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BACKGROUND AND AIM: Hypozincemia is a prevalent adverse consequence in diabetes mellitus (DM) and ß-Thalassemia patients. We aimed to evaluate the level of serum zinc in ß-thalassemia patients with DM and a risk assessment for hypozincemia. METHODS: The study population included transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) with overt DM (fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-h plasma glucose≥200 mg/dL). Serum zinc concentration was measured by the colorimetric method, and the values below 70 µg/dL were defined as hypozincemia. Myocardial and liver T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) were valued by a free contrast MRI. The demographic, clinical, paraclinical, and laboratory data were also recorded. The data belonged to the period from December 2018 until December 2020. RESULTS: Of 64 diabetic ß-thalassemia patients, 41 cases had zinc data in their medical files (aged 38 ± 9 years, 48.8% female). 78.05% of patients (n = 32) were TDT, and 21.95% were NTDT (n = 9). The mean ± standard deviation of zinc level was 110.2 ± 127.6 µg/dL. The prevalence of hypozincemia was 9.76%, 95% confidence interval [CI] 0.27 to 19.24 (four cases). After controlling age, the odds of hypozincemia for using deferasirox (DFX) was 8.77, 95% CI 0.60 to 127.1. In ß-thalassemia patients, the age-adjusted risk of hypozincemia was calculated at 15.85, 95% CI 0.47 to 529.3 for hepatitis C. The adjusted risk of hypozincemia based on age for antacid use was 6.34, 95% CI 0.39 to 102.7. CONCLUSION: In light of this study, as well as hepatitis C, using DFX and antacids is associated with a high risk of hypozincemia amid diabetic ß-thalassemia cases. However, upward bias should be taken into consideration.
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Diabetes Mellitus , Hepatite C , Sobrecarga de Ferro , Talassemia , Talassemia beta , Humanos , Feminino , Masculino , Talassemia beta/complicações , Talassemia beta/tratamento farmacológico , Deferasirox/uso terapêutico , Sobrecarga de Ferro/complicações , Glicemia , Fatores de Risco , Talassemia/epidemiologia , Hepatite C/complicações , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/induzido quimicamente , Zinco , Quelantes de Ferro/uso terapêuticoRESUMO
BACKGROUND AND AIM: This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent ß-thalassemia (TDT) patients. METHODS: This crossover trial consisted of two sequences (AP and PA). In the AP sequence, nine cases received amlodipine 5 mg daily (phase I) and then were switched to placebo (phase II). In PA sequence, 10 patients took the placebo (phase I) and were shifted to amlodipine (phase II). The washout period was 2 weeks. The length of each phase was 6 months. Serum malondialdehyde (MDA, µmol/L), carbonyl (protein CO, µM/L), glutathione (GSH, nM/L), and total antioxidant capacity (TAC, µmol FeSO4/L) were measured in the beginning and at the end of phases I and II. The clinical significance was viewed as a minimum change difference of 5% for each outcome between amlodipine and placebo. RESULTS: Seventeen cases completed the study. According to the baseline MDA values, the adjusted Hedges's g for MDA was -0.59, 95% confidence interval [CI] -1.26 to 0.08. After controlling the baseline protein CO values, Hedges's g computed for protein CO was -0.11, 95% CI -0.76 to 0.55. The estimated values of the adjusted Hedges's g for GSH and TAC were also 0.26, 95% CI -0.40 to 0.91, and 0.42, 95% CI -0.24 to 1.09, respectively. The change difference for MDA was 8.3% (protein CO 2.2%, GSH 3.1%, and TAC 12.9%). CONCLUSION: Clinically, amlodipine therapy is an efficacious adjuvant treatment with conventional iron chelators for improving the levels of MDA and TAC in patients with TDT.
