Regulation of translation initiation through eIF2 alpha (eIF2a) phosphorylation plays a critical ... more Regulation of translation initiation through eIF2 alpha (eIF2a) phosphorylation plays a critical role in cellular homeostasis. eIF2 cycles between GTP-bound active and GDP-bound inactive forms. Phosphorylation of eIF2a on Ser51 blocks eIF2B catalyzed GDP-GTP exchange, reduce the dissociation of eIF2 from eIF2B and inhibits global mRNA translation. Molecular modifiers and effectors of translational control by eIF2a phosphorylation are not fully understood. Global proteomic studies may be useful to elucidate molecular effectors and modifiers of eIF2a phopshorylation using diarylurea compound, BTdCPU, that induces eIF2a phosphorylation by activating heme regulated kinase. We utilized transgenic human prostate cancer (PC-3) cell lines in which endogenous eIF2a is replaced by either a nonphosphorylatable eIF2a mutant (S51A) or a recombinant wild-type eIF2a (WT) to identify differentially expressed proteins by treating PC-3 cells (WT or S51A) with active (BTdCPU)or inactive compound. Two dimensional electrophor...
Objective: Ankaferd® Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vu... more Objective: Ankaferd® Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. The basic mechanism of action for ABS is the formation of an encapsulated protein network that provides focal points for vital erythrocyte aggregation. ABS– induced protein network formation with blood cells, particularly erythrocytes, covers the primary and secondary hemostatic system without disturbing individual coagulation factors. Materials and Methods: To understand the effect mechanisms of ABS on hemostasis, a proteomic analysis using 2D gel electrophoresis and mass spectrometer was performed. Results: Proteins of plant origin in Ankaferd® were NADP-dependent-malic enzyme, ribulose bisphosphatecarboxylase-large chain, maturase K, ATP synthase subunit-beta, ATP synthase subunit-alpha, chalcone-flavanone isomerase-1, chalcone-flavanone isomerase-2, and actin-depolymerizing factor. Furthermore, functi...
Ankaferd blood stopper (ABS) is a novel topical hemostatic agent of plant origin registered for t... more Ankaferd blood stopper (ABS) is a novel topical hemostatic agent of plant origin registered for the management of external hemorrhages, in Turkey. The ABS-induced formation of the protein network with vital erythroid aggregation covers the whole physiological hemostatic process. The aim of this study is to assess prohemostatic and antithrombin effects of ABS on the basis of functional proteomic analyses performed in ABS-treated plasma and serum samples based on the previous hypotheses about ABS action. For this purpose, serum and plasma proteins were separated by 2-dimensional (2D) gel electrophoresis, and proteins were identified using reference plasma gel on Swiss-2DPAGE database. Our results indicated that fibrinogen gamma chain and prothrombin levels just initially decreased first and thereafter enhanced following the ABS exposure. Dual effects of ABS on those critical hemostatic molecules seem to be associated with prohemostatic and antithrombin activities of the hemostatic agent.
Background: Multiple myeloma (MM) is characterized by infiltration of bone marrow (BM) with clona... more Background: Multiple myeloma (MM) is characterized by infiltration of bone marrow (BM) with clonal malignant plasma cells. The percentage of plasma cells in the BM is required for both diagnosis and prognosis. Objective: Intracellular protein screening and quantitative proteomic analysis was performed in myeloma plasma cells with an aim to compare expressions between low (0-9%), intermediate (10-20%) and high (>20%) plasma cell infiltration groups. Methods: BM aspiration samples were collected from newly diagnosed untreated patients with MM. The samples were pooled into three groups according to the plasma cell content (PCC) in the BM: group 1 (0-9%), group 2 (10-20%) and group 3 (>20%). Protein profiles were obtained and proteins were identified by peptide mass fingerprinting analysis. Results: Differentially expressed proteins were detected between all groups. The identified proteins are Endoplasmin, Calreticulin, Protein Disulfide-isomerase, Marginal zone B and B1 cell spec...
