Publications by authors named "Ali Akbar Pourfathollah"

110 Publications

Tumor Microenvironment Changing through Application of MicroRNA-34a Related Mesenchymal Stem Cells Conditioned Medium: Modulation of Breast Cancer Cells toward Non-aggressive Behavior.

Iran J Allergy Asthma Immunol 2021 Apr 17;20(2):221-232. Epub 2021 Apr 17.

Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

Conditioned medium (CM) derived from mesenchymal stem cells (MSCs) contains bioactive molecules including microRNAs (miRs) that could be a potential tool for controlling cancer cells' behavior. Due to the properties of CM, this study assesses the effects of miR-34a related MSC-CM on tumor behavior through the evaluation of migration, invasion, apoptosis, and PDL1 expression in breast cancer cell lines. The miR-34a overexpression vector or scramble control was produced using lentiviral vectors, DNA cloning, and the transfection of the HEK-293T cell line. It was then transduced into human adipose-derived mesenchymal stem cells (hAD-MSCs). MSC-CMs were collected and added onto MDA-MB-231 cell lines. The functional evaluations were performed by transwell, wound healing, and Annexin V/PI methods on the treated MDA-MB-231 cell lines. The PDL1 expression was also assessed by Real-time PCR and western blot. The findings of this study showed that ectopic miR‑34a expression was significantly upregulated in manipulated hASC with miR-34a (p<0.0001). Treatment of MDA-MB-231 cell line with miR-34a-hAD-MSC-CM, scramble-hAD-MSC-CM, or hAD-MSC-CM displayed not only a reduction in the number of migrated or invaded cells (p=0.01) but also an increase in the apoptotic cells in the test group (p=0.02) when compared to the control groups. It also showed down-regulation in the gene (p=0.05) and protein expression levels of PDL1 in the test group. The results of the present study showed that simultaneous application of miR-34a and MSC-CM can be considered as a new method for changing the cancerous microenvironment; and therefore, as a potential strategy in breast cancer therapy.
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April 2021

Evaluation of serum natural autoantibodies reaction in different hematological disorders with prospective view to their probable utilization in predictive medicine.

Asian J Transfus Sci 2020 Jul-Dec;14(2):167-171. Epub 2020 Dec 19.

Department of Immunology, Medical Faculty, Tarbiat Modares University, Tehran, Iran.

Background: There are some antibodies which are present in healthy individuals without any former exposure to foreign antigens; they are known as natural autoantibodies (NAAbs). In recent years, it was shown that they probably contribute to the homeostasis of the whole body and might be present before beginning of some diseases. Thus, as new biomarkers, they are promising factors to diagnose diseases.

Materials And Methods: In this study, we drew upon samples of 924 individuals (600 controls and 324 cases) with underlying diseases of anemia, polycythemia, leukocytosis, thrombocytopenia, thrombocytosis, and pancytopenia. For detection of NAAbs against red blood cell, plasma samples were incubated with their own red cell suspension in 4°C for 18 h. Then, positive samples were evaluated for antibody screening and titration.

Results: Fifty-two (8.6%) controls and 58 (17.9%) cases showed positive reaction (Pv < 0.001). The prevalence of positive antibody screens among auto-positive controls was 53% and 100% among cases; moreover, strength of antibody screen reaction had a mean rank of 22.5 in controls and a mean rank of 38.5 in cases (Pv < 0.001). A significant relation was also observed between ABO blood group and prevalence of NAAbs in controls but not in cases (Pv < 0.05).

Conclusion: The prevalence and potency of NAAbs increased along with hematological changes; moreover, the antibody reactions' pattern and titration showed significant differences between the two groups and these may be useful as biomarker for monitoring and prediction of some hematological diseases.
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http://dx.doi.org/10.4103/ajts.AJTS_15_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983152PMC
December 2020

Noninvasive Fetal Sex Determination by Real-Time PCR and TaqMan Probes.

Rep Biochem Mol Biol 2020 Oct;9(3):315-323

Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Background: Noninvasive fetal sex determination by analyzing Y chromosome-specific sequences is very useful in the management of cases related to sex-linked genetic diseases. The aim of this study was to establish a non-invasive fetal sex determination test using Real-Time PCR and specific probes.

Methods: The study was a prospective observational cohort study conducted from August 2018 to September 2019. Venous blood samples were collected from 25 Iranian pregnant women at weeks 7 to 25 of gestation. Cell-free DNA (cfDNA) was isolated from the plasma of samples and fetal sex was determined by SRY gene analysis using the Real-Time PCR technique. In the absence of SRY detection, the presence of fetal DNA was investigated using cfDNA treated with BstUI enzyme and PCR for the epigenetic marker RASSF1A.

Results: Of the total samples analyzed, 48% were male and 52% female. The RASSF1A assay performed on SRY negative cases also confirmed the presence of cell-free fetal DNA. Genotype results were in full agreement with neonate gender, and the accuracy of noninvasive fetal sex determination was 100%.

Conclusion: Fetal sex determination using the strategy applied in this study is noninvasive and highly accurate and can be exploited in the management of sex-linked genetic diseases.
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http://dx.doi.org/10.29252/rbmb.9.3.315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816785PMC
October 2020

Prevalence and phylogenetic analysis of HTLV-1 in blood donors in Golestan Province, in the Northeast of Iran.

J Virol Methods 2021 04 21;290:114073. Epub 2021 Jan 21.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran. Electronic address:

The human T-lymphotropic virus type 1 (HTLV-1) can cause ATL or TSP. This study evaluates the prevalence of HTLV-1 infection in blood donors in Golestan province. The study was conducted among 4226 blood donors and ELISA test was performed for the initial HTLV-1 screening. Reactive samples were confirmed by Western blot and Electrochemiluminescence tests. Then recalling donors with reactive results was done and genomic DNA from the new sample was extracted and tested using the Nested PCR method and phylogenetic analysis was performed. At first, 8 samples were reactive with ELISA test and 4 samples were confirmed with western blot, Electrochemiluminescence and Nested PCR tests.The sequences of isolates was related to the HTLV-1 virus and subtype a (cosmopolitan) subgroup A.The prevalence of HTLV-1 virus in Golestan province was about 0.09 %.The genotype of virus isolates had a common ancestor with isolates of the Khorasan region.
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http://dx.doi.org/10.1016/j.jviromet.2021.114073DOI Listing
April 2021

Optimizing the recovery of peripheral blood mononuclear cells trapped in leukoreduction filters - A comparison study.

