RESUMEN
Diagnosis and treatment of myocarditis can be challenging, including determining indications for heart transplantation. We present a 6-year medical history of a 54 years old patient with severe morphologically verified viral-negative lymphocytic myocarditis and systemic manifestations (onset of hemorrhagic vasculitis) combined with moderate coronary atherosclerosis, which regressed according to repeated coronary angiography. For 5 years, the patient received immunosuppressive therapy with methylprednisolone and azathioprine with a significant improvement. Repeated relapses of atrial fibrillation required correction of basic therapy and plasmapheresis. The disease was complicated by thyrotoxicosis and multi-organ dysfunction; the autopsy showed persistent myocarditis activity. The myocarditis is a chronic condition and requires a review of the treatment strategy at each stage.
Asunto(s)
Miocarditis , Virosis , Humanos , Persona de Mediana Edad , Miocarditis/diagnóstico , Miocarditis/etiología , Miocarditis/terapia , Miocardio , Inmunosupresores/uso terapéutico , Biopsia , AzatioprinaRESUMEN
AIM: To investigate whether intravenous contrast-enhanced multislice spiral computed tomography (computed tomography) (MSCT) versus myocardial morphological examination can diagnose myocarditis and the non-inflammatory causes of dilated cardiomyopathy (DCM) and evaluate prognosis in patients with the latter. SUBJECTS AND METHODS: A study group consisted of 130 patients, including 95 men (46.8±11.9 years), with DCM (mean left ventricular (LV) end-diastolic dimension (EDD), 6.6±0.8 cm; mean LV ejection fraction (EF), 29.8±9.3%; NYHA functional class (FC) III (II; III)). All the patients underwent intravenous contrast-enhanced 320-slice CT of the heart; myocardial morphological examination was made in 48 patients (endomyocardial biopsy in 29 patients, intraoperative biopsy in 7, and autopsy in 9, and study of the explanted heart in 3). In addition, cardiotropic viral DNA in the blood and myocardium and the level of anticardiolipin antibodies were determined; echocardiography (in all the patients), scintigraphy (n = 45), magnetic resonance imaging (MRI) (n = 21), and coronary angiography (CG) (n = 46), and a genetic consultation were performed. A comparison group comprised 20 patients, including 14 men (69.3±9.2 years), with coronary atherosclerosis (40% or more stenoses) according to MSCT findings in the absence of criteria for DCM (mean LV EDD, 4.8±0.5 cm; mean LV EF, 59.4±4.6%). RESULTS: Morphological/comprehensive examination showed that myocarditis as a cause of DCM was diagnosed in 76 (65%) patients; its concurrence with genetic cardiomyopathies was in 17 more patients (17%). MSCT of the heart revealed lower accumulation areas in 2 (1.5%) patients (type 1 based on the proposed rating scale), delayed myocardial contrast agent accumulation (DMCAA) in 81 (62.3%): subendocardial accumulation (type 2) in 8, intramyocardial accumulation in 4 (type 3), subepicardial accumulation in 52 (type 4), and transmural accumulation in 15 (type 5); DMCAA was not noted in 49 patients. DMCAA was not found in the comparison group. As compared with biopsy, the sensitivity, specificity, predictive value of positive and negative results of the tests in detecting active myocarditis for all the types of DMCAA were 77.4, 47.1, 72.7, and 53.3%, respectively; those for types 3-5 of DMCAA were 77.4, 52.9, 75.0, and 56.3%; those in detecting all the morphological types of myocarditis were 68.3, 28.6, 84.8, and 13.3%, and those for types 3-5 were 65.9, 28.6, 84.4, and 12.5%, respectively. Comparison of the data of MSCT and those of comprehensive examination in all the patients with DCM, the diagnostic significance in detecting myocarditis for all the types of DMCAA was 70.6, 67.9, 88.9 and 38.8%, respectively; that for DMCAA types 3-5 was 60.8, 67.9, 87.3, and 32.3%. In the study group, MSCT also identified the non-compacted myocardium (n = 31 (23.8%)), coronary atherosclerosis (n = 31 (23%)), which is confirmed by CG findings in 15 patients. The patients with DMCAA significantly more frequently showed a relationship with previous infection, acute onset, significantly higher NYHA FCs, end-diastolic and end-systolic LV volumes, and insignificantly lower LV EF. During a mean follow-up periods of 12 (6; 37.25) months, the overall mortality rate was 17.7% (23 deaths); the death + transplantation index was 20% (n = 26). All the types of DMCAA were found to be significantly related to prognosis: in the DMCAA group, the mortality rate was 21.5% versus 7.8% in the non-DMCAA group (odds ratio 3.22; 95% confidence interval, 1.02 to 10.21; p < 0.05). CONCLUSION: MSCT with the assessment of delayed contrast enhancement (and simultaneous CT coronary angiography) can be used for the non-invasive diagnosis of myocarditis in patients with DCM, including that in the presence of contraindications to MRI. DMCAA correlates with the presence of myocarditis, its activity, the degree of functional disorders, and prognosis.