In this study, we used human umbilical vein endothelial cells (HUVEC) as an in vitro model to com... more In this study, we used human umbilical vein endothelial cells (HUVEC) as an in vitro model to compare the cytotoxic activities of the venoms of two Macrovipera lebetina subspecies, M. l. obtusa from southern Anatolia and M. l. lebetina from northern Cyprus. Well-established 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was preferred to assess the cytotoxicity. Our results showed that venom reduced cell viability both in a time and dose-dependent manner. The cytotoxic effect of M. l. lebetina venom on HUVEC is reported for the first time in the present study.
Aim The molecular mechanisms responsible from evolution to malignant monoclonal plasmacytosis is ... more Aim The molecular mechanisms responsible from evolution to malignant monoclonal plasmacytosis is still under investigation. The aim of this prospective study was to analyze the proteomics profile of plasma cells obtained from MGUS, SMM and symptomatic myeloma patients to be able to investigate the differences at protein level between patients with low vs high plasma cell content (PCC). Material and Methods Marrow samples were collected from 30 patients newly diagnosed with Multiple Myeloma (n: 28 symptomatic and n: 1 smoldering (SMM)) and n:1 MGUS) at Ankara University Department of Hematology. Plasma cells were isolated by CD138+ selection before protein extraction. The patients were classified mainly in to three groups according to marrow PCC by flow cytometry: group1: 0-9, group 2: 10-20 and group 3: >20 %. The protein profiles of these three groups were constructed and compared via 2D gel electrophoresis by using PDQuest 8.01 analysis. Up/down regulated protein spots were ide...
Aim : As all other cancer types, multiple myeloma is a complex disease, yet its molecular mechani... more Aim : As all other cancer types, multiple myeloma is a complex disease, yet its molecular mechanism that is not fully understood and needs to be furtherly investigated. Besides, the molecular mechanism responsible from the transition of healthy cells into malignant ones is still under investigation. In such comparative studies, human myeloma cell lines are preferred as positive control, while tonsillar plasma cells are used as negative control. The aim of this study is to perform a comparative proteomic analysis regarding the progression of Multiple Myeloma (MM) by using protein profiles of plasma cells obtained from MGUS, SMM, symptomatic myeloma patients, tonsil plasma cells obtained from healthy individuals and human myeloma cells of cell line origin to elucidate the underlying molecular mechanism involved in myeloma. Material and Methods: Five groups were adopted in the experiment. Of these groups, MM patients were classified mainly into three groups according to marrow plasma c...
Venomous animals use venom; a complex biofluid composed of unique mixtures of proteins and peptid... more Venomous animals use venom; a complex biofluid composed of unique mixtures of proteins and peptides, to act on vital systems of the prey or predator. In bees, venom is solely used for defense against predators. However, the venom composition of bumble bees (Bombus sp.) is largely unknown.Thoracobombussubgenus ofBombus sp.is a diverse subgenus represented by 14 members across Turkey. In this study, we sought out to proteomically characterize the venom of fiveThoracobombusspecies by using bottom-up proteomic techniques. We have obtained two-dimensional polyacrylamide gel (2D-PAGE) images of each venom sample. We have subsequently identified the protein spots by using matrix assisted laser desorption ionization / time of flight mass spectrometry (MALDI-TOF MS). We have identified 47 proteins forBombus humilis; 32 forB. pascuorum, 60 forB. ruderarius; 39 forB. sylvarumand 35 forB. zonatus. Our analyses provide the primary proteomic characterization of five bumble bee species’ venom comp...
