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1.
BMC Immunol ; 22(1): 77, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34920714

RESUMO

BACKGROUND: Inflammatory arthritis including rheumatoid arthritis (RA) and spondyloarthritis (SpA) is characterized by inflammation and destruction of the joints. Approximately one third of patients do not respond to first-line treatments. Nitro-fatty acids are bioactive lipids with anti-inflammatory properties and tissue-protective functions. The nitro-fatty acid 10-NO2-oleic acid (10-NO2-OA) is being tested in clinical trials for patients with fibrotic and inflammatory conditions. Here, we tested whether 10-NO2-OA could inhibit immune reactions involved in the inflammatory and joint destructive processes in inflammatory arthritis. METHODS: Synovial fluid and blood samples were obtained from 14 patients with active RA or SpA. The in vitro models consisted of synovial fluid mononuclear cells (SFMCs) cultured for 48 h, SFMCs cultured for 21 days, and fibroblast-like synovial cells (FLSs) co-cultured with peripheral blood mononuclear cells (PBMCs) for 48 h. Cells were treated with or without 10-NO2-OA or the tumor necrosis factor alpha (TNFα) inhibitor etanercept. Supernatants were analyzed for type I interferon, monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase 3 (MMP3) and tartrate resistant acid phosphatase (TRAP). RESULTS: In SFMCs cultured for 48 h, 10-NO2-OA dose-dependently decreased the secretion of bioactive type I interferons and MCP-1 but not MMP3 (P = 0.032, P = 0.0001, and P = 0.58, respectively). Both MCP-1 and MMP3 were decreased by etanercept (P = 0.0031 and P = 0.026, respectively). In SFMCs cultured for 21 days, 10-NO2-OA significantly decreased the production of MCP-1 but not TRAP (P = 0.027 and P = 0.1523, respectively). Etanercept decreased the production of TRAP but not MCP-1 (P < 0.001 and P = 0.84, respectively). In co-cultures of FLSs and PBMCs, 10-NO2-OA decreased the production of MCP-1 (P < 0.0001). This decrease in MCP-1 production was not seen with etanercept treatment (P = 0.47). CONCLUSION: 10-NO2-OA decreased the release of MCP-1 in three models of inflammatory arthritis. Of particular interest, 10-NO2-OA inhibited type I interferon, and 10-NO2-OA was more effective in reducing MCP-1 production in cultures dominated by FLSs compared with etanercept. Our results encourage clinical investigations of 10-NO2-OA in patients with inflammatory arthritis.


Assuntos
Anti-Inflamatórios/metabolismo , Artrite Reumatoide/metabolismo , Fibroblastos/fisiologia , Leucócitos Mononucleares/imunologia , Ácidos Oleicos/metabolismo , Espondilite Anquilosante/metabolismo , Líquido Sinovial/imunologia , Adulto , Células Cultivadas , Quimiocina CCL2/metabolismo , Técnicas de Cocultura , Etanercepte/farmacologia , Feminino , Humanos , Interferon Tipo I/metabolismo , Masculino , Pessoa de Meia-Idade
2.
Artigo em Inglês | MEDLINE | ID: mdl-29797704

RESUMO

INTRODUCTION: An obturator nerve block (ONB) and a femoral triangle block (FTB) provide effective analgesia after total knee arthroplasty (TKA) without impeding the ambulation, although the ONB produces motor blockade of the hip adductor muscles. The popliteal plexus (PP) in the popliteal fossa is formed by contribution from the tibial nerve and the posterior obturator nerve, innervating intraarticular genicular structures and the posterior capsule of the knee. We hypothesised that a popliteal plexus block (PPB) as a supplement to an FTB would reduce pain after TKA without anaesthetising motor branches from the sciatic nerve in the popliteal fossa. AIM: To assess the analgesic effect of adding a PPB to an FTB in 10 subjects with significant pain after TKA. METHODS: All subjects underwent unilateral TKA with spinal anaesthesia and received an FTB. The cutaneous sensation and the postoperative pain were assessed. The primary outcome was the proportion of subjects with pain above numeric rating scale (NRS) 3 followed by a reduction to NRS 3 or below after conducting a PPB. RESULTS: Ten subjects with a median pain of NRS 5.5 (interquartile range [IQR] 4-8) after unilateral TKA received a PPB. All 10 subjects experienced a reduction in pain to NRS 3 or below (NRS 1.5 [IQR 0-3]) within a mean time of 8.5 (95% CI 6.8-10.2) minutes. Three subjects were completely pain free after the PPB. The ankle muscle strength was not affected. CONCLUSIONS: The PPB provided effective pain relief without affecting the ankle muscle strength in all 10 subjects with significant pain after TKA and an FTB.

