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1.
Palliat Med ; 38(1): 150-155, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37937380

RESUMO

BACKGROUND: Studies have shown the risk factors for COVID-19 severity in children, including comorbidities, but information on the infection course in children with life-limiting conditions is sparse. AIM: To describe the effect of COVID-19 on pediatric patients receiving palliative care due to life-limiting conditions. DESIGN: We conducted retrospective cohort study. The WHO Clinical Progression Scale was used to measure COVID-19 severity. SETTING/PARTICIPANTS: Seven of the 24 invited pediatric palliative care centers participated in this study. We analyzed the medical records of children under palliative care with confirmed COVID-19 (January 2020-April 2022). RESULTS: Records of 60 patients with COVID-19 aged 0.24 to 21.6 years (mean (SD); 9.8 (6.6)) were collected. The largest group of patients with COVID-19 was children with congenital malformations and chromosomal abnormalities (42%); the most common manifestation was fever (85%). Bacterial coinfection was confirmed in 17 (28%) children. Fifteen (25%) children required hospitalization, including four admitted to the Intensive Care Unit. Mild COVID-19 was identified in 44 (73%) children, moderate in 11 (18%), severe in 3 (5%), and death in 2 (3%). Six of the 20 eligible children were vaccinated against SARS-CoV-2, followed by 16 mothers and fathers. CONCLUSION: In the study population initial presentation of COVID-19 was predominantly a mild; however, the small sample size precluded definitive conclusions. For children under palliative care, we should identify if they have an advance care plan for COVID-19, such as desires for intensive care support. Further studies are needed to define the short and long-term effects of COVID-19 in children with life-limiting conditions.


Assuntos
COVID-19 , Humanos , Criança , SARS-CoV-2 , Cuidados Paliativos , Estudos Retrospectivos , Hospitalização
2.
Rheumatol Int ; 44(7): 1337-1343, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38727810

RESUMO

In the course of psoriatic arthritis (PsA), depression occurs much more often than in the general population. Depression can be considered a poor prognostic factor. The aim of the study was to assess the relationships between the occurrence of depression and the levels of proinflammatory cytokines in patients with PsA. The study included 86 (47F/39M) patients with PsA. Only patients with high disease activity (DAPSA > 28) were enrolled in the study. The severity of depressive symptoms was assessed using the Beck Depression Inventory II (BDI-II) for all patients. Additionally, sociodemographic data were collected. All patients were also assessed for the levels of interleukins (IL): IL-1, IL-6, IL-17A, IL-23, and tumor necrosis factor alpha (TNF-α) using the enzyme-linked immunosorbent assay (ELISA) test. In the study group, depression (BDI-II ≥ 14) was diagnosed in 45 patients (52%). Patients with coexisting depression reported higher levels of pain and disease activity on the visual analogue scale compared to patients without depression (8.5 vs. 7.7, p < 0.001 and 9.3 vs. 8.4, p < 0.001, respectively). The mean levels of proinflammatory cytokines [pg/ml], IL-1 and IL-6, were also higher in the group of patients with depression (46.4 vs. 4.7, p < 0.001 and 10.5 vs. 4.9, p < 0.001, respectively). The coexistence of depression in the course of Psoriatic Arthritis (PsA) is associated with higher levels of IL-1 and IL-6. Depression has a negative impact on the perception of the underlying disease and is linked to reduced social and occupational activity.


Assuntos
Artrite Psoriásica , Depressão , Índice de Gravidade de Doença , Humanos , Artrite Psoriásica/psicologia , Masculino , Feminino , Depressão/epidemiologia , Depressão/psicologia , Depressão/sangue , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto , Interleucinas/sangue , Idoso
3.
Int J Mol Sci ; 25(8)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38673738

RESUMO

The high content of bioactive compounds in Aronia melanocarpa fruit offers health benefits. In this study, the anti-atherosclerotic effect of Aronia extracts was assessed. The impact on the level of adhesion molecules and the inflammatory response of human umbilical vein endothelial cells (HUVECs) was shown in relation to the chemical composition and the stage of ripening of the fruits. Samples were collected between May (green, unripe) and October (red, overripe) on two farms in Poland, which differed in climate. The content of chlorogenic acids, anthocyanins, and carbohydrates in the extracts was determined using HPLC-DAD/RI. The surface expression of ICAM-1 and VCAM-1 in HUVECs was determined by flow cytometry. The mRNA levels of VCAM-1, ICAM-1, IL-6, and MCP-1 were assessed using the quantitative real-time PCR method. The farms' geographical location was associated with the quantity of active compounds in berries and their anti-atherosclerotic properties. Confirmed activity for green fruits was linked to their high chlorogenic acid content.