Objective: Ankaferd® Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vu... more Objective: Ankaferd® Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. The basic mechanism of action for ABS is the formation of an encapsulated protein network that provides focal points for vital erythrocyte aggregation. ABSinduced protein network formation with blood cells, particularly erythrocytes, covers the primary and secondary hemostatic system without disturbing individual coagulation factors. Materials and Methods: To understand the effect mechanisms of ABS on hemostasis, a proteomic analysis using 2D gel electrophoresis and mass spectrometer was performed. Results: Proteins of plant origin in Ankaferd ® were NADP-dependent-malic enzyme, ribulose bisphosphatecarboxylase-large chain, maturase K, ATP synthase subunit-beta, ATP synthase subunit-alpha, chalcone-flavanone isomerase-1, chalcone-flavanone isomerase-2, and actin-depolymerizing factor. Furthermore, functional proteomic studies revealed that proteins resembling human peptides have been detected within Ankaferd ® , including ATP synthase, mucin-16 (CD164 sialomucin-like 2 protein), coiled-coil domain containing 141 hypothetical protein LOC283638 isoform 1, hypothetical protein LOC283638 isoform 2, dynactin 5, complex I intermediate-associated protein 30, mitochondrial, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, TP synthase, H+ transporting, mitochondrial actin binding 1 isoform, LIM domain and actin binding 1 isoform a, LIM domain and actin binding 1 isoform b, spectrin alpha non erythrocytic 1, prolactin releasing hormone receptor, utrophin, tet oncogene family member 2 isoform b, protein phosphatase 1 regulatory subunit 12A, NIMA (never in mitosis gene a)-related kinase, ATP-binding cassette protein C12, Homo sapiens malic enzyme 1, mitochondrial NADP(+)-dependent malic enzyme 3, ME2 protein, nuclear factor 1 B-type, abhydrolase domain-containing protein 12B, E3 SUMO-protein ligase PIAS2, alpha-1, 2-glucosyltransferase ALG10-A, cofilin, non-muscle isoform, 18 kDa phosphoprotein, p18, actin-depolymerizing factor (ADF), twinfilin-1, ankyrin repeat and FYVE domain-containing protein 1, usherin precursor, urotensin II receptor, interleukin 4, and midkine. Conclusion: Proteomic analysis of Ankaferd ® represents a true basis for the upcoming Ankaferd ® studies focusing on its wound healing, hemostatic, anti-infective, antineoplastic, and preservative biological actions.
0.58 mg/kg/week IV also received 0.05 mg/kg (maximum dose 1 mg) intrathecal (IT) rhIDU every 3 mo... more 0.58 mg/kg/week IV also received 0.05 mg/kg (maximum dose 1 mg) intrathecal (IT) rhIDU every 3 months beginning at 12-112 days of life. Serum samples for specific, anti-iduronidase IgG antibodies were analyzed by ELISA. After 38-74 weeks of treatment, serum anti-iduronidase antibody (IgG) levels were <1 OD unit/l in all treated pups (tolerance cutoff is 20 OD units/l). In contrast, 8 adult normal and MPS I dogs receiving IV rhIDU developed a mean antibody titer of 149 OD units/l (range 60.2-377.9) after 12 weeks of treatment [1]. MPS I dogs receiving IV rhIDU from birth had a near-normal appearance to the cranium, normalized appearance to skeletal radiographs, less pronounced mitral valve insufficiency, and near-normal heart valve thickness by echocardiography. Two pups infused on the days 1-2 of life (when natural pup mortality is high) died following one treatment. Other adverse events were similar to untreated MPS I dogs. MPS I pups treated from birth with IV +/-IT rhIDU did not develop anti-iduronidase antibodies and had improved efficacy in the hard-totreat skeleton and heart valve. These findings support the argument for early treatment of MPS I disease.