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Antioxidantes , Talassemia beta , Humanos , Anlodipino/uso terapêutico , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Talassemia beta/tratamento farmacológico , Estudos Cross-Over , Glutationa , Malondialdeído , Estresse Oxidativo , Método Duplo-CegoRESUMO
Ferritin is frequently used to screen some dire consequences of iron overload in ß-thalassemia patients. The study aimed to define the best cutoff point of ferritin to screen for cardiac and liver hemosiderosis in these cases. This was a registry-based study on ß-thalassemia patients living throughout Mazandaran province, Iran (n = 1959). In this diagnostic research, the index test was ferritin levels measured by a chemiluminescent immunoassay. As a reference test, T2*-weighted magnetic resonance imaging (T2*-weighted MRI) was applied to determine cardiac and liver hemosiderosis. A cutoff point of 2027 ng/mL for ferritin showed a sensitivity of 50%, specificity 77.4%, PPV 42.1%, and NPV 82.5% for cardiac hemosiderosis (area under curve [AUC] 0.66, 95% CI 0.60-0.71, adjusted odds ratio [OR] 2.05, 95% CI 1.05-4.01). At an optimum cutoff point of 1090 ng/mL, sensitivity 66.7%, specificity 68%, PPV 82.9%, and NPV 46.8% for liver hemosiderosis were estimated (AUC 0.68, 95% CI 0.63-0.73, adjusted OR 3.93, 95% CI 2.02-7.64. The likelihood of cardiac hemosiderosis serum ferritin levels below 2027 ng/mL is 17.5%. Moreover, 82.9% of ß-thalassemia patients with serum ferritin levels above 1090 ng/mL may suffer from liver hemosiderosis, regardless of the grades.
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Hemossiderose , Sobrecarga de Ferro , Talassemia beta , Humanos , Hemossiderose/diagnóstico , Hemossiderose/etiologia , Ferritinas , Talassemia beta/complicações , Fígado/diagnóstico por imagem , Sobrecarga de Ferro/diagnóstico , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND AND AIM: This study examined whether administration of amlodipine could improve myocardial iron loading status in patients with transfusion dependent ß-thalassemia (TDT), through a placebo-controlled, crossover study. METHODS: Amlodipine (5 mg, daily) or placebo were prescribed to all patients (n = 19) for 6 months, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of amlodipine on iron loading was assessed by measuring myocardial T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) and serum ferritin (ng/mL). RESULTS: Seventeen patients completed the study. The mean ± standard deviation [SD] of myocardial MRI T2* at baseline was 9.83 ± 2.67 ms Myocardial MRI T2* value rose to 11.44 ± 4.14 ms post amlodipine treatment in all patients. After placebo, myocardial MRI T2* value reached 10.29 ± 4.01 ms After controlling the baseline measures, Hedges's g for ferritin and myocardial MRI T2* outcomes were estimated 3.84 (95% confidence interval [CI] 2.68 to 4.97) and -1.80 (95% CI -2.58 to -0.10), respectively. CONCLUSION: Amlodipine might improve myocardial MRI T2* and serum ferritin level compared to placebo. However, larger clinical studies are needed to confirm the results.
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Sobrecarga de Ferro , Talassemia beta , Anlodipino/uso terapêutico , Terapia por Quelação , Estudos Cross-Over , Humanos , Sobrecarga de Ferro/tratamento farmacológico , Fígado , Imageamento por Ressonância Magnética , Talassemia beta/tratamento farmacológicoRESUMO
BACKGROUND: In ß-thalassemia major (ß-TM) patients, iron overload is one of the main causes of inflammation. This study investigated whether use of silymarin could improve inflammatory status in patients with ß-TM and iron overload, through a placebo-controlled, crossover study. METHODS: Silymarin (140 mg, 3 times a day) or placebo were prescribed to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of silymarin was assessed by measuring serum C-reactive protein (CRP) (mg/dL), interleukin (IL)-6 (pg/mL), and IL-10 (pg/mL). RESULTS: Sixty-nine patients completed the study. Data analysis showed that compared to the placebo, silymarin could decrease CRP, IL-6, and raise IL-10 signiï¬cantly (the p values for all variables were <0.001). Cohen's d for CRP adjusted according to the baseline CRP value was -1.72, the 95% confidence interval (CI) -2.12 to -1.33. The adjusted Cohen's d equal to -1.12, 95% CI -1.48 to -0.76, and 0.78, 95% CI 0.43-1.12, were also estimated for IL-6 and IL-10, respectively. CONCLUSION: The results of the current study demonstrate that the combination of iron chelation therapy with silymarin can improve inflammatory status in patients with ß-TM in the clinical setting.