Assuntos
Aterosclerose , Frutas , Células Endoteliais da Veia Umbilical Humana , Photinia , Extratos Vegetais , Photinia/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Frutas/química , Aterosclerose/tratamento farmacológico , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Antocianinas/farmacologia , Antocianinas/química , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ácido Clorogênico/farmacologia , Ácido Clorogênico/química , Interleucina-6/metabolismo , Interleucina-6/genética
4.
Blood Cells Mol Dis ; 98: 102709, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36371928

RESUMO

OBJECTIVES: To present the rheumatological manifestations of chronic graft versus host disease (cGVHD) and describe how they differ from primary systemic connective tissue diseases. METHODS: Description of 7 patients with cGVHD with symptoms resembling Sjögren's syndrome and scleroderma, with a critical review of the literature. RESULTS: 7 patients treated at the hematology department, who developed cGVHD with present antinuclear antibodies, were referred to the rheumatology department for further evaluation. All patients presented symptoms of dry eye syndrome confirmed with ophthalmic tests. If the diagnosis of GVHD was not an exclusion criterion, Sjögren's syndrome criteria would be met by 4 of our patients - they presented not only with dryness but also with typical antibodies, inflammatory changes in salivary glands on ultrasound examination, and mononuclear cell infiltration in histopathological examination of labial salivary glands. Additionally, three patients presented with scleroderma-like syndromes, but with symptoms easy to differentiate from systemic sclerosis. CONCLUSION: cGVHD may be difficult to distinguish from Sjögren's syndrome, but such distinction is important due to the different standards of treatment in cGVHD and primary connective tissue diseases.


Assuntos
Doença Enxerto-Hospedeiro , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/patologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia
5.
Molecules ; 28(8)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37110676

RESUMO

Turmeric is a traditional Indian spice that has recently become very popular worldwide because it contains a powerful ingredient called curcumin, which has strong anti-inflammatory properties. Hence, dietary supplements containing extracts rich in curcumin have gained great popularity. The main problems related to curcumin-containing dietary supplements are poor water solubility and the fact that they are often faked by using synthetic curcumin instead of the plant extract. In this article, we propose the use of the 13C CPMAS NMR method to control the quality of dietary supplements. The analysis of 13C CPMAS NMR spectra supported by GIPAW computations allowed us to identify a polymorphic form present in dietary supplements (which affected the solubility of curcumin) and to point out a dietary supplement that could be faked by using synthetic curcumin. Further PXRD and HPLC investigations confirmed that the examined supplement contained synthetic curcumin instead of the genuine extract. Our method can be used for routine control, especially because the investigation is performed directly from the capsule/tablet content and does not require any special sample preparation.


Assuntos
Curcumina , Curcumina/química , Suplementos Nutricionais/análise , Curcuma/química , Extratos Vegetais/química
6.
Rheumatology (Oxford) ; 61(4): 1385-1395, 2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-34142111

RESUMO

OBJECTIVE: To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active RA. METHODS: This double-blind, phase III study randomized (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 [treatment period (TP) 1]. Thereafter, subjects receiving reference adalimumab were randomized (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0-W24 results were previously reported; we present W26-W52 findings. End points were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity. RESULTS: Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in ACR response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive. CONCLUSION: Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03789292.


Assuntos
Antirreumáticos , Artrite Reumatoide , Medicamentos Biossimilares , Adalimumab/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/efeitos adversos , Método Duplo-Cego , Humanos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Clin Anat ; 34(2): 244-262, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33090551

