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1.
Tanaffos ; 22(1): 53-60, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37920325

RESUMO

Background: In severe COVID-19 cases, a hypercoagulable state may occur. Antiphospholipid syndrome-related auto-antibodies (APSRAs) contribute to coagulopathy, but their role in COVID- 19 remains unclear. We aimed to investigate the prevalence of positive APSRAs and their effect on clinical outcomes in confirmed COVID-19 patients. Materials and Methods: In this cross-sectional study, severe hospitalized COVID-19 cases were enrolled. Demographic and clinical data were obtained from the day of admission. APSRAs including IgG and/or IgM anticardiolipin (aCL) and anti-ß2-glycoprotein1 (anti-ß2GP1) as well as lupus anticoagulant (LAC) were measured. Results: In this study, 54 severe COVID-19 cases with positive RT-PCR and chest CT scans were recruited. Positive APSRAs were found in 7 (12.9%) patients. Positive LAC was a more prevalent marker as compared to other tests (11.1%). The prevalence of positive aCL (IgM or IgG) and anti-ß2 GPI (IgM or IgG) was 1.8% (in an elderly woman). Lower oxygen saturation was found in the positive APSRAs group as opposed to the negative APSRAs group (70.3±9 vs. 84.8±9.7%). The mortality rate in the positive APSRAs group was significantly higher relative to the negative APSRAs group (83.3% vs. 27.1%; P-value: 0.01). Likewise, the mechanical ventilation requirement in the positive group was also higher (50% vs. 27.1%, P-value: 0.28). Conclusion: This study indicated that LAC might be associated with critical cases and high mortality of COVID-19. Nonetheless, the mortality was not related to macrothrombotic incidence.

2.
Clin Case Rep ; 11(10): e7955, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37830072

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare hematologic disease that occurs due to immune system dysfunction. Clinical manifestations of this disease are fever, increased ferritin level, cytopenia, and hemophagocytosis in the biopsy report of the bone marrow. We report a 36-year-old woman referred to our hospital with persistent fever, arthralgia in interphalangeal joints, and cutaneous rash on the trunk, was subsequently diagnosed as an adult-onset Still's disease (AOSD), and after bone marrow aspiration, HLH was diagnosed with her.

3.
Clin Case Rep ; 11(7): e7703, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37457994

RESUMO

Granulomatosis with polyangiitis (GPA), a rare form of small vessel vasculitis, may be manifested by multisystem involvement misleading its definitive diagnosis. The involvement of salivary glands is a very rare characteristic of GPA. Herein, we described a case of GPA with submandibular salivary gland involvement followed by reviewing the literature on similar cases. The case was a 31-year-old man, a known case of seronegative peripheral arthritis that referred recently with bilateral enlargement of the parotid and submandibular glands. Pulmonary nodules were also evident in the patient's CT scan. Fine-needle aspiration under ultrasound guidance indicated the presence of degenerated squamoid cells, giant cells, and inflammatory cells with a priority of neutrophils in the submandibular gland, as well as the presence of a cyst containing fluid without the evidence of malignancy in the parotid gland. The positivity for the Anti-neutrophil Cytoplasmic Antibody (C-ANCA) marker was also revealed. The patient was treated with methotrexate, prednisolone, and rituximab which led to a gradual reduction in the size of the glands and the improvement of the patient's clinical symptoms within 1 month after the treatment. Enlargement of salivary glands in the context of inflammatory disorders can raise doubts about the existence of GPA, and therefore imaging evaluation and histopathological assessment with an ANCA test will be necessary to confirm or rule out it.

