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1.
Endosc Int Open ; 12(6): E750-E756, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38847016

RESUMO

Inadequate bowel preparation is common despite various preprocedure interventions. There is a need for an intervention at the time of colonoscopy to combat poor preparation. In this retrospective, observational study of 46 patients, we evaluated the clinical efficacy and feasibility of implementing the third generation of the Pure-Vu EVS System, a US Food and Drug Administration-cleared over-the-scope-based intraprocedural cleansing device, into our practice at the Minneapolis VA Medical Center (Minneapolis, Minnesota, United States). To study clinical efficacy, we measured bowel preparation adequacy before and after using the device, as measured by the Boston Bowel Preparation Score, and reviewed colonoscopy surveillance interval recommendations. Technical success and feasibility of using the device were measured by procedure success rates and duration. We found that BBPS scores increased from 4.4 to 7.9 when using the device. Technical success was achieved 78.3% of the time (36/46 cases). Median colonoscopy duration was 46 minutes, although there was a trend toward shorter procedures over time. This is the first clinical evaluation of the third generation of an intraprocedural cleansing device. We found the device efficacious and easy to use with low procedure failure rates, but it does come with a learning curve. We suspect that adoption of this device mutually will benefit patients and health systems with the potential to improve resource utilization.

2.
ACG Case Rep J ; 11(4): e01320, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38560015

RESUMO

Acute pancreatitis is a common gastroenterological condition that can occur due to several causes. While not required for diagnosis, imaging is often performed and may reveal unexpected findings such as pancreatic masses. Malignancies such as lymphoma are uncommon causes of acute pancreatitis, especially as the initial presentation of malignancy. We present a case of a young patient with acute pancreatitis caused by diffuse large B-cell lymphoma with extranodal disease secondarily involving the pancreas. Our case highlights the importance of keeping a broad differential for acute pancreatitis and considering rare etiologies such as pancreatic lymphoma in patients without another obvious culprit.

5.
Gastrointest Endosc ; 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38092125

RESUMO

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) with use of electrocautery (conventional EMR) has historically been used to remove large duodenal adenomas, however, use of electrocautery can predispose to adverse events including delayed bleeding and perforation. Cold snare EMR (cs-EMR) has been shown to be safe and effective for removal of colon polyps, but data regarding its use in the duodenum is limited. The aim of this study is to evaluate the efficacy and safety of cs-EMR for nonampullary duodenal adenomas ≥1 cm. METHODS: This was a multicenter retrospective study of patients with nonampullary duodenal adenomas ≥1 cm who underwent cs-EMR between October 2014 and May 2023. Patients who received any form of thermal therapy were excluded. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were adverse events and predictors of recurrence. RESULTS: A total of 125 patients underwent resection of 127 nonampullary duodenal adenomas with cs-EMR. Follow up data was available in 89 cases (70.1%). The recurrent adenoma rate was 31.5% (n=28). Adverse events occurred in 3.9% (n=5) with four cases of immediate bleeding (3.1%) and one case of delayed bleeding (0.8%). There were no cases of perforation. The presence of high-grade dysplasia was found to be an independent predictor of recurrence (OR: 10.9 [95% CI: 1.1-102.1], p=0.036). CONCLUSION: This retrospective multicenter study demonstrates that cs-EMR for nonampullary duodenal adenomas is safe and technically feasible with an acceptable recurrence rate. Future prospective studies are needed to directly compare outcomes of cs-EMR with conventional and underwater EMR.

6.
ACG Case Rep J ; 10(12): e01242, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38107608

RESUMO

Liposarcoma is the most common type of soft-tissue sarcoma and typically occurs in the extremities or retroperitoneum. Primary liposarcoma of the pancreas is exceedingly rare, with only 10 cases reported since 1979. We present a patient who was incidentally discovered to have a pancreatic mass on imaging, which was ultimately diagnosed as dedifferentiated pancreatic liposarcoma. We review the clinical and histologic features of pancreatic liposarcoma in this case and in the 10 previously reported cases to increase awareness and knowledge of this rare disease.