Asunto(s)
Cardiomiopatía Dilatada , Corazón , Miocarditis , Miocardio/patología , Tomografía Computarizada Espiral/métodos , Adulto , Anciano , Biopsia/métodos , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/fisiopatología , Angiografía Coronaria/métodos , Diagnóstico Diferencial , Ecocardiografía/métodos , Femenino , Corazón/diagnóstico por imagen , Corazón/fisiopatología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Miocarditis/diagnóstico , Miocarditis/fisiopatología , Gravedad del Paciente , Pronóstico , Reproducibilidad de los ResultadosRESUMEN
The spatial organization and conformational flexibility of neuropeptides of the gallatostatin family was studied by the method of theoretical conformational analysis. It was found that the spatial organization of neuropeptides allows the realization of folded helical structures of the C-terminal pentapeptide, and the flexibility of neuropeptides is due to a great number of low-energy states in the N-terminal fragment of the molecule.
Asunto(s)
Neuropéptidos/química , Secuencia de Aminoácidos , Enlace de Hidrógeno , Modelos Moleculares , Datos de Secuencia Molecular , Estructura Secundaria de Proteína , TermodinámicaRESUMEN
The comparative study of the spatial organization and conformational properties of NmU-8 neuropeptide and its modified analogs with available experimental data has been carried out. The effect of amino acids point mutation on conformational states of native neuropeptide has been discussed. The low-energy conformations responsible for neuropeptide contractile activity was revealed.
Asunto(s)
Neuropéptidos/química , Modelos Moleculares , Neuropéptidos/genética , Mutación Puntual , Conformación ProteicaRESUMEN
Effects induced in bilayer lipid membranes by amphotericin B and its alkyl derivatives was analysed. Inactivation of the antibiotic-dependent multichannel membrane conductance was discovered. Kinetics of membrane conductivity was shown to depend on the antibiotic concentration in the membrane. At concentrations between 10(-8) and 10(-7) M, the resulting conductance appeared to the transient. We suggest that the phenomenon of biphasic kinetics of membrane conductance is the result of a consecutive transformation of polyene channels in the membrane: half-pores are assembled on either side of membrane-nonconducting 1; two half-pores combine to build up a conducting channels-conducting 2, and the conducting channels are disassemled to monomers and nonconducting self-associated forms inside the membrane-disassembled state (nonconducting 3). To explain the transient characteristics of the induced conductance, it is proposed that the antibiotic, present in the solution under self-associated form, binds the membrane and forms pores, then dissociates in the bilayer in a non-active monomeric form. The existence of definite monomers and nonconducting self-associated forms of amphotericin B molecules inside the membrane was estimated from the dependence of kinetic conductance of lipid membranes of amphotericin B and its alkyl derivatives, when the antibiotics are washed out from aqueous medium. Equilibrium between different antibiotic assemblies inside the membrane was demonstrated by the kinetics of conductance decrease following washing the antibiotic. Using circular dichroism measurements, we observed that amphotericin B alkyl derivatives were in self-associated form being susceptible to form pores across cholesterol-containing membranes. The phenomenon of biophasic kinetics was observed only in the cholesterol-containing membrane. The substitution of membrane cholesterol for ergosterol provides monotonic kinetics of membrane conductance at any antibiotic concentration.
Asunto(s)
Anfotericina B/análogos & derivados , Anfotericina B/farmacología , Conductividad Eléctrica , Canales Iónicos/metabolismo , Membranas/metabolismo , Antibacterianos/farmacología , Colesterol/química , Dicroismo Circular , Relación Dosis-Respuesta a Droga , Ergosterol/química , Concentración de Iones de Hidrógeno , Canales Iónicos/efectos de los fármacos , Cinética , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/metabolismo , Lípidos de la Membrana/metabolismo , Potenciales de la Membrana/efectos de los fármacos , Membranas/química , Fosfolípidos/química , Cloruro de Potasio/farmacología , Soluciones , Relación Estructura-Actividad , Factores de Tiempo , Agua/químicaRESUMEN
Modern conceptions of the physicochemical properties of dimethylsulfoxide and polyene antibiotics are reviewed. The results of investigations of independent and mutual effects of polyene antibiotics and dimethylsulfoxide on membrane permeability were analysed. The own experimental data of radioprotective and antitumour action of complex dimethylsulfoxide-polyene antibiotics are presented, and the perspectives of their use in medicine are described.
Asunto(s)
Antibacterianos , Dimetilsulfóxido , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/uso terapéutico , Permeabilidad de la Membrana Celular/efectos de los fármacos , Dimetilsulfóxido/química , Dimetilsulfóxido/farmacología , Dimetilsulfóxido/uso terapéutico , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Macrólidos , Protectores contra Radiación/química , Protectores contra Radiación/farmacología , SolventesRESUMEN
The structures and conformational peculiarities of five members of the callatostatin family of neuropeptides, i.e. Leu- and Met-callatostatins, ranging in size from 8 to 16 amino acid residues have been investigated by a theoretical conformational analysis method. A comparative analysis of the conformational flexibilities of Met-callatostatin with those of the hydroxylated analogues, [Hyp2]- and [Hyp3]-Met-callatostatin has been carried out. Helically packed C-terminal pentapeptide in the structure of all investigated Leu-callatostatins are shown to be possible. The reason for the great number low-energy conformers for the callatostatin N-terminus is discussed.
Asunto(s)
Neuropéptidos/química , Secuencia de Aminoácidos , Animales , Simulación por Computador , Modelos Moleculares , Datos de Secuencia Molecular , Oligopéptidos/química , Fragmentos de Péptidos/química , Conformación Proteica , TermodinámicaRESUMEN
The conformational aspects of interaction of the antibiotic X537A at complexation with serotonin, hydration of molecules and their complex were studied by the methods of theoretical conformational analysis and Monte-Carlo.