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Sobrecarga de Ferro , Silimarina , Talassemia beta , Terapia por Quelação , Estudos Cross-Over , Método Duplo-Cego , Humanos , Inflamação , Interleucina-10 , Interleucina-6 , Sobrecarga de Ferro/tratamento farmacológico , Silimarina/uso terapêutico , Talassemia beta/tratamento farmacológicoRESUMO
Numerous problematic disorders such as vitamin D (Vit-D) deficiency subsequent to large iron loading can be developed in patients with ß-thalassemia. The study aimed to estimate Vit-D insufficiency and its risk factors in patients with ß-thalassemia. In this multicenter and observational study, all ß-thalassemia patients, who referred to 14 hospital-based thalassemia divisions or clinics in Mazandaran province, Iran were included in the study. The data belong to December 2015 until December 2019. The study population was made of transfusion dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) patients. Serum levels of 25-OHD3 have been measured by high performance liquid chromatography (HPLC) method as ng/mL. Demographic and clinical information along with some biological tests, as well as the results of T2*-weighted magnetic resonance imaging were analyzed. Of 1959 registered patients, 487 (24.9%) patients had Vit-D-related data. The prevalence of Vit-D insufficiency (< 30 ng/mL) was 41.9, 95% CI 37.5-46.3. The adjusted risks of moderate to severe liver siderosis and raised AST (aspartate aminotransferase) for Vit-D insufficiency (< 30 ng/mL) were 2.31, 95% CI 1.38-3.89 and 2.62, 95% CI 1.43-4.79, respectively. The receiver operating characteristic (ROC) curve analysis showed that the predictive accuracy of ferritin for Vit-D insufficiency status was 0.61, 95% CI 0.54-0.68 with a cutoff point of 1,078 ng/mL (P = 0.03, sensitivity 67%, specificity 49%, positive predictive value [PPV] 47% and negative predictive value [NPV] 68%). In spite of the national programs for treating Vit-D deficiency and our previous efforts for giving supplements to all patients, Vit-D insufficiency/deficiency is still common in our patients. Also, moderate to severe liver siderosis and raised AST were the independent risk factors for the Vit-D insufficiency.
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Aspartato Aminotransferases/sangue , Fígado/patologia , Siderose/complicações , Deficiência de Vitamina D/complicações , Talassemia beta/complicações , Adulto , Transfusão de Sangue , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Fatores de Risco , Siderose/sangue , Deficiência de Vitamina D/sangue , Talassemia beta/sangueRESUMO
BACKGROUND: Electronic registry system of beta-thalassemia patients was run by Thalassemia Research Center (TRC) in 2017. The aim of the current study was presentation of therapeutic status in these patients at Mazandaran Province, Iran. METHODS: Therapeutic status variables including: Name of cities and hospitals, age and sex of patients, dependent and non-transfusion-dependent, starting age of the blood transfusion and iron-chelating agents, blood group and Rh, washed blood transfusion, abnormal antibody, transfusion reactions, mean hemoglobin during the last 3 months, type of iron chelators, iron chelators dosage, serum ferritin, and the use of hydroxyurea. RESULTS: Overall, 1831 patients were registered [891 male (48.7%)]. Mean age of patients was 30±9.7 yr. Average of hemoglobin levels for female and male were 9.1±5.1 and 9.4±6.3 gr/dl, respectively. Seventy-six percent of transfusion-dependent patients (1385) have received iso-group PRBC (packed red blood cells), after crossmatch. The most common blood group among patient was type O-positive (35.7%). Monotherapy with desferrioxamine was most type of used iron-chelating agent in these patients (47.2%). Mean of ferritin was 3300±7800 (ng/ml). Twenty-eight percent of patients (484) have received hydroxyurea; proportion of male and female was approximately equal. T2 weighted magnetic resonance imaging (MRIT2*) was measured in 62.2% of patients. Moderate and severe hepatosiderosis was 10.1% and 2.9%, respectively. Patients with moderate and severe cardiac siderosis were 11% and 5%, respectively. CONCLUSION: Registry findings are valuable for treatment management and ensuring patients medications. It will also provide accessibility to various levels of patients' information for health care managers and experts to help them make appropriate decisions.