7.
Endoscopy ; 55(12): 1083-1094, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37451284

RESUMO

BACKGROUND: Cold snare endoscopic mucosal resection (CS-EMR) can reduce the risks associated with electrocautery during colon polyp resection. Data on efficacy are variable. This systematic review and meta-analysis aimed to estimate the pooled efficacy and safety rates of CS-EMR. METHODS: We conducted a comprehensive literature search of multiple databases, from inception to March 2023, for studies addressing outcomes of CS-EMR for colon polyps. The weighted pooled estimates with 95 %CIs were calculated using the random effects model. I2 statistics were used to evaluate heterogeneity. RESULTS: 4137 articles were reviewed, and 16 studies, including 2592 polyps in 1922 patients (51.4 % female), were included. Overall, 54.4 % of polyps were adenomas, 45 % were sessile serrated lesions (SSLs), and 0.6 % were invasive carcinomas. Polyp recurrence after CS-EMR was 6.7 % (95 %CI 2.4 %-17.4 %, I2  = 94 %). The recurrence rate was 12.3 % (95 %CI 3.4 %-35.7 %, I2  = 94 %) for polyps ≥ 20 mm, 17.1 % (95 %CI 4.6 %-46.7 %, I2  = 93 %) for adenomas, and 5.7 % (95 %CI 3.2 %-9.9 %, I2  = 50 %) for SSLs. The pooled intraprocedural bleeding rate was 2.6 % (95 %CI 1.5 %-4.5 %, I2  = 51 %), the delayed bleeding rate was 1.5 % (95 %CI 0.8 %-2.7 %, I2  = 18 %), and no perforations or post-polypectomy syndromes were reported, with estimated rates of 0.6 % (95 %CI 0.3 %-1.3 %, I2  = 0 %) and 0.6 % (95 %CI 0.3 %-1.4 %, I2  = 0 %), respectively. CONCLUSION: CS-EMR demonstrated an excellent safety profile for colon polyps, with variable recurrence rates based on polyp size and histology. Large prospective studies are needed to validate these findings.


Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Feminino , Masculino , Pólipos do Colo/cirurgia , Pólipos do Colo/patologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Colonoscopia/efeitos adversos , Colo/patologia , Adenoma/cirurgia , Adenoma/patologia , Neoplasias Colorretais/patologia
8.
VideoGIE ; 8(5): 211-216, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37197159

RESUMO

Background and Aims: The endoscopic powered resection (EPR) device (EndoRotor, Interscope Inc, Northbridge, Mass, USA) is a novel nonthermal device that can be used for polyp and tissue removal in the GI tract. Here, we review the EPR device and illustrate its use for resection of scarred or fibrotic lesions in the GI tract. Methods: In this article and accompanying video, we describe the EPR device features, provide step-by-step instructions for device setup, and review case examples in which the EPR device was used for scarred polyp resection. We also review the current literature describing the use of the EPR device for scarred or challenging polyps. Results: Four lesions with scarring or fibrosis were successfully resected with the EPR device, either with the EPR device alone or as an adjunct to conventional resection methods. No adverse events occurred. A follow-up endoscopy was available in 1 case, which demonstrated no endoscopic or histologic evidence of residual or recurrent lesion. Conclusions: The endoscopic powered resection device can be used alone or as an adjunct to facilitate resection of lesions with significant fibrosis or scarring. This device serves as a useful addition to endoscopists' toolbox in the management of scarred lesions where other modalities might be technically challenging to use.

10.
Obes Surg ; 33(4): 1253-1258, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36810809

RESUMO

PURPOSE: The over-the-scope endoscopic suturing system (ESS) (OverStitch™) is one of the most widely utilized endoscopic suturing systems in current clinical practice; however, data on the adverse events associated with this device is scarce. Our study aims to evaluate the adverse events and complications associated with the over-the-scope ESS using the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. MATERIALS AND METHODS: We analyzed the post-marketing surveillance data from the FDA MAUDE database for the over-the-scope ESS from January 2008 through June 2022. RESULTS: Eighty-three reports were filed from January 2008 to June 2022. Adverse events were classified as device-related complications and patient-related adverse events. Seventy-seven device-related issues and 87 patient adverse events were identified. The most common device-related issue was difficulty to remove after deployment (n=12, 15.58%) followed by mechanical problem (n=10, 12.99%), mechanical jam (n=9, 11.69%), or entrapment of device (n=9, 11.69%). Of the 87 patient-related adverse events, the most common was perforation (n=19; 21.84%), followed by device embedded in tissue or plaque (n=10; 11.49%), and abdominal pain (n=8; 9.20%). Of the 19 patients who experienced perforation, two required open surgical repair and one required laparoscopic surgical repair. CONCLUSION: The overall adverse events from the over-the-scope ESS remain acceptable as evidenced by the number of reported cases since 2008. However, it is important to note that adverse event rates might increase as the use of the device increases; therefore, it is essential for endoscopists to be aware of the potential common and rare adverse events associated with the use of the over-the-scope ESS device.