4.
Mediterr J Rheumatol ; 33(1): 55-62, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35611110

RESUMO

Background: Using Minimum Data Set (MDS) is the first step in creating and developing a health care information system; it includes standard and key data elements to capture and manage patient care. Aims: This study aimed to develop an MDS in order for using it for designing registry of patients with rheumatoid arthritis in Iran. Methods: This study was conducted at two stages in 2018. In stage one, qualitative method and semi-structured interview were used to identify the registry data elements of patients with rheumatoid arthritis. Collected data was analysed using content analysis method. In stage two, using Delphi method, the developed data set was revised and validated by 15 rheumatologists. Descriptive statistics using SPSS software was used to analyse the data in Delphi. Results: The final MDS included 22 data elements, which were divided into two major categories of management data (including demographic data, and admission and discharge) and clinical data (including patient examination, treatment plans, and medication prescribed by physician). Conclusion: Minimum data set is one of the standard data collection tools playing an important role in health care data management. This study presented a MDS as a platform for creating a rheumatoid arthritis registry system in Iran recommended by rheumatologists.

5.
Iran J Allergy Asthma Immunol ; 21(1): 44-54, 2022 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524377

RESUMO

Rheumatoid arthritis (RA) is a multisystem disorder. Various studies have shown the important role of inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-22, MYD88, and toll-like receptor 2 (TLR2) in this disease. In this study, we investigated the anti-inflammatory effects of B-D-Mannuronic acid (M2000), as a new immunosuppressive drug, on the expression of these inflammatory markers in peripheral blood mononuclear cells (PBMCs) of RA patients. The blood samples of active RA patients and healthy volunteers were used for PBMCsl separation. The cells were cultured with LPS (1 µg/mL), low (5 µg/mL), moderate (25 µg/mL), and high (50 µg/mL) doses of M2000 and a single dose of diclofenac (1 µg/mL) to evaluate TNF-α, IL-6, IL-22, MYD88, and TLR2 genes expression by quantitative real-time (qRT-PCR). Cell surface expression and MFI of TLR2 were assessed; using flow cytometry. Our findings exhibited a significant reduction of TNF-α, IL-6, and MYD88 gene expressions after treatment with three doses of M2000 and an optimum dose of diclofenac. TLR2 gene expression was significantly diminished by moderate and high doses of M2000 and a single dose of diclofenac. Moreoversurface expression of TLR2 was significantly downregulated by moderate and high doses of M2000, while MFI of this receptor was significantly reduced by three doses of M2000. The results of this research showed that M2000 was able to significantly reduce the gene expression of inflammatory molecules  TNF-α, IL-6, MYD88, and TLR2 in patients PBMCs. factor-alpha; Rheumatoid arthritis. These data revealed a part of the molecular mechanisms of M2000 in the treatment process.


Assuntos
Artrite Reumatoide , Ácidos Hexurônicos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Diclofenaco , Ácidos Hexurônicos/farmacologia , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Leucócitos Mononucleares/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Transcriptoma , Fator de Necrose Tumoral alfa/metabolismo , Interleucina 22
6.
J Family Med Prim Care ; 11(12): 7725-7734, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36994045

RESUMO

Introduction: Osteoporosis is a common disease among middle-aged and older people. Because bone mineral density (BMD) is obtained by dividing bone mineral content by area, accurate measurement of the surface of the studied area plays an important role. Therefore, the purpose of this study was to investigate the area of the hip and forearm regions based on gender and height. Methods: In a cross-sectional descriptive study of 758 individuals (702 female and 56 male, divided into 2 groups of ≥50 years old and <50 years old), experienced personnel performed densitometry of the forearm and femur using a Hologic device. The results were statistically analyzed using SPSS software version 21. Results: In women ≥50 years old who were of white race, one-third of the forearm BMD showed moderate agreement with the femoral neck BMD, and in this group, total forearm BMD showed moderate agreement with the femoral neck BMD. In women <50 years old of Caucasian race, one-third of the forearm BMD showed good agreement with the femoral trochanter. In the same group of individuals, total forearm BMD also showed very good agreement with the femoral trochanter. In women <50 years old of white race, one-third of the forearm BMD showed good agreement with all 4 regions in the femur (trochanter, intertrochanteric, neck, total), and in the same group of individuals, total forearm BMD showed very good agreement with all 4 regions of the femur. Conclusion: According to the results obtained for comparison of forearm one-third with hip areas, it seems that simultaneous measurement of the forearm one-third area and different hip areas increases the accuracy of total BMD measurement.