Hereditary spherocytosis (HS) is the most common congenital hemolytic anemia in Caucasians, with ... more Hereditary spherocytosis (HS) is the most common congenital hemolytic anemia in Caucasians, with an estimated prevalence ranging from 1:2000 to 1:5000. The molecular defect in one of the erythrocytes (RBC) membrane proteins underlying HS like; spectrin-α, spectrin-β, ankyrin, band 3 and protein 4.2 that lead to membrane destabilization and vesiculation, may change the RBCs into denser and more rigid cells (spherocytes), which are removed by the spleen, leading to the development of hemolytic anemia. It is classified as mild, moderate and severe, according to the degree of the hemolytic anemia and the associated symptoms. Two-dimensional gel electrophoresis (2-DE) is potentially valuable method for studying heritable disorders as HS that involve membrane proteins. This separation technique of proteins based upon two biophysically unrelated parameters; molecular weight and charge, is a good option in clinical proteomics in terms of ability to separate complex mixtures, display post-translational modifications and changes after phosphorylation. In this study, we have used contemporary methods with some modifications for the solubilisation, separation and identification of erythrocyte membrane proteins in normal and in HS RBCs. Spectrin alpha and beta chain, ankyrin and band 3 proteins expression differences were found with PDQuest software 8.0.1. and peptide mass fingerprinting (PMF) analysis performed for identification of proteins in this study.
Ankaferd blood stopper (ABS) is a novel topical hemostatic agent of plant origin registered for t... more Ankaferd blood stopper (ABS) is a novel topical hemostatic agent of plant origin registered for the management of external hemorrhages, in Turkey. The ABS-induced formation of the protein network with vital erythroid aggregation covers the whole physiological hemostatic process. The aim of this study is to assess prohemostatic and antithrombin effects of ABS on the basis of functional proteomic analyses performed in ABS-treated plasma and serum samples based on the previous hypotheses about ABS action. For this purpose, serum and plasma proteins were separated by 2-dimensional (2D) gel electrophoresis, and proteins were identified using reference plasma gel on Swiss-2DPAGE database. Our results indicated that fibrinogen gamma chain and prothrombin levels just initially decreased first and thereafter enhanced following the ABS exposure. Dual effects of ABS on those critical hemostatic molecules seem to be associated with prohemostatic and antithrombin activities of the hemostatic agent.
Regulation of translation initiation through eIF2 alpha (eIF2a) phosphorylation plays a critical ... more Regulation of translation initiation through eIF2 alpha (eIF2a) phosphorylation plays a critical role in cellular homeostasis. eIF2 cycles between GTP-bound active and GDP-bound inactive forms. Phosphorylation of eIF2a on Ser51 blocks eIF2B catalyzed GDP-GTP exchange, reduce the dissociation of eIF2 from eIF2B and inhibits global mRNA translation. Molecular modifiers and effectors of translational control by eIF2a phosphorylation are not fully understood. Global proteomic studies may be useful to elucidate molecular effectors and modifiers of eIF2a phopshorylation using diarylurea compound, BTdCPU, that induces eIF2a phosphorylation by activating heme regulated kinase. We utilized transgenic human prostate cancer (PC-3) cell lines in which endogenous eIF2a is replaced by either a nonphosphorylatable eIF2a mutant (S51A) or a recombinant wild-type eIF2a (WT) to identify differentially expressed proteins by treating PC-3 cells (WT or S51A) with active (BTdCPU)or inactive compound. Two dimensional electrophor...
Objective: Ankaferd® Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vu... more Objective: Ankaferd® Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. The basic mechanism of action for ABS is the formation of an encapsulated protein network that provides focal points for vital erythrocyte aggregation. ABS– induced protein network formation with blood cells, particularly erythrocytes, covers the primary and secondary hemostatic system without disturbing individual coagulation factors. Materials and Methods: To understand the effect mechanisms of ABS on hemostasis, a proteomic analysis using 2D gel electrophoresis and mass spectrometer was performed. Results: Proteins of plant origin in Ankaferd® were NADP-dependent-malic enzyme, ribulose bisphosphatecarboxylase-large chain, maturase K, ATP synthase subunit-beta, ATP synthase subunit-alpha, chalcone-flavanone isomerase-1, chalcone-flavanone isomerase-2, and actin-depolymerizing factor. Furthermore, functi...