Assuntos
Laparoscopia , Obesidade Mórbida , Humanos , Estados Unidos/epidemiologia , Obesidade Mórbida/cirurgia , Laparoscopia/efeitos adversos , Bases de Dados Factuais
11.
Oncologist ; 28(3): e145-e155, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36719033

RESUMO

BACKGROUND: Cancer and anti-cancer treatment (ACT) may be risk factors for severe SARS-CoV-2 infection and limited vaccine efficacy. Long-term longitudinal studies are needed to evaluate these risks. The Scottish COVID cancer immunity prevalence (SCCAMP) study characterizes the incidence and outcomes of SARS-CoV-2 infection and vaccination in patients with solid tumors undergoing ACT. This preliminary analysis includes 766 patients recruited since May 2020. METHODS: Patients with solid-organ cancers attending secondary care for active ACT consented to the collection of routine electronic health record data and serial blood samples over 12 months. Blood samples were tested for total SARS-CoV-2 antibody. RESULTS: A total of 766 participants were recruited between May 28, 2020 and October 31, 2021. Most received cytotoxic chemotherapy (79%). Among the participants, 48 (6.3%) were tested positive for SARS-CoV-2 by PCR. Infection rates were unaffected by ACT, largely aligning with the local population. Mortality proportion was not higher with a recent positive SARS-CoV-2 PCR (10.4% vs 10.6%). Multivariate analysis revealed lower infection rates in vaccinated patients regardless of chemotherapy (HR 0.307 [95% CI, 0.144-0.6548]) or immunotherapy (HR 0.314 [95% CI, 0.041-2.367]) treatment. A total of 96.3% of patients successfully raised SARS-CoV-2 antibodies after >2 vaccines. This was independent of the treatment type. CONCLUSION: This is the largest on-going longitudinal real-world dataset of patients undergoing ACT during the early stages of the COVID-19 pandemic. This preliminary analysis demonstrates that patients with solid tumors undergoing ACT have high protection from SARS-CoV-2 infection following COVID-19 vaccination. The SCCAMP study will evaluate long-term COVID-19 antibody trends, focusing on specific ACTs and patient subgroups.


Assuntos
COVID-19 , Neoplasias , Humanos , SARS-CoV-2 , COVID-19/epidemiologia , Vacinas contra COVID-19 , Estudos Transversais , Estudos Longitudinais , Pandemias , Imunidade , Escócia/epidemiologia , Vacinação , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia
13.
VideoGIE ; 7(11): 410-412, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36407040

RESUMO

Video 1Endoscopic full-thickness resection of gastric ulceration with persistent low-grade dysplasia using full-thickness resection device.

14.
J Pain Symptom Manage ; 63(6): 943-952, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35235857

RESUMO

CONTEXT: People living with HIV infection (PLWH) in the United States continue to experience a high symptom burden despite improvements in antiretroviral therapy. OBJECTIVES: The purpose of this study was to determine if the number and types of symptom clusters differed based on whether symptom occurrence rates or distress ratings were used to create the clusters. METHODS: Data from 2,000 patients with complete symptom occurrence rates and distress scores on the 20-item HIV Symptom Index from their first ambulatory clinic visit at one of six national HIV centers of excellence in the Center for AIDS Research Network of Integrated Clinical Systems were used in these analyses. Exploratory factor analysis was used to create the symptom clusters. RESULTS: The same four symptom clusters (i.e., gastrointestinal, psychological, pain, body image) were identified using occurrence rates and distress ratings. For both dimensions of the symptom experience, the psychological, pain, and body image clusters each had the same symptoms. For the gastrointestinal cluster, four symptoms loaded on the occurrence dimension and six symptoms loaded on the distress dimension. CONCLUSION: The number and types of symptom clusters were relatively similar across the occurrence and distress dimensions of the symptom experience. Symptom clusters in PLWH may provide insights into the development of targeted interventions for multiple co-occurring symptoms.


