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INTRODUCTION/AIMS: T2 magnetic resonance imaging (MRI) mapping has been applied to carpal tunnel syndrome (CTS) for quantitative assessment of the median nerve. However, quantitative changes in the median nerve before and after surgery using T2 MRI mapping remain unclear. We aimed to investigate whether pathological changes could be identified by pre- and postoperative T2 MRI mapping of the median nerve in CTS patients after open carpal tunnel release. METHODS: This was a prospective study that measured median nerve T2 and cross-sectional area (CSA) values at the distal carpal tunnel, hamate bone, proximal carpal tunnel, and forearm levels pre- and postoperatively. Associations between T2, CSA, and nerve conduction latency were also evaluated. RESULTS: A total of 36 patients with CTS (mean age, 64.5 ± 11.7 years) who underwent surgery were studied. The mean preoperative T2 values significantly decreased from 56.3 to 46.9 ms at the proximal carpal tunnel levels (p = .001), and from 52.4 to 48.7 ms at the hamate levels postoperatively (p = .04). Although there was a moderate association between preoperative T2 values at the distal carpal tunnel levels and distal motor latency values (r = -.46), other T2 values at all four carpal tunnel levels were not significantly associated with CSA or nerve conduction latency pre- or postoperatively. DISCUSSION: T2 MRI mapping of the carpal tunnel suggested a decrease in nerve edema after surgery. T2 MRI mapping provides quantitative information on the median nerve before and after surgery.
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Síndrome do Túnel Carpal , Imageamento por Ressonância Magnética , Nervo Mediano , Condução Nervosa , Humanos , Síndrome do Túnel Carpal/cirurgia , Síndrome do Túnel Carpal/diagnóstico por imagem , Nervo Mediano/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Condução Nervosa/fisiologia , Estudos Prospectivos , AdultoRESUMO
OBJECTIVES: This study aimed to compare the pre- and postoperative morphology of the median nerve using three-dimensional (3-D) MRI in patients with carpal tunnel syndrome (CTS). METHODS: We assessed 31 patients with CTS who underwent open carpal tunnel release and T2*-weighted MRI of the wrist preoperatively and at 6 months postoperatively. The median nerve morphology was evaluated on the basis of the cross-sectional areas (CSAs) and cross-sectional volumes (CSVs). The association between these MRI findings and nerve conduction studies was also evaluated. RESULTS: The mean preoperative CSA and CSV values at the proximal carpal tunnel level significantly decreased from 22.2 mm2 and 24.4 mm3 to 16.5 mm2 and 18.1 mm3, respectively, postoperatively. Median nerve swelling at the proximal carpal tunnel level was observed in 29 (94%) and 23 (74%) patients before and after surgery, respectively. The mean preoperative CSA and CSV values at the hamate level significantly increased from 9.9 to 12.3 mm2 and from 10.9 to 13.5 mm3 after surgery, respectively. Nerve narrowing at the hamate bone level was preoperatively observed in 28 (90%) patients and postoperatively in 21 (68%) patients. Preoperative CSA and CSV values at the proximal carpal tunnel were significantly associated with preoperative distal motor and sensory latency. CONCLUSIONS: Visual confirmation of the median nerve morphology using 3-D MRI is useful when considering postoperative recovery and explaining the nerve condition to the patients. KEY POINTS: ⢠The 3-D morphology of the median nerve after carpal tunnel release can be delineated using 3-D MRI. ⢠Preoperative swelling of the median nerve in the 2-D and 3-D planes reflects the severity of carpal tunnel syndrome. ⢠Visual confirmation of the median nerve morphology is useful when considering median nerve recovery after carpal tunnel release and for explaining the condition of the nerve to patients.
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Síndrome do Túnel Carpal , Nervo Mediano , Síndrome do Túnel Carpal/diagnóstico por imagem , Síndrome do Túnel Carpal/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Nervo Mediano/patologia , Punho/diagnóstico por imagem , Articulação do PunhoRESUMO
INTRODUCTION: We investigated the changes in MRI T2 mapping values in subjects with carpal tunnel syndrome (CTS) compared to healthy controls. METHODS: We enrolled 71 patients with CTS and 26 healthy controls. Median nerve T2 values were measured at the distal carpal tunnel, hamate bone, proximal carpal tunnel, and forearm levels. These were compared between patients and controls and correlated with median nerve cross-sectional area (CSA) and nerve conduction measurements. RESULTS: The mean T2 values at the proximal carpal tunnel levels were higher in the CTS group (56.7 ms) than in the control group (51.2 ms, P = .02) and also were higher than at the distal carpal tunnel (51.0 ms, P < .001) and forearm levels (47.6 ms, P < .001). T2 values were not significantly associated with CSA or nerve conduction measurements. DISCUSSION: T2 mapping of the carpal tunnel provides qualitative information on median nerve pathology but does not reflect CTS severity.
