containing NMDAR each significantly reduced nerve injury-induced JNK activation. Double immunostaining showed that NR2B was highly expressed in neurons, indicating the effect of NMDAR antagonists on JNK activation was indirect. We further observed that intrathecal injection of NMDA (twice a day for 3 days) significantly increased spinal JNK phosphorylation. Besides, NMDAR-related JNK activation could be blocked by a neuronal nitric oxide synthase (nNOS) selective inhibitor (7-nitroindazole sodium salt) but not by a nNOS sensitive guanylyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one). Finally, real-time RT-PCR and immunostaining showed that nerve injury-induced interleukin-1beta expression was dependent on astrocytic JNK activation. Treatments targeting NMDAR-nNOS pathway also influenced interleukin-1beta expression, which further confirmed our hypothesis. Taken together, our results suggest that neuronal NMDAR-nNOS pathway could activate astrocytic JNK pathway. Excitatory neuronal transmission initiates astrocytic activation-induced neuroinflammation in this way, which contributes to nerve injury-induced neuropathic pain.
Assuntos
Astrócitos/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neuralgia/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Medula Espinal/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Guanilato Ciclase/antagonistas & inibidores , Hiperalgesia/metabolismo , Indazóis/farmacologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Medição da Dor , Fenóis/farmacologia , Fosforilação/efeitos dos fármacos , Fosforilação/fisiologia , Piperidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Medula Espinal/efeitos dos fármacosRESUMO
PURPOSE: This study compared the biomechanical behaviors of 4 implants in osteoporosis by 3-dimensional finite element analyses. MATERIALS AND METHODS: Finite element models (FEM) of posterior mandible segments with a cylindrical threaded implant, an apical tapered implant, a neck tapered implant (NTI), and an apical expandable implant were created. Bone segments with normal and osteoporotic biomechanical properties were used. Forces of 100 and 30 N were applied along the implant in axial and buccolingual (BL) directions, respectively. Maximum equivalent stresses in the jaw bone and maximum displacement in the implant-abutment complex were evaluated. RESULTS: In osteoporosis, compared with the cylindrical threaded implant, maximum equivalent stress in cortical bones with the apical tapered implant decreased by 10.1% and 6.57% under axial and BL loads, respectively. With the NTI, those values decreased by 10.72% and 7.87%. With the apical expandable implant, those values decreased by 11.3% and 9.60%. In cancellous bones, the maximum equivalent stress with the NTI decreased by 3.56% under a BL load. Maximum displacement in the implant-abutment complex decreased by 17.1% and 9.41% with an apical tapered implant under axial and BL loads, respectively. With the NTI, those decreased by 21.8% and 17.4%. Values in normal bone indicated better stress distributions and less displacement than those in osteoporotic bone. CONCLUSION: Stress distribution in the jaw bone and implant stability in osteoporotic bone were more sensitive to implant designs than those in normal bone. In osteoporotic bone, the expandable implant and the NTI showed better stress distribution, and tapered implants showed better stabilities.
Assuntos
Implantes Dentários , Planejamento de Prótese Dentária , Análise de Elementos Finitos , Imageamento Tridimensional/métodos , Doenças Mandibulares/fisiopatologia , Osteoporose/fisiopatologia , Fenômenos Biomecânicos , Densidade Óssea/fisiologia , Simulação por Computador , Dente Suporte , Prótese Dentária Fixada por Implante , Módulo de Elasticidade , Humanos , Mandíbula/fisiopatologia , Modelos Biológicos , Osseointegração/fisiologia , Estresse Mecânico , Propriedades de SuperfícieRESUMO
BACKGROUND AND OBJECTIVE: Isoflurane has been used as an inhaled anaesthetic for nearly 30 years. Isoflurane inhalation during anaesthesia also produces an anti-nociceptive effect. Whether this occurs at the spinal or supraspinal level remains unknown. With a novel type of liquid isoflurane, the present study examined the effects of intrathecal isoflurane on the nociceptive response and Fos expression in the rat spinal cord. METHODS: Thirty-six rats were randomly assigned to three groups as follows: group A (n = 6), intrathecal physiological saline 50 µl kg⻹; and group B and C (n = 6 each), intrathecal isoflurane at doses of 25 µl kg⻹ or 50 µl kg⻹, respectively. Noxious thermal (Hargreaves test), mechanical (von Frey test) and chemical (formalin 5%, 50 µl) stimuli were applied to a hind paw after intrathecal isoflurane injection to study its anti-nociceptive effect. In addition, the expression of Fos protein and c-fos mRNA in the spinal dorsal horns was detected by immunohistochemistry and real-time reverse transcriptase PCR, respectively. RESULTS: Compared with the physiological saline control, intrathecal isoflurane significantly suppressed spontaneous paw flinches in rats induced by formalin injection and paw withdrawal induced by thermal and mechanical stimuli in a dose-dependent manner. Immunohistochemistry and real-time reverse transcriptase PCR revealed that isoflurane administration inhibited formalin injection-induced c-fos expression in the spinal cord. CONCLUSIONS: These data suggest that isoflurane can exert anti-nociceptive effects at the spinal level by preventing neuronal activation.
