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1.
J Invest Surg ; 36(1): 1-9, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36345760

RESUMO

BACKGROUND/AIMS: Sepsis is one of the major problems encountered in intensive care units, causing organ damage and increasing mortality. Suberosin (SBR) is a type of coumarin with antioxidant and anti-inflammatory activities. The goal of this study is to explore the protective effects of SBR on the lungs in a rat model of sepsis. METHODS: Male Wistar rats were utilized in this study. A cecal ligation and puncture (CLP) model was applied to induce sepsis. Rats were separated into six groups with nine animals in each group, including healthy control, SBR, CLP, and CLP + SBR (5, 10, and 20 mg/kg) groups. Superoxide dismutase (SOD), glutathione (GSH) enzyme activities, and malondialdehyde (MDA) level were measured via enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) were evaluated by real-time polymerase chain reaction (RT-PCR). Histopathological changes in the lungs were investigated with hematoxylin and eosin (H&E). RESULTS: MDA levels and GSH and SOD enzyme activities were negatively affected in the CLP group, but SBR treatment ameliorated these oxidative stress parameters in the SBR1-3 groups (p< 0.05). The mRNA expressions of TNF-α and IL-1ß were increased in the CLP group, and SBR treatment decreased those expression levels in a dose-dependent manner (p < 0.05). Organ damage and necrosis were seen in the CLP group and were alleviated in the SBR3 group. Immunohistochemical (IHC) analysis of lung tissues demonstrated decreased TNF-α and IL-1ß immunopositivity in the SBR1-3 groups (p< 0.05). CONCLUSIONS: SBR ameliorated sepsis-related lung injury in a dose-dependent manner. This compound has significant potential as a future agent in the treatment of sepsis.


Assuntos
Lesão Pulmonar , Sepse , Ratos , Masculino , Animais , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo , Ratos Wistar , Sepse/complicações , Sepse/tratamento farmacológico , Cumarínicos/farmacologia , Ligadura/efeitos adversos , Pulmão/patologia , Punções , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , RNA Mensageiro , Modelos Animais de Doenças
2.
Sci Rep ; 12(1): 19441, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376345

RESUMO

Aiming to improve the postoperative outcome of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), the effect of physical prehabilitation (PP) was investigated in experimental model. Male Wistar rats (n = 106) divided to PP and sedentary (S) groups underwent ALPPS. Changes in liver weight, Ki67 index and liver volume by magnetic resonance imaging (MRI) were evaluated. Liver function was assessed by laboratory parameters and 99mTc-mebrofenin single-photon emission computed tomography (SPECT) hepatobiliary scintigraphy (HBS). Utilizing endotoxemia model mortality and septic parameters were investigated. Liver mass (p < 0.001), Ki67 index (p < 0.001) and MRI liver volume (p < 0.05) increased in the PP group compared to the S group. Both standard laboratory parameters (p < 0.001) and HBS (p < 0.05) showed enhanced liver function in the PP group compared to the S group. The vulnerability of animals improved in the PP group, as mortality decreased (p < 0.001), while septic laboratory parameters improved (p < 0.05) compared to the S group in the endotoxemia model. Our study demonstrated for the first time the beneficial role of PP on not only volumetric but also functional liver regeneration and postoperative vulnerability after ALLPS.


Assuntos
Endotoxemia , Neoplasias Hepáticas , Humanos , Ratos , Animais , Masculino , Hepatectomia/métodos , Veia Porta/cirurgia , Antígeno Ki-67 , Exercício Pré-Operatório , Resultado do Tratamento , Ratos Wistar , Fígado/cirurgia , Regeneração Hepática , Ligadura , Modelos Teóricos
3.
Wiad Lek ; 75(9 pt 2): 2256-2261, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36378705