Hematol Transfus Cell Ther 2020 Dec 21. Epub 2020 Dec 21.

Tarbiat Modares University, Faculty of Medical Science, Tehran, Iran.

Introduction: The isolation of captured peripheral blood mononuclear cells (PBMNCs) from leukoreduction filters (LRFs) can be of great importance in terms of bringing the lost cells back into use.

Objective: The aim of this study was to evaluate various methods based on their potential to recover the peripheral blood cells from LRFs with a focus on mononuclear cells (MNCs).

Method: For cell isolation from LRFs, three distinct methods (back-flushing, direct and vacuum pump) were compared through the calculation of the yield of isolated MNCs. The viability of extracted cells was determined by the flow cytometry technique. Moreover, the recovered MNCs were characterized regarding the presence of blood stem cell purification. The cell culture, microscopic observation, and immunophenotyping were employed to characterize the blood stem cells (hematopoietic, mesenchymal and progenitor endothelial stem cells).

Results: The yield of isolation obtained in the back-flushing, direct and vacuum pump methods were 17.7 ± 1.28, 17.3 ± 0.96 and 21.2 ± 0.90 percent, respectively. Although the highest potential for total blood cell recovery belonged to the vacuum pump method, the lowest cell viability (85.73 ± 4.84%) was observed in this method. However, the isolation process of the back-flushing and direct methods had less effect on cell viability. The characterization of the isolated MNCs displayed that the dominant positive phenotype was for CD34/CD45, indicating hematopoietic stem cells. In addition, the endothelial stem/progenitor cells were significantly detected as CD31/CD133 positive cells.

Conclusion: According to our results and considering the safety and efficiency potential of each of the applied methods, the back-flushing in comparison with the other methods can be considered a suitable procedure for MNC isolation from LRFs.
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http://dx.doi.org/10.1016/j.htct.2020.09.155DOI Listing
December 2020

Leukocyte reduction filters as an alternative source of peripheral blood leukocytes for research.

Hematol Transfus Cell Ther 2020 Dec 24. Epub 2020 Dec 24.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran; Tarbiat Modares University, Faculty of Medical Sciences, Tehran, Iran. Electronic address:

Introduction: Peripheral blood leukocytes are a suitable cell model for science research. However, blood samples from healthy volunteers are limited in volume and difficult to obtain due to the complexity of volunteer recruitment.

Objective: Therefore, it is urgent to find an alternative source of peripheral blood leukocytes.

Method: One of the possibilities is the use of leukocyte reduction filters (LRFs) in blood banks that is used for preparation of leukoreduced blood products. More than 90% of the leukocytes are trapped in the leukofilters allowing the desired blood product to pass through.

Results: It has been reported that the biological function of leukocytes collected from the filters are no different from those isolated from buffy coats, leukapheresis products and whole blood (WB) cells. Moreover, LRFs are waste products that are discarded after leukoreduction.

Conclusion: Thus, leukofilters represent an economic source of human cell populations that can be used for a variety of investigative purposes, with no cost. In the present study, we reviewed the different usage of LRFs in the research, clinical and commercial applications.
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http://dx.doi.org/10.1016/j.htct.2020.10.963DOI Listing
December 2020

Evaluation of effective factors in the acceptance of mobile health technology using the unified theory of acceptance and use of technology (UTAUT), case study: Blood transfusion complications in thalassemia patients.

Med J Islam Repub Iran 2020 22;34:83. Epub 2020 Jul 22.

Department of Immunology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.

Mobile health or MHealth refers to the use of mobile phone in healthcare services to enhance the health level of people. Before using MHealth, it is necessary to study the effective factors in physicians' adoption and acceptance of technology in the field of thalassemia. This cross sectional study was conducted using the survey and correlation methods. The statistical population of the study consisted of hematologists who were selected using the convenience sampling method. In this study, 58 questionnaires along with structural equations modeling based on partial least squares were used. SPSS and SMART PLS2 were used for data analysis. P values less than 0.05 were considered as statistically significant. Based on the outcomes of the model from all theories, the coefficient of variation seems to be positive and the possibility of test is lower than 5%. The results indicated that all factors introduced in the proposed model are significantly effective in MHealth technology adoption. In this study, using the inputs from hematologists in hospitals and clinics in Tehran, it was aimed to find the factors affecting the hematologists' decision to use mobile health technology in reducing the complications of blood transfusion in patients with thalassemia who needed blood transfusion. Thus, plans were made determine to priorities and the existing conditions to implement this new system. Also, the strengths and weaknesses of each factor were measured to improve the weaker factors. UTAUT was used to determine the acceptance factors. After reviewing the results, the use of this model is recommended to physicians.
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http://dx.doi.org/10.34171/mjiri.34.83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711029PMC
July 2020

Convalescent Plasma against COVID-19: A Broad-Spectrum Therapeutic Approach for Emerging Infectious Diseases.

Microorganisms 2020 Nov 5;8(11). Epub 2020 Nov 5.

Laboratory for Clinical and Epidemiological Virology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium.