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INTRODUCTION: Pulmonary arterial hypertension (PAH) is relatively prevalent in patients with thalassemia. PAH treatment is necessary as the prevalence of Doppler-estimated PAH and the resultant mortality is high in such patients. MATERIALS AND METHODS: This study aimed at evaluating the effect of bosentan therapy on patients with thalassemia suspected of PAH. Based on pulsed Doppler echocardiography, all the cases were suspected of severe PAH. Consequently, bosentan was initiated at a dose of 62.5 mg twice a day for 4 weeks, which was increased to 62.5-125 mg twice a day, if no adverse side effects were observed. RESULTS: The results of this study showed that pulmonary artery pressure (PAP) decreased after the administration of bosentan in three cases, from 160 to 120, 110 to 65, and 60 to 25 mmHg; in other words, the PAP reduced in the mentioned cases by 25%, 36.4%, and 58.4%, respectively. CONCLUSION: In this study, PAP improved after bosentan therapy in patients with ß-thalassemia suspected of PAH; however, further studies are required to confirm the findings.
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INTRODUCTION: The benefit of annual administration of zoledronic acid in the management of thalassemia-associated osteoporosis is unknown. AIM: The aims of this study were to evaluate the efficacy of treatment with two different dosing regimens of IV zoledronic acid (annually versus every 3 months) for increasing low bone mineral density (BMD) in patients with osteoporosis associated with ß-thalassemia as annually and 3-monthly on bone density in patients. MATERIALS AND METHODS: This retrospective, single-center study analyzed patients' clinical records and bone density measurements. Those enrolled in the study were 14 to 53 years of age, had documented ß-thalassemia, and were treated with IV zoledronic acid on either an annual or every 3 months dosing regimen. Dual-energy X-ray absorptiometry was used to obtain the z-score for BMD in the lumbar spine and femoral neck. RESULTS: Thirty-four patients were enrolled in the study; 15 (44.1%) had been treated annually, and 19 (55.9%) had been treated every month. In patients receiving treatment with the once-yearly dose of zoledronic acid, significant increases were observed in the lumbar spine BMD z-score, from -2.45 ± 0.69 to -1.97 ± 0.82 (P=0.02). When comparing BMD across the two treatment regimens, the mean lumbar spine BMD was 0.82 greater (95% CI 0.31, 1.33, P=0.003) and the mean femoral neck BMD 0.37 greater (95% CI -0.15, 0.87, P=0.1) in the group receiving annual zoledronic acid treatment. CONCLUSIONS: In patients with thalassemia-associated osteopenia, annual treatment with zoledronic acid increases lumbar spine bone density while being more effective, less expensive, and associated with fewer adverse events than dosing every 3 months.