RESUMO

OBJECTIVE: The aim: To study changes of the expression of synaptophysin (Syn) and vascular endothelial growth factor (VEGF) in neurons of the sensorimotor cortex (SMC) to reveal after unilateral ligation of the carotid artery, sensitization with brain antigen and their combination. PATIENTS AND METHODS: Materials and methods: Experimental animals - Wistar rats (260-290 g). Experimental models: mobilization of the left common carotid artery, ligation of the indicated artery, sensitization with cerebral antigen, combination of sensitization with cerebral antigen and ligation of the carotid artery. Methods: immunohistochemistry, quantitative densitometric assessment. RESULTS: Results: Dyscirculatory disorders of cerebral blood supply during unilateral mobilization or ligation of the common carotid artery, sensitization with cerebral antigen lead in rats to a transient decrease in synaptophysin expression and phase changes in VEGF expression in the SMC from the lesion side. These changes occur in the absence of morphological changes in the cerebral cortex. CONCLUSION: Conclusions: The absence of morphological changes in the SMC in the short term (10-30 days) after minor trauma to the common carotid artery (separation from the bed and n.vagus) or its ligation is accompanied by a transient decrease in Syn expression and some increase in VEGF, which may reflect a violation of synaptic function and the general metabolic activity of neurons. Sensitization with a brain antigen, leading to an increase in the level of anti-brain antibodies and immune complexes in the blood of rats, can act as an independent damaging factor for the brain, and also potentiates and prolongs changes caused by impaired blood circulation.


Assuntos
Córtex Sensório-Motor , Fator A de Crescimento do Endotélio Vascular , Animais , Ratos , Sinaptofisina/metabolismo , Ratos Wistar , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Artéria Carótida Primitiva/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Ligadura
4.
J Coll Physicians Surg Pak ; 32(11): 1470-1473, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36377017

RESUMO

OBJECTIVE: To determine the predictive factors affecting the recurrence or persistence of anal fistula of demographic and technical variables. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of General Surgery and Radiology, Private Ortadogu Hospital General, Turkey, between 2014 and 2020. METHODOLOGY: The recurrence, persistence, and complication rates of 176 patients who underwent LIFT were compared with demographic and technical data by multivariate logistic regression analysis. Inclusion criteria were patients with anal fistula cryptoglandular origin. Exclusion criteria included patients with intersphincteric fistula, rectovaginal fistula, abscess, pilonidal sinus fistula, and inflammatory bowel disease. Recurrence was defined as the opening of a fistula that persisted after 3 months. RESULTS: The mean age was 38.6±9.0 years. The mean BMI was 31.9±5.7 Kg/m2. There were no statistically significant differences between the two groups concerning, age, the complexity of fistula tract(s), the surgical technique of suture versus ligation, operation time, and seton placement duration. Twenty-three patients had previous fistula surgery. Twenty-One patients had previously required seton drainage. Higher BMI, being male, having a prior fistula surgery, and having a height IFO >15 were independent risk factors for recurrence (OR =1.28, 5.69, 23.39, and 15.38 respectively). CONCLUSION: Higher BMI, male gender, having a prior fistula surgery, and having a height IFO >15 were independent risk factors for recurrence. KEY WORDS: LIFT, Anal fistula, Recurrence, Wexner incontinence score (WIS), Male, Prior fistula surgery, height 1FO.


Assuntos
Canal Anal , Fístula Retal , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Canal Anal/cirurgia , Resultado do Tratamento , Recidiva Local de Neoplasia , Fístula Retal/cirurgia , Fístula Retal/etiologia , Ligadura/métodos , Recidiva , Estudos Retrospectivos
5.
BMJ Case Rep ; 15(11)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36379620

RESUMO

Non-valvular atrial fibrillation (NVAF) is the most common cause of cardioembolic stroke. The left atrial appendage (LAA) is the major source of cardiac emboli in patients with NVAF. Anticoagulation (AC) is the standard of care for stroke prevention in atrial fibrillation (AF), but many patients are intolerant of AC. Surgical exclusion of the LAA may result in incomplete closure and is associated with an increased risk of embolism. We report a case of a woman in her 50s with a history of persistent AF, mitral valve prolapse s/p repair with surgical LAA exclusion, and multifocal haemorrhagic stroke presented for elective LAA closure who underwent a Watchman placement successfully. This case demonstrates that a percutaneous approach for occlusion of the LAA when surgical exclusion was incomplete may be feasible with appropriate planning. Clinical outcome data for this patient group are needed.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Embolia , Acidente Vascular Cerebral , Feminino , Humanos , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Embolia/complicações , Ligadura , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
6.
Trials ; 23(1): 920, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36316694