Ankaferd blood stopper (ABS) is a novel topical hemostatic agent of plant origin registered for t... more Ankaferd blood stopper (ABS) is a novel topical hemostatic agent of plant origin registered for the management of external hemorrhages, in Turkey. The ABS-induced formation of the protein network with vital erythroid aggregation covers the whole physiological hemostatic process. The aim of this study is to assess prohemostatic and antithrombin effects of ABS on the basis of functional proteomic analyses performed in ABS-treated plasma and serum samples based on the previous hypotheses about ABS action. For this purpose, serum and plasma proteins were separated by 2-dimensional (2D) gel electrophoresis, and proteins were identified using reference plasma gel on Swiss-2DPAGE database. Our results indicated that fibrinogen gamma chain and prothrombin levels just initially decreased first and thereafter enhanced following the ABS exposure. Dual effects of ABS on those critical hemostatic molecules seem to be associated with prohemostatic and antithrombin activities of the hemostatic agent.
Background: Multiple myeloma (MM) is characterized by infiltration of bone marrow (BM) with clona... more Background: Multiple myeloma (MM) is characterized by infiltration of bone marrow (BM) with clonal malignant plasma cells. The percentage of plasma cells in the BM is required for both diagnosis and prognosis. Objective: Intracellular protein screening and quantitative proteomic analysis was performed in myeloma plasma cells with an aim to compare expressions between low (0-9%), intermediate (10-20%) and high (>20%) plasma cell infiltration groups. Methods: BM aspiration samples were collected from newly diagnosed untreated patients with MM. The samples were pooled into three groups according to the plasma cell content (PCC) in the BM: group 1 (0-9%), group 2 (10-20%) and group 3 (>20%). Protein profiles were obtained and proteins were identified by peptide mass fingerprinting analysis. Results: Differentially expressed proteins were detected between all groups. The identified proteins are Endoplasmin, Calreticulin, Protein Disulfide-isomerase, Marginal zone B and B1 cell spec...
In this study, we used human umbilical vein endothelial cells (HUVEC) as an in vitro model to com... more In this study, we used human umbilical vein endothelial cells (HUVEC) as an in vitro model to compare the cytotoxic activities of the venoms of two Macrovipera lebetina subspecies, M. l. obtusa from southern Anatolia and M. l. lebetina from northern Cyprus. Well-established 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was preferred to assess the cytotoxicity. Our results showed that venom reduced cell viability both in a time and dose-dependent manner. The cytotoxic effect of M. l. lebetina venom on HUVEC is reported for the first time in the present study.
Aim The molecular mechanisms responsible from evolution to malignant monoclonal plasmacytosis is ... more Aim The molecular mechanisms responsible from evolution to malignant monoclonal plasmacytosis is still under investigation. The aim of this prospective study was to analyze the proteomics profile of plasma cells obtained from MGUS, SMM and symptomatic myeloma patients to be able to investigate the differences at protein level between patients with low vs high plasma cell content (PCC). Material and Methods Marrow samples were collected from 30 patients newly diagnosed with Multiple Myeloma (n: 28 symptomatic and n: 1 smoldering (SMM)) and n:1 MGUS) at Ankara University Department of Hematology. Plasma cells were isolated by CD138+ selection before protein extraction. The patients were classified mainly in to three groups according to marrow PCC by flow cytometry: group1: 0-9, group 2: 10-20 and group 3: >20 %. The protein profiles of these three groups were constructed and compared via 2D gel electrophoresis by using PDQuest 8.01 analysis. Up/down regulated protein spots were ide...