3.
Phys Rev E ; 95(2-1): 022605, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28297870

RESUMO

We study, using Langevin dynamics simulations, the change in composition of a binary colloidal mixture confined in a finite-length channel, induced by an external field. The field-induced transition from a near-bulk composition to an inverted population is studied as a function of time, for different field strengths and system parameters. For state points corresponding to reversible field cycles, the cyclic filling and emptying of the channel by the minority species are compared. Extrapolation of the physical relaxation times to the colloidal regime is performed through a series of simulations at increasing value of the damping parameter. For state points at which the mixture is unstable at zero field, reproducible irreversible cycles are illustrated. For reversible field cycles, the scaling with the particles size of the characteristic cycling time is discussed.

4.
Vox Sang ; 112(3): 219-228, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28198084

RESUMO

BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, randomized controlled trial. Participants received intravenous iron (n = 97) or oral iron (n = 99), and completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and haematological and iron parameters were measured. Primary outcome was the aggregated change in physical fatigue score from baseline to 12 weeks postpartum. RESULTS: The difference in physical fatigue score was -0·97 (95% CI: -1·65; -0·28, P = 0·006) in favour of intravenous iron, but did not meet the predefined difference of 1·8. Across visits, we found statistically significant differences in fatigue and depression scores, as well as in haematological and iron parameters, all in favour of intravenous iron. There were no serious adverse reactions. CONCLUSION: A single dose of intravenous iron was associated with a statistically significant reduction in aggregated physical fatigue within 12 weeks after postpartum haemorrhage compared to standard medical care with oral iron below the prespecified criteria of clinical superiority. As patient-reported outcomes improved significantly and intravenous iron resulted in a fast hematopoietic response without serious adverse reactions, intravenous iron may be a useful alternative after postpartum haemorrhage if oral iron is not absorbed or tolerated.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Fadiga/prevenção & controle , Ferro/administração & dosagem , Hemorragia Pós-Parto/patologia , Administração Oral , Adulto , Área Sob a Curva , Fadiga/etiologia , Feminino , Hemoglobinas/análise , Humanos , Infusões Intravenosas , Período Pós-Parto , Gravidez , Curva ROC , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Nat Commun ; 8: 14391, 2017 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-28186168

RESUMO

Innate immune activation by macrophages is an essential part of host defence against infection. Cytosolic recognition of microbial DNA in macrophages leads to induction of interferons and cytokines through activation of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Other host factors, including interferon-gamma inducible factor 16 (IFI16), have been proposed to contribute to immune activation by DNA. However, their relation to the cGAS-STING pathway is not clear. Here, we show that IFI16 functions in the cGAS-STING pathway on two distinct levels. Depletion of IFI16 in macrophages impairs cGAMP production on DNA stimulation, whereas overexpression of IFI16 amplifies the function of cGAS. Furthermore, IFI16 is vital for the downstream signalling stimulated by cGAMP, facilitating recruitment and activation of TANK-binding kinase 1 in STING complex. Collectively, our results suggest that IFI16 is essential for efficient sensing and signalling upon DNA challenge in macrophages to promote interferons and antiviral responses.