RESUMO

BACKGROUND: Although many efforts have been made to decrease the incidence of anastomotic leak (AL), it remains one of the most serious complications of rectal cancer surgery. Many previous studies have reported an association between the ligation level of the inferior mesenteric artery (IMA) (high or low) and the incidence of AL after rectal cancer surgery. However, we cannot draw a solid conclusion because of the low quality and heterogeneity of those studies. Therefore, this study aims to investigate the impact of the IMA ligation level on the occurrence of AL after minimally invasive anterior resection of rectal cancer. METHODS/DESIGN: Patients with primary rectal cancer without distant metastases will be included after screening. They will be randomly assigned (1:1) to receive high or low ligation of the IMA. The primary endpoint is AL incidence; secondary endpoints are quality of life; urinary, sexual, and defecatory functions; and 3-year disease-free survival. We hypothesized that the incidence rate of AL would be 15% and 5% in the high- and low-ligation groups, respectively. With a two-sided α of 0.05 and a power of 0.8, the sample size is calculated to be 314 patients (157 per group), considering a 10% dropout rate. DISCUSSION: Although many studies have compared the short- and long-term outcomes of high and low ligation of the IMA in rectal cancer surgery, it is still debatable. This trial aims to help draw a more solid conclusion regarding the association between the IMA ligation level and AL incidence after rectal cancer surgery. We also hope to contribute to standardizing the method of rectal cancer surgery in this trial. TRIAL REGISTRATION: Clinical Research Information Service KCT0003523. Registered on February 18, 2019.


Assuntos
Fístula Anastomótica , Neoplasias Retais , Humanos , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Ligadura/métodos , Artéria Mesentérica Inferior/cirurgia , Artéria Mesentérica Inferior/patologia , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia
9.
J Cardiothorac Surg ; 17(1): 259, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36203167

RESUMO

BACKGROUND: Post-esophagectomy chylothorax is a relatively rare but potentially lethal complication. The treatment strategy of post-esophagectomy chylothorax remains a subject of debate which mainly focuses on the indication and timing of surgical intervention. For cases in which the leakage site is not localized, a mass ligation of the thoracic duct above diaphragm is advocated as the surgical procedure is believed to ensure sealing all the accessory ducts that could be the source of the chylothorax. But in this paper, we report a case of post-esophagectomy chylothorax which was refractory to mass ligation of thoracic duct above diaphragm. CASE PRESENTATION: A 59-year old man suffered from high output chylothorax (> 1000 ml/24 h for more than 30 days) after esophagectomy through left thoracotomy. Considering the failure of lymphangiography, we performed mass ligation of thoracic duct above diaphragm. However, we failed to close the chylous leakage. Finally, we found that a rare variated tributary of thoracic duct was the resource of the chylous output. Both the variation of lymphatic system and the coincidence of injured site lead to the invalidness of reoperation. After definitely ligating the variated tributary, chylothorax was cured. CONCLUSION: This case supplies a direct evidence that mass ligation of thoracic duct is of no avail in some refractory chylothorax, which indicates the importance of chylous leakage localization.


