losartan-potassium and Hemangioma

Mutations in the tumor suppressor gene von Hippel-Lindau (VHL) underlie a hereditary cancer syndrome-VHL disease-and are also frequently observed in sporadic renal cell carcinoma of the clear cell type (ccRCC). VHL disease is characterized by malignant and benign tumors in a few specific tissues, including ccRCC, hemangioblastoma and pheochromocytoma. The etiology of these tumors remains unresolved.. Conditional inactivation of the VHL gene in mouse (Vhlh) was generated to examine the pathophysiological role of the VHL gene function. Specific cell populations were isolated by fluorescence-activated cell sorting (FACS) and bone marrow transplants were performed to identify the Vhlh-inactivated cells responsible for the phenotype.. Previously we showed that inactivation of Vhlh in a subpopulation of kidney distal tubule cells resulted in hyperplastic clear-cell lesions and severe inflammation and fibrosis. Here, we show that this knockout mouse strain also develops Hif-2α-dependent vascular overgrowth (hemangioma) and extramedullary erythropoiesis in the liver. However, Vhlh inactivation was not detected in the liver parenchyma. We instead demonstrate that in these mice, Vhlh is inactivated in liver granulocytes and that hemangiomas are partially rescued in knockout mice reconstituted with wild-type hematopoietic stem cells, indicating the involvement of bone-marrow-derived leukocyte. Interestingly, bone marrow from knockout mice failed to generate the liver phenotype in wild-type recipients, suggesting that an additional cell type that is not derived from the bone marrow is involved in the development of the hemangioma phenotype.. These results support the idea that the development of a full-blown VHL disease phenotype requires inactivation of the VHL gene not only in the tumor proper, but also in the stromal compartment.

Topics: Animals; Biomarkers; Disease Models, Animal; Erythropoietin; Flow Cytometry; Gene Silencing; Granulocytes; Hemangioma; Hematopoiesis, Extramedullary; Hematopoietic Stem Cells; Homeodomain Proteins; Leukocytes; Liver; Liver Neoplasms; Mice; Mice, Knockout; Mutation; Phenotype; Von Hippel-Lindau Tumor Suppressor Protein

Parkinson's disease (PD) is a severe neurodegenerative disorder caused by progressive loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. The molecular mechanism of PD pathogenesis is unclear. Mutations in the

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Erythropoietin; Gene Expression Regulation, Neoplastic; Hemangioma; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Liver Neoplasms; Mice; Mice, Knockout; Neoplasm Proteins

Diffuse neonatal hemangiomatosis (DNH) is a rare condition characterized by the concomitant development of multiple cutaneous infantile hemangiomas (IH) and visceral hemangiomas. Recently, an association between erythropoietin treatment and an increased incidence of infantile hemangioma was noted. A Japanese male infant was born via cesarean section at 27 weeks of gestation. Following the commencement of erythropoietin treatment for anemia of prematurity, he developed multiple cutaneous hemangiomas, high cardiac output heart failure and hepatomegaly. Abdominal imaging indicated comorbidity of diffuse infantile hepatic hemannigomas, resulting in the final diagnosis of DNH. The discontinuation of erythropoietin treatment and long-term therapy with propranolol improved the hepatic lesions and cutaneous hemangiomas. The possibility of multiple organ involvement and the exacerbating effects of erythropoietin treatment should be considered in cases in which multiple cutaneous hemangiomas develop in preterm infants receiving erythropoietin treatment.

Topics: Adrenergic beta-Antagonists; Anemia, Neonatal; Erythropoietin; Gestational Age; Hemangioma; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Joint Instability; Magnetic Resonance Imaging; Male; Phimosis; Propranolol; Skin Abnormalities

Infantile haemangiomas are benign vascular neoplasms that occur frequently in premature infants. The authors hypothesised that in addition to gestational age and birth weight, erythropoietin therapy may influence the incidence of these soft tissue tumours in preterm infants.. 2563 infants born prematurely and admitted to the Division of Neonatology, University of Heidelberg Medical School were investigated in a retrospective analysis. Hospital charts for all infants were reviewed for clinical data. The primary endpoint was the percentage of infants who had received erythropoietin treatment and were diagnosed with a haemangioma.. Haemangiomas were diagnosed in 4.3% (n=110) of the 2563 preterm infants. These 110 infants had a median gestational age of 29 weeks (IQR 27-33 weeks) and the female:male ratio was 1.8:1. A higher incidence of haemangiomas (12-15%) was detected in premature infants with a lower gestational age (<31 weeks). Erythropoietin therapy was shown to be an independent risk factor after adjusting for all other known factors and oxygen therapy in multivariable analysis (HR 2.82, 95% CI 1.55 to 5.12). Subgroup analysis revealed that the effect was more pronounced in male than female infants (HR 3.61, 95% CI 1.52 to 8.57).. This retrospective study demonstrates that erythropoietin treatment is associated with an increase in the incidence of these benign vascular tumours after adjusting for all other factors.