Assuntos
DNA/metabolismo , Macrófagos/metabolismo , Proteínas Nucleares/metabolismo , Nucleotídeos Cíclicos/metabolismo , Fosfoproteínas/metabolismo , Células Cultivadas , Perfilação da Expressão Gênica , Células HEK293 , Humanos , Imunidade Inata/genética , Interferons/imunologia , Interferons/metabolismo , Macrófagos/imunologia , Macrófagos/virologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mutação , Proteínas Nucleares/genética , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Fosfoproteínas/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Interferência de RNA , Transdução de Sinais/genética , Células THP-1
6.
Vox Sang ; 112(2): 122-131, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28010050

RESUMO

BACKGROUND AND OBJECTIVES: There are no randomized trials comparing intravenous iron to RBC transfusion for the treatment of severe postpartum anaemia. The objectives of this study were to evaluate the feasibility of randomizing women with severe postpartum anaemia secondary to postpartum haemorrhage to RBC transfusion or intravenous iron, and to describe patient-reported outcomes, and haematological and iron parameters. MATERIALS AND METHODS: Women with a postpartum haemorrhage exceeding 1000 ml and an Hb between 5·6 and 8·1 g/dl were randomized to 1500 mg of intravenous iron (n = 7) isomaltoside or RBC transfusion (n = 6). Participants completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and blood samples were drawn at inclusion, daily during the first week and at weeks 3, 8 and 12. RESULTS: We screened 162 women and included 13 (8%). There was no significant difference between groups in fatigue or depression scores. RBC transfusion was associated with a higher Hb on day 1, inhibition of reticulocytosis during the first week and low iron levels. Intravenous iron was associated with increased reticulocytosis during the first week, repleted iron stores and a higher Hb in weeks 3-12. CONCLUSION: This pilot study shows that intravenous iron could be an attractive alternative to RBC transfusion in severe postpartum anaemia, and that a larger trial is needed and feasible.


Assuntos
Anemia/terapia , Dissacarídeos/administração & dosagem , Transfusão de Eritrócitos , Compostos Férricos/administração & dosagem , Adulto , Anemia/tratamento farmacológico , Anemia/patologia , Depressão/patologia , Dissacarídeos/farmacologia , Transfusão de Eritrócitos/efeitos adversos , Fadiga , Estudos de Viabilidade , Feminino , Compostos Férricos/farmacologia , Hemoglobinas/análise , Humanos , Infusões Intravenosas , Projetos Piloto , Hemorragia Pós-Parto/etiologia , Período Pós-Parto , Gravidez , Reticulocitose/efeitos dos fármacos , Índice de Gravidade de Doença
7.
Eur J Pain ; 20(2): 263-73, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25929250

RESUMO

BACKGROUND: Until now, nonivamide/nicoboxil ointment has not been tested in a randomized trial for the treatment of acute non-specific low back pain. METHODS: This phase III randomized, double-blind, active- and placebo-controlled, multi-centre trial investigated efficacy, safety and tolerability of topical nicoboxil 2.5%/nonivamide 0.4% for treatment of acute non-specific low back pain [primary endpoint: pain intensity (PI) difference between pre-dose baseline and 8 h after the first application]. RESULTS: Patients (n = 805), 18-74 years of age were treated for up to 4 days with nicoboxil 2.5%/nonivamide 0.4%, nicoboxil 2.5%, nonivamide 0.4% or placebo ointment. Pre-dose baseline pain intensity (6.6 on a 0- to 10-point numerical rating scale) was reduced by 1.049 points with placebo, by 1.428 points with nicoboxil, by 2.252 points with nonivamide and by 2.410 points with nicoboxil/nonivamide after 8 h (p < 0.0001 for nicoboxil/nonivamide vs. placebo, nicoboxil; p = 0.4171 for nicoboxil/nonivamide vs. nonivamide). At the end of treatment, the combination provided more pronounced PI reduction (3.540 points) compared with nicoboxil (2.371, p < 0.0001), nonivamide (3.074, p = 0.0259) and placebo (1.884, p < 0.0001). Low back mobility scores on Day 1 were better for the combination compared with all other treatments (p < 0.044); on Day 2-4, scores were better than for placebo and nicoboxil (p < 0.003). Patients assessed efficacy of the combination as greater than of the comparators (p ≤ 0.0129). All treatments were tolerated well. No treatment-related serious adverse events were reported. CONCLUSION: Nicoboxil/nonivamide ointment is an effective, well-tolerated medication for the treatment of acute non-specific low back pain.