Assuntos
Quilotórax , Neoplasias Esofágicas , Quilotórax/etiologia , Quilotórax/cirurgia , Diafragma/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Humanos , Ligadura/efeitos adversos , Ligadura/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Ducto Torácico/cirurgia
10.
Neurosci Lett ; 790: 136890, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36181963

RESUMO

Neuropathic pain is a serious health problem, but optimal drug treatments remain lacking. It has been known that the compound NS5806 is a Kv4.3 activator, which increases Kv4.3-mediated K+ current to reduce neuronal excitability. In this study, we investigated the molecular and cellular mechanisms underlying the analgesic effect of NS5806 in neuropathic pain induced by peripheral nerve injury. Using lumbar (L)5/L6 spinal nerve ligation (SNL) in rats, we found that, without changing the basal nociception, the analgesic effect of NS5806 (220 µg/kg) peaked at 4 h and lasted for 8 h after intraperitoneal injection. Multiple doses of NS5806 reduced not only SNL-upregulated proinflammatory mediators in the DRG and spinal cord on day 1 and day 4 after L5/L6 SNL, but also SNL-evoked expansion of DRG macrophages and spinal microglia on day 4. Furthermore, at 10 min after L5 SNL, NS5806 pretreatment for 4 h suppressed SNL-induced phosphorylated extracellular signal-regulated kinase (pERK) in both Kv4.3+ and Kv4.3- neurons in the dorsal root ganglion (DRG) and superficial spinal dorsal horn, indicating that the action of NS5806 is not restricted to Kv4.3+ neurons. In vitro kinase activity assays revealed that NS5806 weakly inhibited ERK2, MEK1, MEK2, and c-Raf in the ERK pathway. Since NS5806 and the ERK pathway inhibitors have similar antinociceptive characteristics, this study suggests that NS5806 also acts as an ERK pathway inhibitor to attenuate neuropathic pain.


Assuntos
Neuralgia , Traumatismos dos Nervos Periféricos , Ratos , Animais , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Ratos Sprague-Dawley , Nervos Espinhais/lesões , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Gânglios Espinais/metabolismo , Corno Dorsal da Medula Espinal/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Ligadura , Analgésicos/farmacologia , Analgésicos/uso terapêutico
11.
Ann Card Anaesth ; 25(4): 522-524, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36254921

RESUMO

We present the peri-procedural anesthetic management in a case of transcatheter closure of an unligated patent vertical vein (VV) in a 2-year-old male child operated case of obstructed supra cardiac total anomalous pulmonary venous connection (TAPVC) who presented with significant left to right shunt causing symptoms of right heart failure. The procedure was carried out successfully under deep sedation and monitored anesthesia care (MAC) and had some specific clinical implications from the anesthetic management perspective which are highlighted and discussed in this report.


Assuntos
Anestésicos , Veias Pulmonares , Síndrome de Cimitarra , Pré-Escolar , Humanos , Masculino , Ligadura , Veias Pulmonares/anormalidades , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Procedimentos Cirúrgicos Vasculares
12.
Biomed Pharmacother ; 155: 113834, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36271584

RESUMO

Si-Wu-Tang (SWT), a traditional Chinese medicine formula firstly recorded from the Tang dynasty, has been reported to alleviate gynecological and liver diseases. We preliminarily demonstrated that SWT could improve liver fibrosis via modulating intestinal microbiota, but little was known about the mechanisms linking its therapeutic effects to the reshaped immune microenvironment within fibrotic livers. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis murine model to evaluate the hepatoprotective effects and potential mechanisms of SWT. The high-performance liquid chromatography, RNA sequencing and other molecular biological techniques were also performed in our study. Our data demonstrated that SWT significantly improved BDL-induced liver fibrosis and inflammatory responses by inhibiting the expression of genes associated with extracellular matrix synthesis and degradation. Combined with the analysis of immune cell infiltration and gene set enrichment analysis (GSEA), we found that SWT remarkably repaired the unbalanced immune microenvironment by modulating the biological functions of different immune cells, especially for macrophages, neutrophils and CD8+ T cells. In addition, SWT significantly inhibited the activation of M2-like macrophages to reduce the release of profibrotic-cytokines and prevented the activation of neutrophils to suppress neutrophil extracellular trap formation. SWT also efficiently promoted the apoptosis of activated hepatic stellate cells via Fas/FasL signaling pathway, which might be mediated by CD8+ tissue-resident memory T cells. In conclusion, our research not only unraveled the intricate mechanisms underlying the hepatoprotective activities of SWT against liver fibrosis but also provided a novel therapeutic strategy for the treatment of liver fibrosis and its relative complications.