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Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Colo do Fêmur/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Osteoporose/etiologia , Ácido Zoledrônico/administração & dosagem , Talassemia beta/complicações , Absorciometria de Fóton , Adulto , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Irã (Geográfico) , Masculino , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Talassemia beta/tratamento farmacológico , Talassemia beta/fisiopatologiaRESUMO
This study aimed to determine the potential iron-chelating effects of silymarin in patients with ß-thalassemia major receiving standard iron-chelation therapy. We evaluated whether addition of silymarin to standard iron-chelation therapy could improve iron burden markers and liver and cardiac function in these patients, via a placebo-controlled, crossover clinical study. Silymarin (140 mg) or placebo were administered thrice daily to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other groups. Silymarin efficacy was assessed by measuring serum iron level, ferritin level, total iron-binding capacity and liver and cardiac function on magnetic resonance imaging. Silymarin treatment resulted in a negative change in the serum iron and ferritin levels and a positive change in the total iron-binding capacity levels (treatment effect, p < .001, p = .06, and p = .05, respectively). Silymarin treatment led to positive changes in cardiac and liver function in both treatment sequences of study; however, this was not statistically significant. There was a negative change in liver iron concentration in both treatment sequences (treatment effect, p = .02). In conclusion, combined iron-chelation and silymarin therapy was effective for improving the iron-burden status in patients with ß-thalassemia major.
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Terapia por Quelação/métodos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Silimarina/uso terapêutico , Talassemia beta/tratamento farmacológico , Adulto , Estudos Cross-Over , Feminino , Humanos , Quelantes de Ferro/farmacologia , Masculino , Silimarina/farmacologia , Adulto JovemRESUMO
BACKGROUND & AIMS: Blood transfusion therapy is lifesaving for individuals with ß-thalassemia major (ß-TM). Iron burden following blood transfusion is the main cause of oxidative stress (OS) and organ dysfunction in these patients. The aim of this study was to evaluate the effects of silymarin on serum antioxidant and oxidative status in patients with ß-TM. METHODS: A crossover, randomized controlled trial was performed on 82 thalassemia patients. In two periods of 12 weeks, patients received 420mg silymarin (divided into three equal 140-mg daily doses) and placebo. The washout period between the two phases was two weeks. Serum malondialdehyde (MDA), protein carbonyl (CO), total antioxidant capacity (TAC), and reduced glutathione (GSH) were measured before and after both periods. RESULTS: Sixty-nine patients completed the study. Mean serum MDA and protein CO significantly decreased in all patients with ß-TM after three months of treatment with silymarin. At the end of the study, serum MDA decreased from 20.36±20.11 to 4.79±4.71µmol/l (compared to 17.81±16.05µmol/l after administration of placebo), and protein CO dropped from 0.31±0.28 to 0.11±0.09mM/l (compared to 0.24±0.17mM/l with placebo). Additional laboratory parameters (such as serum TAC and plasma GSH) were also significantly elevated after therapy with silymarin. At the end of the study, serum TAC increased in all patients from 620.7±202.64 to 971.83±328.16µmol FeSO4/l (compared to 672.22±206.88µmol FeSO4/l with placebo), and GSH increased from 46.16±41.68 to 195.35±210.98nM/l (compared to 58.52±48.95nM/l with placebo). The treatment effect of silymarin was measured using a mixed-effects model of variance analysis for changes in MDA, protein CO, TAC, and GSH, with significant effects being demonstrated for each laboratory parameter (P<0.001, P=0.002, P<0.001, and P<0.001, respectively). CONCLUSIONS: Silymarin was effective in decreasing serum OS and enhancing serum antioxidant capability in patients with ß-thalassemia major. Silymarin given as an adjuvant therapy to standard iron chelators may provide an improvement in the OS measurements obtained in these patients, with accompanying benefit.
