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1.
Adv Exp Med Biol ; 1267: 101-115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32894479

RESUMO

Pathogenic bacteria colonize or disseminate into cells and tissues by inducing large-scale remodeling of host membranes. The physical phenomena underpinning these massive membrane extension and deformation are poorly understood. Invasive strategies of pathogens have been recently enriched by the description of a spectacular mode of opening of large transendothelial cell macroaperture (TEM) tunnels correlated to the dissemination of EDIN-producing strains of Staphylococcus aureus via a hematogenous route or to the induction of gelatinous edema triggered by the edema toxin from Bacillus anthracis. Remarkably, these highly dynamic tunnels close rapidly after they reach a maximal size. Opening and closure of TEMs in cells lasts for hours without inducing endothelial cell death. Multidisciplinary studies have started to provide a broader perspective of both the molecular determinants controlling cytoskeleton organization at newly curved membranes generated by the opening of TEMs and the physical processes controlling the dynamics of these tunnels. Here we discuss the analogy between the opening of TEM tunnels and the physical principles of dewetting, stemming from a parallel between membrane tension and surface tension. This analogy provides a broad framework to investigate biophysical constraints in cell membrane dynamics and their diversion by certain invasive microbial agents.


Assuntos
Bactérias/patogenicidade , Membrana Celular/microbiologia , Membrana Celular/patologia , Células Endoteliais/microbiologia , Células Endoteliais/patologia , Molhabilidade , Membrana Celular/metabolismo , Edema/metabolismo , Edema/microbiologia , Edema/patologia , Células Endoteliais/metabolismo , Humanos , Tensão Superficial
2.
PLoS One ; 15(8): e0232302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822373

RESUMO

Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality. Antisecretory factor (AF), an endogenous protein, is detectable in most tissues and in plasma. The biologically active site of the protein is located in an 8-peptide sequence, contained in a synthetic 16-peptide fragment, named AF-16. The protein as well as the peptide AF-16 has multiple modulatory effects on abnormal fluid transport and edema formation/resolution as well as in a variety of inflammatory conditions. Apart from its' anti-secretory and anti-inflammatory characteristics, AF is an inhibitor of capillary leakage in intestine. It is not known whether the protein AF or the peptide AF-16 can ameliorate symptoms in sepsis. We hypothesized that AF-16 decreases the degree of hemodynamic instability, the need of fluid resuscitation, vasopressor dose and tissue edema in fecal peritonitis. To test the hypothesis, we induced peritonitis and sepsis by injecting autologous fecal solution into abdominal cavity of anesthetized pigs, and randomized (in a blind manner) the animals to intervention (AF-16, n = 8) or control (saline, n = 8) group. After the onset of hemodynamic instability (defined as mean arterial pressure < 60 mmHg maintained for > 5 minutes), intervention with AF-16 (20 mg/kg (50 mg/ml) in 0.9% saline) intravenously (only the vehicle in the control group) and a protocolized resuscitation was started. We recorded respiratory and hemodynamic parameters hourly for twenty hours or until the animal died and collected post mortem tissue samples at the end of the experiment. No differences between the groups were observed regarding hemodynamics, overall fluid balance, lung mechanics, gas exchange or histology. However, liver wet-to-dry ratio remained lower in AF-16 treated animals as compared to controls, 3.1 ± 0.4, (2.7-3.5, 95% CI, n = 8) vs 4.0 ± 0.6 (3.4-4.5, 95% CI, n = 8), p = 0.006, respectively. Bearing in mind the limited sample size, this experimental pilot study suggests that AF-16 may inhibit sepsis induced liver edema in peritonitis-sepsis.


Assuntos
Edema/tratamento farmacológico , Peptídeos/farmacologia , Peritonite/complicações , Sepse/complicações , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Edema/complicações , Edema/patologia , Edema/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hemoglobinas/metabolismo , Interleucina-6/sangue , Lactatos/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Peptídeos/uso terapêutico , Projetos Piloto , Troca Gasosa Pulmonar/efeitos dos fármacos , Suínos , Fator de Necrose Tumoral alfa/sangue , Resistência Vascular/efeitos dos fármacos
3.
Dermatol Online J ; 26(6)2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32815689

RESUMO

We present a 32-year old woman with a 9-year history of upper facial swelling. A workup by the ophthalmology department led to the diagnosis of Melkersson-Rosenthal syndrome. Re-evaluation in our dermatology clinic confirmed a diagnosis of Morbihan disease. Herein, we review case reports and case series of upper facial swelling in the dermatologic and ophthalmologic literature. Although the two entities share histopathological changes, they tend to have different clinical presentations. Melkersson-Rosenthal syndrome appears to be more likely diagnosed in the ophthalmologic literature when the clinical presentation and histopathology may be more consistent with Morbihan disease. In a patient with upper facial swelling, an absence of orolabial swelling, and lack of facial neuropathy, we argue for a diagnosis of Morbihan disease over Melkersson-Rosenthal syndrome, especially if the patient has a history of rosacea.