7.
Clin Case Rep ; 9(10): e04931, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34667608

RESUMO

COVID-19 should be considered as a new triggering factor for autoimmune disorders like DM-lupus overlap syndrome. We recommend that patients presenting with dermatomyositis during this pandemic be screened for COVID-19.

8.
Iran J Allergy Asthma Immunol ; 20(5): 574-583, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34664816

RESUMO

Rheumatoid arthritis (RA) is considered as an autoimmune-related condition in which the overproduction of pro-inflammatory cytokines leads to an inflammatory cascade. N-acetylcysteine (NAC) is a potent anti-inflammatory and anti-oxidant agent. We aimed to explore the impact of oral NAC on cytokines activities and clinical indicators in RA patients. In this placebo-controlled randomized double-blind clinical trial, 41 active RA patients were allocated in either NAC (600 mg, twice a day) or placebo group, as add-on therapy to the routine regimen, for 8 weeks. Disease activity score with an erythrocyte sedimentation rate (DAS28-ESR), and serum concentrations of interleukin (IL)-1ß and IL-17 were assessed at baseline and end of the trial for all participants in the test and control groups. The reduction of the DAS28-ESR was higher considerably in the NAC group compared to that of the control group. No statistically significant differences were seen in the reduction of IL-1ß and IL-17 cytokines between the NAC and control groups. In addition, improvements in the patient global assessment, number of tender joints, number of swollen joints, and the ESR rates were in favor of the NAC group. Our findings reveal that NAC may have a beneficial effect on all of the clinical features of RA. However, non-significant variations in the IL-1ß and IL-17 levels suggest an alternative way of NAC effectiveness without influencing the measured cytokines. Nevertheless, these results need to be confirmed by further investigations.


Assuntos
Acetilcisteína/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Biomarcadores , Mediadores da Inflamação/metabolismo , Administração Oral , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/etiologia , Sedimentação Sanguínea , Proteína C-Reativa , Citocinas/sangue , Citocinas/metabolismo , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Índice de Gravidade de Doença , Resultado do Tratamento
9.
BMC Musculoskelet Disord ; 22(1): 582, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172019

RESUMO

BACKGROUND: Despite having higher bone mineral density (BMD) values, type 2 diabetes mellitus (T2DM) patients are at increased risk of fracture. Trabecular bone score (TBS) obtained by evaluating bone microarchitecture might be a more accurate factor for determining bone strength in T2DM patients. In this study, we aimed at investigating the mean values of lumbar spine (LS) TBS, LS-BMD, and femoral neck BMD in T2DM patients and controls, as well as the ability of LS-TBS and BMD in distinguishing between T2DM patients and controls. METHODS: This case-control study was conducted on 150 patients with T2DM (129 women, 21 men) and 484 controls (424 women, 60 men) in Tehran, Iran. LS-TBS along with femoral neck BMD and LS-BMD was computed using dual-energy X-ray absorptiometry images. Diagnostic accuracy and discriminative capacity of LS-TBS, femoral neck BMD, and LS-BMD between the case and control groups were assessed. RESULTS: T2DM patients showed significantly lower LS-TBS values compared to the control group in the total population and in women. However, in T2DM patients, femoral neck BMD and LS-BMD were found to be significantly higher in the total population and in men, respectively, compared to the control group. Based on area under the curve (AUC) and after adjusting for age and BMI, TBS, LS-BMD, and femoral neck BMD were shown to have the acceptable ability in distinguishing T2DM patients and controls. CONCLUSION: Besides higher BMD and lower TBS values in T2DM patients compared to controls, a similar acceptable discriminative ability of LS-TBS, LS-BMD, and femoral neck BMD in differentiating between T2DM patients and controls was observed in the total population and in women.