RESUMO

Iatrogenic nerve injury during surgery is a major source of concern for both patients and surgeons. This study aimed to identify the nerves most commonly injured during surgery, along with the commonly associated operative procedures. A literature search was conducted using the PubMed database to identify nerves commonly injured during surgery, along with the surgical procedure associated with the injury. The following 11 nerves, ranked in order with their associated surgical procedures, were found to be the most commonly injured: (a) intercostobrachial nerve in axillary lymph node dissections and transaxillary breast augmentations, (b) vestibulocochlear nerve in cerebellopontine tumor resections and vestibular schwannoma removals, c) facial nerve in surgeries of the inner ear and cheek region, (d) long thoracic nerve in axillary lymph node dissections, (e) spinal accessory nerve in surgeries of the posterior triangle of the neck and cervical lymph node biopsies, (f) recurrent laryngeal nerve in thyroid surgeries, (g) genitofemoral nerve in inguinal hernia and varicocele surgeries, (h) sciatic nerve in acetabular fracture repairs and osteotomies, (i) median nerve in carpal tunnel release surgeries, (j) common fibular nerve in varicose vein and short saphenous vein surgeries, and (k) ulnar nerve in supracondylar fracture surgeries. Although the root cause of iatrogenic nerve injury differs for each nerve, there are four unifying factors that could potentially decrease this risk for all peripheral nerves. These four influencing factors include knowledge of potential anatomical variations, visual identification of at-risk nerves during the procedure, intraoperative nerve monitoring, and expertise of the surgeon.


Assuntos
Doença Iatrogênica , Traumatismos dos Nervos Periféricos/etiologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Humanos
8.
Thorax ; 75(12): 1089-1094, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32917840

RESUMO

OBJECTIVE: To determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers. DESIGN: A cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020. SETTING: University Hospitals Birmingham NHS Foundation Trust (UHBFT), UK. PARTICIPANTS: 545 asymptomatic healthcare workers were recruited while at work. Participants were invited to participate via the UHBFT social media. Exclusion criteria included current symptoms consistent with COVID-19. No potential participants were excluded. INTERVENTION: Participants volunteered a nasopharyngeal swab and a venous blood sample that were tested for SARS-CoV-2 RNA and anti-SARS-CoV-2 spike glycoprotein antibodies, respectively. Results were interpreted in the context of prior illnesses and the hospital departments in which participants worked. MAIN OUTCOME MEASURE: Proportion of participants demonstrating infection and positive SARS-CoV-2 serology. RESULTS: The point prevalence of SARS-CoV-2 viral carriage was 2.4% (n=13/545). The overall seroprevalence of SARS-CoV-2 antibodies was 24.4% (n=126/516). Participants who reported prior symptomatic illness had higher seroprevalence (37.5% vs 17.1%, χ2=21.1034, p<0.0001) and quantitatively greater antibody responses than those who had remained asymptomatic. Seroprevalence was greatest among those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%), with lower rates observed in participants working in intensive care (14.8%). BAME (Black, Asian and minority ethnic) ethnicity was associated with a significantly increased risk of seropositivity (OR: 1.92, 95% CI 1.14 to 3.23, p=0.01). Working on the intensive care unit was associated with a significantly lower risk of seropositivity compared with working in other areas of the hospital (OR: 0.28, 95% CI 0.09 to 0.78, p=0.02). CONCLUSIONS AND RELEVANCE: We identify differences in the occupational risk of exposure to SARS-CoV-2 between hospital departments and confirm asymptomatic seroconversion occurs in healthcare workers. Further investigation of these observations is required to inform future infection control and occupational health practices.


Assuntos
Anticorpos Antivirais/sangue , Doenças Assintomáticas , COVID-19/diagnóstico , Pessoal de Saúde/estatística & dados numéricos , Pandemias , SARS-CoV-2/imunologia , Adulto , COVID-19/epidemiologia , COVID-19/virologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , SARS-CoV-2/genética , Estudos Soroepidemiológicos
9.
Molecules ; 25(14)2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679898

RESUMO

Aronia melanocarpa (Michx.) Elliott's (chokeberry) besides anthocyanins contains significant amounts of hydroxycinnamic acids: Chlorogenic and its isomer neochlorogenic acid. They exhibit antioxidant, anti-inflammatory, antidiabetic, and antibacterial activities, thus they can have a significant impact on the health-promoting properties of Aronia. The aim of our research was to determine the changes in the content of chlorogenic acids (CGAs) and anthocyanins during fruit development and ripening, with a particular emphasis on acids. Aronia fruit samples were collected from July to October on two organic farms in Poland. The chemical composition of the extracts was determined by NMR spectroscopy and HPLC-DAD. 1H-NMR and HPLC data were analyzed using chemometric analysis and multivariate statistics (PCA). The results showed that the content of chlorogenic acids and anthocyanins changes during ripening and depends on the time of harvest and the region of cultivation. A correlation between the time of CGAs reduction and the appearance of anthocyanins was also noticed. The result of our research was also a database in the form of NMR parameters, which allows analysis of the metabolite profile and tracking of its changes. The 1H-NMR spectrum showing anthocyanin and CGA resonance can be considered the Aronia berry fingerprint.