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Síndrome do Túnel Carpal/diagnóstico por imagem , Nervo Mediano/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
Microchannel (MC) emulsification for the preparation of monodisperse oil-in-water (O/W) and water-in-oil-in-water (W/O/W) emulsions containing palm oil as the oil phase was investigated for application as basic material solid/semi-solid lipid microspheres for delivery carriers of nutrients and drugs. Emulsification was characterized by direct observation of droplet generation under various operation conditions, as such, the effects of type and concentration of emulsifiers, emulsification temperature, MC structure, and flow rate of to-be-dispersed phase on droplet generation via MC were investigated. Sodium caseinate (SC) was confirmed as the most suitable emulsifier among the examined emulsifiers, and monodisperse O/W and W/O/W emulsions stabilized by it were successfully obtained with 20 to 40 µm mean diameter (dm) using different types of MCs.
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Emulsões/química , Lipídeos/química , Óleo de Palmeira/química , Água/química , Caseínas/química , Caseínas/farmacologia , Emulsificantes/química , Emulsões/farmacologia , Microesferas , Óleo de Palmeira/farmacologia , Tamanho da Partícula , TemperaturaRESUMO
OBJECTIVE: We examined the surgical outcomes of the Sauvé-Kapandji (S-K) procedure using a headless compression screw and a metal cancellous screw in patients with rheumatoid arthritis (RA). METHODS: This retrospective study included 41 RA patients who underwent the S-K procedure for distal radioulnar joint disorders with two screws: headless compression screws (HCS group, n = 20) and cannulated cancellous screws (CCS group, n = 21). Clinical and radiographic outcomes were assessed 1 year after surgery. Radiographic outcomes included bony union of the distal radioulnar joint (DRUJ), bone resorption around the screw, a screw back-out, and use of additional K-wire. We investigated any complications related to the screw head. RESULTS: All 20 patients in the HCS group showed bone fusion of the DRUJ. In the CCS group, an asymptomatic non-union was observed in one patient and additional K-wire was needed to stabilize the DRUJ in three patients. No patients complained of any complications related to the screw head in the HCS group, while the CCS group demonstrated the hardware protrusion in two patients who complained of tenderness or discomfort at the screw head. CONCLUSIONS: The use of a headless compression screw in the S-K procedure is useful in patients with RA.
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Artrite Reumatoide/cirurgia , Artrodese/métodos , Parafusos Ósseos , Articulação do Punho/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Resultado do Tratamento , Articulação do Punho/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Aberrant expression of T helper cell (Th) cytokines is believed to play a central role in the pathogenesis of systemic lupus erythematosus (SLE). While the glomerulus is one of the major targets of lupus inflammation, little is known about the cytokine expression in glomeruli. The current study aimed to explore the profiles of Th cytokine gene expressions in isolated glomeruli of lupus-prone mice. METHODS: Glomeruli were purified from lupus-prone MRL/lpr mice using the magnetic microbead method. Expressions of cytokine genes representing the Th subset and FoxP3 were examined using real-time polymerase chain reaction. Serum levels of these cytokines were also measured by enzyme-linked immunosorbent assay. MRL/n mice were used as controls. Histologic glomerular damages were scored semiquantitatively. To examine the role of TNF-α in glomerular damage, we administered etanercept, a TNF-α antagonist, into the subjects. RESULTS: Glomerular gene expressions of TNF-α in lpr mice increased with week postpartum and reached statistically significant levels at 16 weeks compared with those of the glomeruli from control mice. Expressions of IFN-γ, IL-4 and FoxP3 also increased, but the difference was not significant. There was a significant increase in serum levels of TNF-α, IFN-γ, and IL-17 and decrease in those of IL-4. Among the genes examined, TNF-α significantly correlated with glomerular damage score. Administration of etanercept did not affect glomerular cytokine expressions or proteinuria and failed to ameliorate histologic glomerular damages. CONCLUSION: Our data suggest that Th1 cytokines, especially TNF-α, are dominantly expressed in the glomeruli of lupus-prone mice, but its pathophysiological role remains unclear.