Assuntos
Diabetes Mellitus Tipo 2 , Fraturas por Osteoporose , Absorciometria de Fóton , Densidade Óssea , Osso Esponjoso , Estudos de Casos e Controles , Feminino , Colo do Fêmur , Humanos , Irã (Geográfico) , Vértebras Lombares , Masculino
10.
Curr Drug Discov Technol ; 18(1): 65-74, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31657689

RESUMO

BACKGROUND: Based on the encouraging results of phase III clinical trial of ß-Dmannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. METHODS: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 µg/mL) of M2000 and optimum dose (1 µg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. RESULTS: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression was downregulated significantly followed by the treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after the treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by the treatment of these cells with a high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by the treatment of these cells with a high dose of M2000 and optimum dose of diclofenac. CONCLUSION: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.


Assuntos
Artrite Reumatoide , Ácidos Hexurônicos/farmacologia , Leucócitos Mononucleares/imunologia , Anti-Inflamatórios/farmacologia , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Células Cultivadas , Quimiocina CCL2/análise , Diclofenaco/farmacologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Receptores CXCR4/análise , Receptores de Quimiocinas/análise , Membrana Sinovial/imunologia
13.
Neurol Sci ; 41(9): 2331-2338, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32656713

RESUMO

BACKGROUND: Olfactory dysfunction has shown to accompany COVID-19. There are varying data regarding the exact frequency in the various study population. The outcome of the olfactory impairment is also not clearly defined. OBJECTIVE: To find the frequency of olfactory impairment and its outcome in hospitalized patients with positive swab test for COVID-19. METHODS: This is a prospective descriptive study of 100 hospitalized COVID-19 patients, randomly sampled, from February to March 2020. Demographics, comorbidities, and laboratory findings were analyzed according to the olfactory loss or sinonasal symptoms. The olfactory impairment and sinonasal symptoms were evaluated by 9 Likert scale questions asked from the patients. RESULTS: Ninety-two patients completed the follow-up (means 20.1 (± 7.42) days). Twenty-two (23.91%) patients complained of olfactory loss and in 6 (6.52%) patients olfactory loss was the first symptom of the disease. The olfactory loss was reported to be completely resolved in all but one patient. Thirty-nine (42.39%) patients had notable sinonasal symptoms while rhinorrhea was the first symptom in 3 (3.26%). Fifteen patients (16.3%) had a taste impairment. Patients with sinonasal symptoms had a lower age (p = 0.01). There was no significant relation between olfactory loss and sinonasal symptoms (p = 0.07). CONCLUSIONS: Sudden olfactory dysfunction and sinonasal symptoms have a considerable prevalence in patients with COVID-19. No significant association was noted between the sinonasal symptoms and the olfactory loss, which may suggest that other mechanisms beyond upper respiratory tract involvement are responsible for the olfactory loss.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Hospitalização/tendências , Transtornos do Olfato/diagnóstico por imagem , Seios Paranasais/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Adulto , Idoso , COVID-19 , Infecções por Coronavirus/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Estudos Prospectivos , SARS-CoV-2 , Resultado do Tratamento
14.
Immunopharmacol Immunotoxicol ; 42(3): 228-236, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32223462

