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1.
Sci Rep ; 7(1): 14898, 2017 11 02.
Article in English | MEDLINE | ID: mdl-29097799

ABSTRACT

Platelets can be found on the surface of inflamed and ruptured atherosclerotic plaques. Thus, targeting of activated platelets may allow for molecular imaging of vulnerable atherosclerotic lesions. We here investigated microbubbles (MB) functionalized with the selectin ligand sialyl Lewisa individually (MBsLea) or dually with sLea and an antibody targeting ligand-induced binding sites of the activated GPIIb/IIIa receptor (MBDual). Assessed by in vitro flow chamber, targeted MB exhibited increased adhesion to platelets as compared to MBControl. While MBsLea rolled slowly on the platelets' surface, MBDual enhanced the percentage of firm adhesion. In vivo, MB were investigated by ultrasound in a model of ferric chloride induced non-occlusive carotid artery thrombosis. MBsLea and MBDual revealed a higher ultrasound mean acoustic intensity than MBControl (p < 0.05), however MBDual demonstrated no additional increase in mean signal intensity as compared to MBsLea. The degree of carotid artery stenosis on histology correlated well with the ultrasound acoustic intensity of targeted MB (p < 0.05). While dual targeting of MB using fast binding carbohydrate polymers and specific antibodies is a promising strategy to support adhesion to activated platelets under arterial shear stress, these advantages seem not readily translatable to in vivo models.


Subject(s)
Blood Platelets/pathology , Contrast Media/analysis , Microbubbles , Platelet Activation , Thrombosis/diagnostic imaging , Animals , Antibodies, Immobilized/analysis , Antibodies, Immobilized/metabolism , Blood Platelets/metabolism , CA-19-9 Antigen , Carotid Arteries/diagnostic imaging , Carotid Arteries/metabolism , Carotid Arteries/pathology , Contrast Media/metabolism , Female , Ligands , Mice, Inbred C57BL , Oligosaccharides/analysis , Oligosaccharides/metabolism , Platelet Glycoprotein GPIIb-IIIa Complex/metabolism , Selectins/metabolism , Thrombosis/metabolism , Thrombosis/pathology , Ultrasonography
2.
Eur J Med Res ; 12(12): 595-603, 2007 Dec 14.
Article in English | MEDLINE | ID: mdl-18024271

ABSTRACT

BACKGROUND: To determine the frequency of essential cardiovascular risk factors in different vascular ocular diseases. - METHODS: We compiled cardiovascular risk factor findings (RFs) from 416 patients with non-inflammatory ocular vascular occlusions in a retrospective study: 134 patients with BRAO, 253 patients with CRAO, and 29 patients with hemi-CRAO. 274 (65.9 %) male and 142 (34.1 %) female patients were examined. Mean age of all patients was 66 years (range: 18-90). The right eye was involved in 221 (53.1 %), left eye in 193 (46.4 %), and both eyes in 2 patients (0.5 %). - RESULTS: Cardiovascular risk factors (RFs) were found in 243 patients. Three hundred and eight (308) out of 406 patients (75.9 %) presented with arterial hypertension. Hypertension was present in 96 patients with BRAO (73.8 %), in 197 patients with CRAO (79.8 %), and in 15 patients with hemi-CRAO (78.9 %). - RFs such as arterial hypertension, carotid artery diseases, diabetes mellitus, hyperlipidemia, hyperuricemia, and chronic smoking did not differ statistically between patients with BRAO, CRAO or hemi--CRAO. But visible emboli in retinal arteries were observed in patients with BRAO (47 %,), or hemi-CRAO (41.4 %), much more often than in patients with CRAO (11.1 %). - CONCLUSIONS: No statistical differences between the RFs of patients with BRAO, CRAO, or hemi-CRAO were noted. We maintain that every patient with retinal arterial obstruction should undergo extensive examination of essential RFs.