Assuntos
Edema/diagnóstico , Síndrome de Melkersson-Rosenthal/diagnóstico , Adulto , Diagnóstico Diferencial , Edema/patologia , Eritema/diagnóstico , Feminino , Humanos , Rosácea/complicações , Rosácea/diagnóstico , Pele/patologia
6.
Ann Rheum Dis ; 79(8): 1063-1069, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32522743

RESUMO

OBJECTIVES: To determine the prevalence of bone marrow oedema (BME) at the sacroiliac joint (SIJ) in early postpartum (EPP), nulliparous (NP) and late postpartum (LPP) women, and to identify factors associated with BME presence at the SIJ. METHODS: Three groups were obtained: NP (never given birth), EPP (given birth within 12 months) and LPP (given birth more than 24 months). The primary outcome was the presence of BME and/or structural lesions (erosions, osteophytes, ankylosis and sclerosis) at the SIJ MRI. RESULTS: BME prevalence was greater among EPP (33%) than NP (14%, p=0.001), but was not different to LPP (21%, p=0.071). The Assessment of SpondyloArthritis international Society (ASAS) MRI criteria for sacroiliitis were positive in 75%, 71% and 80%, respectively, of EPP, NP and LPP women with BME. EPP (38%) had similar prevalence of sclerosis than LPP (28%, p=0.135), but greater than NP (18%, p=0.001). Lastly, EPP (28%) had similar prevalence of osteophytes than LPP (42%) and NP (27%), although there was a difference between LPP and NP (p=0.006). CONCLUSIONS: EPP have higher BME prevalence at the SIJ than NP, EPP tend to have higher BME prevalence compared with LPP and BME presence decreases with time from delivery. Three-quarters of women with BME at the SIJ had a positive ASAS MRI criteria for sacroiliitis, indicating that BME presence as the main criterion for a positive diagnosis can lead to false-positive results. SIJ MRIs should not be interpreted in isolation, since age, time from delivery and other factors may outweigh the pertinence of MRI findings. Trial registration number NCT02956824.


Assuntos
Período Pós-Parto , Sacroileíte/diagnóstico por imagem , Espondilartrite/diagnóstico por imagem , Dor nas Costas/etiologia , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Edema/diagnóstico por imagem , Edema/patologia , Feminino , Humanos , Inflamação/diagnóstico por imagem , Inflamação/etiologia , Inflamação/patologia , Imagem por Ressonância Magnética , Paridade , Gravidez , Prevalência , Articulação Sacroilíaca/patologia , Sacroileíte/etiologia , Sacroileíte/patologia , Espondilartrite/patologia
7.
Int J Nanomedicine ; 15: 3497-3509, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547009

RESUMO

Purpose: The existing treatment modalities for rheumatoid arthritis are less effective and safe, therefore it is essential to develop new treatments that particularly target the inflamed joints with decreased off-target side-effects. The current study proposes a nanoparticle-based therapeutic approach to target the anti-oxidant defense system of arthritic Balb/c mice. Methods: Biogenic selenium nanoparticles (SeNPs) were synthesized by using Trachyspermum ammi seed extract and were evaluated for their toxicological, as well as their therapeutic potential in collagen-induced arthritic mice. Results: The tested doses of SeNPs had no significant toxic effects on liver, kidney, spleen, and serum biochemical parameters in comparison to healthy mice. The SeNPs treatment reduced the disease severity, as demonstrated by decreased paw edema along with reduced lymphocytic cellular infiltration in the histopathological findings. SeNPs also revealed dose-independent improvement in the redox state of inflamed synovium by significantly improving the activity of antioxidant enzymes in comparison to the arthritic controls. Conclusion: It is therefore concluded that nano-selenium in combination with TAE extract showed enhanced therapeutic efficacy as compared to their individual effects.