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Citocinas/metabolismo , Glomérulos Renais/metabolismo , Nefrite Lúpica/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Animais , Produtos Biológicos/farmacologia , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Etanercepte/farmacologia , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Nefrite Lúpica/genética , Nefrite Lúpica/imunologia , Nefrite Lúpica/patologia , Camundongos Endogâmicos MRL lpr , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Fatores de TempoRESUMO
Lecithin-cholesterol acyltransferase (LCAT) is an enzyme involved in maintaining cholesterol homeostasis. In familial LCAT deficiency (FLD), abnormal lipid deposition causes renal injury and nephrotic syndrome, frequently progressing to ESRD. Here, we describe a 63-year-old Japanese woman with no family history of renal disease who presented with nephrotic syndrome. The laboratory data revealed an extremely low level of serum HDL and undetectable serum LCAT activity. Renal biopsy showed glomerular lipid deposition with prominent accumulation of foam cells, similar to the histologic findings of FLD. In addition, she had subepithelial electron-dense deposits compatible with membranous nephropathy, which are not typical of FLD. A mixing test and coimmunoprecipitation study demonstrated the presence of an inhibitory anti-LCAT antibody in the patient's serum. Immunohistochemistry and immunofluorescence detected LCAT along parts of the glomerular capillary walls, suggesting that LCAT was an antigen responsible for the membranous nephropathy. Treatment with steroids resulted in complete remission of the nephrotic syndrome, normalization of serum LCAT activity and HDL level, and disappearance of foam cell accumulation in renal tissue. In summary, inhibitory anti-LCAT antibody can lead to glomerular lesions similar to those observed in FLD.
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Glomerulonefrite Membranosa/etiologia , Rim/patologia , Deficiência da Lecitina Colesterol Aciltransferase/diagnóstico , Síndrome Nefrótica/etiologia , Feminino , Imunofluorescência , Glomerulonefrite Membranosa/patologia , Humanos , Imuno-Histoquímica , Deficiência da Lecitina Colesterol Aciltransferase/complicações , Deficiência da Lecitina Colesterol Aciltransferase/patologia , Pessoa de Meia-Idade , Síndrome Nefrótica/patologiaRESUMO
OBJECTIVES: To examine the efficacy and safety of multi-target therapy using tacrolimus (TAC), mycophenolate mofetil (MMF) and a steroid as initial treatment for active lupus nephritis (LN). METHODS: We conducted a retrospective analysis of the data of 16 consecutive patients who received the multi-target therapy for active Classes III-V LN at our department. We also compared the outcomes of the multi-target therapy with those of TAC therapy (TAC + steroid), a study of which we had conducted previously in 13 patients with active LN (TAC group). RESULTS: All the patients treated with multi-target therapy achieved complete remission (CR) (mean, 4.6 ± 3.8 months; range, 1-15 months). The clinical profiles of the patients of the multi-target group were similar to those of the TAC group at baseline, except for a significantly higher level of proteinuria (4.6 ± 2.8 vs. 2.5 ± 2.1 g/gCr, p = 0.033) in the former. The CR rate at 6 months was significantly higher in the multi-target group as compared with that in the TAC group (81% vs. 38%, p = 0.018). Two cases of serious adverse events were associated with cytomegalovirus infection in the multi-target group, namely gastric ulcer and pancytopenia, both of which were successfully treated by antiviral therapy. CONCLUSIONS: Multi-target therapy was effective as initial treatment for active LN, with CR achieved early and in a high percentage of patients. Although this therapy was generally well tolerated, it is important to bear in mind the associated risk of cytomegalovirus infection.