In the lack of an effective vaccine and antiviral treatment, convalescent plasma (CP) has been a promising therapeutic approach in past pandemics. Accumulating evidence in the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic corroborates the safety of CP therapy and preliminary data underline the potential efficacy. Recently, the Food and Drug Administration (FDA) permitted CP therapy for coronavirus disease 2019 (COVID-19) patients under the emergency use authorization, albeit additional clinical studies are still needed. The imminent threat of a second or even multiple waves of COVID-19 has compelled health authorities to delineate and calibrate a feasible preparedness algorithm for deploying CP as an immediate therapeutic intervention. The success of preparedness programs depends on the interdisciplinary actions of multiple actors in politics, science, and healthcare. In this review, we evaluate the current status of CP therapy for COVID-19 patients and address the challenges that confront the implementation of CP. Finally, we propose a pandemic preparedness framework for future waves of the COVID-19 pandemic and unknown pathogen outbreaks.
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http://dx.doi.org/10.3390/microorganisms8111733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694357PMC
November 2020

Association of TLR3 single nucleotide polymorphisms with susceptibility to HTLV-1 infection in Iranian asymptomatic blood donors.

Rev Soc Bras Med Trop 2020 22;53:e20200026. Epub 2020 Jun 22.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

Introduction: The human T-lymphotropic virus type 1 (HTLV-1) has a single-stranded RNA genome and expresses specific proteins that have oncogenic potential. Approximately 15 to 20 million people worldwide have been infected by this virus. Changes in protein or gene expression are the effects of single nucleotide polymorphisms (SNPs) within the Toll-like receptor 3 (TLR3) gene. The function and efficacy of signal transduction also lead to modified immune responses. The present study aimed to investigate the association of SNPs within TLR3 (rs3775291 and rs3775296) with susceptibility to HTLV-1 infection in Iranian asymptomatic blood donors.

Methods: This study was performed on 100 HTLV-1-infected asymptomatic blood donors and 118 healthy blood donors. Genomic DNA from all participants was purified and then amplified using specific PCR primers. SNPs within TLR3 were evaluated using the restriction fragmentation length polymorphism technique, and the results were analyzed using SPSS software (version 22).

Results: The frequencies of the TLR3 (rs3775296) CC, CA, AA genotypes were 70%, 24%, and 6% in the patient group, and 50.8%, 44.9%, and 4.2% in the control group, respectively. There was a significant difference in the frequency distribution of TLR3 (rs3775296) genotypes and alleles, but not in the frequency distribution of TLR3 (rs3775291) genotypes between the patient and control groups.

Conclusions: The TLR3 SNP rs3775296 was significantly associated with HTLV-1 infection and may be a protective factor against this viral infection.
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http://dx.doi.org/10.1590/0037-8682-0026-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310369PMC
June 2020

Different Immune Responses in Dangerous O Blood Donors.

Iran J Pathol 2020 ;15(1):34-40

Blood Transfusion Research Centre, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

Background & Objective: Dangerous O is very important to transfusion medicine and there has been reports by Food and Drug Administration (FDA) regarding some death relating incidences. As high iso-antibody production is closely associated with different immune reactions, a survey on the different immune response of dangerous O donors can lead to understanding their immune response profile. Objectives were to assess different immune responses in dangerous O cases.

Methods: Two groups of donors were selected after performing titration as a high titer (>512) and non-high titer (<128). Then CBC, CD markers, total immunoglobulin, complement assay, anti-VZV, -CMV, -EBV, -HSV, -Rubella, -, -HBV, -ASO, total protein and albumin, protein electrophoresis, lymphocyte proliferation, and gene expression of INF-gamma, IL2/4/10 were evaluated on both study groups.

Results & Conclusion: Total IgG, IgM, and IgA was higher in high titer group. Moreover, after using PHA and LPS, gamma globulins and lymphocyte proliferation were significantly higher in high titer cases. Real-time PCR also showed higher IL-2 production in high titer group. Identification of high responder's characteristics can be efficient in many complications. Moreover, high titer donors are dangerous for transfusion medicine. This pilot study showed differences in immune responses between HR and LR O blood donors for the first time. So, other aspects of the immune system such as genetic differences can be surveyed.
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http://dx.doi.org/10.30699/IJP.2019.77233.1728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995684PMC
January 2020

Effect of methyl jasmonate and 3-bromopyruvate combination therapy on mice bearing the 4 T1 breast cancer cell line.

J Bioenerg Biomembr 2020 04 20;52(2):103-111. Epub 2020 Jan 20.

Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, 14115-331, Iran.

Cancer cells apply the Warburg pathway to meet their increased metabolic demands caused by their rapid growth and proliferation and also creates an acidic environment to promote cancer cell invasion. 3-bromopyruvate (3-BrP) as an anti-cancer agent disrupts glycolytic pathway. Moreover, one of the mechanism of actions of Methyl Jasmonate (MJ) is interference in glycolysis. Hence, the aim of this study was to evaluate MJ and 3-BrP interaction. MTT assay was used to determine IC50 and synergistic concentrations. Combination index was applied to evaluate the drug- drug interaction. Human tumor xenograft breast cancer mice was used to evaluate drug efficacy in vivo. Tumor size was considered as a drug efficacy criterion. In addition to drug efficacy, probable side effects of these drugs including hepatotoxicity, renal failure, immunotoxicity, and losing weight were evaluated. Serum alanine aminotransferase and aspartate aminotransferase for hepatotoxicity, serum urea and creatinine level for the possibility of renal failure and changes in body weight were measured to evaluate drug toxicity. IL10 and TGFβ secretion in supernatant of isolated splenocytes from treated mice were assessed to check immunotoxicity. 3-BrP synergistically augmented the efficacy of MJ in the specific concentrations. This polytherapy was more effective than monotherapy of 3-BrP, MJ, and also surprisingly cyclophosphamide as a routine treatment for breast cancer in the tumor bearing mice. These results have been shown by decrease in tumor volume and increase of tumor growth inhibition percentage. This combination therapy didn't have any noticeable side effects on kidney, liver, and immune system and body weight.
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http://dx.doi.org/10.1007/s10863-019-09811-wDOI Listing
April 2020

The First Comprehensive Study of H-Deficient Phenotypes in Iran.

Transfus Med Hemother 2019 Oct 30;46(5):376-380. Epub 2018 Oct 30.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

Background: The lack of correct blood grouping practices can lead to missing of the rare Bombay Oh phenotype and subjecting patients to the risk of severe hemolytic transfusion reaction. In the absence of blood donor registry, transfusion management of patients is a challenge. We performed this study in order to estimate the prevalence of the Bombay blood group (Oh) in Iran and to determine whether consanguinity plays a role in the prevalence of Oh group.