Assuntos
Antocianinas/química , Ácido Clorogênico/química , Frutas/química , Photinia/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética
10.
Molecules ; 25(6)2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32192161

RESUMO

The aim of the present study was to determine the antioxidant and antimicrobial properties in freeze-dried extracts of rose fruits (Rosa rugosa) obtained using various extraction techniques and to determine the effect of a selected extract on bacterial survival in model fluids imitating protein food. Ethanolic extracts from rose fruits showed higher antioxidant activity compared to other tested extracts. The rose fruits aqueous extract showed the highest inhibitory activity against most of the 10 bacterial strains tested. From the group of Gram-positive bacteria, the Bacillus cereus strain proved to be the most sensitive to the action of the rose extract. From the Gram-negative bacteria: Escherichia coli and Klebsiella pneumoniae were the most sensitive. The reduction in the number of bacterial cells in matrices imitating protein food depended on the concentration of the aqueous extract used. However, at none of the concentrations used was a complete inhibition of bacterial growth observed. We have confirmed that the traditional extraction and freeze-drying of rose fruits is still suitable for the food industry due to obtaining extracts with good antibacterial and antioxidant properties and the use of bio-solvents, such as water or ethanol, which are easily available in high purity and completely biodegradable.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Frutas/química , Extratos Vegetais/farmacologia , Rosa/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Água
11.
Pol J Radiol ; 84: e112-e117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019603

RESUMO

PURPOSE: The aim of the study was to evaluate the relationship between the diameter and aneurysmal dilatation of the paraumbilical vein (PUV) and the presence of portosystemic collateral shunts and their relationship with age and portal vein diameter. MATERIAL AND METHODS: The retrospective analysis, performed in the II Department of Radiology, Medical University Hospital in Warsaw, included 126 patients (77 males and 49 females) with patent umbilical vein and signs of portal hypertension due to liver cirrhosis. All patients underwent contrast enhanced abdominal CT. The average age was 54.7 ±12.98. We analysed the number and type of portosystemic collateral channels in respect of age, sex, presence of oesophageal varices, and the diameter of the paraumbilical vein and the portal vein. RESULTS: Our results disclosed statistically significant negative correlation between patient age and diameter of paraumbilical vein, number of portosystemic collateral channels and diameter of portal vein and positive correlation between diameter of paraumbilical vein and diameter of portal vein. A statistically significant difference in diameter of portal vein and number of collateral channels was found in groups with and without oesophageal varices. No significant difference in age and portal vein diameter was found in these groups. CONCLUSIONS: Our study showed that younger patients with liver cirrhosis are characterised by wider paraumbilical veins and higher number of portosystemic collateral channels. The presence of oesophageal varices does not correlate with age, sex, diameter of paraumbilical vein, and number of collateral portosystemic channels.