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Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Prednisolona/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Prednisolona/efeitos adversos , Indução de Remissão , Estudos Retrospectivos , Tacrolimo/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
Substrate specificity in non-aqueous esterification catalyzed by commercial lipases activated by hydration-aggregation pretreatment was investigated. Four microbial lipases from Rhizopus japonicus, Burkholderia cepacia, Rhizomucor miehei, and Candida antarctica (fraction B) were used to study the effect of the carbon chain length of saturated fatty acid substrates on the esterification activity with methanol in n-hexane. Hydration-aggregation pretreatment had an activation effect on all lipases used, and different chain length dependencies of esterification activity for lipases from different origins were demonstrated. The effects of various acidic substrates with different degrees of unsaturation, aromatic rings, and alcohol substrates with different carbon chain lengths on esterification activity were examined using R. japonicus lipase, which demonstrated the most remarkable activity enhancement after hydration-aggregation pretreatment. Furthermore, in the esterification of myristic acid with methanol catalyzed by the hydrated-aggregated R. japonicus lipase, maximum reaction rate (5.43 × 10-5 mmol/(mg-biocat min)) and Michaelis constants for each substrate (48.5â¯mM for myristic acid, 24.7â¯mM for methanol) were determined by kinetic analysis based on the two-substrate Michaelis-Menten model.
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A novel immobilized chitosanase was developed and utilized to produce chitosan oligosaccharides (COSs) via chitosan hydrolysis. Magnetite-agar gel particles (average particle diameter: 338 µm) were prepared by emulsifying an aqueous agar solution dispersing 200-nm magnetite particles with isooctane containing an emulsifier at 80 °C, followed by cooling the emulsified mixture. The chitosanase from Bacillus pumilus was immobilized on the magnetite-agar gel particles chemically activated by introducing glyoxyl groups with high immobilization yields (>80%), and the observed specific activity of the immobilized chitosanase was 16% of that of the free enzyme. This immobilized chitosanase could be rapidly recovered from aqueous solutions by applying magnetic force. The thermal stability of the immobilized chitosanase improved remarkably compared with that of free chitosanase: the deactivation rate constants at 35 °C of the free and immobilized enzymes were 8.1 × 10-5 and 3.9 × 10-8 s-1, respectively. This immobilized chitosanase could be reused for chitosan hydrolysis at 75 °C and pH 5.6, and 80% of its initial activity was maintained even after 10 cycles of use. COSs with a degree of polymerization (DP) of 2-7 were obtained using this immobilized chitosanase, and the product content of physiologically active COSs (DP ≥ 5) reached approximately 50%.
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Ágar , Bacillus , Quitosana , Estabilidade Enzimática , Enzimas Imobilizadas , Glicosídeo Hidrolases , Oligossacarídeos , Quitosana/química , Quitosana/metabolismo , Enzimas Imobilizadas/metabolismo , Enzimas Imobilizadas/química , Glicosídeo Hidrolases/metabolismo , Glicosídeo Hidrolases/química , Oligossacarídeos/química , Oligossacarídeos/metabolismo , Oligossacarídeos/biossíntese , Hidrólise , Bacillus/enzimologia , Ágar/química , Géis/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Óxido Ferroso-Férrico/química , Biocatálise , Concentração de Íons de Hidrogênio , CinéticaRESUMO
Hand osteoarthritis (HOA), characterized by an earlier onset age and reduced susceptibility to mechanical stress compared with knee and hip osteoarthritis, is considered a suitable disease for identifying predictive biomarkers of osteoarthritis. In particular, DNA methylation variants, expected to contribute to HOA susceptibility, hold potential as osteoarthritis biomarkers. In this study, leukocyte DNA methylation patterns were analyzed in blood samples from patients with HOA, aiming to identify disease-specific biomarkers for osteoarthritis. Using DNA methylation microarrays, we analyzed samples from three subjects with HOA and three age- and gender-matched healthy individuals. For validation, pyrosequencing analysis was conducted using samples from 16 to 9 subjects with and without HOA, respectively. From 735,026 probes in the DNA methylation array, the Top 100 CpG sites associated with HOA, based on low adjusted P-values, including those targeting bone morphogenetic protein 7 (BMP7), SBF2-AS1, PLOD2, ICOS, and CSF1R were identified. Validation analysis revealed significantly higher methylation levels in the BMP7-related site in the HOA group compared with the control group, even after adjusting for age, gender, and body mass index (p = 0.037). In contrast, no significant difference was observed in the other selected CpG sites between the HOA and control groups. This study highlights the significantly increased frequency of methylation at the specific BMP7 site in leukocytes of patients with HOA, suggesting its potential as a biomarker for HOA. Measurement of methylation levels at the CpG sites identified in this study offers a potential approach to prevent future osteoarthritis progression, providing valuable insights into disease management.