Methods: This is a descriptive study in the Immunohematology Reference Laboratory of the Iranian Blood Transfusion Organization (IBTO) Tehran, Iran, over a period of 7 years. All donor blood samples showing blood group O and a strong initial reaction with blood group O RBC control cells were tested with anti-H lectin. Also blood samples from blood group O patients were tested with anti-H lectin if all cells on both antibody screening tests and antibody identification panels were reactive with negative auto control test. Specialized tests like adsorption/elution technique and inhibition assay for determination of secretor status were performed on Oh cases. Any history of consanguineous marriages were recorded. All variables were categorical variables, and percentage and proportions were calculated manually.

Results: Analysis of the results of over 7 million first-time blood donors in Iran showed that the most common ABO blood group was O, with 2,520,000 (36%) subjects. 56 Oh individuals' (donors and patients) phenotypes (0.0008%) were detected. Consanguinity was observed in 50 cases (89%).

Conclusions: This study shows that the prevalence of Bombay blood group in the general population of Iran is relatively high (0.0008%) and associated with consanguineous marriage. Thus, consanguinity is still an important risk factor present.
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http://dx.doi.org/10.1159/000491880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876581PMC
October 2019

Comparison of standard coagulation testing with thromboelastometry tests in cardiac surgery.

J Cardiovasc Thorac Res 2019 13;11(4):300-304. Epub 2019 Oct 13.

Departments of Immunology, Faculty of Medicine, Tarbiat Modares University of Medical Sciences, Tehran, Iran.

According to the several evidences, using thromboelastometry as a point of care test can be effective in reduction in blood loss and transfusion requirements in cardiac surgeries. However, there are limited data regarding to the comparison of thromboelastometry and the standard coagulation tests. In this study, we compared thromboelastometry and standard coagulation tests (PT, PTT and fibrinogen level) in patients under combined coronary-valve surgery. Forty adult patients who were under on-pump combined coronary-valve surgery were included in this study. Thromboelastometry tests Fibtem, Intem, Extem and Heptem), along with standard coagulation tests (PT, PTT and fibrinogen assay) were simultaneously performed in two time points, before and after the pump (pre-CPB and post-CPB, respectively). A total of 80 blood samples were analyzed. There were no significant correlation between PT test and the CT-Extem parameter as well as PTT and CT-Intem parameter either in pre-CPB and post-CPB ( >0.05). On the contrary, fibrinogen level had high correlation with A10-Fibtem and A10-Extem in pre-PCB ( <0.05). 82% of PT and 84% of PTT measurements were outside the reference range, while abnormal CT in Extem and Intem was observed in 17.9%. For management of bleeding, adequate perioperative haemostatic monitoring is indispensable during cardiac surgery. Standard coagulation tests are time consuming and cannot be interchangeably used with thromboelastomety and relying on their results to decide whether blood transfusion is necessary, leads to the inappropriate transfusion.
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http://dx.doi.org/10.15171/jcvtr.2019.48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891038PMC
October 2019

Investigating the route of administration and efficacy of adipose tissue-derived mesenchymal stem cells and conditioned medium in type 1 diabetic mice.

Inflammopharmacology 2020 Apr 18;28(2):585-601. Epub 2019 Nov 18.

Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Type 1 diabetes (T1D) is a chronic autoimmune disease destroying the insulin-producing beta cells. Recently, stem cell therapy has been tested to treat T1D. In the present study, we aim to investigate the effects of intraperitoneal and intravenous infusion of multipotent mesenchymal stem/stromal cells (MSCs) and MSC-conditioned medium (MSC-CM) in an experimental model of diabetes, induced by multiple injections of Streptozotocin (STZ). The adipose tissue-derived MSC and MSC-CM were isolated from C57Bl/6 male mice and characterized. Later, MSC and MSC-CM were injected intraperitoneally or intravenously into mice. The blood glucose, urinary glucose, and body weight were measured, and the percentages of CD4+ CD25+ FOXP3+ T cells as well as the levels of IFN-γ, TGF-β, IL-4, IL-17, and IL-10 were evaluated. Our results showed that both intraperitoneal and intravenous infusions of MSC and MSC-CM could decrease the blood glucose, recover pancreatic islets, and increase the levels of insulin-producing cells. Furthermore, the percentage of CD4+ CD25+ FOXP3+ T cells was increased after intraperitoneal injection of MSC or MSC-CM and intravenous injection of MSCs. After intraperitoneal injection of the MSC and MSC-CM, the levels of inflammatory cytokines reduced, while the levels of anti-inflammatory cytokines increased. Together current data showed that although both intraperitoneal and intravenous administration had beneficial effects on T1D animal model, but intraperitoneal injection of AD-MSC and AD-MSC-CM was more effective than systemic administration.
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http://dx.doi.org/10.1007/s10787-019-00661-xDOI Listing
April 2020

Doxorubicin-induced senescence through NF-κB affected by the age of mouse mesenchymal stem cells.

J Cell Physiol 2020 03 13;235(3):2336-2349. Epub 2019 Sep 13.

Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

The senescence is proposed as a defense mechanism against many anticancer drugs. This complication is marked by differences in cell appearance and inner structures underlying the impairment in function. In this experiment, doxorubicin-induced senescence was assessed in mesenchymal stem cells (MSCs) isolated from the bone marrow of different-aged Balb/c mice (1, 8, and 16 months old). In addition, doxorubicin kinetics in culture medium were investigated to compare the drug absorption rate by different-aged MSCs. Several methods were exerted including Sandwich ELISA for NF-κB activation, propidium iodide staining for cell cycle analysis, Flow-fluorescent in-situ hybridization (Flow-FISH) assay for telomere length measurement, and specific staining for evaluation of β-galactosidase. Determination of doxorubicin in a medium was performed by high-performance liquid chromatography technique. Following doxorubicin exposure, cells underwent substantial telomere shortening, cell cycle arresting in G2 phase, and increased β-galactosidase activity. Interestingly, the enhanced level of NF-κB was observed in all age groups. The highest and lowest sensitivity to telomere shortening attributed to 1- and 8-month-old MSCs, respectively. In consistent with Flow-FISH results, the β-galactosidase activity was higher in young-aged MSCs after treatment. Statistical analysis indicated a correlation between the reduction of telomere length and cessation in G2 phase. Regarding the obtained kinetics equations, the rate of doxorubicin absorption by all aged MSCs followed the same trend. In conclusion, the changing of some elements involved in doxorubicin-induced senescence can be affected by the age of the cells significantly in young MSCs than two other age groups. Hereupon, these changing patterns can open new insights to develop anticancer therapeutic strategies.
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http://dx.doi.org/10.1002/jcp.29140DOI Listing
March 2020

Ensuring effective financing of national blood systems in support of universal health coverage.

East Mediterr Health J 2019 08 19;25(6):371-373. Epub 2019 Aug 19.

Director, International Quality Management (IQM) Consulting and Professor of International Development of Transfusion Medicine, Zuidhorn, The Netherlands.

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http://dx.doi.org/10.26719/2019.25.6.371DOI Listing
August 2019

Immunomodulatory effects of Calcitriol in acute spinal cord injury in rats.

Int Immunopharmacol 2019 Sep 2;74:105726. Epub 2019 Jul 2.

Department of Pharmacology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran. Electronic address:

Pharmacological therapy options for spinal cord injury (SCI) in acute phase have so far been limited, thus we focused on Calcitriol, FDA-approved biologically active form of vitamin D whose neuroprotective effects are increasingly recognized, to ameliorating damage following acute SCI in rats. Calcitriol (1 μg/kg) treatment for 7 consecutive days after SCI was compared SCI control and Sham control rat groups. Calcitriol-treated group had significantly improved outcome in standard functional recovery evaluation test (BBB) 12 weeks after SCI compared to SCI control, which was confirmed by increased ventral horn motor neurons in Calcitriol-treated group. In addition, proliferation test performed on lymphocytes from spleen and lymph nodes one week after SCI showed that calcitriol injection has a significant regulatory effect on Division Index (DI) in response to MBP stimulation compared to control SCI groups, which was associated with significant reduction in IFN-γ and IL-17A secretion and leukocyte infiltration into injury site. Along with confirmation of immunoregulatory aspects of Calcitriol treatment against myelin antigens in SCI, this study has shown that reducing the extent of progressive tissue loss by Calcitriol therapy in acute phase, could result in better recovery after SCI.
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http://dx.doi.org/10.1016/j.intimp.2019.105726DOI Listing
September 2019

Effective ways to retain first-time blood donors: a field-trial study.

Transfusion 2019 09 19;59(9):2893-2898. Epub 2019 Jun 19.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

Background: Regular blood donors are the cornerstone of blood safety. Understanding the donors' behavior to donate blood improves blood donor retention programs. The purpose of this study is to evaluate the return rate of first-time blood donors following different interventions to identify effective ways to retain first-time donors.

Study Design And Methods: The study was conducted on 1356 first-time blood donors at four main blood centers in Iran. The donors were randomly assigned based on different interventions (phone calls, educational letter, emotional letter, incentive, motivational meeting, and no intervention) to six groups. The return rate of donors was defined as a second attempt to donate within 6 months after the first donation. Return rate and 95% confidence intervals (CIs) were calculated and compared among different groups.

Results: A total of 394 (29%) donors returned within 6 months for a second donation (95% CI, 0.26-0.31). The return rate in the emotional letter group, educational letter, phone reminder, incentives, motivational meeting, and control groups was 36% (95% CI, 0.31-0.42), 33.2% (95% CI, 0.27-0.38), 31.5% (95% CI, 0.25-0.37), 30% (95% CI, 0.22-0.38), 22% (95% CI, 0.17-0.27) and 22.1% (95% CI, 0.17-0.27), respectively.

Conclusions: This study provides evidence supporting the fact that more first-time blood donors can be motivated to donate again by implementing targeted interventions. It demonstrates that emotional letters, educational letters, and phone reminders were effective in improving the return rate of first-time donors.
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http://dx.doi.org/10.1111/trf.15404DOI Listing
September 2019

Simultaneous regulation of miR-451 and miR-191 led to erythroid fate decision of mouse embryonic stem cell.

Iran J Basic Med Sci 2019 Apr;22(4):432-438

Department of Hematology, School of Para Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.

Objectives: Various microRNAs (miRNAs) are expressed during development of mammalian cells, when they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. miR-191 and miR-451 have been shown to be critical regulators of hematopoiesis and have important roles in the induction of erythroid fate decision. So, the aim of this study is investigation of the miR-191 and miR-451 roles in the controlling mouse embryonic stem cell (mESC) differentiation toward the erythroid lineage.

Materials And Methods: mESCs were infected with either pCDH-miR-Off-191 viruses in pCDH-miR-Off-191 group or simultaneously with pCDH-miR-Off-191 and pCDH-miR-451 lentiviruses in simultaneous group. Then, the expression profiles of erythroid specific transcription factors and globin genes were analyzed using QRT-PCR on day 14 and 21 of differentiation. Flow cytometry analysis was used to evaluate of TER119 and CD235a erythroid specific surface markers.

Results: Gata-1, Klf-1, Epor and globin chains were found to be expressed in pCDH-miR-Off-191 and in simultaneous groups. The majority of globin chains showed changes in their expression levels with progression of differentiation from day 14 to day 21. Flow cytometry results showed that miR-451 up- regulation and miR-191 down-regulation is associated with the expression of TER119 and CD235a. Of these two groups analyzed, simultaneous group was most significantly potent in stimulation of erythroid fate decision of mESCs.