Assuntos
Dor Aguda/tratamento farmacológico , Capsaicina/análogos & derivados , Dor Lombar/tratamento farmacológico , Ácidos Nicotínicos/uso terapêutico , Adolescente , Adulto , Idoso , Capsaicina/efeitos adversos , Capsaicina/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Nicotínicos/efeitos adversos , Resultado do Tratamento , Adulto Jovem
8.
Clin Exp Immunol ; 180(2): 233-42, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25639337

RESUMO

Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases affecting joints, gut, skin and entheses. The inflammatory process involves activation of Toll-like receptor (TLR)-2 and TLR-4 and production of cytokines and chemokines such as monocyte chemoattractant protein 1 (CCL2/MCP-1). This proinflammatory chemokine recruits monocytes to sites of inflammation and is central in the development of several immune-mediated inflammatory diseases. Interleukin (IL)-19 is a member of the IL-10 family of cytokines. IL-19-deficient mice are more susceptible to innate-mediated colitis and develop more severe inflammation in response to injury. In this work, we studied inducers of IL-19 production and effect of IL-19 on the production of CCL2/MCP-1 and proinflammatory cytokines in peripheral blood mononuclear cells (PBMCs) from healthy controls (HCs) and in PBMCs and synovial fluid mononuclear cells (SFMCs) from SpA patients. Further, we measured IL-19 in plasma from HCs and in plasma and synovial fluid from SpA patients. Constitutive IL-19 expression was present in both PBMCs and SFMCs and the secretion of IL-19 was increased by TLR-2 and TLR-4 ligands. Neutralizing IL-19 in HC PBMCs and SpA SFMCs resulted in increased production of CCL-2/MCP-1. IL-19 concentrations were decreased in synovial fluid compared with plasma and associated inversely with disease activity in SpA. SpA SFMCs produced less IL-19 in response to LPS compared with HC PBMCs. These findings indicate that IL-19 production is diminished in SpA. Taken together, impaired IL-19 control of the innate immune system might be involved in the pathogenesis of SpA.


Assuntos
Imunidade Inata , Interleucinas/imunologia , Leucócitos Mononucleares/imunologia , Espondilite Anquilosante/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia , Adulto , Animais , Quimiocina CCL2/sangue , Quimiocina CCL2/imunologia , Regulação da Expressão Gênica/imunologia , Humanos , Interleucinas/sangue , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Espondilite Anquilosante/sangue , Espondilite Anquilosante/patologia , Líquido Sinovial/imunologia , Líquido Sinovial/metabolismo , Receptor 2 Toll-Like/agonistas , Receptor 2 Toll-Like/sangue , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/sangue
9.
Scand J Med Sci Sports ; 25(1): e1-10, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24650079

RESUMO

Achilles tendon rupture is a frequent injury with an increasing incidence. Until now, there is no consensus regarding optimal treatment. The aim of this review was to illuminate and summarize randomized controlled trials comparing surgical and non-surgical treatment of Achilles tendon ruptures during the last 10 years. Seven articles were found and they were all acceptable according to international quality assessment guidelines. Primary outcomes were re-ruptures, other complications, and functional outcomes. There was no significant difference in re-ruptures between the two treatments, but a tendency to favoring surgical treatment. Further, one study found an increased risk of soft-tissue-related complications after surgery. Patient satisfaction and time to return to work were significantly different in favor of surgery in one study, and there was also better functional outcome after surgery in some studies. These seven studies indicate that surgical patients have a faster rehabilitation. However, the differences between surgical and non-surgical treatment appear to be subtle and it could mean that rehabilitation is more important, rather than the actual initial treatment. Therefore, further studies will be needed in regard to understanding the interplay between acute surgical or non-surgical treatment, and the rehabilitation regimen for the overall outcome after Achilles tendon ruptures.