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OBJECTIVES: To investigate the clinical characteristics and risk factors of Pneumocystis jirovecii pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with adalimumab. METHODS: We conducted a multicenter, retrospective, case-control study to compare RA patients treated with adalimumab with and without PCP. Data from 17 RA patients who were diagnosed with PCP and from 89 RA patients who did not develop PCP during adalimumab treatment were collected. RESULTS: For the PCP patients, the median age was 68 years old, with a median RA disease duration of eight years. The median length of time from the first adalimumab injection to the development of PCP was 12 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 5.0 mg/day and 8.0 mg/week, respectively. The patients with PCP were significantly older (p < 0.05) and had more structural changes (p < 0.05) than the patients without PCP. Computed tomography of the chest revealed ground-glass opacity without interlobular septal boundaries in the majority of the patients with PCP. Three PCP patients died. CONCLUSIONS: PCP may occur early in the course of adalimumab therapy in patients with RA. Careful monitoring, early diagnosis, and proper management are mandatory to secure a good prognosis for these patients.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Adalimumab , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Estudos de Casos e Controles , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/etiologia , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Estudos Retrospectivos , Fatores de RiscoRESUMO
We studied the encapsulation of iohexol (Ihex), a nonionic contrast agent used for X-ray computational tomography, into lipid vesicles using the multiple emulsification-solvent evaporation method to formulate a nanosized contrast agent. This lipid vesicle preparation method consists of three steps: (1) primary emulsification for producing water-in-oil (W/O) emulsions containing fine water droplets that will be converted to the internal water phase of the lipid vesicles, (2) secondary emulsification for formulating multiple water-in-oil-in-water (W/O/W) emulsions encapsulating the fine water droplets containing Ihex, and (3) solvent evaporation to remove the oil phase solvent (n-hexane) and to form lipid bilayers surrounding the fine inner droplets, resulting in the formation of lipid vesicles encapsulating Ihex. As the diameter and Ihex concentration of the primary W/O emulsion droplets decreased, a higher Ihex encapsulation yield was obtained for the final lipid vesicles. The entrapment yield of Ihex in the final lipid vesicles varied significantly with the emulsifier (Pluronic® F-68) concentration in the external water phase of W/O/W emulsion, and the highest yield (65%) was obtained when the emulsifier concentration was 0.1 wt%. We also investigated the powderization of lipid vesicles encapsulating Ihex via lyophilization. The powderized vesicles were dispersed in water after rehydration and maintained their controlled diameters. The entrapment yield of Ihex in powderized lipid vesicles was maintained for over 1 month at 25 ËC, while significant leakage of Ihex was observed in the lipid vesicles suspended in the aqueous phase.
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Meios de Contraste , Água , Solventes , Emulsões , Bicamadas Lipídicas , Tomografia Computadorizada por Raios XRESUMO
Recovery after acute kidney injury is impaired in the elderly, but the precise mechanism for such age-related incompetence remains unclear. By in vivo bromodeoxyuridine (BrdU) labeling, renal progenitor cells (label-retaining cells; LRCs) were identified in tubules of normal rat kidney and were shown to be the origin of proliferating cells after injury. In the present study, the involvement of LRCs in the age-related decline of tubular recovery after injury was examined. After 1 wk of BrdU labeling followed by a 2-wk chase period, ischemia-reperfusion injury was induced in 7-wk-, 7-mo-, and 12-mo-old rats. Age-related decreases in DNA synthesis and cell proliferation in renal tubules after injury were found. The number of LRCs also significantly declined with age. At 24 h after reperfusion, the number of LRCs significantly increased in all ages of rats tested. There was no significant difference in the ratio of LRC division among rats of different ages. The area of the rat endothelial cell antigen (RECA)-1-positive capillary network declined with age. When renal tubules isolated from rats treated with BrdU label were cocultured with human umbilical vein endothelial cells (HUVEC), the number of LRCs significantly increased compared with tubules cultured without HUVEC. These data suggest that the reduced capacity of tubular regeneration in the aging kidney is partly explained by the shortage of LRC reserves. The size of the LRC pool might be regulated by the surrounding peritubular capillary network.