Conclusion: Together, present data demonstrate that down-regulation of miR-191 alone can enhance the differentiation of mESCs. However, the simultaneous effect of miR-451up-regulation and miR-191 down-regulation is much stronger and can have more practical use in artificial blood production.
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http://dx.doi.org/10.22038/ijbms.2019.27919.6795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535200PMC
April 2019

Implications of immunotherapy with high-dose glatiramer acetate in acute phase of spinal cord injury in rats.

Immunopharmacol Immunotoxicol 2019 Feb 30;41(1):150-162. Epub 2019 Apr 30.

a Department of Immunology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran.

Recently, many researches with different viewpoints have focused on application of immunotherapy agents in treatment of spinal cord injury (SCI) according to neuroprotective results in some neurodegenerative disease. Glatiramer acetate (GA) is the most commonly used drug for Multiple sclerosis (MS) patients that exerts an immunomodulatory effect against Myelin basic protein (MBP) antigen. High-dose (2mg/kg) treatment of GA for 28 consecutive days after SCI was compared with its low-dose (0.5 mg/kg) treatment, SCI control and Sham control rat groups. High-dose GA group had significantly worsened outcome in standard functional recovery evaluation test (BBB) 12 weeks after SCI compared to SCI control and low-dose GA groups, which was confirmed by augmented spinal cavity volume and reduced ventral horn motor neurons in high-dose GA group; however, there was no significant difference between low-dose GA and control SCI group. In addition, proliferation test performed on lymphocytes from spleen and lymph nodes one week after SCI showed that high-dose GA injection has more significant effect on Division Index (DI) in response to MBP stimulation compared to low-dose GA and control SCI groups, which was associated with significant increase in IFN-γ, IL-4, and IL-17A secretion. Along with confirmation of deleterious aspects of autoimmunity resulting from autoreactive lymphocytes against myelin antigens in SCI, this study has shown that high-dose immunotherapy using GA, especially in acute phase after SCI, overwhelms any neuroprotective effect of adoptive immune system.
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http://dx.doi.org/10.1080/08923973.2019.1566362DOI Listing
February 2019

A country-wide comparison of cost recovery and financing systems of blood and blood products.

East Mediterr Health J 2019 Mar 19;25(2):104-110. Epub 2019 Mar 19.

IQM Consulting for International Development of Quality Management in Transfusion Medicine, University of Groningen, Netherlands.

Background: As blood is a scarce and expensive resource, irrational blood usage places huge burden on health expenditures. In response to this challenge, governments and health care providers are developing different strategies to optimize blood utilization. Among these strategies is trying to raise the public awareness on the actual costs of the blood production and changing the cost recovery systems of blood and blood components.

Aims: This study aims to compare cost recovery and financing systems of blood and blood products in different countries.

Methods: This research was an email-based survey of 30 countries from four HDI categories. All related literature was reviewed.

Results: Out of 28 countries, 19 have blood and blood products that are provided totally free of charge to the patients. In nine countries blood and blood products are totally or partially chargeable to the patients.

Conclusions: In countries with low and lower-middle income economies, total or partial costs of blood and blood products are recovered directly from the patients. While countries in which blood and blood products are 'free of charge' for patients are mostly categorized in upper-middle- or high-income economies with well-developed healthcare and insurance systems. There is no clear relation between blood usage and the type of cost recovery system. However, having an efficient cost recovery system will help blood establishments to sustain their service delivery.
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http://dx.doi.org/10.26719/emhj.18.020DOI Listing
March 2019

Evaluation of anticancer activity of α-defensins purified from neutrophils trapped in leukoreduction filters.

Life Sci 2019 May 29;224:249-254. Epub 2019 Mar 29.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

Aims: The α-defensins or human neutrophil peptides (HNP 1-3) that exist in azurophilic granules are found to have anticancer activity. The pattern of disulfide bonds in α-defensins is crucial for the functional properties. Therefore, synthesis using the chemical and recombinant approaches is a challenging. A safe source for the production of α-defensins can be the use of leukoreduction filters in blood banks that contain large quantities of neutrophils and are discarded after use. The aim of this study was to purify α-defensins from neutrophils trapped in leukofilters and to investigate its anticancer activity.

Materials And Methods: Immunoprecipitation was performed to purify α-defensins and the presence of protein was confirmed by Western Blot. The Jurkat T-cell line was incubated with different concentrations (5, 10 and 15 μg/ml) of purified HNP1-3 for 16 h. Cell viability was measured using a WST-1 assay and apoptosis was analyzed for Annexin V/PI markers. Caspase-3/7 activity was determined using fluorescence assay. The effects of purified α-defensins were compared to commercial HNP 1-3.

Key Findings: Purified HNP 1-3 decreased the viability at 10 and 15 μg/ml and commercial HNP 1-3 at 15 μg/ml concentrations. Following to the purified HNP1-3 treatment, the percentage of Annexin V positive population and caspase-3 activity were significantly increased compared to control (p = 0.000 and p = 0.001, respectively) and commercial HNP1-3 (p = 0.034 and p = 0.018, respectively).

Significance: Results indicated the anticancer activity of HNP1-3 which can be used as future chemotherapeutic drugs. Furthermore, leukofilters can be considered as economic source for purifying these peptides.
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http://dx.doi.org/10.1016/j.lfs.2019.03.072DOI Listing
May 2019

A review of blood usage and wastage in a tertiary heart center.

Acta Clin Belg 2020 Apr 4;75(2):96-103. Epub 2018 Dec 4.

Department of Medical Laboratory Sciences, School of Allied Medical sciences, Mazandaran University of Medical Sciences, Sari, Iran.