Assuntos
Linfócitos T CD8-Positivos , Cirrose Hepática , Camundongos , Animais , Fibrose , Cirrose Hepática/tratamento farmacológico , Ligadura , Citocinas , Ductos Biliares , Fígado
13.
J Vis Exp ; (188)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36282702

RESUMO

Management of chronic pain remains challenging to this day, and current treatments are associated with adverse effects, including tolerance and addiction. Chronic neuropathic pain results from lesions or diseases in the somatosensory system. To investigate potential therapies with reduced side effects, animal pain models are the gold standard in preclinical studies. Therefore, well-characterized and well-described models are crucial for the development and validation of innovative therapies. Partial ligation of the sciatic nerve (pSNL) is a procedure that induces chronic neuropathic pain in mice, characterized by mechanical and thermal hypersensitivity, ongoing pain, and changes in limb temperature, making this model a great fit to study neuropathic pain preclinically. pSNL is an advantageous model to study neuropathic pain as it reproduces many symptoms observed in humans with neuropathic pain. Furthermore, the surgical procedure is relatively fast and straightforward to perform. Unilateral pSNL of one limb allows for comparison between the ipsilateral and contralateral paws, as well as evaluation of central sensitization. To induce chronic neuropathic hypersensitivity, a 9-0 non-absorbable nylon thread is used to ligate the dorsal third of the sciatic nerve. This article describes the surgical procedure and characterizes the development of chronic neuropathic pain through multiple commonly used behavioral tests. As a plethora of innovative therapies are now being investigated to treat chronic pain, this article provides crucial concepts for standardization and an accurate description of surgeries required to induce neuropathic pain.


Assuntos
Dor Crônica , Neuralgia , Humanos , Camundongos , Animais , Dor Crônica/etiologia , Dor Crônica/terapia , Nylons , Neuralgia/etiologia , Nervo Isquiático/patologia , Modelos Animais de Doenças , Ligadura , Analgésicos/uso terapêutico , Hiperalgesia
14.
Arch Oral Biol ; 143: 105528, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36063643

RESUMO

OBJECTIVE: The objective of this study was to summarize and compare the local and systemic impact of different models of experimental periodontitis in mice. DESIGN: After defining the PICO strategy, was performed a search for articles in English following the PRISMA guidelines in PubMed, Embase, Scopus, Web of Science, Cochrane and LILACS databases. The search strategy provided 8815 articles from which were selected experimental studies comparing the local and/or systemic effects of two or more models for the induction of periodontitis in mice according to the inclusion and exclusion criteria. RESULTS: After selection, 7 articles that met the inclusion criteria for the review. Were analyzed differences between the following experimental models of periodontitis in mice: ligature, gavage, injection of bacteria, ligation embedded in bacteria and association between them. CONCLUSION: Although most experimental models of periodontitis are efficient in causing alveolar bone loss, there are differences in their characteristics. In ligature, an acute process is established and the host tends to repair itself, decreasing the significance of this loss over time. In models where bacterial challenge is added bone loss appears to be significant with longer induction time, indicating the presence of a chronic condition. Regarding systemic outcomes, gavage showed greater potential for modulating the host's response with systemic inflammatory changes, proving to be more promising between periodontitis and chronic systemic diseases.


Assuntos
Perda do Osso Alveolar , Periodontite , Perda do Osso Alveolar/etiologia , Animais , Bactérias , Modelos Animais de Doenças , Ligadura/efeitos adversos , Camundongos , Periodontite/microbiologia
15.
J Am Heart Assoc ; 11(17): e025784, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36056734