RESUMO

Context: miR-146a, its targets (IRAK1, TRAF6) and NF-κB transcription factor play a fundamental role in rheumatoid arthritis (RA). Positive effects of drug ß-d-mannuronic acid (M2000) were proven on their expression in the HEK-Blue hTLR2 cell line, and results of its phase III clinical trial on RA patients were encouraging.Objective: This research aimed to investigate the effects of M2000 on expression of these genes and serum levels of IL-6 and TNF-α as pro-inflammatory cytokines in RA patients.Material and methods: In this study (Trial Registration Number: IRCT2017100213739N10), 12 RA patients (according to the American College of Rheumatology criteria) and 12 healthy subjects (as control group) were selected. The gene expression of miR-146a, IRAK1, TRAF6, and NF-κB were measured at the baseline and after 12 weeks M2000 therapy, using quantitative real-time PCR method. Moreover, the serum levels of IL-6 and TNF-α were evaluated at the similar times by ELISA method.Results: Our findings showed that the gene expression of miR-146a, IRAK1, TRAF6, and NF-κB significantly decreased after 12 weeks M2000 therapy in RA patients (0.81-, 0.68-, 0.79-, 0.82-fold, with p < .05, p < .01, p < .01, p < .05, respectively). Furthermore, the serum levels of IL-6 and TNF-α significantly reduced in these patients after 12 weeks M2000 therapy (both with p < .05).Conclusions: The present research results determined the part of molecular mechanisms of drug M2000 in RA treatment, based on the expression and function modification of miR-146a, IRAK1, TRAF6, NF-κB, IL-6 and TNF-α.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Citocinas/sangue , Ácidos Hexurônicos/uso terapêutico , Quinases Associadas a Receptores de Interleucina-1/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs/genética , Adolescente , Adulto , Idoso , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
15.
Drug Dev Res ; 81(3): 295-304, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31675124

RESUMO

The positive impacts of ß-d-mannuronic acid (M2000) on the gene expression of miR-155, its target molecules (SOCS1 and SHIP1), and NF-κB transcription factor were demonstrated in a study using the HEK293-TLR2 cell line. This new drug has been approved as a safe and effective medication by a randomized, multinational, phase III clinical trial on RA patients. The present study aimed to evaluate the oral administration effect of M2000 on the expression levels of the mentioned genes in RA patients. This research was conducted on 12 RA patients and 12 healthy individuals. After extraction of total RNA from PBMCs of patients and synthesis of cDNA, the expression levels of miR-155, SOCS1, SHIP1, and NF-κB genes were measured through quantitative Real-time PCR at baseline and after 12 weeks of M2000 therapy. Our findings showed that the miR-155 gene expression level significantly decreased in the M2000-treated patients compared with the baseline (0.76-fold, with p < .05). The expression levels of SOCS1 and SHIP1 genes significantly increased in the patients treated with M2000 compared with the before treatment (1.46-, 1.54-fold, with p < .01, p < .05, respectively). In addition, it was found that the gene expression level of the NF-κB transcription factor significantly reduced in M2000-treated patients compared with the baseline (0.81-fold, with p < .05). This study showed that the oral administration of M2000 was able to reduce the expression of the miR-155, increase the expression of SOCS1 and SHIP1, and decrease the NF-κB gene expression (Trial Registration Number: IRCT2017100213739N10).


Assuntos
Artrite Reumatoide/tratamento farmacológico , Ácidos Hexurônicos/farmacologia , Imunossupressores/farmacologia , MicroRNAs/genética , Administração Oral , Adolescente , Adulto , Idoso , Artrite Reumatoide/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases/genética , Proteína 1 Supressora da Sinalização de Citocina/genética , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-31729947

RESUMO

BACKGROUND: Regarding the leukocytes infiltration into the synovium of Rheumatoid Arthritis (RA) patients is mostly mediated by chemokine ligands and receptors, and following the efficient and motivating results of international Phase III clinical trial of ß-D-Mannuronic acid (M2000) patented EP067919 (2017), as a novel anti-inflammatory drug, in patients with RA, the present research was designed. OBJECTIVES: This study aimed to assess the oral administration effects of this new drug on gene expression of some chemokine receptors and ligands, including CXCR4, CXCR3, CCR2, CCR5 and CCL2/MCP-1 in PBMCs of patients with active form of RA. METHODS: Twelve patients suffering from RA, with inadequate response to conventional drugs were selected (Clinical trial identifier IRCT2017100213739N10) and 1000mg/day of M2000 was orally administrated to them for 12 weeks. The mRNA expression of target molecules was then evaluated in PBMCs of the patients before and after treatment with M2000 using real-time PCR and was compared to healthy controls. Patents related to this study were also reviewed. RESULTS: The results showed that M2000 was able to significantly down-regulate the mRNA expression of CXCR4, CCR2 and CCL2/MCP-1 in the PBMCs of the RA patients. It should be noted that the gene expression situation of the target molecules was in coordinate with the clinical and paraclinical assessments in the patients. CONCLUSION: Taken together, the results of this investigation revealed the part of molecular and immunological mechanisms of drug Mannuronic acid (M2000) in the treatment of RA, based on chemokine ligands and receptors mediated processes.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Quimiocinas/metabolismo , Ácidos Hexurônicos/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Reumatoide/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Ácidos Hexurônicos/farmacologia , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Patentes como Assunto , Receptores de Quimiocinas/genética , Adulto Jovem
17.
BMC Pharmacol Toxicol ; 20(1): 39, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269977

