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1.
Eur J Pediatr ; 182(7): 3129-3138, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37097445

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the breakdown of immune tolerance. Impairment of the cellular immunity is primarily evaluated by the levels of the cytokines which can help in predicting the course of ITP. We aimed to assess the levels of IL4 and IL6 in children with ITP and evaluate their role in the pathogenesis and prognosis of this disease. A prospective cohort study was carried on 60 children (15 patients with newly diagnosed ITP, 15 patients with persistent ITP, 15 patients with chronic ITP and 15 healthy children as a control group). Serum IL-4 and serum IL-6 were measured using Human IL-4 and IL-6 ELISA kit in patients and controls. Patients with newly diagnosed and persistent ITP had significantly higher levels of IL4 and IL6 compared to patients with chronic ITP and healthy controls (p < 0.001). The mean serum level of IL4 was 762.0, 741.0, 364.6 and 436.8 pg/ml, and the mean serum level of IL6 was 178.5, 164.4, 57.9 and 88.4 pg/ml for patients with newly diagnosed, persistent, chronic ITP and healthy controls respectively. Serum IL-4 was significantly higher in patients who achieved remission than those who did not improve on first line therapy. CONCLUSION: Serum IL-4 and IL-6 may have a role in the pathogenesis of primary ITP. IL-4 seems to be a good predictor to treatment response. WHAT IS KNOWN: • There is a delicate balance of specific cytokine levels in immune thrombocytopenia, which has an important role in the immune system and is known to be deregulated in autoimmune diseases. changes in IL-4 and IL-6 might be involved in the pathogenesis of newly diagnosed ITP in both paediatric and adult patients. • We conducted this research study to measure the serum level of IL-4 and IL-6, in newly diagnosed, persistent and chronic ITP patients and study their relation to disease pathogenesis as well as patient's outcome. WHAT IS NEW: • We found that IL4 seems to be a good predictor to treatment response and it was a very interesting observation in our study, and to the best of our knowledge, there is no published data about this finding.


Assuntos
Púrpura Trombocitopênica Idiopática , Adulto , Humanos , Criança , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/etiologia , Interleucina-6 , Interleucina-4 , Estudos Prospectivos , Citocinas , Prognóstico
2.
Medicine (Baltimore) ; 101(28): e29894, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35839018

RESUMO

ATP binding Cassette gene member 1 (ABCB1) polymorphism has been incriminated in susceptibility to many malignant, infectious and autoimmune diseases. Recently, it was reported that ABCB1 polymorphisms might have a link to disease progression as well as response to therapy. We aimed to study the association between ABCB1 gene polymorphism and glucocorticoid response in children with newly diagnosed immune thrombocytopenia (ITP). A case control study was conducted on 90 newly diagnosed children with ITP and 90 healthy controls over a period of 1 year. ABCB1 (C3435T) polymorphism was determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) in patients and controls. There was no significant difference between patients and controls as regards to frequency of different ABCB1 genotypes (CC, CT, and TT genotypes were 44.4%, 36.7%, and 18.9% respectively in patients and 48.9%, 38.9%, and 12.2% respectively in controls, P value = 0.18). 80% of patients who received steroids alone or steroids in combination with intravenous immunoglobulin showed complete recovery. There was highly significant relationship between ABCB1 genotypes and response to steroids where 55 % of responders had CC (wild) genotype while 40 % of nonresponders had TT (mutant) genotype. We concluded that ABCB1 gene polymorphism may contribute to the response to steroids in Egyptian children with ITP where patients with homozygous CC genotype responded better to steroids than patients with homozygous TT genotype. These results may help us choose the appropriate initial treatment in these children.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Glucocorticoides , Púrpura Trombocitopênica Idiopática , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Estudos de Casos e Controles , Criança , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Humanos , Polimorfismo de Nucleotídeo Único , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/genética , Esteroides
3.
Medicine (Baltimore) ; 101(49): e31938, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36626503