: Blood is a vital resource that its utilization is ever increasing throughout the world and blood wastage is a global challenge that needs to be controlled. Most blood resources are used during complications of pregnancy, trauma, severe childhood anemia, gynecology, cancers, surgery, hematology disorders, and chronic diseases. Units that are expired, broken bags, returning the blood unit after 30 min, blood clotted units, etc., which are due to lack of awareness may result in the wastage of blood products. The objective of this study is to analyze the usage and wastage of blood and its products in Mazandaran heart center.: In this retrospective study, the survey was carried out on the data that were obtained from Mazandaran heart center of Sari, Iran during 2012-2017. Data included details of usage and wastage on blood and its product units. MS Excel 2016 and SPSS 16.0 were used in analysis and diagrams.: A total of 35,686 blood units were consumed, which included 55.7% packed red blood cells (PRBCs), 33.9% platelets (Plts), 8.9% fresh-frozen-plasma (FFP), and 8.9% cryoprecipitates. Moreover, 823 blood units including 41.4% FFP, 37.2% PRBCs, and 21.4% Plts were wasted mostly because of inappropriate order (70.6%). Cross-match to transfusion ratio was 1.13. The intensive care unit reported the highest level of blood intake by 45.0%. The blood group O+ was the most frequent by 34.8%. In addition, blood wastage has decreased over study period by approximately 10.0%.: Our study showed not only the increasing pattern of blood usage but also the dropping pattern of blood wastage due to hemovigilance performance and additional training in our healthcare center. We found that the main reason for the blood wastage in this center is an excessive order of blood units.
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http://dx.doi.org/10.1080/17843286.2018.1555113DOI Listing
April 2020

The role of access to affordable and quality assured blood and blood products for achieving Universal Health Coverage (Editorial).

East Mediterr Health J 2018 Jun 10;24(3):235-236. Epub 2018 Jun 10.

Head & Medical Director, Dubai Blood Donation Center, Dubai, United Arab Emirates (Former Director, WHO Collaborating Centre for Training and Research in Blood Transfusion, Sharjah, United Arab Emirates).

The theme of World Health Day 2018 is 'Universal health coverage: everyone, everywhere' under the slogan 'Health for All'. Universal Health Coverage (UHC), as pertains to blood and blood products, means that all individuals and communities have access to affordable and timely supplies of safe and quality-assured blood and blood products. Blood and blood products are essential components in the proper management of women suffering from bleeding associated with pregnancy and childbirth; children suffering from severe anaemia due to malaria and malnutrition; patients with blood and bone marrow disorders and immune deficiency conditions; victims of trauma, emergencies, disasters and accidents; and patients undergoing advanced medical and surgical procedures.
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http://dx.doi.org/10.26719/2018.24.3.235DOI Listing
June 2018

Immunomodulatory Effects of Blood Transfusion on Tumor Size, Metastasis, and Survival in Experimental Fibrosarcoma.

Indian J Hematol Blood Transfus 2018 Oct 24;34(4):697-702. Epub 2018 May 24.

2Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

In spite of efforts, blood transfusion is still accompanied with adverse effects such as transfusion-related immunomodulation (TRIM). The current study aimed to evaluate the effects of allogeneic, syngeneic, fresh and storage blood transfusion on the growth and metastasis of tumors and survival in fibrosarcoma bearing BALB/c mice. Twenty-five BALB/c mice were grouped into five groups of equal size. All groups were injected 1.2 × 10 WEHI-164 cells subcutaneously to induce fibrosarcoma tumor. After expansion of the tumor, in four groups (except for the control group), hemorrhage-induced anemia was developed. Twenty-four hours later, blood deficit was replaced by fresh allogeneic, storage allogeneic, fresh syngeneic and storage syngeneic blood transfusion, respectively. After a blood transfusion, for 13 days, the tumor size and survival of the mice were evaluated. In the day 20, the mice were sacrificed and their spleen tissues were evaluated for TRIM induced metastasis. Tumor size increase in the groups that received allogeneic (fresh and storage) and storage syngeneic blood transfusion was significantly higher than the control group ( value < 0.05). However, no significant difference was present in survival between the experiment groups and the control group. There was no metastasis in none of groups at the end of the study. Allogeneic and storage blood transfusion could have immunomodulatory effects such as increased tumor size. However, it seems that fresh and syngeneic blood transfusion have no effects on tumor growth in fibrosarcoma bearing mice. Further evidence may prove that more attention is warranted in blood transfusion into cancer cases.
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http://dx.doi.org/10.1007/s12288-018-0962-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186234PMC
October 2018

Enhanced CD40 and ICOSL expression on dendritic cells surface improve anti-tumor immune responses; effectiveness of mRNA/chitosan nanoparticles.

Immunopharmacol Immunotoxicol 2018 Oct 28;40(5):375-386. Epub 2018 Sep 28.

b Department of Biotechnology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran.

To improve dendritic cells (DCs) function, we targeted DCs to over express CD40 and inducible costimulator ligand (ICOSL) costimulatory molecules along with total messenger RNA (mRNA) of tumor cells to achieve a safe and effective system for treatment of tumor. We generated CD40 and ICOSL mRNA and manipulated DCs using chitosan nanoparticles and also lipofectamine transfection system then examined and . Mice bone marrow derived DCs pulsed with total tumor mRNA/CD40 mRNA or ICOSL mRNA showed higher expression of DCs maturation markers (CD40, ICOSL, CD86, and MHC-II) and accelerated secretion of pro-inflammatory cytokines. Co-culture of DCs with T cells enhanced proliferation of T cells and shift toward stronger Th1 cytokine responses especially in presence of CD40 over expressed DCs. Intra-tumor administration of manipulated DCs to 4T1 tumor mice model showed delay in growth of tumor volume, trend to increase in mice survival, and stronger anti-tumor cytokines production in splenocytes of mice model (with higher efficacy of mRNA/chitosan nanoparticle system). Hence, we suggest that targeting intra-tumor DCs to elicit expression of CD40 and ICOSL and present broad range of tumor antigens could yield effective anti-tumor responses. In this regard, CD40 molecule manipulation trigger stronger functions, while mRNA/chitosan nanoparticles system could provide a high potent tool for targeting strategies.
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http://dx.doi.org/10.1080/08923973.2018.1510959DOI Listing
October 2018

The Prevalence and Trends of Hepatitis B, Hepatitis C, and HIV among Voluntary Blood Donors in Kohgiluyeh and Boyer-Ahmad Transfusion Center, Southwestern Iran.