Aim : As all other cancer types, multiple myeloma is a complex disease, yet its molecular mechani... more Aim : As all other cancer types, multiple myeloma is a complex disease, yet its molecular mechanism that is not fully understood and needs to be furtherly investigated. Besides, the molecular mechanism responsible from the transition of healthy cells into malignant ones is still under investigation. In such comparative studies, human myeloma cell lines are preferred as positive control, while tonsillar plasma cells are used as negative control. The aim of this study is to perform a comparative proteomic analysis regarding the progression of Multiple Myeloma (MM) by using protein profiles of plasma cells obtained from MGUS, SMM, symptomatic myeloma patients, tonsil plasma cells obtained from healthy individuals and human myeloma cells of cell line origin to elucidate the underlying molecular mechanism involved in myeloma. Material and Methods: Five groups were adopted in the experiment. Of these groups, MM patients were classified mainly into three groups according to marrow plasma c...
Venomous animals use venom; a complex biofluid composed of unique mixtures of proteins and peptid... more Venomous animals use venom; a complex biofluid composed of unique mixtures of proteins and peptides, to act on vital systems of the prey or predator. In bees, venom is solely used for defense against predators. However, the venom composition of bumble bees (Bombus sp.) is largely unknown.Thoracobombussubgenus ofBombus sp.is a diverse subgenus represented by 14 members across Turkey. In this study, we sought out to proteomically characterize the venom of fiveThoracobombusspecies by using bottom-up proteomic techniques. We have obtained two-dimensional polyacrylamide gel (2D-PAGE) images of each venom sample. We have subsequently identified the protein spots by using matrix assisted laser desorption ionization / time of flight mass spectrometry (MALDI-TOF MS). We have identified 47 proteins forBombus humilis; 32 forB. pascuorum, 60 forB. ruderarius; 39 forB. sylvarumand 35 forB. zonatus. Our analyses provide the primary proteomic characterization of five bumble bee species’ venom comp...
Objective: Ankaferd® Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vu... more Objective: Ankaferd® Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. The basic mechanism of action for ABS is the formation of an encapsulated protein network that provides focal points for vital erythrocyte aggregation. ABSinduced protein network formation with blood cells, particularly erythrocytes, covers the primary and secondary hemostatic system without disturbing individual coagulation factors. Materials and Methods: To understand the effect mechanisms of ABS on hemostasis, a proteomic analysis using 2D gel electrophoresis and mass spectrometer was performed. Results: Proteins of plant origin in Ankaferd ® were NADP-dependent-malic enzyme, ribulose bisphosphatecarboxylase-large chain, maturase K, ATP synthase subunit-beta, ATP synthase subunit-alpha, chalcone-flavanone isomerase-1, chalcone-flavanone isomerase-2, and actin-depolymerizing factor. Furthermore, functional proteomic studies revealed that proteins resembling human peptides have been detected within Ankaferd ® , including ATP synthase, mucin-16 (CD164 sialomucin-like 2 protein), coiled-coil domain containing 141 hypothetical protein LOC283638 isoform 1, hypothetical protein LOC283638 isoform 2, dynactin 5, complex I intermediate-associated protein 30, mitochondrial, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, TP synthase, H+ transporting, mitochondrial actin binding 1 isoform, LIM domain and actin binding 1 isoform a, LIM domain and actin binding 1 isoform b, spectrin alpha non erythrocytic 1, prolactin releasing hormone receptor, utrophin, tet oncogene family member 2 isoform b, protein phosphatase 1 regulatory subunit 12A, NIMA (never in mitosis gene a)-related kinase, ATP-binding cassette protein C12, Homo sapiens malic enzyme 1, mitochondrial NADP(+)-dependent malic enzyme 3, ME2 protein, nuclear factor 1 B-type, abhydrolase domain-containing protein 12B, E3 SUMO-protein ligase PIAS2, alpha-1, 2-glucosyltransferase ALG10-A, cofilin, non-muscle isoform, 18 kDa phosphoprotein, p18, actin-depolymerizing factor (ADF), twinfilin-1, ankyrin repeat and FYVE domain-containing protein 1, usherin precursor, urotensin II receptor, interleukin 4, and midkine. Conclusion: Proteomic analysis of Ankaferd ® represents a true basis for the upcoming Ankaferd ® studies focusing on its wound healing, hemostatic, anti-infective, antineoplastic, and preservative biological actions.