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Antioxidantes/farmacologia , Transfusão de Sangue , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Silimarina/farmacologia , Talassemia beta/terapia , Adolescente , Adulto , Antioxidantes/metabolismo , Estudos Cross-Over , Feminino , Glutationa/sangue , Humanos , Ferro/sangue , Masculino , Malondialdeído/sangue , Fitoterapia , Carbonilação Proteica/efeitos dos fármacos , Adulto JovemRESUMO
Diabetes mellitus (DM) is one of the potential complications in patients with transfusion-dependent ß-thalassemia major (ß-TM). In this case-controlled study, we examined the pancreatic iron levels in outpatients with ß-TM. In this study, cases of patients with ß-TM and DM were gender- and age-matched with control subjects, who were non-diabetic and had normal blood glucose on standard oral glucose tolerance (OGTT) tests. One of four diagnoses [normal, pre-diabetes, impaired glucose tolerance (IGT), DM] was made according to the American Diabetes Association (ADA) criteria. The T2*-weighted magnetic resonance imaging (T2*-weighted MRI) of the heart, liver, and pancreas was performed using a 1.5 Tesla scanner. The study enrolled 26 diabetic cases, 17 non-diabetic cases, and eight cases of IGT or pre-diabetes cases. The severity of pancreatic and cardiac iron siderosis was significantly different between the groups. We found a statistically significant difference at 5.6 ms in the T2*-weighted MRI values for the pancreas between patients with normal vs. abnormal glucose metabolism [p < 0.009; odds ratio (OR): 11.2; 95% confidence interval (95% CI): 1.32-94.4)]. The receiver operating characteristic (ROC) curve for the 5.6 ms cutoff led to an area under the curve (AUC) of 0.69 (95% CI: 55.0-84.0; p < 0.02), with sensitivity and specificity of 94.0 and 42.0%, respectively. There was a moderate positive correlation between pancreatic and cardiac T2*-weighted MRI (r = 0.4; p < 0.001), and a weak correlation between the pancreas and the liver (r = 0.38; p < 0.005). To conclude, we have introduced a cutoff of 5.6 ms on T2*-weighted MRI of the pancreas for prediction of abnormal glucose metabolism in ß-TM patients.
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Complicações do Diabetes/diagnóstico , Complicações do Diabetes/metabolismo , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/etiologia , Imageamento por Ressonância Magnética , Pâncreas/patologia , Talassemia beta/complicações , Adolescente , Adulto , Biomarcadores , Transfusão de Sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Glucose/metabolismo , Humanos , Lactente , Recém-Nascido , Ferro/metabolismo , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Curva ROC , Adulto Jovem , Talassemia beta/terapiaRESUMO
BACKGROUND: The hematologic response to hydroxyurea (HU) is varied among ß-thalassemia (BT) patients. The BCL11A and SOX6 genes are involved in response to HU. This study aimed to investigate the in-vitro responsiveness of HU among BT major patients homozygote for IVSII-1G>A mutation and XmnI single nucleotide polymorphism (SNP) in order to find whether the in-vitro Hb concentration is a predictor of clinical (HU) responsiveness. METHODS: In this case-control study, twenty BT patients homozygote for IVSII-1G>A mutation and XmnI SNP from Thalassemia Research Center, Sari, Iran in 2015 were selected and categorized into two groups of 10 Responder (R) and 10 Non-Responder (NR) according to their clinical HU response. Ten healthy individuals as a control group were also selected. Hematopoietic erythroid progenitors were expanded from peripheral blood. Hb concentration was measured using photometry method. The flow cytometry and real-time PCR methods were applied for the analysis of cell surface markers (CD71 and CD235a) and gene expression (BCL11A and SOX6), respectively. RESULTS: R and NR groups produced higher amount of Basic Hb than C group in cell culture medium at day 14 (P<0.05). After HU treatment, in R group, Hb levels was significantly elevated in comparison to NR and C group (P<0.05). BCL11A expression was decreased after exposure to HU in all groups while SOX6 expression was only down-regulated in C group, and its expression was increased in R and NR groups after HU treatment. CONCLUSION: Since different factors including wide networks of intracellular factors and individual differences between patients can affect response to HU in patients, the increasing Hemoglobin on culture medium alone cannot predict clinical responsiveness to that drug.