12.
Ann Rheum Dis ; 77(2): 234-240, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29042358

RESUMO

OBJECTIVES: Efficacy, safety and immunogenicity results from the phase III study of SB2, a biosimilar of reference infliximab (INF), were previously reported through 54 weeks. This transition period compared results in patients with rheumatoid arthritis (RA) who switched from INF to SB2 with those in patients who maintained treatment with INF or SB2. METHODS: Patients with moderate to severe RA despite methotrexate treatment were randomised (1:1) to receive SB2 or INF at weeks 0, 2 and 6 and every 8 weeks thereafter until week 46. At week 54, patients previously receiving INF were rerandomised (1:1) to switch to SB2 (INF/SB2 (n=94)) or to continue on INF (INF/INF (n=101)) up to week 70. Patients previously receiving SB2 continued on SB2 (SB2/SB2 (n=201)) up to week 70. Efficacy, safety and immunogenicity were assessed up to week 78. RESULTS: Efficacy was sustained and comparable across treatment groups. American College of Rheumatology (ACR) 20 responses between weeks 54 and 78 ranged from 63.5% to 72.3% with INF/SB2, 66.3%%-69.4% with INF/INF and 65.6%-68.3% with SB2/SB2. Treatment-emergent adverse events during this time occurred in 36.2%, 35.6% and 40.3%, respectively, and infusion-related reactions in 3.2%, 2.0% and 3.5%. Among patients who were negative for antidrug antibodies (ADA) up to week 54, newly developed ADAs were reported in 14.6%, 14.9% and 14.1% of the INF/SB2, INF/INF and SB2/SB2 groups, respectively. CONCLUSIONS: The efficacy, safety and immunogenicity profiles remained comparable among the INF/SB2, INF/INF and SB2/SB2 groups up to week 78, with no treatment-emergent issues or clinically relevant immunogenicity after switching from INF to SB2. TRIAL REGISTRATION NUMBER: NCT01936181; EudraCT number: 2012-005733-37.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/administração & dosagem , Infliximab/administração & dosagem , Adolescente , Adulto , Idoso , Anticorpos/sangue , Antirreumáticos/efeitos adversos , Artrite Reumatoide/imunologia , Medicamentos Biossimilares/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Infliximab/efeitos adversos , Infliximab/imunologia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
13.
Ann Rheum Dis ; 76(1): 58-64, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26318384

RESUMO

OBJECTIVES: To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy. METHODS: This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence. RESULTS: 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was -1.88% (95% CI -10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF. CONCLUSIONS: SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF. TRIAL REGISTRATION NUMBER: NCT01936181.


Assuntos
Antirreumáticos/farmacocinética , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/farmacocinética , Medicamentos Biossimilares/uso terapêutico , Infliximab/farmacocinética , Infliximab/uso terapêutico , Adulto , Idoso , Anticorpos/sangue , Antirreumáticos/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Infliximab/efeitos adversos , Infliximab/imunologia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Equivalência Terapêutica , Resultado do Tratamento
14.
Rheumatology (Oxford) ; 56(10): 1771-1779, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28957563

RESUMO

Objectives: SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage. Methods: In this phase III, double-blind, parallel-group, multicentre study, patients with moderate to severe RA despite MTX were randomized (1:1) to receive 3 mg/kg of either SB2 or INF at 0, 2, 6 and every 8 weeks thereafter. Dose escalation by 1.5 mg/kg up to a maximum dose of 7.5 mg/kg was allowed after week 30. Efficacy, safety and immunogenicity were measured at each visit up to week 54. Radiographic damage evaluated by modified total Sharp score was measured at baseline and week 54. Results: A total of 584 patients were randomized to receive SB2 (n = 291) or INF (n = 293). The rate of radiographic progression was comparable between SB2 and INF (mean modified total Sharp score difference: SB2, 0.38; INF, 0.37) at 1 year. ACR responses, 28-joint DAS, Clinical Disease Activity Index and Simplified Disease Activity Index were comparable between SB2 and INF up to week 54. The incidence of treatment-emergent adverse events and anti-drug antibodies were comparable between treatment groups. Such comparable trends of efficacy, safety and immunogenicity were consistent from baseline up to 54 weeks. The pattern of dose increment was also comparable between SB2 and INF. Conclusion: SB2 maintained similar efficacy, safety and immunogenicity with INF up to 54 weeks in patients with moderate to severe RA. Radiographic progression was comparable at 1 year. Trial registration: ClinicalTrials.gov (http://clinicaltrials.gov; NCT01936181) and EudraCT (https://www.clinicaltrialsregister.eu; 2012-005733-37).


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/administração & dosagem , Infliximab/administração & dosagem , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico por imagem , Medicamentos Biossimilares/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia/métodos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
15.
Cell Biochem Funct ; 35(5): 269-277, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28749080