RESUMO

BACKGROUND: Data is limited on comparison of acute and chronic methotrexate (MTX) poisoning. Methotrexate is an anti-folate drug that may be prescribed in some malignant or chronic inflammatory conditions. The aim of the current study was to compare signs and symptoms, complications, treatment and final outcome of acute and chronic MTX toxicity. METHOD: In a retrospective study in a referral center between March 2010 and March 2018, all patients who had been referred with the history of MTX poisoning and hospitalized due to acute or chronic poisoning were evaluated and compared. RESULTS: Of the total 27 patients admitted during the study period, 13 had referred with acute (group 1; consumption of MTX for less than 7 days) and 14 had referred with chronic toxicity (group 2; consumption of MTX for more than 7 days). Mean age was significantly higher in the second group (P < 0.001). Median total dose of MTX was similar between the groups (P = 0.90). Mucosal ulcers and skin lesions (P < 0.001 and 0.02, respectively) were the only symptoms significantly different between the two groups. Leukopenia (P < 0.001), thrombocytopenia (P < 0.001), and anemia (P = 0.04) were significantly more common in the second group. Blood urea nitrogen and creatinine were also significantly higher in the second group of the patients (P < 0.001 and P = 0.048). Median leucovorin administered dose was 200 mg [14, 480] versus 150 mg [75, 187] (P = 0.69) in groups 1 and 2, respectively. CONCLUSIONS: Chronic MTX poisoning is more serious than acute toxicity and accompanies higher dermatologic, hematologic, and hepatic complications necessitating more aggressive treatments including administration of higher doses of leucovorin or bone marrow stimulants such as G-CSF. This may be attributable to the underlying diseases and features (including older ages) which predispose these patients to complications.


Assuntos
Antimetabólitos Antineoplásicos/intoxicação , Antagonistas do Ácido Fólico/intoxicação , Imunossupressores/intoxicação , Metotrexato/intoxicação , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Doença Crônica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
IEEE Trans Nanobioscience ; 18(2): 156-169, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30703034

RESUMO

The possibility to guide and control magnetic nanoparticles in a non-invasive manner has spawned various applications in biotechnology, such as targeted drug delivery and sensing of biological substances. These applications are facilitated by the engineering of the size, selective chemical reactivity, and general chemical composition of the employed particles. Motivated by their widespread use and favorable properties, in this paper, we provide a theoretical study of the potential benefits of magnetic nanoparticles for the design of molecular communication systems. In particular, we consider a magnetic nanoparticle-based communication in a microfluidic channel where an external magnetic field is employed to attract the information-carrying particles to the receiver. We show that the particle transport affected by the Brownian motion, fluid flow, and an external magnetic field can be mathematically modeled as diffusion with drift. Thereby, we reveal that the key parameters determining the magnetic force are the particle size and the magnetic field gradient. Moreover, we derive an analytical expression for the channel impulse response, which is used to evaluate the potential gain in the expected number of observed nanoparticles due to the magnetic field. Furthermore, adopting the symbol error rate as performance metric, we show that using magnetic nanoparticles can enable a reliable communication in the presence of disruptive fluid flow. The numerical results obtained by the particle-based simulation validate the accuracy of the derived analytical expressions.