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There are few papers on the combination therapy of deferiprone (DFP) and deferasirox (DFX) in iron-overloaded patients with transfusion-dependent ß-thalassemia major (ß-TM). A total of 6 patients with ß-TM (5 males and 1 female) with a mean age of 23.8±5.8 years (ranging from 17 to 31) used this treatment regimen. The mean doses of DFP and DFX were 53.9±22.2 and 29.3±6.8 mg/kg/day, respectively. The duration of treatment was 11.5±4.6 months. Their serum ferritin levels were measured to be 2800±1900 and 3400±1600 ng/mL before and after treatment, respectively (p<0.6). Their cardiac magnetic resonance imaging (MRI) T2* values were 16.69±15.35 vs 17.38±5.74 millisecond (ms) before and after treatment, respectively (p < 0.9). Although there was no significant difference between their cardiac MRI T2* values before and after treatment statistically, the values improved after combination therapy with DFP and DFX in most of the patients. Liver MRI T2 * values were changed from 2.12±0.98 to 3.03±1.51 ms after treatment (p < 0.01); Further, their liver T2* values and liver iron concentration (LIC) were improved after treatment. Our study found that cardiac MRI T2* values, liver MRI T2* values, and LIC were improved after combination therapy with DFP and DFX in ß-TM patients and that DFP and DFX combination therapy could be used to alleviate cardiac and liver iron loading.
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Carrier frequency of the ßS allele has been reported to be 0.19% in Mazandaran province, northern Iran. Haplotype analysis of the ßS allele helps trace the origin of its encoded hemoglobin (Hb) variant, Hb S, in a region. The aim of this study was to investigate the haplotypes associated with ßS alleles in Mazandaran province. Capillary electrophoresis was carried out to detect individuals suspected to have a ßS allele(s). DNA analysis (PCR-RFLP) was used for final confirmation. To identify 5' to 3' ß-globin gene cluster haplotypes associated with ßS alleles, family linkage analysis was applied. Six polymorphic sites (HincII 5' to ε, XmnI 5' to Gγ, HindIII in Gγ, HindIII in Aγ, HincII 3' to ψß and AvaII in ß) were investigated using the PCR-RFLP method. Five different haplotypes were linked to ßS alleles, while ßA alleles were associated with nine haplotypes. Among the ßS alleles, 53.9% were associated with the Benin (----++) haplotype, and the Arab-Indian (+++-++) haplotype had the second-highest frequency (23%). Unlike southern provinces, where the Arab-Indian haplotype is prominent, the Benin haplotype is the most frequent haplotype in northern Iran, and this may represent a founder effect. Since the Benin haplotype does not carry the XmnI polymorphism 5' to the Gγ gene, which is responsible for high expression of Hb F, a severe form of sickle cell disease can be anticipated in patients that are homozygous for the ßS allele in the northern region.
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Anemia Falciforme/genética , Haplótipos , Hemoglobina Falciforme/genética , Globinas beta/genética , Alelos , Humanos , Irã (Geográfico) , Polimorfismo de Fragmento de RestriçãoRESUMO
Major ß-thalassemia (ß-TM) is one of the most common inherited hemolytic types of anemia which is caused as a result of absent or reduced synthesis of ß-globin chains of hemoglobin. This defect results in red blood cells lysis and chronic anemia that can be treated by multiple blood transfusions and iron chelation therapy. Without iron chelation therapy, iron overload will cause lots of complications in patients. Antioxidant components play an important role in the treatment of the disease. Silymarin is an antioxidant flavonoid isolated from Silybum marianum plant. In the present study, we reviewed clinical and experimental studies investigating the use of silymarin prior to September 1, 2015, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases and we evaluated the potential effects of silymarin on controlling the complications induced by iron overload in patients with ß-TM. Based on the results of the present study, we can conclude that silymarin may be useful as an adjuvant for improving multiple organ dysfunctions.
