AIM:To observe the expression of vascula r endothelial growth factor(VEGF)and Factor VIII related antigen(FVIII-R Ag )in rats brain tissue in the bor-der zone of the hematoma,and explore the relationship between the e...AIM:To observe the expression of vascula r endothelial growth factor(VEGF)and Factor VIII related antigen(FVIII-R Ag )in rats brain tissue in the bor-der zone of the hematoma,and explore the relationship between the expres-sion of VEGF and the brain angionesis after intracerebral hmorrhage(ICH).METHODS:Rat of model of ICH was induced by inje ction of collagenase physiological saline into the right caudate nucleus.The immunohistoch emical methods were performed by using diff erent antisera of VEGF and FVIII-R Ag in serial sections of rats brain at 12h,1d,3d and 7d after ICH respec-tively.RESULTS:T he amount of VEGF positive cells was markedly in-creased,and reached the highest at 7th day in the border zone after ICG(P<0.01),but there were no significant diffe rence among the mean value of A of cells at different time points(P>0.05).Compared with the controls,both the FVIII-R Ag positive endothelial cells and the A of cells were signific antly different in experimental ICH goups after 1day.CONCLUSION:The up-regulated expression of VEGF might i nduce proliferation of endothelial cell and angiogenesis in the border zone a fter ICH in rats.展开更多
<strong>Background: </strong>ABO blood group distribution defers with racial and geographic variations. They are related to diseases like cardiovascular diseases, cerebral thromboembolism. ABO blood group ...<strong>Background: </strong>ABO blood group distribution defers with racial and geographic variations. They are related to diseases like cardiovascular diseases, cerebral thromboembolism. ABO blood group system may influence coagulation factor VIII which may increase the future risk of thrombosis. <strong>Aim:</strong> To assess the relation of ABO blood group with coagulation factor VIII in healthy adults.<strong> Material and Methods: </strong>A prospective type of analytical cross-sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka from July 2019 to June 2020. After obtaining ethical clearance, a total of 190 healthy adults were selected from different areas of Dhaka city based on inclusion and exclusion criteria, with ages ranging from 18 - 45 years. The subjects were interviewed and detailed history regarding personal, family, medical and drug were taken. Prior to sample collection, informed written consent was taken from the participants. Individuals of blood group A were selected as group A, blood group B as group B, blood group AB as group AB and blood group O as group O. Coagulation factor VIII was measured in the Department of Hematology and BMT Unit, Dhaka Medical College Hospital, Dhaka. Blood grouping was done in the Department of Physiology, Dhaka Medical College, Dhaka. <strong>Statistical Analysis:</strong> For statistical analysis, ONE way ANOVA followed by Bonferroni test were considered using SPSS 25.0 version. <strong>Results: </strong>In this study, blood group B was most common (33.2%). Coagulation factor VIII was significantly higher (p < 0.001) in blood group A (105.76% ± 11.82%), B (112.00% ± 15.02%), AB (109.80% ± 11.93%) than blood group O (82.00% ± 12.86%). No significant difference was observed among A, B and AB blood groups regarding coagulation factor VIII. <strong>Conclusions:</strong> It can be concluded that blood group A, B, AB individuals may have more chance of thrombosis due to significantly higher coagulation factor VIII than blood group O individuals.展开更多
Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progre...Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.展开更多
BACKGROUND Hemophilia, an uncommon yet consequential hereditary bleeding disorder, manifests as two clinically indistinguishable forms that hinder the normal functioning of the coagulation cascade. This impairment ren...BACKGROUND Hemophilia, an uncommon yet consequential hereditary bleeding disorder, manifests as two clinically indistinguishable forms that hinder the normal functioning of the coagulation cascade. This impairment renders individuals more susceptible to excessive bleeding during significant surgical interventions. Moreover, individuals with severe hemophilia frequently encounter recurring hemarthrosis, resulting in progressive joint destruction and, subsequently, the need for hip and knee replacement surgeries.CASE SUMMARY The patient was a 53-year-old man with hemophilia A as the underlying disease and had self-injected factor Ⅷ twice weekly for several decades. He had undergone ankle fusion surgery for recurrent hemarthrosis at the Department of Orthopedic Surgery 1 mo prior and was referred to our department because of skin necrosis after a hematoma at the surgical site. An anterolateral thigh perforator free flap was created after three cycles of factor Ⅷ administration in addition to the concomitant administration of tranexamic acid(TXA)(Transamin 250 mg cap, 1 cap tid, q8h). After the operation, from postoperative days(PODs) 1-5, the factor Ⅷ dose and interval were maintained, and q12h administration was tapered to q24h administration after POD 6. Because the patient’s flap was stable 12 d after the operation, factor Ⅷ administration was tapered to twice a week. At 6 mo follow-up, the patient recovered well without any complications.CONCLUSION To the best of our knowledge, there are very few reports of successful free flaps in patients with hemophilia, and none have been reported in patients with hemophilia A. Moreover, there are several reports on the efficacy of TXA in free flaps in general patients;however, there are no case reports of combining factor Ⅷ and TXA in patients with hemophilia. Therefore, we report this case to contribute to future academic research.展开更多