RESUMO

Glucocorticoids are important for skeletal muscle energy metabolism, regulating glucose utilization, insulin sensitivity, and muscle mass. Nicotinamide adenine dinucleotide phosphate-dependent 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1)-mediated glucocorticoid activation in the sarcoplasmic reticulum (SR) is integral to mediating the detrimental effects of glucocorticoid excess in muscle. 11ß-Hydroxysteroid dehydrogenase type 1 activity requires glucose-6-phosphate transporter (G6PT)-mediated G6P transport into the SR for its metabolism by hexose-6-phosphate dehydrogenase (H6PDH) for NADPH generation. Here, we examine the G6PT/H6PDH/11ß-HSD1 triad in differentiating myotubes and explore the consequences of muscle-specific knockout of 11ß-HSD1 and H6PDH. 11ß-Hydroxysteroid dehydrogenase type 1 expression and activity increase with myotube differentiation and in response to glucocorticoids. Hexose-6-phosphate dehydrogenase shows some elevation in expression with differentiation and in response to glucocorticoid, while G6PT appears largely unresponsive to these particular conditions. When examining 11ß-HSD1 muscle-knockout mice, we were unable to detect significant decrements in activity, despite using a well-validated muscle-specific Cre transgene and confirming high-level recombination of the floxed HSD11B1 allele. We propose that the level of recombination at the HSD11B1 locus may be insufficient to negate basal 11ß-HSD1 activity for a protein with a long half-life. Hexose-6-phosphate dehydrogenase was undetectable in H6PDH muscle-knockout mice, which display the myopathic phenotype seen in global KO mice, validating the importance of SR NADPH generation. We envisage these data and models finding utility when investigating the muscle-specific functions of the 11ß-HSD1/G6PT/H6PDH triad.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , Antiporters/genética , Desidrogenases de Carboidrato/genética , Proteínas de Transporte de Monossacarídeos/genética , Músculo Esquelético/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Animais , Antiporters/metabolismo , Desidrogenases de Carboidrato/metabolismo , Metabolismo Energético/genética , Glucocorticoides/genética , Glucocorticoides/metabolismo , Glucose/metabolismo , Resistência à Insulina/genética , Camundongos , Camundongos Knockout , Proteínas de Transporte de Monossacarídeos/metabolismo , Retículo Sarcoplasmático/genética , Retículo Sarcoplasmático/metabolismo
16.
Clin Anat ; 29(5): 633-7, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27087350

RESUMO

Trisomy 12 is a rare aneuploidy and fetuses with this defect tend to spontaneously abort. However, mosaicism allows this anomaly to manifest itself in live births. Due to the fact that mosaicism represents a common genetic abnormality, trisomy 12 is encountered more frequently than expected at a rate of 1 in 500 live births. Thus, it is imperative that medical practitioners are aware of this aneuploidy. Moreover, this genetic disorder may result from a complete or partial duplication of chromosome 12. A partial duplication may refer to a specific segment on the chromosome, or one of the arms. On the other hand, a complete duplication refers to duplication of both arms of chromosome 12. The combination of mosaicism and the variable duplication sites has led to variable phenotypes ranging from normal phenotype to Potter sequence to gross physical defects of the various organ systems. This article provides a review of the common anatomical variation of the different types of trisomy 12. This review revealed that further documentation is needed for trisomy 12q and complete trisomy 12 to clearly delineate the constellation of anomalies that characterize each genetic defect. Clin. Anat. 29:633-637, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Trissomia/patologia , Cromossomos Humanos Par 12 , Humanos , Mosaicismo
17.
Clin Anat ; 29(5): 638-42, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27087450

RESUMO

Turner syndrome (TS) is one of the most common sex chromosome abnormalities and results from total or partial monosomy of the X chromosome. It occurs in 1 in 2000 newborn girls and is also believed to be present in a larger proportion of conceptuses. There are various anatomic anomalies that have been associated with TS and the consequences of late recognition of these anomalies can be devastating. Aortic dilation and dissection occur at increased rates in TS patients and contribute to the decreased life expectancy of these patients. Such cases have prompted the need for early identification and continuous monitoring. Other anatomic variations increase morbidity in this population, and negatively impact the social and reproductive aspects of their lives. In this review, we summarize the cardiovascular, neurological, genitourinary, otolaryngolical, craniofacial, and skeletal defects associated with TS. To elucidate these morphological variations, novel illustrations have also been constructed. Clin. Anat. 29:638-642, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Síndrome de Turner/patologia , Feminino , Humanos
18.
Clin Anat ; 29(5): 628-32, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27087248