Assuntos
Anestésicos Inalatórios/farmacologia , Isoflurano/farmacologia , Dor/tratamento farmacológico , Proteínas Proto-Oncogênicas c-fos/efeitos dos fármacos , Anestésicos Inalatórios/administração & dosagem , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Genes fos/efeitos dos fármacos , Genes fos/genética , Injeções Espinhais , Isoflurano/administração & dosagem , Masculino , Células do Corno Posterior/efeitos dos fármacos , Células do Corno Posterior/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismoRESUMO
Neurofibromatosis type 1, an autosomal dominant inherited disease, presents pathologic symptoms of multiple systems, including neurofibromatosis, skeletal dysplasia, café-au-lait spots in skins, and so on. A 45-year-old man with neurofibromatosis type 1 was reported in this article. The patient presented a giant neurofibroma in his head and neck, dysplasia of skull, facial bones and spinal columns, and multiple café-au-lait spots in systematic skins. Satisfactory curative effects were obtained in this case after tumor resection and prosthesis implantation.
Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Neurofibroma/cirurgia , Neurofibromatose 1/cirurgia , Angiografia Digital , Manchas Café com Leite/patologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurofibroma/patologia , Neurofibromatose 1/patologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Neuropathic pain is an intractable clinical problem. Intrathecal ketamine, a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, is reported to be useful for treating neuropathic pain in clinic by inhibiting the activity of spinal neurons. Nevertheless, emerging studies have disclosed that spinal astrocytes played a critical role in the initiation and maintenance of neuropathic pain. However, the present clinical therapeutics is still just concerning about neuronal participation. Therefore, the present study is to validate the coadministration effects of a neuronal noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine and astrocytic cytotoxin L-α-aminoadipate (LAA) on spinal nerve ligation (SNL)-induced neuropathic pain. RESULTS: Intrathecal ketamine (10, 100, 1000 µg/kg) or LAA (10, 50, 100 nmol) alleviated SNL-induced mechanical allodynia in a dose-dependent manner respectively. Phosphorylated NR1 (pNR1) or glial fibrillary acidic protein (GFAP) expression was down-regulated by intrathecal ketamine (100, 1000 µg/kg) or LAA (50, 100 nmol) respectively. The combination of ketamine (100 µg/kg) with LAA (50 nmol) showed superadditive effects on neuropathic pain compared with that of intrathecal administration of either ketamine or LAA alone. Combined administration obviously relieved mechanical allodynia in a quick and stable manner. Moreover, down-regulation of pNR1 and GFAP expression were also enhanced by drugs coadministration. CONCLUSIONS: These results suggest that combining NMDAR antagonist ketamine with an astrocytic inhibitor or cytotoxin, which is suitable for clinical use once synthesized, might be a potential strategy for clinical management of neuropathic pain.