Background: In Africa, hemophilia is underdiagnosed and carriers have long been considered free from bleeding symptoms. However, recent research has begun to reveal hemostatic abnormalities and bleeding manifestations...Background: In Africa, hemophilia is underdiagnosed and carriers have long been considered free from bleeding symptoms. However, recent research has begun to reveal hemostatic abnormalities and bleeding manifestations in carriers of hemophilia A, particularly due to excessive inactivation of normal X chromosomes. Objective: To describe the bleeding symptoms and hemostatic abnormalities in carriers of hemophilia A (HA) in Benin. Methods: This study was conducted as a prospective cross-sectional investigation between April 2021 to March 2022. The study population consisted of identified through pedigrees of persons with hemophilia A being treated in various hospitals in Benin. Data were collected through interviews conducted by trained physician and each carrier underwent a biological workup. Results: A total of 71 hemophilia A carriers were included and 38 of whom were obligatory carriers. Thirty-one carriers (43.7%) reported abnormal bleeding symptoms. Menorrhagia has (71%) being the most important manifestation, followed by bleeding during or after childbirth (45.2%). Among the 71 carriers, 45 were of reproductive age. Of whom 22 (48.8%) had a Higham score exceeding 100. Activated partial thromboplastin time was prolonged in 7 carriers (9.9%). The mean activity factor VIII:C (FVIII:C) levels were 68.8 ± 34.9 IU/dL. The average FVIII:C level in obligatory carriers was 56.9% and among potential carriers, the average FVIII:C level was higher at 80.4%. However twelve female carriers (16.9%) had FVIII:C levels < 40%. The FVIII:C/FvWAg ratio was below 0.7 in 73.2% of female drivers. Obligatory carriers (p = 0.00003) and FVIII;C/FvWAg ratio = 0.003) were statistically associated with abnormal bleeding symptoms, while blood group O (p = 0.0002) and FVIII/FvWAg ratio = 0.0016) were associated with a higher risk of menorrhagia. Conclusion: In Benin, carriers of haemophilia A present bleeding symptoms and haemostatic abnormalities. Further studies on a larger number of carriers are needed to better characterize and manage these patients.展开更多
文摘AIM:To observe the expression of vascula r endothelial growth factor(VEGF)and Factor VIII related antigen(FVIII-R Ag )in rats brain tissue in the bor-der zone of the hematoma,and explore the relationship between the expres-sion of VEGF and the brain angionesis after intracerebral hmorrhage(ICH).METHODS:Rat of model of ICH was induced by inje ction of collagenase physiological saline into the right caudate nucleus.The immunohistoch emical methods were performed by using diff erent antisera of VEGF and FVIII-R Ag in serial sections of rats brain at 12h,1d,3d and 7d after ICH respec-tively.RESULTS:T he amount of VEGF positive cells was markedly in-creased,and reached the highest at 7th day in the border zone after ICG(P<0.01),but there were no significant diffe rence among the mean value of A of cells at different time points(P>0.05).Compared with the controls,both the FVIII-R Ag positive endothelial cells and the A of cells were signific antly different in experimental ICH goups after 1day.CONCLUSION:The up-regulated expression of VEGF might i nduce proliferation of endothelial cell and angiogenesis in the border zone a fter ICH in rats.
文摘<strong>Background: </strong>ABO blood group distribution defers with racial and geographic variations. They are related to diseases like cardiovascular diseases, cerebral thromboembolism. ABO blood group system may influence coagulation factor VIII which may increase the future risk of thrombosis. <strong>Aim:</strong> To assess the relation of ABO blood group with coagulation factor VIII in healthy adults.<strong> Material and Methods: </strong>A prospective type of analytical cross-sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka from July 2019 to June 2020. After obtaining ethical clearance, a total of 190 healthy adults were selected from different areas of Dhaka city based on inclusion and exclusion criteria, with ages ranging from 18 - 45 years. The subjects were interviewed and detailed history regarding personal, family, medical and drug were taken. Prior to sample collection, informed written consent was taken from the participants. Individuals of blood group A were selected as group A, blood group B as group B, blood group AB as group AB and blood group O as group O. Coagulation factor VIII was measured in the Department of Hematology and BMT Unit, Dhaka Medical College Hospital, Dhaka. Blood grouping was done in the Department of Physiology, Dhaka Medical College, Dhaka. <strong>Statistical Analysis:</strong> For statistical analysis, ONE way ANOVA followed by Bonferroni test were considered using SPSS 25.0 version. <strong>Results: </strong>In this study, blood group B was most common (33.2%). Coagulation factor VIII was significantly higher (p < 0.001) in blood group A (105.76% ± 11.82%), B (112.00% ± 15.02%), AB (109.80% ± 11.93%) than blood group O (82.00% ± 12.86%). No significant difference was observed among A, B and AB blood groups regarding coagulation factor VIII. <strong>Conclusions:</strong> It can be concluded that blood group A, B, AB individuals may have more chance of thrombosis due to significantly higher coagulation factor VIII than blood group O individuals.