Assuntos
Tendão do Calcâneo/lesões , Humanos , Recidiva , Ruptura/terapia
10.
J Chem Phys ; 140(21): 211101, 2014 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-24907981

RESUMO

In the late 1970s, Hubbard and Onsager predicted that adding salt to a polar solution would result in a reduced dielectric permittivity that arises from the unexpected tendency of solvent dipoles to align opposite to the applied field. Here we develop a novel non-equilibrium molecular dynamics simulation approach to determine this decrement accurately. Using a thermodynamic consistent all-atom force field we show that for an aqueous solution containing sodium chloride around 4.8 mol/l, this effect accounts for 12% of the total dielectric permittivity. The dielectric decrement can be strikingly different if a less accurate force field for the ions is used. Using the widespread GROMOS parameters, we observe in fact an increment of the dielectric permittivity rather than a decrement, caused by ion pairing and introduced by a too low dispersion force.


Assuntos
Eletrólitos/química , Sódio/química , Soluções/química , Termodinâmica , Compostos Clorados/química , Cinética , Simulação de Dinâmica Molecular , Potássio/química , Sais/química , Solventes/química , Água/química
11.
Artigo em Inglês | MEDLINE | ID: mdl-25615219

RESUMO

The local approach to computing electrostatic interactions proposed by Maggs and adapted by Rottler and Pasichnyk for molecular-dynamics simulations is extended to situations where the dielectric background medium is inhomogeneous. We furthermore correct a problem of the original algorithm related to the correct treatment of the global dipole moment, provide an error estimate for the accuracy of the algorithm, and suggest a different form of the treatment of the self-energy problem. Our implementation is highly scalable on many cores, and we have validated and compared its performance against theoretical predictions and simulation data obtained by other algorithmic approaches.

12.
BJOG ; 119(5): 596-604, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22313728

RESUMO

OBJECTIVE: To examine the association between intended mode of delivery and severe postpartum haemorrhage. DESIGN: A retrospective cohort study. SETTING: Material from a nationwide study in Denmark. POPULATION: Danish women giving birth in 2001-08. METHODS: We compared use of red blood cell transfusion by intended mode of delivery in the total population (n = 382 266), in low-risk nulliparous women (n = 147 132) and in women with a previous caesarean delivery (n = 25 156). MAIN OUTCOME MEASURE: Red blood cell transfusion within 7 days of delivery. RESULTS: In the total population the crude transfusion rates for women with planned caesarean delivery and intended vaginal delivery were 2.24 and 1.75%. After adjustment for maternal age, body mass index, birthweight, smoking, parity, number of infants and previous caesarean delivery, the risk of red blood cell transfusion was significantly lower in women with planned caesarean delivery compared with intended vaginal delivery (odds ratio 0.82; 95% CI 0.73-0.92; P < 0.01). In low-risk nulliparous women and in women with a previous caesarean delivery the transfusion rates were lower for planned caesarean delivery compared with intended vaginal delivery before and after adjustment. CONCLUSION: Compared with intended vaginal delivery, planned caesarean delivery was associated with a reduced risk of severe postpartum haemorrhage indicated by use of red blood cell transfusion.


Assuntos
Parto Obstétrico/efeitos adversos , Hemorragia Pós-Parto/etiologia , Adolescente , Adulto , Peso ao Nascer , Índice de Massa Corporal , Cesárea/efeitos adversos , Cesárea/estatística & dados numéricos , Parto Obstétrico/estatística & dados numéricos , Dinamarca/epidemiologia , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Humanos , Idade Materna , Hemorragia Pós-Parto/epidemiologia , Gravidez , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Adulto Jovem
13.
Eur J Clin Nutr ; 66(5): 585-90, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22166897