Assuntos
Antirreumáticos/uso terapêutico , Apiaceae/química , Artrite Reumatoide/tratamento farmacológico , Nanopartículas/química , Selênio/toxicidade , Selênio/uso terapêutico , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antirreumáticos/farmacologia , Artrite Reumatoide/patologia , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Bovinos , Edema/patologia , Feminino , Fígado/efeitos dos fármacos , Fígado/enzimologia , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Oxirredução , Extratos Vegetais/química , Selênio/administração & dosagem , Selênio/farmacologia , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Baço/efeitos dos fármacos , Baço/patologia
8.
J Clin Neurosci ; 78: 428-430, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32534722

RESUMO

Intraneural haemangiomas are rare tumours that can affect peripheral nerves. We describe a case of a 10-year-old female with an incidental finding of a common peroneal nerve lesion following knee injury. MRI demonstrated avid heterogeneous enhancement and peri-lesional oedema, and an open biopsy was performed revealing haemangioma on histopathological analysis. The patient was managed with observation and remains intact at 24-month follow-up.


Assuntos
Hemangioma/patologia , Traumatismos do Joelho/complicações , Imagem por Ressonância Magnética/métodos , Nervos Periféricos/patologia , Neuropatias Fibulares/diagnóstico , Criança , Edema/etiologia , Edema/patologia , Feminino , Cistos Glanglionares/diagnóstico , Cistos Glanglionares/patologia , Hemangioma/diagnóstico por imagem , Humanos , Achados Incidentais , Nervo Fibular/patologia , Neuropatias Fibulares/etiologia , Neuropatias Fibulares/patologia
9.
AAPS PharmSciTech ; 21(5): 145, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430787

RESUMO

The present study demonstrates the solubility and dissolution of flufenamic acid (FLF)/ß-cyclodextrin (ß-CD)/Soluplus® supramolecular ternary inclusion complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and the microwave irradiation method. The prepared inclusion complexes were evaluated for physicochemical characterization and anti-inflammatory activity using a murine paw edema mol. The phase solubility studies demonstrated 4.59-fold and 17.54-fold enhancements in FLF solubility with ß-CD alone and ß-CD:Soluplus® combination compared with pure FLF, respectively. The in vitro drug release results revealed a significant improvement (P < 0.05) in the release pattern compared with pure FLF. Maximum release was found with flufenamic acid binary and ternary complexes prepared using the microwave irradiation method, i.e., 75.23 ± 3.12% and 95.36 ± 3.23% in 60 min, respectively. The physicochemical characterization results showed complex formation and conversion of the crystalline form of FLF to an amorphous form. The SEM study revealed the presence of a more agglomerated and amorphous structure of the solid particles, which confirmed the formation of complexes. The anti-inflammatory effect of the complex was higher than pure FLF. Therefore, the FLF:ß-CD:Soluplus® inclusion complex may be a very valuable formulation with improved solubility, dissolution, and anti-inflammatory effect.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Ácido Flufenâmico/química , Ácido Flufenâmico/farmacologia , Polietilenoglicóis/química , Polivinil/química , beta-Ciclodextrinas/química , Animais , Varredura Diferencial de Calorimetria , Carragenina , Cristalização , Composição de Medicamentos , Edema/induzido quimicamente , Edema/patologia , Excipientes , Masculino , Micro-Ondas , Ratos , Ratos Wistar , Solubilidade , beta-Ciclodextrinas/farmacologia
10.
Eur J Clin Invest ; 50(7): e13259, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32353898

RESUMO

BACKGROUND: The clinical features of COVID-19 pneumonia range from a mild illness to patients with a very severe illness with acute hypoxemic respiratory failure requiring ventilation and Intensive Care Unit admission. AIMS: To provide a brief overview of the existing evidence for such differences in host response and outcome, and generate hypotheses for divergent patterns and avenues for future research, by highlighting similarities and differences in histopathological appearance between COVID-19 and influenza as well as previous coronavirus outbreaks, and by discussing predisposition through genetics and underlying disease. MATERIALS AND METHOD: We assessed the available early literature for histopathological patterns of COVID-19 pneumonia and underlying risk factors. RESULT: The histopathological spectrum of COVID-19 pneumonia includes variable patterns of epithelial damage, vascular complications, fibrosis and inflammation. Risk factors for a fatal disease include older age, respiratory disease, diabetes mellitus, obesity and hypertension. DISCUSSION: While some risk factors and their potential role in COVID-19 pneumonia are increasingly recognized, little is known about the mechanisms behind episodes of sudden deterioration or the infrequent idiosyncratic clinical demise in otherwise healthy and young subjects. CONCLUSION: The answer to many of the remaining questions regarding COVID-19 pneumonia pathogenesis may in time be provided by genotyping as well careful clinical, serological, radiological and histopathological phenotyping.