基金Supported by a grant from Medical Technology Research Center for Health Development of China National Health and Family Planning Commission(No.W2012FZ007)
文摘Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.
文摘BACKGROUND Hemophilia, an uncommon yet consequential hereditary bleeding disorder, manifests as two clinically indistinguishable forms that hinder the normal functioning of the coagulation cascade. This impairment renders individuals more susceptible to excessive bleeding during significant surgical interventions. Moreover, individuals with severe hemophilia frequently encounter recurring hemarthrosis, resulting in progressive joint destruction and, subsequently, the need for hip and knee replacement surgeries.CASE SUMMARY The patient was a 53-year-old man with hemophilia A as the underlying disease and had self-injected factor Ⅷ twice weekly for several decades. He had undergone ankle fusion surgery for recurrent hemarthrosis at the Department of Orthopedic Surgery 1 mo prior and was referred to our department because of skin necrosis after a hematoma at the surgical site. An anterolateral thigh perforator free flap was created after three cycles of factor Ⅷ administration in addition to the concomitant administration of tranexamic acid(TXA)(Transamin 250 mg cap, 1 cap tid, q8h). After the operation, from postoperative days(PODs) 1-5, the factor Ⅷ dose and interval were maintained, and q12h administration was tapered to q24h administration after POD 6. Because the patient’s flap was stable 12 d after the operation, factor Ⅷ administration was tapered to twice a week. At 6 mo follow-up, the patient recovered well without any complications.CONCLUSION To the best of our knowledge, there are very few reports of successful free flaps in patients with hemophilia, and none have been reported in patients with hemophilia A. Moreover, there are several reports on the efficacy of TXA in free flaps in general patients;however, there are no case reports of combining factor Ⅷ and TXA in patients with hemophilia. Therefore, we report this case to contribute to future academic research.
文摘Background: In Africa, hemophilia is underdiagnosed and carriers have long been considered free from bleeding symptoms. However, recent research has begun to reveal hemostatic abnormalities and bleeding manifestations in carriers of hemophilia A, particularly due to excessive inactivation of normal X chromosomes. Objective: To describe the bleeding symptoms and hemostatic abnormalities in carriers of hemophilia A (HA) in Benin. Methods: This study was conducted as a prospective cross-sectional investigation between April 2021 to March 2022. The study population consisted of identified through pedigrees of persons with hemophilia A being treated in various hospitals in Benin. Data were collected through interviews conducted by trained physician and each carrier underwent a biological workup. Results: A total of 71 hemophilia A carriers were included and 38 of whom were obligatory carriers. Thirty-one carriers (43.7%) reported abnormal bleeding symptoms. Menorrhagia has (71%) being the most important manifestation, followed by bleeding during or after childbirth (45.2%). Among the 71 carriers, 45 were of reproductive age. Of whom 22 (48.8%) had a Higham score exceeding 100. Activated partial thromboplastin time was prolonged in 7 carriers (9.9%). The mean activity factor VIII:C (FVIII:C) levels were 68.8 ± 34.9 IU/dL. The average FVIII:C level in obligatory carriers was 56.9% and among potential carriers, the average FVIII:C level was higher at 80.4%. However twelve female carriers (16.9%) had FVIII:C levels < 40%. The FVIII:C/FvWAg ratio was below 0.7 in 73.2% of female drivers. Obligatory carriers (p = 0.00003) and FVIII;C/FvWAg ratio = 0.003) were statistically associated with abnormal bleeding symptoms, while blood group O (p = 0.0002) and FVIII/FvWAg ratio = 0.0016) were associated with a higher risk of menorrhagia. Conclusion: In Benin, carriers of haemophilia A present bleeding symptoms and haemostatic abnormalities. Further studies on a larger number of carriers are needed to better characterize and manage these patients.