Assuntos
Ácido 2-Aminoadípico/uso terapêutico , Analgésicos/uso terapêutico , Astrócitos/patologia , Ketamina/uso terapêutico , Neuralgia/tratamento farmacológico , Ácido 2-Aminoadípico/administração & dosagem , Ácido 2-Aminoadípico/farmacologia , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Hiperalgesia/complicações , Hiperalgesia/tratamento farmacológico , Hiperalgesia/patologia , Hiperalgesia/fisiopatologia , Injeções Espinhais , Ketamina/administração & dosagem , Ketamina/farmacologia , Ligadura , Masculino , Atividade Motora/efeitos dos fármacos , Neuralgia/complicações , Neuralgia/patologia , Neuralgia/fisiopatologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Teste de Desempenho do Rota-Rod , Nervos Espinhais/efeitos dos fármacos , Nervos Espinhais/patologiaRESUMO
BACKGROUND AND OBJECTIVE: Ketamine has been widely used in paediatric anaesthesia but its influence on development in infants and toddlers still remains unclear. In order to elucidate the influence of ketamine on brain development in neonatal rats, semiquantitative reverse transcriptase PCR, quantitative reverse transcriptase PCR and immunohistochemistry assays were performed to detect the expression of N-methyl-D-aspartate receptor subtypes expression. METHODS: Seven-day-old rats were divided into two random groups. All of them were injected with ketamine intraperitoneally at postnatal day (PND) 7; one group was sacrificed at PND 7, but the other group was sacrificed at PND 28. Each group was divided into five random subgroups. RESULTS: In the semiquantitative reverse transcriptase PCR and quantitative reverse transcriptase PCR experiments, ketamine treatment caused a marked increase in mRNA expression in all subtypes at PND 7 and in NR2A subtypes at PND 28. Immunohistochemistry results indicated that NR2A, 2B and 2C receptor protein increased significantly at PND 7, and NR2A receptor protein increased at PND 28. CONCLUSIONS: Exposure to ketamine resulted in an increase in N-methyl-D-aspartate receptor subunits at PND 7, and this increase persisted to PND 28 in NR2A.
Assuntos
Anestésicos Dissociativos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Ketamina/farmacologia , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Fatores Etários , Animais , Animais Recém-Nascidos , Feminino , Masculino , Subunidades Proteicas/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Cervical cancer is one of the leading causes of cancer-associated mortality among females; however, the underlying molecular mechanisms of its carcinogenesis remain largely unclear. Previous comprehensive genomic studies have revealed prevalent estrogen receptor 1 (ESR1) mutations in breast cancer, which are rare in certain other types of cancer. To the best of our knowledge, it is unknown whether ESR1 mutations also exist in cervical cancer. Considering the evidence that cervical cancer shares certain genetic aberrations with breast cancer, and that the progression of both breast and cervical cancers can be affected by estrogen, it is possible that cervical cancer may also harbor ESR1 mutations. In the present study, a total of 260 Chinese cervical cancer samples with distinct subtypes were tested for the presence of ESR1 mutations. A total of three heterozygous missense ESR1 mutations, p.K303R (c.908A>G), p.T311M (c.932C>T) and p.Y537C (c.1610A>G), were identified in 3/207 (1.4%) cervical squamous cell carcinoma samples, which were absent in 27 adenosquamous carcinomas and 26 adenocarcinomas samples. Of the three individuals with an ESR1mutation, 1 patient was also diagnosed with ovarian endometriosis and the other 2 patients were diagnosed with a uterine fibroid. A bioinformatics analysis suggested that these ESR1 mutations may be pathogenic by promoting the development of cervical cancer. Furthermore, a previous comprehensive study confirmed that individuals with cervical squamous cell carcinoma possessed ESR1 mutations. These combined studies indicate that ESR1 mutations may participate in the carcinogenesis of cervical squamous cell carcinoma, albeit at a low frequency. In conclusion, the present study identified three potentially pathogenic ESR1 mutations in Chinese cervical squamous cell carcinoma samples, but not in other subtypes.
RESUMO
In recent years, with continuous research efforts targeted at studying the effects of pre- and after-treatment of inhaled anesthetics, significant progress has been made regarding the common clinical use of low concentrations of inhaled sevoflurane and its effect on induced central ischemia tolerance by pre- and post-treatment. In this study, we collected, analyzed, classified, and summarized recent literature regarding the effect of sevoflurane on central ischemia tolerance and its related mechanisms. In addition, we provide a theoretical basis for the clinical application of sevoflurane to protect the central nervous system and other important organs against ischemic injury.