Subject(s)
Cardiovascular Diseases/epidemiology , Retinal Artery Occlusion/complications , Adult , Aged , Aged, 80 and over , Amaurosis Fugax/complications , Amaurosis Fugax/diagnosis , Anticoagulants/therapeutic use , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/diagnosis , Female , Humans , Hypertension/complications , Hypertension/diagnosis , Male , Middle Aged , Phenprocoumon/therapeutic use , Retinal Artery Occlusion/drug therapy , Risk Factors
3.
Eur J Med Res ; 10(7): 296-304, 2005 Jul 29.
Article in English | MEDLINE | ID: mdl-16055401

ABSTRACT

BACKGROUND: Ophthalmic complications due to heart tumors are rare. PATIENTS: This case report describes two patients with ocular complications, caused by a suspected cardiac tumor. A 56-year-old woman with arterial hypertension had a severe episode of headache coinciding with an acute loss of vision in her right eye and left-sided hemiparesis. A 20-year-old woman noticed sudden transient visual loss in her right eye. RESULT: The 56-year-old woman had an infarction on the right side of the middle and posterior cerebral arteries and, simultaneously, a central retinal artery occlusion (CRAO) in her right eye. Echocardiography revealed a tumor in the left atrium. The tumor disappeared after treatment with phenprocoumon within a few days. The diagnosis of a cardiac thrombus was made. The 20-year-old woman noticed recurrent episodes of sudden, transient visual loss in her right eye. A branch retinal arterial occlusion (BRAO) in her right eye was diagnosed. Echocardiography revealed a myxoma in the left atrium. The tumor was successfully excised surgically. CONCLUSION: In any vascular disturbance in the eye suspected to be embolic in origin, echocardiography should be carried out in order to exclude the presence of a heart disease.


Subject(s)
Heart Neoplasms/complications , Myxoma/complications , Neoplastic Cells, Circulating , Retinal Artery Occlusion/etiology , Adult , Anticoagulants/therapeutic use , Female , Heart Atria/pathology , Heart Neoplasms/pathology , Heart Neoplasms/surgery , Humans , Middle Aged , Myxoma/pathology , Myxoma/surgery , Neoplastic Cells, Circulating/drug effects , Neoplastic Cells, Circulating/pathology , Phenprocoumon/therapeutic use , Retinal Artery Occlusion/drug therapy , Retinal Artery Occlusion/pathology , Treatment Outcome
4.
Neuropediatrics ; 34(5): 270-3, 2003 Jun.
Article in English | MEDLINE | ID: mdl-14598234

ABSTRACT

Danon disease (DD) is a rare lysosomal glycogen storage disease with normal acid maltase activity, which is characterised clinically by cardiomyopathy and myopathy, and a variable degree of mental retardation. The causative gene, LAMP2, has been mapped to chromosome Xq24-q25. LAMP2 encodes a lysosome-associated membrane glycoprotein. We identified a novel LAMP2 mutation of the exon 8 splice acceptor site (IVS7-1G --> A) in an affected male and female, which predicts abnormal splicing. Both affected individuals presented solely with hypertrophic cardiomyopathy. Muscle weakness and mental impairment were absent. Diagnosis of Danon disease was established by muscle biopsy, when the male index patient developed transient severe muscle weakness following heart transplantation. Typical biopsy findings were also found in a heart muscle specimen. Demonstration of the LAMP2 mutation in affected male and female siblings is compatible with X-linked dominant inheritance. Danon disease should be actively looked for in cardiomyopathy patients.


Subject(s)
Antigens, CD/genetics , Chromosomes, Human, X/genetics , Glycogen Storage Disease Type II/genetics , Glycogen Storage Disease Type II/metabolism , Glycogen/genetics , Glycogen/metabolism , Point Mutation/genetics , Adult , Antigens, CD/metabolism , Cardiomyopathies/pathology , Cardiomyopathies/surgery , DNA Mutational Analysis , Exons/genetics , Female , Glycogen Storage Disease Type II/pathology , Heart Transplantation , Humans , Lysosomal-Associated Membrane Protein 2 , Lysosomal Membrane Proteins , Male , Muscle, Skeletal/pathology , Muscle, Smooth/pathology
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