Assuntos
Infecções por Coronavirus/patologia , Edema/patologia , Inflamação/patologia , Pneumonia Viral/patologia , Mucosa Respiratória/patologia , Trombose/patologia , Fatores Etários , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Diabetes Mellitus/epidemiologia , Fibrose , Predisposição Genética para Doença , Antígenos HLA/genética , Humanos , Hipertensão/epidemiologia , Inflamação/imunologia , Influenza Humana/patologia , Obesidade/epidemiologia , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Polimorfismo Genético , Mucosa Respiratória/imunologia , Sistema Respiratório/patologia , Fatores de Risco , Serina Endopeptidases/genética , Síndrome Respiratória Aguda Grave/patologia
11.
Endocrine ; 68(2): 251-252, 2020 May.
Artigo em Inglês | MEDLINE | ID: covidwho-133478
12.
13.
An Acad Bras Cienc ; 92(1): e20181120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321020

RESUMO

the focus ofthis study was to testthe hypothesisthatthere would be no difference betweenthe biocompatibility of silicon dioxide nanofilms used as antimicrobial agents. Sixty male Wistar rats were divided into 4 groups (n=15): Group C (Control,Polyethylene), Group AR (Acrylic Resin), Group NP (Acrylic Resin coated with NP-Liquid), Group BG (Acrylic Resin coated with Bacterlon).the animals were sacrificed with 7,15 and 30 days and tissues analyzed as regardsthe events of inflammatory infiltrate, edema, necrosis, granulation tissue, mutinucleated giant cells, fibroblasts and collagen. Kruskal-Wallis and Dunn tests was used (P<0.05). Intense inflammatory infiltrate was shown mainly in Groups BG and AR, with significant difference from Control Group inthe time interval of 7days (P=0.004). Necrosis demonstrated significant difference between Group BG and Control Group (P<0.05) inthe time intervals of 7 days. For collagen fibers,there was significant difference betweenthe Control Group and Groups AR and BG inthe time interval of 7 days (P=0.006), and between BG and Control Groups inthe time intervals of 15 days (P=0.010).the hypothesis was rejected. Bacterlon demonstratedthe lowest level, and NP-Liquid Glassthe highest level of tissue compatibility, and best cell repair.the coating with NP-Liquid Glass was demonstrated to be highly promising for clinical use.


Assuntos
Resinas Acrílicas/farmacologia , Materiais Biocompatíveis/farmacologia , Edema/induzido quimicamente , Necrose/induzido quimicamente , Dióxido de Silício/farmacologia , Tela Subcutânea/patologia , Resinas Acrílicas/química , Animais , Materiais Biocompatíveis/química , Edema/patologia , Masculino , Teste de Materiais , Modelos Animais , Necrose/patologia , Ratos , Ratos Wistar , Dióxido de Silício/química , Tela Subcutânea/efeitos dos fármacos
14.
Ulus Travma Acil Cerrahi Derg ; 26(2): 171-177, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32185753

RESUMO

BACKGROUND: Studies evaluating the recovery of the zone of stasis is an important issue in burn research. In this study, we aimed to evaluate and compare the efficiency of an anti-ischemic and vasodilatory agent, a topical agent containing 2% nitroglycerin with 1% silver sulfadiazine, and bacitracin-neomycin sulfate in the zone of stasis histomorphologically and immunohistochemically. METHODS: We conducted an experimental study using 30 Wistar-Albino rats, each weighing 250-300 grams. The rats were divided randomly into five groups (six rats in each group). In this study, the "comb model," which was deemed to be the most appropriate experimental model to produce an injury with predictable zones and was first described by Regas and Erhlich, was used. The following were applied to the zone of stasis after creating a burn model in 0, 24, and 48 hours: topical 2% nitroglycerin, 1% silver sulfadiazine, bacitracin-neomycin sulfate, and Vaseline-lanolin (sham). After 72 hours, biopsies were performed from the zone of stasis and evaluated by histomorphological and immunohistochemical CD 34 (expressed in human endothelial and hematopoietic cells) and D 2-40 (expressed in the endothelium of lymphatic capillaries) methods. The results were evaluated using the chi-square test. RESULTS: Compared with the other groups, a statistically significant difference was found in edema, inflammation, and vascular proliferation in the nitroglycerin group. Significantly more intense staining for CD 34 was found in the nitroglycerin group compared with the other groups. Immunohistochemical staining for D 2-40 was also found statistically significant in the nitroglycerin group (p<0.05). CONCLUSION: A topical containing 2% nitroglycerin increases vascular proliferation in the zone of stasis affects the recovery and may be used as a new agent in burn injury treatment.