RESUMO

BACKGROUND/OBJECTIVES: In studies performed in mice, rose hip powder has been shown to both prevent and reverse high-fat diet-induced obesity and glucose intolerance as well as reduce plasma levels of cholesterol. The aim of this study was to investigate whether daily intake of rose hip powder over 6 weeks exerts beneficial metabolic effects in obese individuals. SUBJECTS/METHODS: A total of 31 obese individuals with normal or impaired glucose tolerance were enrolled in a randomized, double-blind, cross-over study in which metabolic effects of daily intake of a rose hip powder drink over 6 weeks was compared with a control drink. Body weight, glucose tolerance, blood pressure, blood lipids and markers of inflammation were assessed in the subjects. RESULTS: In comparison with the control drink, 6 weeks of daily consumption of the rose hip drink resulted in a significant reduction of systolic blood pressure (-3.4%; P=0.021), total plasma cholesterol (-4.9%; P=0.0018), low-density lipoprotein (LDL) cholesterol (-6.0%; P=0.012) and LDL/HDL ratio (-6.5%; P=0.041). The Reynolds risk assessment score for cardiovascular disease was decreased in the rose hip group compared with the control group (-17%; P=0.007). Body weight, diastolic blood pressure, glucose tolerance, and plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, incretins and markers of inflammation did not differ between the two groups. CONCLUSIONS: Daily consumption of 40 g of rose hip powder for 6 weeks can significantly reduce cardiovascular risk in obese people through lowering of systolic blood pressure and plasma cholesterol levels.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Obesidade/tratamento farmacológico , Fitoterapia , Rosa , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Método Duplo-Cego , Feminino , Frutas , Intolerância à Glucose/sangue , Intolerância à Glucose/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , Medição de Risco , Fatores de Risco
14.
J Eur Acad Dermatol Venereol ; 26(5): 597-601, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21605175

RESUMO

BACKGROUND: Hand eczema is a common and persistent disease with a relapsing course. Clinical data suggest that once daily treatment with corticosteroids is just as effective as twice daily treatment. OBJECTIVES: The aim of this study was to compare once and twice daily applications of a strong corticosteroid cream in addition to maintenance therapy with a moisturizer in patients with a recent relapse of hand eczema. METHODS: The study was a parallel, double-blind, randomized, clinical trial on 44 patients. Twice daily application of a strong corticosteroid cream (betamethasone valerate 0.1%) was compared with once daily application, where a urea-containing moisturizer was substituted for the corticosteroid cream in the morning. The investigator scored the presence of eczema and the patients judged the health-related quality of life (HRQoL) using the Dermatology Life Quality Index (DLQI), which measures how much the patient's skin problem has affected his/her life over the past week. The patients also judged the severity of their eczema daily on a visual analogue scale. RESULTS: Both groups improved in terms of eczema and DLQI. However, the clinical scoring demonstrated that once daily application of corticosteroid was superior to twice daily application in diminishing eczema, especially in the group of patients with lower eczema scores at inclusion. CONCLUSIONS: Twice daily use of corticosteroids was not superior to once daily use in treating eczema. On the contrary, the clinical assessment showed a larger benefit from once daily treatment compared with twice daily, especially in the group of patients with a moderate eczema at inclusion.


Assuntos
Betametasona/uso terapêutico , Eczema/tratamento farmacológico , Glucocorticoides/uso terapêutico , Betametasona/administração & dosagem , Método Duplo-Cego , Eczema/fisiopatologia , Glucocorticoides/administração & dosagem , Humanos , Cooperação do Paciente , Qualidade de Vida
15.
J Chem Theory Comput ; 8(3): 936-47, 2012 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-26593356