Assuntos
Antineoplásicos , Infecções por HIV , Antineoplásicos/uso terapêutico , Análise Fatorial , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Dor/tratamento farmacológico , Dor/epidemiologia , Síndrome
15.
Pediatr Blood Cancer ; 68(5): e28850, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33369068

RESUMO

PURPOSE: This randomized cross-over group pilot trial assessed feasibility of recruiting survivors from a long-term follow-up clinic to an exercise group and measured whether outdoor or indoor exercise sessions better supported exercise motivation and behaviors in survivors of cancer. METHODS: Sixteen adolescent and young adult survivors of any cancer completed indoor and outdoor exercise sessions in this randomized cross-over pilot trial. Measures of physical activity, motivation, and fatigue were taken 2 weeks before and 2 weeks after indoor sessions and 2 weeks before and 2 weeks after outdoor sessions. Measures of physical activity and fatigue were also taken during each exercise session. RESULTS: Initial recruiting of 19 participants met recruiting goals. Survivors who attended the most sessions lived an average of 8.7 km closer to the clinic. Objectively measured physical activity intensity was 0.63 metabolic equivalents of a task (METs) per minute greater during outdoor exercise sessions as compared to indoor exercise sessions. There were no meaningful differences in long term, habitual physical activity behavior, motivation, or fatigue in the weeks following the outdoor exercise sessions as compared to the indoor exercise sessions. CONCLUSIONS: This study shows the feasibility of recruiting survivors from a long-term follow-up clinic to community-based exercise groups. Although this brief pilot intervention did not show significant effects on habitual physical activity behavior or motivation in adolescent and young adult survivors of cancer, the greater exercise intensity during the outdoor exercise sessions indicate that holding group exercise sessions for survivors outdoors may promote greater intensity during exercise.


Assuntos
Sobreviventes de Câncer , Exercício Físico , Adolescente , Adulto , Estudos Cross-Over , Fadiga , Feminino , Humanos , Masculino , Motivação , Projetos Piloto , Adulto Jovem
16.
Front Oncol ; 10: 591399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33520704

RESUMO

Invasive lobular carcinoma accounts for 5%-15% of all invasive breast cancers, with a marked increase in incidence rates over the past two decades. Distinctive biological hallmarks of invasive lobular carcinoma include the loss of cell adhesion molecule E-cadherin leading to cells with a discohesive morphology, proliferating into single-file strands and estrogen receptor positivity. These key molecular features can make diagnosis difficult, as invasive lobular carcinoma is challenging to detect both physically and with current standard imaging. Treatment of invasive lobular carcinoma strongly favors endocrine therapy due to low chemosensitivity and lower rates of pathological response as a result. This review will summarize the distinct biological and molecular features of invasive lobular carcinoma, focusing on the diagnostic challenges faced and the subsequent surgical and medical management strategies. Prospective therapeutic options will also be explored, highlighting how furthering our understanding of the unique biology of lobular breast carcinoma is essential in guiding and informing the treatment of patients in the future.