RESUMO
Cleft palate is one of the most common congenital malformations of the oral and maxillofacial region, with an incidence rate of around 0.1%. Early surgical repair is the only method for treatment of a cleft lip and palate. However, because of the use of inhalation anesthesia in children and the physiological characteristics of the cleft palate itself combined with the particularities of cleft palate surgery, the incidence rate of postoperative emergence agitation (EA) in cleft palate surgery is significantly higher than in other types of interventions. The exact mechanism of EA is still unclear. Although restlessness after general anesthesia in children with cleft palate is self-limiting, its effects should be considered by clinicians. In this paper, the related literature on restlessness after surgery involving general anesthesia in recent years is summarized. This paper focuses on induction factors as well as prevention and treatment of postoperative restlessness in children with cleft palate after general anesthesia. The corresponding countermeasures to guide clinical practice are also presented in this paper.
RESUMO
OBJECTIVE: To study the protective effect of hyperoxia solution on acute lung injury caused by phosgene poisoning by observing the changes of PaO2 and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity in serum and Glutathione (GSH/GSSG) contents in lung tissues. METHODS: The rabbits were divided into normal control group, hyperoxia solution (H0) and balance salt (BS) groups. Group HO and Group BS inhaled phosgene and the former was given intravenously hyperoxia solution (which was replaced by balance salt solution in Group BS). The content of MDA and the activity of SOD in serum were observed at different time points, the amount of GSH and GSSG in lung tissue were also measured. RESULTS: (1) The serum MDA contents increased and PaO2, SOD activity decreased significantly in Group HO and Group BS along with time increasing as compared with control group. The contents of GSH in lung tissue decreased in two groups compared with that in control group, however the contents of GSSG ascended instead. (2) At 3 and 8 h of the experiment, PaO2 of Group HO [(9.91 +/- 0.49), (9.15 +/- 0.46) mm Hg respectively] were significantly higher than those of Group BS [(9.03 +/- 0.76), (8.11 +/- 0.57) mm Hg respectively] (P < 0.01). The contents of MDA of Group HO (3.66 +/- 0.35), (5.31 +/- 0.15) micromol/L respectively] were lower than those of Group BS [(4.32 +/- 0.26), (7.4 +/- 0.33) micromol/L respectively] (P < 0.01). SOD activity in Group HO [(237.37 +/- 29.96), (208.10 +/- 18.80) NU/ml respectively] were higher than those of Group BS [(195.02 +/- 21.44), (144.87 +/- 21.26) NU/ml respectively] (P < 0.05 or P < 0.01). The content of GSSG lung tissue in Group HO (423.67 +/- 38.21) micromol/L were lower than those of Group BS (523.85 +/- 43.14) mol/L (P < 0.01). There were no significant differences in the content of GSH in lung tissues between Group HO and group BS. CONCLUSION: Hyperoxia solution can reduce acute lung injury of rabbits following phosgene poisoning.
Assuntos
Lesão Pulmonar Aguda/metabolismo , Pulmão/efeitos dos fármacos , Oxigênio/farmacologia , Fosgênio/intoxicação , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Animais , Glutationa Peroxidase/metabolismo , Hiperóxia , Pulmão/metabolismo , Pulmão/patologia , Malondialdeído/análise , Oxigênio/administração & dosagem , Coelhos , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: To investigate the effect of puerarin on the neural function and the histopathological changes after ischemic spinal cord injury in rabbits. METHODS: Thirty male New Zealand white rabbits were randomly divided into three groups as follows: puerarin group (n=10) receiving intravenous infusion of 30 mg/kg puerarin for 10 minutes, control group (n=10) receiving intravenous infusion of the same volume of normal saline as puerarin for 10 minutes, and sham operation group (n=10) undergoing only the surgical exposure of the abdominal aorta. Temporary spinal cord ischemia was induced by infrarenal aortic occlusion for 20 minutes and followed by reperfusion. The neural status was scored with the Tarlov criteria at 8, 12, 24 and 48 hours after reperfusion. All the animals were killed at 48 hours after reperfusion and the spinal cords (L5) were removed immediately for histopathological study. RESULTS: The neural function scores at 8, 12, 24 and 48 hours after reperfusion were higher in the puerarin group and sham operation group than those in the control group (P<0.05). More normal motor neurons in the anterior horn of spinal cord were present in the puerarin group and sham operation group than those in the control group (P<0.01). There was a strong correlation between the final neural function scores and the number of normal motor neurons in the anterior horn of spinal cord (r=0.839, P<0.01). CONCLUSIONS: Puerarin can significantly ameliorate the neural function and the histopathological damages after transient spinal cord ischemia in rabbits.