RESUMO

Trisomy 18 is the second most common aneuploidy after trisomy 21. Due to its multi-systemic defects, it has a poor prognosis with a 50% chance of survival beyond one week and a <10% chance of survival beyond one year of life. However, this prognosis has been challenged by the introduction of aggressive interventional therapies for patients born with trisomy 18. As a result, a review of the anatomy associated with this defect is imperative. While any of the systems can be affected by trisomy 18, the following areas are the most likely to be affected: craniofacial, musculoskeletal system, cardiac system, abdominal, and nervous system. More specifically, the following features are considered characteristic of trisomy 18: low-set ears, rocker bottom feet, clenched fists, and ventricular septal defect. Of particular interest is the associated cardiac defect, as surgical repairs of these defects have shown an improved survivability. In this article, the anatomical defects associated with each system are reviewed. Clin. Anat. 29:628-632, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Trissomia/patologia , Cromossomos Humanos Par 18/genética , Diagnóstico Pré-Natal , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomía do Cromossomo 18
19.
Reumatologia ; 54(5): 227-235, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27994266

RESUMO

INTRODUCTION: Adipose tissue exerts widespread effects on the metabolism and immune system, but its activity differs between the genders. In the general population low-grade adipose tissue inflammation contributes to development of diseases of affluence. Little is known about the systemic impact of peripheral fat tissue in osteoarthritis (OA) and rheumatoid arthritis (RA), characterized by chronic, low- and high-grade systemic inflammation, respectively. To clarify this we evaluated the secretory activity of subcutaneous abdominal adipose tissue (SAAT) obtained from male patients affected with RA (n = 21) and OA (n = 13), and assessed its association with body mass and composition, demographic, clinical and laboratory data. MATERIAL AND METHODS: Basal and interleukin (IL)-1ß-triggered secretion of selected adipocytokines from SAAT explants was measured by specific enzyme-linked immunosorbent assays (ELISA). Patients' body composition was evaluated by bioelectric impendence technique. RESULTS: Rheumatoid SAAT secreted more adiponectin and macrophage migration inhibitory factor (MIF) than respective osteoarthritis tissue. In both RA and OA patient groups, stimulation of SAAT explants with IL-1ß (1 ng/ml/100 mg tissue) significantly up-regulated release of pro-(IL-6, IL-8, tumor necrosis factor - TNF) and anti-inflammatory (IL-10) cytokines but had no effect on the secretion of adiponectin, leptin, MIF and hepatocyte growth factor (HGF). Compared with RA, patients with OA were more obese. In RA patients SAAT-released adiponectin and TNF inversely correlated with body mass index (BMI) and visceral fat rating (FVSC). In addition, SAAT-secreted adiponectin and leptin positively correlated with DAS28 and disease duration, respectively. In the OA group tissue-released TNF positively correlated with patients' age. CONCLUSIONS: We conclude that in RA male patients adipocytokines originating from SAAT are of clinical importance because: (i) adiponectin and TNF may contribute to maintenance of normal body composition and mass, (ii) in addition adiponectin may play a pathogenic role. Moreover, in both RA and OA male patients secretory activity of SAAT may vary with time.

20.
Mol Microbiol ; 92(6): 1299-312, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24779437

RESUMO

We investigated the in vivo relevance of the impact of sarA and saeRS on protease production using derivatives of the USA300 strain LAC. The results confirmed that mutation of saeRS or sarA reduces virulence in a bacteremia model to a comparable degree. However, while eliminating protease production restored virulence in the sarA mutant, it had little impact in the saeRS mutant. Additionally, constitutive activation of saeRS (saeRS(C)) enhanced the virulence of LAC and largely restored virulence in the isogenic sarA mutant. Based on these results, together with our analysis of the representative virulence factors alpha toxin, protein A (Spa), and extracellular nucleases, we propose a model in which the attenuation of saeRS mutants is defined primarily by decreased production of such factors, while constitutive activation of saeRS increases virulence, and reverses the attenuation of sarA mutants, because it results in both increased production and decreased protease-mediated degradation of these same factors. This regulatory balance was also apparent in a murine model of catheter-associated infection, with the results suggesting that the impact of saeRS on nuclease production plays an important role during the early stages of these infections that is partially offset by increased protease production in sarA mutants.


Assuntos
Proteínas de Bactérias/metabolismo , Staphylococcus aureus Resistente à Meticilina/enzimologia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Peptídeo Hidrolases/metabolismo , Proteínas Quinases/metabolismo , Animais , Bacteriemia/microbiologia , Bacteriemia/patologia , Proteínas de Bactérias/genética , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/patologia , Modelos Animais de Doenças , Camundongos , Fatores de Transcrição , Virulência
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