Assuntos
Queimaduras , Nitroglicerina/farmacologia , Animais , Queimaduras/metabolismo , Queimaduras/patologia , Modelos Animais de Doenças , Edema/metabolismo , Edema/patologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Ratos , Sulfadiazina de Prata/farmacologia , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia
15.
Am J Gastroenterol ; 115(2): 224-233, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31913192

RESUMO

OBJECTIVES: Mast cells (MCs) are increased in eosinophilic esophagitis (EoE). Endoscopic abnormalities, symptoms, and epithelial changes can persist after treatment despite a reduction of esophageal eosinophilia. It is unknown whether this could be due to persistent MC infiltration. We aimed to determine whether patients with histologically inactive (HI) EoE (defined as <15 eosinophils per high-powered field) with persistent symptoms, endoscopic, or epithelial abnormalities after treatment have increased MCs. METHODS: Secondary analysis of prospective data from 93 children with EoE undergoing post-treatment endoscopy between 2011 and 2015. Thirty-five non-EoE controls were included. Immunohistochemistry for tryptase, an MC marker, was performed on mid and distal esophageal biopsies. Total and degranulated intraepithelial MCs per high-powered field (MC/hpf) were quantified. Symptoms and endoscopic findings were recorded at time of endoscopy. MC/hpf were compared between HI-EoE and control, and among HI-EoE based on endoscopic and histologic findings, and symptoms. Nine clinical remission (CR) patients were identified, with absence of endoscopic abnormalities and symptoms. RESULTS: MC/hpf were increased in HI-EoE compared with control (17 ± 11 vs 8 ± 6, P < 0.0). Patients with persistent endoscopic abnormalities had increased total (20 ± 12 vs 13 ± 10, P = 0.001) and degranulated (8 ± 6 vs 5 ± 4, P = 0.002) MC/hpf, with no difference in eosinophils. MC/hpf predicted furrowing (odds ratio = 1.06, P = 0.01) and rings (odds ratio = 1.05, P = 0.03) after controlling for treatment type, proton-pump inhibitor, eosinophils, and duration of therapy. Patients with persistent basal zone hyperplasia and dilated intercellular spaces had increased MC/hpf. Eosinophils were weakly correlated with MC/hpf in the mid (r = 0.30, P < 0.001) and distal (r = 0.29, P < 0.001) esophagus. Clinical remission patients had lower MC/hpf compared with patients with persistent symptoms and/or endoscopic abnormalities. DISCUSSION: MC density is increased in patients with endoscopic and epithelial abnormalities, as well as a few symptoms, despite resolution of esophageal eosinophilia after treatment. This association warrants further study to ascertain whether MCs play an eosinophil independent role in EoE.


Assuntos
Esofagite Eosinofílica/patologia , Eosinófilos/patologia , Mastócitos/patologia , Adolescente , Corticosteroides/uso terapêutico , Criança , Pré-Escolar , Dietoterapia/métodos , Edema/patologia , Esofagite Eosinofílica/fisiopatologia , Esofagite Eosinofílica/terapia , Esofagoscopia , Exsudatos e Transudatos , Feminino , Humanos , Masculino
16.
Am J Forensic Med Pathol ; 41(1): 64-66, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31714289

RESUMO

A lingual abscess is a rare but potentially life-threatening disorder. Since the introduction of antibiotics, the incidence of posterior lingual abscesses has significantly declined; however, this condition is often missed on physical examination or misdiagnosed as another condition. The consequence of this misdiagnosis can be severe because airway obstruction with subsequent difficult or unattainable intubation can develop and lead rapidly to death. Being relatively rare yet potentially lethal, consideration of a lingual abscess at the time of autopsy is important; otherwise, it may be missed. During most autopsies, the base of the tongue is often examined grossly in a cursory fashion, if at all, and microscopic sections of this region are not commonly used. As this case report will illustrate, such an approach would most likely miss this important condition.


