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1.
Neuro Endocrinol Lett ; 40(2): 68-74, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31785212

ABSTRACT

BACKGROUND: Left ventricular non-compaction (LVNC) is a rare form of cardiomyopathy resulting from a disorder of endomyocardial morphogenesis associated with significantly increased risk of cardiovascular morbidity and premature mortality. Despite the widespread use of echocardiography, LVNC is commonly overlooked, often due to lack of knowledge about this disorder. METHODS AND RESULTS: A complex diagnostic process and follow-up was analysed in 24 patients diagnosed with LVNC between March 2002 and February 2016 (16 boys, 8 girls; age at presentation 9 days - 18 years; follow-up 2-7 years). 17 patients were initially overlooked and followed-up for different diagnoses. After retrospective evaluation by a senior specialist in paediatric cardiology, LVNC was identified in 3 patients initially diagnosed with dilated cardiomyopathy, 11 patients followed-up with various forms of arrhythmias, and 3 patients with congenital heart disease. The diagnosis of LVNC was confirmed using magnetic resonance imaging in all patients. The classical triad of complications - heart failure, ventricular arrhythmias and systemic embolic events - was not confirmed in this study, electrocardiographic findings were abnormal in 87.5% of patients. Isolated non-compaction of the left ventricular myocardium was a dominant form of non-compaction. CONCLUSIONS: The high variability of morphological findings and clinical manifestations of LVNC results in frequent overlooking of this disorder. Therefore, it is important to make the specialists more familiar with this condition and its pathology. Magnetic resonance imaging represents a conducive method to make correct diagnosis of LVNC under several specific conditions, particularly in case of non-conclusive echocardiographic finding.


Subject(s)
Delayed Diagnosis/statistics & numerical data , Isolated Noncompaction of the Ventricular Myocardium/diagnosis , Isolated Noncompaction of the Ventricular Myocardium/epidemiology , Magnetic Resonance Imaging , Adolescent , Child , Child, Preschool , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Predictive Value of Tests , Retrospective Studies , Risk Factors , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/epidemiology
2.
Neuro Endocrinol Lett ; 37(4): 308-312, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27857048

ABSTRACT

OBJECTIVES: Prognosis of patients with anomalous origin of the left coronary artery from pulmonary artery has dramatically improved as a result of both, early diagnosis and improvements in surgical techniques. Post surgical complications are rare and most patients show quick improvement of the left ventricular performance after repair with complete functional recovery within one year after surgery. Exercise-induced electrocardiographic changes have been found in patients postoperatively and scars and perfusion deficits of the left ventricle may not be detected by standard echocardiographic evaluation. METHODS: Authors present 6 cases of anomalous origin of the left coronary artery from pulmonary artery observed at Martin Univesity Hospital and Pediatric Cardiology Clinic over the last eight-year period. In order to assess the presence of myocardial injury, cardiovascular magnetic resonance imaging with late gadolinium enhancement technique was performed in all 6 cases one year after surgical correction. RESULTS: One patient died 1.5 year after surgical treatment. One year after surgery, the heart size and myocardial functions returned to normal in all patients. Cardiovascular magnetic resonance imaging demonstrated subendocardial late gadolinium enhancement in varios segments of the left ventricle, representing myocardial fibrosis in all patients one year after surgical correction. CONCLUSION: Because of the presence of scarr tissue, the long term prognosis of these patients remains unclear. The damaged tissue may have arrhythmogenic potential, therefore close follow-up, excercise testing and avoidance of high-level sport activities may be needed.


Subject(s)
Cardiac Surgical Procedures , Cicatrix/pathology , Coronary Vessel Anomalies/surgery , Myocardium/pathology , Postoperative Complications/pathology , Pulmonary Artery/surgery , Child , Child, Preschool , Cicatrix/diagnostic imaging , Echocardiography , Female , Fibrosis , Humans , Infant , Magnetic Resonance Imaging , Male , Postoperative Complications/diagnostic imaging , Pulmonary Artery/abnormalities
3.
J Med Chem ; 49(21): 6400-7, 2006 Oct 19.
Article in English | MEDLINE | ID: mdl-17034145

ABSTRACT

Comblike glycodendrimers were prepared by the chemoselective ligation of cysteine-modified glycopeptides (1-7) with a 3-maleimidopropionate-modified linear synthetic carrier (8). Glycodendrimers bearing mono-, di-, or tri-Tn clusters (9-11) were tested as inhibitors using plant and mammalian lectins. In the former group, the Codium fragile lectin showed moderate discrimination among 9, 10, and 11. In the latter group, A and B isoforms of rat NKR-P1 lectin strongly discriminated between 9 and 10. 10 caused a 4-fold increase in killing of the NK resistant tumor cell lines at concentrations as low as 10(-8) M. Surprisingly, 11 interacted exclusively with the rat NKR-P1B isoform and inhibited efficiently natural killing in both rats and humans, even in the presence of the activating compounds 9 and 10. Dinitrophenol haptenization or influenza virus hemagglutinin T-cell epitope conjugation increased the immunogenicity of the parent compounds and resulted in the production of Tn specific antibodies.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate/chemistry , Dendrimers/chemical synthesis , Killer Cells, Natural/drug effects , Lectins/chemistry , 2,4-Dinitrophenol/chemistry , Animals , Antibody Formation , Antigens, Tumor-Associated, Carbohydrate/immunology , Cysteine/chemistry , Cytotoxicity, Immunologic , Dendrimers/chemistry , Dendrimers/pharmacology , Epitopes , Female , Glycopeptides/chemistry , Haptens , Hemagglutinin Glycoproteins, Influenza Virus/chemistry , Humans , Immunoglobulin G/biosynthesis , Immunoglobulin M/biosynthesis , Jurkat Cells , Killer Cells, Natural/immunology , Mice , Mice, Inbred BALB C , Plant Lectins/chemistry , Protein Binding , Protein Isoforms/chemistry , Rats , Receptors, Immunologic/chemistry , T-Lymphocytes/immunology
4.
J Med Chem ; 46(10): 1989-96, 2003 May 08.
Article in English | MEDLINE | ID: mdl-12723961

ABSTRACT

A series of 2-(thioalkyl)pentanedioic acids were synthesized and evaluated as inhibitors of glutamate carboxypeptidase II (GCP II, EC 3.4.17.21). The inhibitory potency of these thiol-based compounds against GCP II was found to be dependent on the number of methylene units between the thiol group and pentanedioic acid. A comparison of the SAR of the thiol-based inhibitors to that of the phosphonate-based inhibitors provides insight into the role of each of the two zinc-binding groups in GCP II inhibition. The most potent thiol-based inhibitor, 2-(3-mercaptopropyl)pentanedioic acid (IC(50) = 90 nM), was found to be orally bioavailable in rats and exhibited efficacy in an animal model of neuropathic pain following oral administration.


Subject(s)
Analgesics/chemical synthesis , Carboxypeptidases/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Glutarates/chemical synthesis , Sulfhydryl Compounds/chemical synthesis , Administration, Oral , Analgesics/chemistry , Analgesics/pharmacology , Animals , Biological Availability , Carboxypeptidases/chemistry , Constriction, Pathologic/complications , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Glutamate Carboxypeptidase II , Glutarates/chemistry , Glutarates/pharmacology , Hot Temperature , Hyperalgesia/drug therapy , Hyperalgesia/etiology , Male , Pain/drug therapy , Pain/etiology , Peripheral Nervous System Diseases/complications , Rats , Rats, Sprague-Dawley , Sciatic Nerve , Structure-Activity Relationship , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/pharmacology
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