17.
J Neurointerv Surg ; 10(1): 22-24, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28119375

RESUMO

BACKGROUND: Access to endovascular therapy (ET) in cases of acute ischemic stroke may be limited, and rapid transfer of eligible patients to hospitals with endovascular capability is needed. OBJECTIVE: To determine the optimal timing of diagnostic CT angiography to confirm large vessel occlusion (LVO). METHODS: Of 57 emergency department transfers to Mount Sinai Hospital (MSH) for possible ET from January 2015 through March 2016, 39 (68%) underwent ET, among whom 22 (56%) had CT angiography before transfer and 17 (44%) had CT angiography on arrival. We compared mean outside hospital arrival to groin puncture (OTG) time between the two groups using t-tests and Wilcoxon rank sum tests. OTG was defined as the difference between groin puncture and outside hospital arrival time minus ambulance travel time. RESULTS: Average age was 73±13 years and average National Institute of Health Stroke Scale score was 19±5. There was no difference in average OTG time between the two groups (191 min for CT angiography at outside hospital vs 190 min for CT angiography at MSH (p=0.99 for t-test and 0.69 for rank sum test)). Among the 18 patients who were transferred but did not receive ET, 10 had no LVO, 5 had large established infarcts on arrival and 3 had post-tissue plasminogen activator hemorrhage. In 9/10 patients without LVO, CT angiography was not performed before transfer. CONCLUSIONS: CT angiography timing in the transfer process does not affect OTG time, but 90% of patients without LVO had not had CT angiography before transfer. Hence, it might be beneficial to obtain a CT angiogram at the outside hospital, if it can be acquired and read rapidly, to avoid the cost and potential clinical deterioration associated with unnecessary transfers.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Virilha/diagnóstico por imagem , Transferência de Pacientes/métodos , Punções , Acidente Vascular Cerebral/diagnóstico por imagem , Tempo para o Tratamento , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Angiografia por Tomografia Computadorizada/tendências , Feminino , Virilha/irrigação sanguínea , Humanos , Pessoa de Meia-Idade , Transferência de Pacientes/tendências , Punções/tendências , Estudos Retrospectivos , Acidente Vascular Cerebral/terapia , Tempo para o Tratamento/tendências , Ativador de Plasminogênio Tecidual/administração & dosagem
18.
Pain Res Treat ; 2016: 8364762, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27069684

RESUMO

Aim. Nonsteroidal anti-inflammatory drugs or opioids are commonly used to control surgical pain following veterinary and clinical procedures. This study evaluated the efficacy of postoperative ketorolac or buprenorphine following abdominal surgery. Main Methods. Mean arterial pressure (MAP), heart rate, animal activity, corticosterone levels, and a nociceptive sensitivity assay were used to evaluate 18 adult male Sprague-Dawley rats which underwent aortic artery occlusion for implantation of a radiotelemetry device. The animals were treated postoperatively with intraperitoneal injections of vehicle, ketorolac (10 mg/kg), or buprenorphine (0.06 mg/kg) every 8 hours for 3 days. Key Findings. There were no consistent significant changes in any of the telemetry parameters after treatment with ketorolac compared with no saline treatment with the exception of increased MAP in the buprenorphine group during the first 48 hours when compared with other treatment groups. There was a sustained increase in fecal corticosterone levels from baseline on days 2-7 with buprenorphine compared with vehicle- or ketorolac-treated animals. All treatment conditions displayed reduced paw withdrawal thresholds (PWTs) from day 1 to day 21 following surgery. Compared with the vehicle treatment group, buprenorphine-treated animals exhibited significantly lower PWT levels from day 4 to 14 days. Significance. Given the prolonged increase in fecal corticosterone levels and pronounced changes in tactile hyperalgesia behavior in rodents subjected to buprenorphine treatment, these data suggest that ketorolac may be superior to buprenorphine for the treatment of postprocedure pain behavior in rodents.

19.
J Neurointerv Surg ; 8(11): 1129-1135, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26747878

RESUMO

BACKGROUND: With a recent surge of clinical trials, the treatment of ischemic stroke has undergone dramatic changes. OBJECTIVE: To evaluate the impact of evidence and a revamped stroke protocol on a large healthcare system. METHODS: A retrospective review of 69 patients with ischemic stroke treated with intra-arterial therapy was carried out. Cohort 1 included patients treated before implementation of a new stroke protocol, and cohort 2 after implementation. Angiographic outcome was graded using the Thrombolysis in Cerebral Infarction (TICI) score. Clinical outcomes were assessed using the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). RESULTS: Primary outcomes comparing cohorts demonstrated decreased arrival-to-puncture time (cohort 2: 104 vs cohort 1: 181 min, p<0.001), similar TICI 2b/3 rates (86.5% vs 81.3%, p=0.5530), and similar percentage of patients with discharge mRS 0-2 (18.9% vs 21.9%, p=0.7740). Notable secondary outcomes for cohort 2 included decreased puncture-to-first pass time (34 vs 53 min, p <0.001), increased TICI 3 rates (37.8% vs 18.8%, p=0.0290), a trend toward greater improvements in NIHSS on postoperative day 1 (6.8 vs 2.6, p=0.0980) and discharge (9.5 vs 6.7, p=0.1130), and a trend toward increased percentage of patients discharged with mRS 0-3 (48.6% vs 34.4%, p=0.3280 NS). There were similar rates of symptomatic intracerebral hemorrhage (10.8% vs 9.4%, p=0.9570) and death (10.8% vs 15.6%, p=0.5530). CONCLUSIONS: An interdisciplinary and rapid response to the emergence of strong clinical evidence can result in dramatic changes in a large healthcare system.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Atenção à Saúde/métodos , Atenção à Saúde/tendências , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente/tendências , Estudos Retrospectivos , Trombectomia/métodos , Trombectomia/tendências , Resultado do Tratamento
20.
J Neuroinflammation ; 9: 200, 2012 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-22898544