RESUMO

We demonstrate explicitly how the two seemingly different particle mesh Ewald methods, the smooth particle mesh Ewald (SPME) and the particle-particle particle mesh (P3M), can be mathematically transformed into each other. This allows us in particular to convert the error estimate of the P3M method in the energy-conserving scheme (also known as "P3M with analytic differentiation") into an error estimate for the SPME method, via a simple change of the lattice Green function. Our error estimate is valid for any values of the SPME parameters (mesh size, spline interpolation order, Ewald splitting parameter, real-space cutoff distance), including odd orders of splines. The problem with the self-forces is avoided thanks to an analytical formula that allows to subtract them directly within the particle mesh calculation. Plots of the accuracy of the SPME forces are provided for a wide range of parameter values. The main use of the error estimate is to allow a simulation program to scan quickly the multidimensional parameter space to find the best set of parameters to achieve a target accuracy at the smallest computational cost. As a byproduct, we show how a SPME code can be transformed into a P3M version by changing a few lines of code. We demonstrate also that the P3M lattice Green function can be approximated by a closed form expression, computable on-the-fly, that provides essentially the same accuracy as the full function.

16.
J Chem Phys ; 135(18): 184110, 2011 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-22088055

RESUMO

The interlaced and non-interlaced versions of the dipolar particle-particle particle-mesh (P(3)M) method implemented using the analytic differentiation scheme (AD-P(3)M) are presented together with their respective error estimates for the calculation of the forces, torques, and energies. Expressions for the optimized lattice Green functions, and for the Madelung self-forces, self-torques and self-energies are given. The applicability of the theoretical error estimates are thoroughly tested and confirmed in several numerical examples. Our results show that the accuracy of the calculations can be improved substantially when the approximate (mesh computed) Madelung self-interactions are subtracted. Furthermore, we show that the interlaced dipolar AD-P(3)M method delivers a significantly higher accuracy (which corresponds approximately to using a twice finer mesh) than the conventional method, allowing thereby to reduce the mesh size with respect to the non-interlaced version for a given accuracy. In addition, we present similar expressions for the dipolar ik-differentiation interlaced scheme, and we perform a comparison with the AD interlaced scheme. Rough tests for the relative speed of the dipolar P(3)M method using ik-differentiation and the interlaced/non-interlaced AD schemes show that when FFT computing time is the bottleneck, usually when working at high precisions, the interlaced AD-scheme can be several times faster than the other two schemes. For calculations with a low accuracy requirement, the interlaced version can perform worse than the ik and the non-interlaced AD schemes.

17.
Diabetes Obes Metab ; 12(11): 976-82, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20880344

RESUMO

AIM: Clinical studies have suggested a role for dietary glycaemic index (GI) in body weight regulation and diabetes risk. Here, we investigated the long-term metabolic effects of low and high glycaemic diets using the C57BL/6J mouse model. METHODS: Female C57BL/6J mice were fed low or high glycaemic starch in either low-fat or medium-fat diets for 22 weeks. Oral and intravenous glucose tolerance tests were performed to investigate the effect of the experimental diets on glucose tolerance and insulin resistance. RESULTS: In this study, a high glycaemic diet resulted in impaired oral glucose tolerance compared to a low glycaemic diet. This effect was more pronounced in the group fed a medium-fat diet, suggesting that a lower dietary fat content ameliorates the negative effect of a high glycaemic diet. No effect on body weight or body fat content was observed in either a low-fat diet or a medium-fat diet. Static incubation of isolated islets did not show any differences in basal (3.3 mM glucose) or glucose-stimulated (8.6 and 16.7 mM glucose) insulin secretion between mice fed a low or high glycaemic diet. CONCLUSION: Together, our data suggest that the impaired glucose tolerance seen after a high glycaemic diet is not explained by altered ß-cell function.


Assuntos
Dieta para Diabéticos , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Animais , Peso Corporal/fisiologia , Dieta com Restrição de Gorduras , Feminino , Teste de Tolerância a Glucose/métodos , Índice Glicêmico , Secreção de Insulina , Camundongos , Camundongos Endogâmicos C57BL
18.
Phys Chem Chem Phys ; 12(8): 1817-21, 2010 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-20145847

RESUMO

The molecular polarization in a 1,3-dimethylimidazolium chloride ([DMIM][Cl]) ionic liquid is analyzed for a bulk liquid via the Car-Parrinello approach. The analysis reveals that the electric dipole moments of cations and anions are characterized by large fluctuations, however these are primarily due to the molecules in the immediate surroundings. These results on one hand shed light on some basic physical and chemical features of this liquid, and on the other represent a fundamental handle for the development of accurate classical force fields; this aspect is extensively discussed and some suggestions are made.