0.58 mg/kg/week IV also received 0.05 mg/kg (maximum dose 1 mg) intrathecal (IT) rhIDU every 3 mo... more 0.58 mg/kg/week IV also received 0.05 mg/kg (maximum dose 1 mg) intrathecal (IT) rhIDU every 3 months beginning at 12-112 days of life. Serum samples for specific, anti-iduronidase IgG antibodies were analyzed by ELISA. After 38-74 weeks of treatment, serum anti-iduronidase antibody (IgG) levels were <1 OD unit/l in all treated pups (tolerance cutoff is 20 OD units/l). In contrast, 8 adult normal and MPS I dogs receiving IV rhIDU developed a mean antibody titer of 149 OD units/l (range 60.2-377.9) after 12 weeks of treatment [1]. MPS I dogs receiving IV rhIDU from birth had a near-normal appearance to the cranium, normalized appearance to skeletal radiographs, less pronounced mitral valve insufficiency, and near-normal heart valve thickness by echocardiography. Two pups infused on the days 1-2 of life (when natural pup mortality is high) died following one treatment. Other adverse events were similar to untreated MPS I dogs. MPS I pups treated from birth with IV +/-IT rhIDU did not develop anti-iduronidase antibodies and had improved efficacy in the hard-totreat skeleton and heart valve. These findings support the argument for early treatment of MPS I disease.
Hereditary spherocytosis (HS) is the most common congenital hemolytic anemia in Caucasians, with ... more Hereditary spherocytosis (HS) is the most common congenital hemolytic anemia in Caucasians, with an estimated prevalence ranging from 1:2000 to 1:5000. The molecular defect in one of the erythrocytes (RBC) membrane proteins underlying HS like; spectrin-α, spectrin-β, ankyrin, band 3 and protein 4.2 that lead to membrane destabilization and vesiculation, may change the RBCs into denser and more rigid cells (spherocytes), which are removed by the spleen, leading to the development of hemolytic anemia. It is classified as mild, moderate and severe, according to the degree of the hemolytic anemia and the associated symptoms. Two-dimensional gel electrophoresis (2-DE) is potentially valuable method for studying heritable disorders as HS that involve membrane proteins. This separation technique of proteins based upon two biophysically unrelated parameters; molecular weight and charge, is a good option in clinical proteomics in terms of ability to separate complex mixtures, display post-translational modifications and changes after phosphorylation. In this study, we have used contemporary methods with some modifications for the solubilisation, separation and identification of erythrocyte membrane proteins in normal and in HS RBCs. Spectrin alpha and beta chain, ankyrin and band 3 proteins expression differences were found with PDQuest software 8.0.1. and peptide mass fingerprinting (PMF) analysis performed for identification of proteins in this study.
Ankaferd blood stopper (ABS) is a novel topical hemostatic agent of plant origin registered for t... more Ankaferd blood stopper (ABS) is a novel topical hemostatic agent of plant origin registered for the management of external hemorrhages, in Turkey. The ABS-induced formation of the protein network with vital erythroid aggregation covers the whole physiological hemostatic process. The aim of this study is to assess prohemostatic and antithrombin effects of ABS on the basis of functional proteomic analyses performed in ABS-treated plasma and serum samples based on the previous hypotheses about ABS action. For this purpose, serum and plasma proteins were separated by 2-dimensional (2D) gel electrophoresis, and proteins were identified using reference plasma gel on Swiss-2DPAGE database. Our results indicated that fibrinogen gamma chain and prothrombin levels just initially decreased first and thereafter enhanced following the ABS exposure. Dual effects of ABS on those critical hemostatic molecules seem to be associated with prohemostatic and antithrombin activities of the hemostatic agent.
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Papers by Duygu Demiralp