RESUMO

Intense contemporary research is directed towards validating novel biomarkers to predict acute kidney injury (AKI) in children undergoing cardiothoracic surgeries. We aimed to evaluate the role of cystatin C in early prediction of AKI following cardiac surgery in children with congenital heart disease. Prospective observational cohort study was conducted on 40 children with congenital heart disease undergoing cardiac surgery. 40 healthy children with matched age and sex were enrolled as a control group. Children were subjected to physical examination, routine blood tests, echocardiography, and measurement of plasma cystatin C level on different occasions. The median age of the patients was 3.65 years, a range from 1 to 5 years with no significant difference regarding the age and sex of cases and control groups. The mean serum cystatin C level in patients was 0.75 ±â€…0.15, 1.35 ±â€…0.34 and 1.21 ±â€…0.38 mg/dL (preoperative, at 6 h and at 24 h postoperative, respectively) with statistically significant difference P < .05. 30% of the patients developed postoperative AKI with significantly higher serum cystatin C at 6 hours postoperative >1.33 mg/dL compared to preoperative level p P < .05. Serum cystatin C level was positively correlated with cardiac bypass time, ischemic time and length of hospital stay at 6 hours postoperative. Serum cystatin C is a sensitive marker for early detection of AKI following cardiac surgery in children with congenital heart disease and it was positively correlated with cardiac bypass time, ischemic time and length of hospital stay.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Pré-Escolar , Humanos , Lactente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Biomarcadores , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Creatinina , Cistatina C/sangue , Cardiopatias Congênitas/cirurgia , Valor Preditivo dos Testes , Estudos Prospectivos
4.
Eur J Pharmacol ; 905: 174188, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34004210

RESUMO

Type 1 diabetes mellitus (T1DM) is one of the autoimmune diseases characterized by beta-cell dysfunction with serious health complications. Br-MSCs represent a novel valid candidate in regenerative medicine disciplines. Yet, the full potential of Br-MSCs in managing type 1 diabetes remains elusive. Indeed, this study was designed to explore a novel approach investigating the possible regenerative capacity of Br-MSCs in type1 diabetic islet on the level of the cellular mRNA expression of different molecular pathways involved in pancreatic beta-cell dysfunction. Sixty adult male Sprague-Dawley rats were randomly assigned into 3 groups (20 rats each); the control group, type1 diabetic group, and the type 1 diabetic Br-MSCs treated group. And, for the first time, our results revealed that intraperitoneally transplanted Br-MSCs homed to the diabetic islet and improved fasting blood glucose, serum insulin level, pancreatic oxidative stress, upregulated pancreatic mRNA expression for: regenerative markers (Pdx1, Ngn3, PCNA), INS, beta-cell receptors (IRS1, IRß, PPARγ), pancreatic growth factors (IGF-1, VEGFß1, FGFß), anti-inflammatory cytokine (IL10) and anti-apoptotic marker (BCL2) too, Br-MSCs downregulated pancreatic mRNA expression for: inflammatory markers (NFKß, TNFα, IL1ß, IL6, IL8, MCP1), apoptotic markers for both intrinsic and extrinsic pathways (FAS, FAS-L, P53, P38, BAX, Caspase3), ER stress markers (ATF6, ATF3, ATF4, BIP, CHOP, JNK, XBP1) and autophagy inhibitor (mTOR). In conclusion, Br-MSCs could be considered as a new insight in beta cell regenerative therapy improving the deteriorated diabetic islet microenvironment via modulating; ER stress, inflammatory, and apoptotic signaling pathways besides, switching on the cellular quality control system (autophagy) thus enhancing beta-cell function.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diabetes Mellitus Tipo 1/metabolismo , Estresse do Retículo Endoplasmático , Proteínas de Homeodomínio/genética , Células Secretoras de Insulina/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proteínas do Tecido Nervoso/genética , Antígeno Nuclear de Célula em Proliferação/genética , Transativadores/genética , Animais , Apoptose/genética , Diabetes Mellitus Experimental/metabolismo , Estresse do Retículo Endoplasmático/genética , Controle Glicêmico , Inflamação/genética , Insulina/genética , Células Secretoras de Insulina/patologia , Peroxidação de Lipídeos , Masculino , Transplante de Células-Tronco Mesenquimais , Leite Humano/química , Leite Humano/metabolismo , Estresse Oxidativo , Ratos Sprague-Dawley , Receptor de Insulina/genética , Transdução de Sinais , Regulação para Cima
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