RESUMO

The burden of patent ductus arteriosus (PDA) continues to be significant. In view of marked differences in preterm infants versus more mature, term counterparts (viewed on a continuum with adolescent and adult patients), mechanisms regulating ductal patency, genetic contributions, clinical consequences, and diagnostic and treatment thresholds are discussed separately, when appropriate. Among both preterm infants and older children and adults, a range of hemodynamic profiles highlighting the markedly variable consequences of the PDA are provided. In most contemporary settings, transcatheter closure is preferable over surgical ligation, but data on longer-term outcomes, particularly among preterm infants, are lacking. The present review provides recommendations to identify gaps in PDA diagnosis, management, and treatment on which subsequent research can be developed. Ultimately, the combination of refined diagnostic thresholds and expanded treatment options provides the best opportunities to address the burden of PDA. Although fundamental gaps remain unanswered, the present review provides pediatric and adult cardiac care providers with a contemporary framework in PDA care to support the practice of evidence-based medicine.


Assuntos
Permeabilidade do Canal Arterial , Adolescente , Criança , Permeabilidade do Canal Arterial/diagnóstico , Permeabilidade do Canal Arterial/terapia , Hemodinâmica , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Ligadura
16.
Eur J Cardiothorac Surg ; 62(5)2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36149284

RESUMO

Primary pulmonary vein (PV) stenosis is a challenging condition to manage. Recently, extrinsic compression of the PV is being detected has cause of narrowing and subsequent turbulence. This can be managed without direct intervention on the PV, reducing the risk of recurrence. We report a case of extrinsic compression of the PV due to cardiomegaly, relieved after patent ductus arteriosus ligation.


Assuntos
Permeabilidade do Canal Arterial , Canal Arterial , Veias Pulmonares , Cardiomegalia/complicações , Cardiomegalia/etiologia , Permeabilidade do Canal Arterial/complicações , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/cirurgia , Humanos , Ligadura/efeitos adversos , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia
17.
Int Immunopharmacol ; 112: 109219, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36084541

RESUMO

Neuropathic pain caused by nerve injury presents with severe spontaneous pain and a range of comorbidities, including deficits in higher executive functioning, none of which are adequately treated with current analgesics. Interleukin-6 (IL-6), a proinflammatory cytokine, is critically involved in the development and maintenance of central sensitization. However, the roles of IL-6 in neuropathic pain and related comorbidities have yet to be fully clarified. The present study examined the effect of MR16-1, an anti-IL-6 receptor antibody and inhibits IL-6 activity, on allodynia and cognitive impairment in mice with neuropathic pain following partial sciatic nerve ligation (PSNL). Significant upregulation of IL-6 expression was observed in the hippocampus in PSNL mice. Intranasal administration of MR16-1 significantly improved cognitive impairment but not allodynia in PSNL mice. Intranasal MR16-1 blocked PSNL-induced degenerative effects on hippocampal neurons. Intraperitoneal administration of MR16-1 suppressed allodynia but not cognitive impairment of PSNL mice. The findings suggest that cognitive impairment associated with neuropathic pain is mediated through changes in hippocampus induced by IL-6. These data also suggest that IL-6 mediated peripheral inflammation underlies allodynia, and IL-6 mediated inflammation in the central nervous system underlies cognitive impairment associated with neuropathic pain, and further suggest the therapeutic potential of blocking IL-6 functioning by blocking its receptor.


Assuntos
Neuralgia , Camundongos , Animais , Neuralgia/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Nervo Isquiático/lesões , Analgésicos/uso terapêutico , Ligadura , Citocinas/metabolismo , Inflamação/tratamento farmacológico
18.
Int J Mol Sci ; 23(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36142743