Assuntos
Abscesso/patologia , Obstrução das Vias Respiratórias/etiologia , Doenças da Língua/patologia , Edema/patologia , Humanos , Masculino , Pessoa de Meia-Idade
17.
J Plast Surg Hand Surg ; 54(1): 59-65, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31702408

RESUMO

The aim of this study was to verify the possibility of preparation and effectiveness of the use of blood plasma containing an effector of ischemic tolerance activated by applying two sublethal stresses to a donor. As sublethal stresses, two periods of 20-minute hindlimb ischemia were used with a two-day interval between them. Active plasma was isolated six hours after the second hindlimb ischemia. The effectiveness of active plasma as well as remote postconditioning was tested after three hours of tourniquet-induced ischemia on the gastrocnemius muscle. The wet/dry ratio of gastrocnemius muscle (degree of tissue oedema), nitroblue tetrazolium reduction (tissue necrosis), and CatWalk test (hind limb functionality) were evaluated 24 h after the end of ischemia. Three hours of ischemia increased muscle oedema and necrosis in comparison to control by 26.72% (p < 0.001) and 41.58% (p < 0.001) respectively. Remote ischemic postconditioning as well as injection of conditioned blood plasma significantly prevented these changes, even when they were applied one or three hours after the end of ischemia. Equally effective double-conditioned plasma appears to have better prospects in life-threatening situations such as stroke and myocardial infarction.


Assuntos
Membro Posterior/irrigação sanguínea , Pós-Condicionamento Isquêmico/métodos , Músculo Esquelético/irrigação sanguínea , Plasma , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Edema/patologia , Músculo Esquelético/patologia , Necrose , Distribuição Aleatória , Ratos Wistar
18.
Stroke ; 51(1): 129-136, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31744426

RESUMO

Background and Purpose- Patients with active malignancy are at risk for intracerebral hemorrhage (ICH). We aimed to characterize perihematomal edema (PHE) and hematoma volumes after spontaneous nontraumatic ICH in patients with cancer without central nervous system involvement. Methods- Patients with active malignancy who developed ICH were retrospectively identified through automated searches of institutional databases. Control patients were identified with ICH and without active cancer. Demographic and cancer-specific data were obtained by chart review. Hematoma and PHE volumes were determined using semiautomated methodology. Univariate and multivariate linear regression models were created to assess which variables were associated with hematoma and PHE expansion. Results- Patients with cancer (N=80) and controls (N=136) had similar demographics (all P>0.20), although hypertension was more prevalent among controls (P=0.004). Most patients with cancer had received recent chemotherapy (n=45, 56%) and had recurrence of malignancy (n=43, 54%). Patients with cancer were thrombocytopenic (median platelet count 90 000 [interquartile range, 17 500-211 500]), and most had undergone blood product transfusion (n=41, 51%), predominantly platelets (n=38, 48%). Thirty-day mortality was 36% (n=29). Patients with cancer had significantly increased PHE volumes (23.67 versus 8.61 mL; P=1.88×10-9) and PHE-to-ICH volume ratios (2.26 versus 0.99; P=2.20×10-16). In multivariate analyses, variables associated with PHE growth among patients with cancer were ICH volume (ß=1.29 [95% CI, 1.58-1.30] P=1.30×10-5) and platelet transfusion (ß=15.67 [95% CI, 3.61-27.74] P=0.014). Variables associated with 30-day mortality were ICH volume (odds ratio, 1.06 [95% CI, 1.03-1.10] P=6.76×10-5), PHE volume (odds ratio, 1.07 [95% CI, 1.04-1.09] P=7.40×10-6), PHE growth (odds ratio, 1.05 [95% CI, 1.01-1.10] P=0.01), and platelet transfusion (odds ratio, 1.48 [95% CI, 1.22-1.79] P=0.0001). Conclusions- Patients with active cancer who develop ICH have increased PHE volumes. PHE growth was independent of thrombocytopenia but associated with blood product transfusion. Thirty-day mortality was associated with PHE and ICH volumes and blood product transfusion.