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Envelhecimento/fisiologia , Rim/citologia , Rim/fisiologia , Regeneração/fisiologia , Células-Tronco/fisiologia , Animais , Bromodesoxiuridina , Células Cultivadas , Técnicas de Cocultura , Células Endoteliais , Regulação da Expressão Gênica , Humanos , Rim/lesões , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão , Coloração e RotulagemRESUMO
OBJECTIVE: To examine whether IL-6 promotes angiogenesis by modulating angiopoietin (Ang) expression in RA. METHODS: Synovial fibroblasts derived from RA patients (RASFs) and human umbilical vein endothelial cells (HUVECs) were co-cultured for 6 days with or without recombinant IL-6, VEGF or Ang-1. HUVECs were stained with anti-CD31 antibody and their growth was determined by quantifying the CD31-positive area. SFs were collected from RA (n = 25) and OA (n = 7) patients. RESULTS: In the co-culture system, IL-6 and VEGF significantly enhanced HUVEC growth to a similar extent. However, the morphology of proliferating cells was distinct between IL-6- and VEGF-stimulated HUVEC. HUVEC stimulated with IL-6 exhibited small, loose clusters surrounded by dispersed single cells, suggesting destabilized angiogenesis by IL-6. In the supernatants, IL-6 up-regulated VEGF compared with controls and Ang-2, while it down-regulated Ang-1. In contrast, down-regulation of Ang-1 was not observed with VEGF stimulation. Consistent with the destabilized morphology, stimulation with IL-6 decreased cell surface expression of vascular endothelial cadherin (VE-cadherin) on HUVEC, presumably by inducing internalization. Interestingly, adding recombinant Ang-1 partially inhibited IL-6-induced morphological changes in HUVEC including a destabilized morphology with small, loose clusters and internalization of VE-cadherin. In SFs from RA patients, VEGF was negatively correlated with Ang-1 (r = -0.559, P=0.004). CONCLUSION: IL-6 not only enhances VEGF expression but also inhibits Ang-1 signalling by directly down-regulating Ang-1 expression and up-regulating Ang-2, an antagonist of Ang-1. These synergistic effects may play a critical role in destabilized angiogenesis in RA.
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Angiopoietina-1/metabolismo , Artrite Reumatoide/imunologia , Interleucina-6/farmacologia , Neovascularização Patológica/tratamento farmacológico , Angiopoietina-1/farmacologia , Artrite Reumatoide/patologia , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Neovascularização Patológica/patologia , Proteínas Recombinantes , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
OBJECTIVE: In RA, response to TNF blockers may be associated with a profile of cytokine production unique to each patient. This study sought to predict the response to biologic agents by examining pro-inflammatory cytokine synthesis in stimulated whole blood cultures (WBCs). METHODS: We measured the concentration of TNF-α, IL-1ß and IL-6 in supernatants of lipopolysaccharide (LPS)-stimulated WBCs obtained from RA patients (n = 41) before anti-TNF therapy (infliximab, 13; etanercept, 26; and adalimumab, 2) and from healthy controls (n = 12). At 24 weeks after biologics, whole bloods were again drawn from 14 of 41 patients. Response was defined by the European League Against Rheumatism response criteria after 24 weeks of therapy. RESULTS: Among 41 patients, 32 were responders (good 14/moderate 18), while 9 were non-responders. All cytokines measured were significantly lower in RA patients than in controls. In RA, IL-1ß production was lower in non-responders than in responders [median (interquartile range): 3.5 (1.5-9.4) vs 10.0 (5.1-93.1) pg/ml, P = 0.048]. The area under the curve from a receiver operating characteristic curve analysis for the prediction of response using IL-1ß was 0.717 (95% CI 0.520, 0.914). The sensitivity and specificity of IL-1ß (cut-off value 4.84 pg/ml) was 78.1 and 77.8%, respectively. All cytokines were significantly higher 6 months later compared with their respective baseline. CONCLUSION: IL-1ß measurement in LPS-stimulated WBC is useful to predict responsiveness to anti-TNF agents. Cytokine production capacities in LPS-stimulated WBCs are up-regulated by biologics.