Assuntos
Computadores Moleculares , Nanopartículas de Magnetita , Modelos Teóricos , Campos Magnéticos , Fenômenos Magnéticos , Microfluídica , Nanotecnologia , Tamanho da Partícula
19.
Inflammopharmacology ; 27(5): 911-921, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30604197

RESUMO

BACKGROUND: The oral administration of drug ß-D-mannuronic acid (M2000) showed a potent therapeutic effect in phase I/II study in rheumatoid arthritis (RA) patients. Here, our aim is to assess the efficacy and safety of this new drug in RA patients under a multinational, randomized placebo-controlled phase III clinical trial. METHOD: Patients (n = 288) with active disease at baseline and inadequate response to conventional drugs were randomly allocated to three groups; (1) receiving mannuronic acid at a dose of two capsules (500 mg) per day orally for 12 weeks, (2) placebo-controlled, and (3) conventional. The primary endpoints were the America College of Rheumatology 20 response (ACR20), 28-joint disease activity score (DAS28) and Modified Health Assessment Questionnaire-Disability Index (M-HAQ-DI). In addition, the participants were followed-up for safety assessment. RESULTS: In this phase III trial, after 12 weeks of treatment, there was a significant reduction in ACR20 between mannuronic-treated patients compared to placebo and conventional groups. Moreover, there was a similar significant improvement for DAS28 following mannuronic therapy. The statistical analysis showed a significant reduction in the swollen and tender joint count in mannuronic-treated patients compared with the placebo group. On the other side, mannuronic acid showed no-to-very low adverse events in comparison to placebo. CONCLUSION: The results of this multinational, phase III clinical trial provided a potent evidence base for the use of ß-D-mannuronic acid as a new highly safe and efficient drug in the treatment of RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Ácidos Hexurônicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
20.
IEEE Trans Nanobioscience ; 18(1): 31-42, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30235144

RESUMO

Although many exciting applications of molecular communication (MC) systems are envisioned to be at microscale, the MC testbeds reported in the literature so far are mostly at macroscale. This may partially be due to the fact that controlling an MC system at microscale is challenging. To link the macroworld to the microworld, we propose and demonstrate a biological signal conversion interface that can also be seen as a microscale modulator. In particular, the proposed interface transduces an optical signal, which is controlled using a light-emitting diode, into a chemical signal by changing the pH of the environment. The modulator is realized using Escherichia coli bacteria as microscale entity expressing the light-driven proton pump gloeorhodopsin from Gloeobacter violaceus. Upon inducing external light stimuli, these bacteria locally change their surrounding pH level by exporting protons into the environment. To verify the effectiveness of the proposed optical-to-chemical signal converter, we analyze the pH signal measured by a pH sensor, which serves as a receiver. We develop an analytical parametric model for the induced chemical signal as a function of the applied optical signal. Using this model, we derive a training-based channel estimator that estimates the parameters of the proposed model to fit the measurement data based on a least square error approach. We further derive the optimal maximum likelihood detector and a suboptimal low-complexity detector to recover the transmitted data from the measured received signal. It is shown that the proposed parametric model is in good agreement with the measurement data. Moreover, for an example scenario, we show that the proposed setup is able to successfully convert an optical signal representing a sequence of binary symbols into a chemical signal with a bit rate of 1 bit/min and recover the transmitted data from the chemical signal using the proposed estimation and detection schemes. The proposed modulator may form the basis for future MC testbeds and applications at microscale.


Assuntos
Computadores Moleculares , Escherichia coli , Modelos Biológicos , Modelos Químicos , Bacteriorodopsinas/química , Bacteriorodopsinas/metabolismo , Escherichia coli/química , Escherichia coli/metabolismo , Concentração de Íons de Hidrogênio , Bombas de Próton , Processamento de Sinais Assistido por Computador , Transdução de Sinais/fisiologia
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