Assuntos
Edema Encefálico/patologia , Hemorragia Cerebral/patologia , Hematoma/patologia , Neoplasias/complicações , Idoso , Edema Encefálico/complicações , Hemorragia Cerebral/complicações , Edema/complicações , Edema/patologia , Feminino , Hematoma/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença
19.
Anesth Analg ; 130(2): 525-534, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30801357

RESUMO

BACKGROUND: Metformin, an adenosine monophosphate (AMP)-activated protein kinase activator, as well as a common drug for type 2 diabetes, has previously been shown to decrease mechanical allodynia in mice with neuropathic pain. The objective of this study is to determine if treatment with metformin during the first 3 weeks after fracture would produce a long-term decrease in mechanical allodynia and improve a complex behavioral task (burrowing) in a mouse tibia fracture model with signs of complex regional pain syndrome. METHODS: Mice were allocated into distal tibia fracture or nonfracture groups (n = 12 per group). The fracture was stabilized with intramedullary pinning and external casting for 21 days. Animals were then randomized into 4 groups (n = 6 per group): (1) fracture, metformin treated, (2) fracture, saline treated, (3) nonfracture, metformin treated, and (4) nonfracture, saline treated. Mice received daily intraperitoneal injections of metformin 200 mg/kg or saline between days 14 and 21. After cast removal, von Frey force withdrawal (every 3 days) and burrowing (every 7 days) were tested between 25 and 56 days. Paw width was measured for 14 days after cast removal. AMP-activated protein kinase downregulation at 4 weeks after tibia fracture in the dorsal root ganglia was examined by immunohistochemistry for changes in the AMP-activated protein kinase pathway. RESULTS: Metformin injections elevated von Frey thresholds (reduced mechanical allodynia) in complex regional pain syndrome mice versus saline-treated fracture mice between days 25 and 56 (difference of mean area under the curve, 42.5 g·d; 95% CI of the difference, 21.0-63.9; P < .001). Metformin also reversed burrowing deficits compared to saline-treated tibial fracture mice (difference of mean area under the curve, 546 g·d; 95% CI of the difference, 68-1024; P < .022). Paw width (edema) was reduced in metformin-treated fracture mice. After tibia fracture, AMP-activated protein kinase was downregulated in dorsal root ganglia neurons, and mechanistic target of rapamycin, ribosomal S6 protein, and eukaryotic initiation factor 2α were upregulated. CONCLUSIONS: The important finding of this study was that early treatment with metformin reduces mechanical allodynia in a complex regional pain syndrome model in mice. Our findings suggest that AMP-activated protein kinase activators may be a viable therapeutic target for the treatment of pain associated with complex regional pain syndrome.


Assuntos
Síndromes da Dor Regional Complexa/tratamento farmacológico , Modelos Animais de Doenças , Edema/tratamento farmacológico , Metformina/administração & dosagem , Tempo para o Tratamento , Animais , Síndromes da Dor Regional Complexa/etiologia , Síndromes da Dor Regional Complexa/patologia , Edema/etiologia , Edema/patologia , Feminino , Hipoglicemiantes/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Fraturas da Tíbia/complicações , Fraturas da Tíbia/tratamento farmacológico , Fraturas da Tíbia/patologia
20.
Arch Physiol Biochem ; 126(1): 74-81, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30320514

RESUMO

This study evaluated the anti-inflammatory potential of a 40% prethanol extract of Trifolium pratense leaves (40% PeTP) using in vitro (RAW264.7 cells) and in vivo (carrageenan-induced inflammation model) experiments. Pretreatment with 40% PeTP significantly inhibited the LPS-induced expression of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines, including tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in RAW264.7 cells, without inducing cytotoxicity. The inhibitory effects of 40% PeTP are mediated through suppression of the nuclear translocation of nuclear factor (NF)-κB and the phosphorylation of mitogen-activated protein kinases (MAPKs). Oral administration of 40% PeTP at 50, 100, and 200 mg/kg of body weight suppressed carrageenan-induced oedema in a dose-dependent manner. Collectively, our results suggested that 40% PeTP exerts potential anti-inflammatory effects by suppressing the activation of the NF-κB and MAPK pathways in vitro, and by reducing carrageenan-induced paw oedema in vivo.


Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/genética , NF-kappa B/genética , Extratos Vegetais/farmacologia , Trifolium/química , Administração Oral , Animais , Carragenina/administração & dosagem , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/antagonistas & inibidores , Dinoprostona/biossíntese , Modelos Animais de Doenças , Esquema de Medicação , Edema/induzido quimicamente , Edema/genética , Edema/patologia , Regulação da Expressão Gênica , Inflamação , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Folhas de Planta/química , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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