19.
Benef Microbes ; 1(2): 189-96, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21840806

RESUMO

Today, the gut microbiota is considered a key organ in host nutritional metabolism and recent data have suggested that alterations in gut microbiota contribute to the development of type 2 diabetes and obesity. Accordingly, a whole range of beneficial effects relating to inflammation and gut health have been observed following administration of probiotics to both humans and different animal models. The objective of this study was to evaluate the metabolic effects of an oral probiotic supplement, Lactobacillus plantarum DSM 15313, to high-fat diet (HFD) fed C57BL/6J mice, a model of human obesity and early diabetes. The mice were fed the experimental diets for 20 weeks, after which the HFD had induced an insulin-resistant state in both groups compared to the start of the study. The increase in body weight during the HFD feeding was higher in the probiotic group than in the control group, however, there were no significant differences in body fat content. Fasting plasma glucose levels were lower in the group fed the probiotic supplement, whereas insulin and lipids were not different. Caecal levels of short-chain fatty acids were not significantly different between the groups. An oral glucose tolerance test showed that the group fed probiotics had a significantly lower insulin release compared to the control group, although the rate of glucose clearance was not different. Taken together, these data indicate that L. plantarum DSM 15313 has anti-diabetic properties when fed together with an HFD.


Assuntos
Glicemia , Dieta/métodos , Gorduras/administração & dosagem , Lactobacillus plantarum/fisiologia , Plasma/química , Probióticos/administração & dosagem , Tecido Adiposo/fisiologia , Animais , Peso Corporal/fisiologia , Ceco/química , Diabetes Mellitus/prevenção & controle , Ácidos Graxos Voláteis/análise , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/prevenção & controle
20.
Br J Sports Med ; 44(2): 134-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18381824

RESUMO

BACKGROUND: Anterior knee tendon problems are seldom reported in badminton players although the game is obviously stressful to the lower extremities. HYPOTHESES: Painful anterior knee tendons are common among elite badminton players. The anterior knee tendons exhibit colour Doppler activity. This activity increases after a match. Painful tendons have more Doppler activity than tendons without pain. STUDY DESIGN: Cohort study. METHODS: 72 elite badminton players were interviewed about training, pain and injuries. The participants were scanned with high-end ultrasound equipment. Colour Doppler was used to examine the tendons of 64 players before a match and 46 players after a match. Intratendinous colour Doppler flow was measured as colour fraction (CF). The tendon complex was divided into three loci: the quadriceps tendon, the proximal patellar tendon and the insertion on the tibial tuberosity. RESULTS: Interview: Of the 72 players, 62 players had problems with 86 tendons in the lower extremity. Of these 86 tendons, 48 were the anterior knee tendons. Ultrasound: At baseline, the majority of players (87%) had colour Doppler flow in at least one scanning position. After a match, the percentage of the knee complexes involved did not change. CF increased significantly in the dominant leg at the tibial tuberosity; single players had a significantly higher CF after a match at the tibial tuberosity and in the patellar tendon both before and after a match. Painful tendons had the highest colour Doppler activity. CONCLUSIONS: Most elite badminton players had pain in the anterior knee tendons and intratendinous Doppler activity both before and after match. High levels of Doppler activity were associated with self-reported ongoing pain.


Assuntos
Lesões do Ligamento Cruzado Anterior , Traumatismos do Joelho/diagnóstico por imagem , Ligamento Patelar/lesões , Esportes com Raquete/lesões , Adolescente , Adulto , Ligamento Cruzado Anterior/irrigação sanguínea , Ligamento Cruzado Anterior/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Masculino , Dor/etiologia , Ligamento Patelar/irrigação sanguínea , Ligamento Patelar/diagnóstico por imagem , Ultrassonografia Doppler , Adulto Jovem
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