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The discovery of fetal DNA (f-DNA) opens the possibility of early non-invasive procedure for detection of paternally inherited mutation of beta-thalassemia. Since 2002, some studies have examined the sensitivity and specificity of this method for detection of paternally inherited mutation of thalassemia in pregnant women at risk of having affected babies. We conducted a systematic review of published articles that evaluated using this method for early detection of paternally inherited mutation in maternal plasma. A sensitive search of multiple databases was done in which nine studies met our inclusion criteria. The sensitivity and specificity was 99 and 99 %, respectively. The current study found that detection of paternally inherited mutation of thalassemia using analysis of cell-free fetal DNA is highly accurate. This method could replace conventional and invasive methods.
Assuntos
DNA/sangue , Diagnóstico Pré-Natal/métodos , Talassemia beta/sangue , Talassemia beta/diagnóstico , Sistema Livre de Células , DNA/genética , Feminino , Feto/metabolismo , Humanos , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Talassemia beta/genéticaRESUMO
Several types of hemoglobin D (Hb D) are distinguishable by DNA analysis, and the aim of this study was to identify the types of Hb D variant and ß-globin gene haplotypes linked to Hb D in Mazandaran Province, northern Iran. Fifty five individuals were identified as Hb D carriers, and PCR-RFLP analysis revealed that all 55 had the Hb D-Los Angeles type. To identify haplotypes associated with the ß(D) allele, family linkage analysis, using the PCR-RFLP method for seven polymorphisms in the ß-globin gene cluster, was carried out on families of 23 of these 55 individuals. We observed three different haplotypes in association with Hb D-Los Angeles. In most cases (91.4%) ß(D) alleles were linked to haplotype I [+ - - - - + +]. Haplotype II [- + + - + + +] and an atypical haplotype [- + + - - + -] were each in association with the ß(D) allele in only one case (4.3%). This is the first report worldwide of the [- + + - - + -] haplotype in association with Hb D-Los Angeles. We conclude that more than 90% of the evaluated Hb D-Los Angeles alleles in Mazandaran have the same origin, and the two rare haplotypes may represent different genetic origins and/or other molecular events, such as gene conversion or recombination, in the region.
Assuntos
Haplótipos , Hemoglobinas Anormais/genética , Família Multigênica , Globinas beta/genética , Alelos , Análise Mutacional de DNA , Índices de Eritrócitos , Ligação Genética , Humanos , Irã (Geográfico) , MutaçãoRESUMO
Pleurotus porrigens is an culinary-medicinal mushroom. It is locally called sadafi and is found in the northern regions of Iran, especially in Mazandaran. This mushroom is used to prepare a variety of local and specialty foods. Because of the phenol and flavonoid contents and the strong iron-chelating activity of this mushroom, it was selected for an assay of in vivo iron-chelating activity. Methanolic extract was administered intraperitoneally to iron-overloaded mice at two dosages (200 and 400 mg/kg/24 hours) for a total of 20 days, with a frequency of 5 times a week for 4 successive weeks. The total iron content was determined by atomic absorption spectroscopy. Plasma Fe3+ content was determined using a kit. Liver sections were stained by hematoxylin and eosin and Perls stain. A significant decrease in the plasma concentration of iron was observed in mice treated with extracts (P < 0.001). The animals showed a dramatic decrease in plasma Fe3+ content when compared with the control group (P < 0.001). Also, Perls stain improved the smaller amount of deposited iron in the liver of iron-overloaded mice treated with the extract. Liver sections revealed a marked reduction in the extent of necrotic hepatocytes, fibrous tissues, and pseudo-lobules. A high-performance liquid chromatography method was developed to simultaneously separate 7 phenolic acids in extract. Rutin (1.784 ± 0.052 mg g(-1) of extract) and p-coumaric acid (1.026 ± 0.043 mg g(-1) of extract) were detected as the main flavonoid and phenolic acids in extract, respectively. The extract exhibited satisfactory potency to chelate excessive iron in mice, potentially offering new natural alternatives to treat patients with iron overload. More studies are needed to determine which compounds are responsible for these biological activities.