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Anticorpos Monoclonais/farmacologia , Antirreumáticos/farmacologia , Artrite Reumatoide/sangue , Células Sanguíneas/efeitos dos fármacos , Interleucina-1beta/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Anticorpos Monoclonais Humanizados/farmacologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Células Sanguíneas/metabolismo , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Etanercepte , Feminino , Humanos , Imunoglobulina G/farmacologia , Infliximab , Interleucina-1beta/análise , Lipopolissacarídeos/farmacologia , Masculino , Valor Preditivo dos Testes , Curva ROC , Receptores do Fator de Necrose Tumoral/uso terapêutico , Resultado do TratamentoRESUMO
The 'lipid-coated ice-droplet hydration method' was applied for the preparation of milliliter volumes of a suspension of giant phospholipid vesicles containing in the inner aqueous vesicle pool in high yield either calcein, α-chymotrypsin, fluorescently labeled bovine serum albumin or dextran (FITC-BSA and FITC-dextran; FITC=fluorescein isothiocyanate). The vesicles had an average diameter of ca. 7-11 µm and contained 20-50% of the desired molecules to be entrapped, the entrapment yield being dependent on the chemical structure of the entrapped molecules and on the details of the vesicle-formation procedure. The 'lipid-coated ice droplet hydration method' is a multistep process, based on i) the initial formation of a monodisperse water-in-oil emulsion by microchannel emulsification, followed by ii) emulsion droplet freezing, and iii) surfactant and oil removal, and replacement with bilayer-forming lipids and an aqueous solution. If one aims at applying the method for the entrapment of enzymes, retention of catalytic activity is important to consider. With α-chymotrypsin as first model enzyme to be used with the method, it was shown that high retention of enzymatic activity is possible, and that the entrapped enzyme molecules were able to catalyze the hydrolysis of a membrane-permeable substrate which was added to the vesicles after their formation. Furthermore, one of the critical steps of the method that leads to significant release of the molecules from the water droplets was investigated and optimized by using calcein as fluorescent probe.
Assuntos
Quimotripsina/administração & dosagem , Dextranos/administração & dosagem , Fluoresceína-5-Isotiocianato/análogos & derivados , Lipossomos/química , Fosfolipídeos/química , Soroalbumina Bovina/administração & dosagem , Animais , Bovinos , Emulsões/química , Fluoresceína-5-Isotiocianato/administração & dosagem , Água/químicaRESUMO
We describe a case of relapsed granulomatosis with polyangiitis (Wegener's) (GPA) that presented with abdominal pain. (18)F-fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET)/computed tomography (CT) clearly depicted an inflammation of the left peri-iliac arterial soft tissue, which was thought to be the cause of the ureteral obstruction and hydronephrosis. Our case shows that peri-iliac arterial inflammation occurs in GPA and causes hydronephrosis. In addition, FDG-PET/CT is a useful tool for management of this systemic inflammatory disease.
Assuntos
Granulomatose com Poliangiite/diagnóstico , Hidronefrose/diagnóstico , Poliangiite Microscópica/diagnóstico , Idoso , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Fluordesoxiglucose F18 , Glucocorticoides/uso terapêutico , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Hidronefrose/etiologia , Hidronefrose/cirurgia , Imunossupressores/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Poliangiite Microscópica/complicações , Poliangiite Microscópica/tratamento farmacológico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Recidiva , Indução de Remissão , Tomografia Computadorizada de Emissão , Tomografia Computadorizada por Raios XRESUMO
Capsaicin (CAP) demonstrates a potential for application in the food and pharmaceutical industries owing to its various attractive health benefits, including anti-cancer, anti-inflammatory, and antioxidant activities. However, the application of CAP is often limited by its low solubility in water, low bioavailability, and strong pungency. In this study, a simple one-step method for the stable encapsulation and dispersion of CAP in aqueous media was developed using polyelectrolyte complex particles formed by chitosan (CHI) and oleic acid (OA). Homogeneous particles with mean diameters below 1 µm were successfully prepared via spontaneous molecular complexation by mixing an aqueous solution of CHI with an ethanolic solution of OA and CAP. CAP was incorporated into the hydrophobic domains of the CHI-OA complex particles through hydrophobic interactions between the alkyl chains of OA and CAP. The factors affecting CAP encapsulation were investigated, and a maximum encapsulation yield of approximately 100% was obtained. The CHI-OA-CAP complex particles could be stored for more than 3 months at room temperature (22-26 °C) without resulting in macroscopic phase separation or degradation of CAP. We believe that our findings provide a useful alternative encapsulation technique for CAP and contribute to expanding its practical application.