Iran J Public Health 2018 Jul;47(7):944-951

Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.

Background: Transfusion transmissible infections (TTIs) are a common complication of blood transfusion. Evaluation and monitoring the prevalence rate of TTIs in blood donors is a valuable indicator of donor selection and blood safety. We analyzed the trends of these infections among blood donors at Kohgiluyeh and Boyer-Ahmad transfusion service (KBTC) during 10 years.

Methods: Viral screening and confirmatory tests were carried out on 180304 voluntary donations from 2005-2014. The annual prevalence rates of hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV infections per 100000 donations and 95% confidence interval were calculated. Chi-square test was applied to obtain the -value.

Results: The overall prevalence was 0.13% for HBV and 0.06% for HCV while there were only three positive cases for HIV. The annual trend fluctuated during the time period studied. Compared to first-time donors, regular and repeat donors were significantly less likely to be positive for these infections. Outstandingly, this study provides first data in TTIs seropositivity rates among blood donors in our region; surprisingly were lower compared to other reports of Iran.

Conclusion: The trends of TTIs prevalence in this study provide additional evidence that safety measures employed by the KBTC have been effective in maintaining a safe blood supply. The lower prevalence of TTIs in our study compared with other Iranian studies and also the general population reflects the efficacy of donor selection and education procedures in KBTC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119582PMC
July 2018

Meeting the Challenges of International Crises: The Experience of the Iranian Blood Transfusion Organization.

Disaster Med Public Health Prep 2019 06 1;13(3):410-413. Epub 2018 Aug 1.

6Harvard Humanitarian Initiative,Harvard University,Cambridge,Massachusetts.

ABSTRACTCrises require a timely and well-prepared response by health services, especially those that are directly engaged with the lives of the patients such as blood services. The Iranian Blood Transfusion Organization as a single national authority of blood transfusion has left many crises behind. In this study, we examined the main international crises that the blood transfusion organization has faced during its 44-year history and objectively evaluated the methods for crisis risk reduction, both administrative and operational, all of which have led to fundamental advances in the organization. By proper planning and effective strategy setting, the Iranian Blood Transfusion Organization has managed to cope with international threats and in some cases has turned threats into opportunities to implement new, permanent administrative and operational strategies. It is not prudent for blood transfusion centers to develop their disaster risk reduction strategies on an individual-country basis in a world where global risk and crisis factors are rapidly increasing. Reduction of risk for blood transfusion centers must become a strategic priority nationally and globally. (Disaster Med Public Health Preparedness. 2019;13:410-413).
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http://dx.doi.org/10.1017/dmp.2018.71DOI Listing
June 2019

Evaluation of age effects on doxorubicin-induced toxicity in mesenchymal stem cells.

Med J Islam Repub Iran 2017 17;31:98. Epub 2017 Dec 17.

Toxicology and Animal Poisoning Research Center, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

Doxorubicin, by aggregating in bone marrow, causes genotoxic effects, and thus reduces the repair ability of cells. The present study was conducted as an in vitro evaluation of age effects on the cytotoxicity induced by doxorubicin in mesenchymal stem cells (MSCs). The MSCs of female BALB/c mice aged 1, 8, and 16 months were separated, characterized, and subsequently evaluated in cellular growth media. After 24 hours, exposure of the MSCs of the 3 groups of mice to doxorubicin (25, 50, 100, 200, 400, 800, 1200 nM) and cytotoxicity were assessed, and the sublethal dose was determined using flow cytometry technique and lactate dehydrogenase (LDH) release assay. The IC50 values determined by flow cytometry for the separated MSCs of 1 young, 8 middle- aged, and 16 old mice were and respectively. Interestingly, the results of these 2 methods in determining cytotoxicity were in agreement, and a concentration of approximately 25 nM was considered to be the shared sublethal dose for different ages. The results indicated that MSCs of middle-aged mice were more resistant to the toxic effects of the drug. Besides, MSCs separated from the old mice were the most sensitive to chemotherapy and its side effects such as disruptions of cell proliferation and viability. These disruptions can be ascribed to the alteration of function and physiological processes with age. Determining proper concentration of doxorubicin drug to destruct cancerous cells based on age and individual sensitivity can minimize the amount of toxicity.
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http://dx.doi.org/10.14196/mjiri.31.98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014798PMC
December 2017

Comparative Evaluation of Biochemical and Hematological Parameters of Pre-Storage Leukoreduction during RBC Storage.

Int J Hematol Oncol Stem Cell Res 2018 Jan;12(1):35-42

Laboratory Hematology and Blood Bank, Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

Some of the red cell storage lesions (RCSLs) take place during red blood cell (RBC) storage and may reduce the function of these cells dramatically, which mostly caused by residual leucocytes in blood components. This study was planned to observe the biochemical and hematological changes in pre-storage leukoreduced RBC (LR-RBC) compared with unfiltered RBC during storage. Ten unit RBCs were collected, processed and stored according to Iranian standard operating procedure (SOP) of Iranian Blood Transfusion Organization (IBTO). Every unit was split into two equal parts, unfiltered RBC and LR-RBC. Samples were collected and tested on weeks of storage. Biochemical parameters such as lactate dehydrogenase (LDH), lactate concentration and glucose-6-phosphate dehydrogenase (G6PD) enzyme activity were measured by auto-analyzer. In addition, hematology analyzer was used to monitor the change of RBC indices such as (MCV), (MCH) and (MCHC). In this study, both groups showed progressive increase of LDH and lactate levels, and also G6PD activity decreased during storage. Mean of LDH and lactate in unfiltered RBC was significantly increased compared with LR-RBC during all days of storage (< 0.05). There was statically significant decrease in the G6PD enzyme activity between the two groups and weeks of storage (< 0.05). However, the RBC indices remained within the expected levels in both groups. LR-RBC and RBC both exhibited RCSL during storage, but LR-RBC is effective in reducing Red cell storage lesion (RCSL) also improves the quality of stored red blood cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018247PMC
January 2018