RESUMO

BACKGROUND: Multiple adverse events are associated with the use of morphine for the treatment of chronic non-cancer pain, including opioid-induced hyperalgesia (OIH). Mechanisms of OIH are independent of opioid tolerance and may involve the morphine metabolite morphine-3-glucuronide (M3G). M3G exhibits limited affinity for opioid receptors and no analgesic effect. Previous reports suggest that M3G can act via the Toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD-2) heterodimer in the central nervous system to elicit pain. METHODS: Immunoblot and immunocytochemistry methods were used to characterize the protein expression of TLR4 present in lumbar dorsal root ganglion (DRG). Using in vitro intracellular calcium and current clamp techniques, we determined whether TLR4 activation as elicited by the prototypical agonists of TLR4, lipopolysaccharide (LPS) and M3G, contributed to changes in intracellular calcium and increased excitation. Rodents were also injected with M3G to determine the degree to which M3G-induced tactile hyperalgesia could be diminished using either a small molecule inhibitor of the MD-2/TLR4 complex in rats or TLR4 knockout mice. Whole cell voltage-clamp recordings were made from small- and medium-diameter DRG neurons (25 µm < DRG diameter <45 µm) for both control and M3G-treated neurons to determine the potential influence on voltage-gated sodium channels (NaVs). RESULTS: We observed that TLR4 immunoreactivity was present in peptidergic and non-peptidergic sensory neurons in the DRG. Non-neuronal cells in the DRG lacked evidence of TLR4 expression. Approximately 15% of assayed small- and medium-diameter sensory neurons exhibited a change in intracellular calcium following LPS administration. Both nociceptive and non-nociceptive neurons were observed to respond, and approximately 40% of these cells were capsaicin-insensitive. Increased excitability observed in sensory neurons following LPS or M3G could be eliminated using Compound 15, a small molecule inhibitor of the TLR4/MD-2 complex. Likewise, systemic injection of M3G induced rapid tactile, but not thermal, nociceptive behavioral changes in the rat, which were prevented by pre-treating animals with Compound 15. Unlike TLR4 wild-type mice, TLR4 knockout mice did not exhibit M3G-induced hyperalgesia. As abnormal pain sensitivity is often associated with NaVs, we predicted that M3G acting via the MD-2/TLR4 complex may affect the density and gating of NaVs in sensory neurons. We show that M3G increases tetrodotoxin-sensitive and tetrodotoxin-resistant (NaV1.9) current densities. CONCLUSIONS: These outcomes provide evidence that M3G may play a role in OIH via the TLR4/MD-2 heterodimer complex and biophysical properties of tetrodotoxin-sensitive and tetrodotoxin-resistant NaV currents.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Derivados da Morfina/farmacologia , Células Receptoras Sensoriais/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Cálcio/metabolismo , Feminino , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Hiperalgesia/fisiopatologia , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/genética , Lectinas/metabolismo , Lipopolissacarídeos/farmacologia , Antígeno 96 de Linfócito/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação/genética , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Fosfopiruvato Hidratase/metabolismo , Estimulação Física , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/metabolismo , Transdução de Sinais/genética , Bloqueadores dos Canais de Sódio/farmacologia , Tetrodotoxina/farmacologia , Receptor 4 Toll-Like/genética , Tato/efeitos dos fármacos
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