RESUMO

Sepsis is an uncontrolled response to inflammatory infection and is associated with high levels of mortality and morbidity. Rg4 is a rare ginsenoside mainly found in the leaves of Panax ginseng C. A. Meyer and the major protopanaxatriol-type ginsenoside of black ginseng. In this study, we determined whether Rg4 affects cecal ligation and puncture (CLP)-induced sepsis. Animals were separated into the following six groups: control group, CLP-operated group, CLP plus maslinic acid (MA), and CLP plus Rg4 (5, 10, or 15 mg/kg). Survival rate, body weight changes, inflammatory cytokines, and histological analyses were assessed. Human endothelial cells were activated with the high-mobility group box 1 (HMGB1) protein and Rg4. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used to assess inflammation and gene expression, respectively. After CLP surgery, the Rg4-administered group exhibited a higher survival rate and body weight compared with the untreated control group. Rg4 treatment reduced cytokine levels, including tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, as well as nitric oxide (NO) levels and renal inflammation. After Rg4 treatment of HMGB1-activated cells, the expressions of toll-like receptor (TLR) 4 and TNF-α were decreased, and the activation of phosphoinositide 3-kinase (PI3K)/AKT signaling increased cell viability. In summary, Rg4 inhibited inflammation and exhibited a protective effect against CLP-induced sepsis, thereby reinforcing cell survival against septic responses.


Assuntos
Ginsenosídeos , Proteína HMGB1 , Panax , Sepse , Animais , Peso Corporal , Citocinas/metabolismo , Células Endoteliais/metabolismo , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Proteína HMGB1/genética , Humanos , Inflamação , Ligadura , Óxido Nítrico , Panax/metabolismo , Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Punções , Sepse/tratamento farmacológico , Sepse/etiologia , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa
19.
Eur J Cardiothorac Surg ; 62(4)2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36083021

RESUMO

Vascular clips are currently acknowledged as a safe and efficient tool for vessel ligation in every surgical field. Here, we describe a case of massive haemoptysis due to perforation of both the aorta and bronchus, caused by a titanium clip that was placed between them 3 years ago. The present case highlights the rare but life-threatening complications that clips can cause in the mediastinum, especially when placed between a fixed structure and a large blood vessel or respiratory tract.


Assuntos
Instrumentos Cirúrgicos , Titânio , Aorta/diagnóstico por imagem , Aorta/cirurgia , Brônquios/diagnóstico por imagem , Brônquios/cirurgia , Humanos , Ligadura , Instrumentos Cirúrgicos/efeitos adversos
20.
Naunyn Schmiedebergs Arch Pharmacol ; 395(12): 1557-1572, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36097067

RESUMO

Lung injury is a significant complication associated with cholestasis/cirrhosis. This problem significantly increases the risk of cirrhosis-related morbidity and mortality. Hence, finding effective therapeutic options in this field has significant clinical value. Severe inflammation and oxidative stress are involved in the mechanism of cirrhosis-induced lung injury. Taurine (TAU) is an abundant amino acid with substantial anti-inflammatory and antioxidative properties. The current study was designed to evaluate the role of TAU in cholestasis-related lung injury. For this purpose, bile duct ligated (BDL) rats were treated with TAU (0.5 and 1% w: v in drinking water). Significant increases in the broncho-alveolar lavage fluid (BALF) level of inflammatory cells (lymphocytes, neutrophils, basophils, monocytes, and eosinophils), increased IgG, and TNF-α were detected in the BDL animals (14 and 28 days after the BDL surgery). Alveolar congestion, hemorrhage, and fibrosis were the dominant pulmonary histopathological changes in the BDL group. Significant increases in the pulmonary tissue biomarkers of oxidative stress, including reactive oxygen species formation, lipid peroxidation, increased oxidized glutathione levels, and decreased reduced glutathione, were also detected in the BDL rats. Moreover, significant myeloperoxidase activity and nitric oxide levels were seen in the lung of BDL rats. It was found that TAU significantly blunted inflammation, alleviated oxidative stress, and mitigated lung histopathological changes in BDL animals. These data suggest TAU as a potential protective agent against cholestasis/cirrhosis-related lung injury.


Assuntos
Colestase , Lesão Pulmonar , Pneumonia , Ratos , Animais , Taurina/farmacologia , Taurina/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Estresse Oxidativo , Ductos Biliares/cirurgia , Colestase/tratamento farmacológico , Colestase/metabolismo , Ligadura/efeitos adversos , Antioxidantes/uso terapêutico , Cirrose Hepática/patologia , Fibrose , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Pneumonia/patologia , Fígado
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