Topics: Birth Weight; Erythropoietin; Female; Germany; Gestational Age; Hemangioma; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Prevalence; Recombinant Proteins; Retrospective Studies

To report the results of immunohistochemical analyses of a retinal angioma obtained from a patient with von Hippel-Lindau (VHL) disease.. A 13-year-old girl with VHL disease presented with bilateral retinal angiomas and decreased vision in the right eye. Although transpupillary thermotherapy was performed to treat the angiomas, the tractional and exudative retinal detachment progressed OD, requiring vitreous surgery. Intraoperatively, a large retinal angioma was excised together with the surrounding retina to aid in reattaching the retina. The excised tissue was prepared for standard histopathology and immunohistochemistry.. Histological examination showed that the excised tissue was made up of highly vascularized cells, and the retina was gliotic. The stromal cells had intracytoplasmic vacuoles and were located between the numerous vessels. These findings are identical to those of a hemangioblastoma. The stromal cells stained positively for vascular endothelial growth factor and neuron specific enolase, and weakly for glial fibrillary acidic protein. Some of the stromal cells stained positively for inhibin alpha. Isolated erythropoietin-positive cells, indicative of developmentally arrested angioblasts, were observed among the endothelial cells.. The results indicate that stromal cells in retinal angiomas are neuroectodermal in origin with immunohistochemical features, for example, inhibin alpha, similar to cerebellar hemangioblastomas and renal cell carcinomas associated with VHL disease.

Topics: Adolescent; Erythropoietin; Female; Glial Fibrillary Acidic Protein; Hemangioma; Humans; Immunoenzyme Techniques; Inhibins; Phosphopyruvate Hydratase; Retinal Neoplasms; Stromal Cells; Vascular Endothelial Growth Factor A; von Hippel-Lindau Disease

Topics: Erythropoietin; Female; Hemangioma; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Lip Neoplasms; Male; Recombinant Proteins

A giant hemangioma of the tongue was resected in a 16-year-old otherwise healthy young man (ASA I). Despite a total blood loss of 4,300 ml, corresponding to 105% of the patients intravascular blood volume, no allogeneic red blood cells had to be transfused intraoperatively. Besides minimization of intraoperative blood loss with preoperative alcohol injections into the tumor, ligation of large tumor-perfusing arteries, application of fibrin glue, skillful surgical technique, positioning of the surgical field above the level of the heart, controlled hypotension and maintenance of normothermia, acute normovolemic hemodilution (augmented by preoperative administration of recombinant human erythropoetin - rhEpo) and autotransfusion of lost blood were used for recovery of autologous blood. Under the protection of hyperoxia, a decrease of the hemoglobin (Hb) concentration to 4.2 g/dl was bridged by extreme normovolemic hemodilution. No signs of immanent or manifest tissue hypoxia were encountered. Retransfusion of autologous red blood cells was only started when surgical control of bleeding was achieved. Additionally a total of 4 units of fresh frozen plasma were infused for stabilization of plasma coagulation. After a 9-hour surgical duration, the patient was transferred to the intensive care unit, normotensive (with low-dose infusion of norepinephrin) and normothermic with a Hb concentration of 5.6 g/dl. In the face of an increasing lactacidosis 2 units of packed red blood cells were transfused on post surgical day 1.

Topics: Adolescent; Anesthesia, General; Blood Loss, Surgical; Blood Preservation; Blood Transfusion, Autologous; Erythrocyte Transfusion; Erythropoietin; Fibrin Tissue Adhesive; Hemangioma; Hemodilution; Humans; Male; Plasma; Recombinant Proteins; Tissue Adhesives; Tongue Neoplasms

von Hippel-Lindau (VHL) disease is a pleomorphic familial tumor syndrome that is characterized by the development of highly vascularized tumors. Homozygous disruption of the VHL gene in mice results in embryonic lethality. To investigate VHL function in the adult we have generated a conditional VHL null allele (2-lox allele) and null allele (1-lox allele) by Cre-mediated recombination in embryonic stem cells. We show here that mice heterozygous for the 1-lox allele develop cavernous hemangiomas of the liver, a rare manifestation of the human disease. Histologically these tumors were associated with hepatocellular steatosis and focal proliferations of small vessels. To study the cellular origin of these lesions we inactivated VHL tissue-specifically in hepatocytes. Deletion of VHL in the liver resulted in severe steatosis, many blood-filled vascular cavities, and foci of increased vascularization within the hepatic parenchyma. These histopathological changes were similar to those seen in livers from mice heterozygous for the 1-lox allele. Hypoxia-inducible mRNAs encoding vascular endothelial growth factor, glucose transporter 1, and erythropoietin were up-regulated. We thus provide evidence that targeted inactivation of mouse VHL can model clinical features of the human disease and underline the importance of the VHL gene product in the regulation of hypoxia-responsive genes in vivo.

Topics: Albumins; Alleles; Animals; Erythropoietin; Genes, Tumor Suppressor; Hemangioma; Heterozygote; Ligases; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Mutant Strains; Phenotype; Polycythemia; Proteins; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Vascular Neoplasms; Von Hippel-Lindau Tumor Suppressor Protein

Topics: Diseases in Twins; Erythropoietin; Hemangioma; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Recombinant Proteins

Topics: Adult; Erythropoietin; Hemangioma; Humans; Liver Neoplasms; Male; Polycythemia

Topics: Adolescent; Adult; Animals; Carcinoma, Hepatocellular; Erythropoietin; Female; Hemangioma; Humans; Kidney Neoplasms; Liver Neoplasms; Male; Neoplasms; Polycythemia; Rats

Topics: Animals; Cerebellar Neoplasms; Epoetin Alfa; Erythropoietin; Hemangioblastoma; Hemangioma; Hematopoiesis; Pathology; Rabbits; Research