Amiloidose cardíaca: cardiomiopatia infiltrativa com comportamento hemodinâmico restritivo ­ relato de caso / Cardiac amyloidosis: infiltrative cardiomyopathy with restrictive hemodynamic behavior ­ case report

A amiloidose é uma condição rara que descreve um grupo heterogêneo de distúrbios que cursam com a deposição extracelular de agregados proteicos fibrilares em tecidos e órgãos. Relata-se aqui o caso de paciente do sexo masculino, com 76 anos de idade, que, há 2 meses, iniciou quadro progressivo de dispneia aos mínimos esforços. Na investigação, observou-se aumento cardíaco global, e o ecocardiograma evidenciou cardiopatia restritiva infiltrativa e derrame pericárdico. Pela elevada suspeição clínica, foi solicitada ressonância magnética cardíaca, que foi altamente sugestiva de amiloidose cardíaca. Dessa forma, assim como no caso relatado, o acometimento cardíaco possui como principal forma de manifestação o tipo miocardiopatia restritivo, sendo um quadro de insuficiência cardíaca crônica com etiologia de difícil diagnóstico em pacientes acima de 50 anos, com prognóstico bastante reservado. Assim, apesar de permanecer como um desafio diagnóstico para o clínico, sua hipótese deve sempre ser aventada na ausência de outra causa que justifique tais achados (AU)

Early Left Ventricular Systolic Dysfunction Detected by Two-Dimensional Speckle-Tracking Echocardiography in Young Patients with Congenital Generalized Lipodystrophy.

PURPOSE: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by the absence of functional adipocytes resulting in ectopic lipid storage, metabolic disorders and early cardiovascular disease. Two-dimensional speckle-tracking (2D-STE) allows the detection of early abnormalities in myocardial function. We aimed to evaluate myocardial deformation in a large sample of CGL patients using 2D-STE. PATIENTS AND METHODS: A cross-sectional study of 22 patients with CGL and 22 healthy subjects, matched for sex and age, was conducted from 2013 to 2018. All participants had undergone standard conventional echocardiography (ECHO) and 2D-STE. Determination of blood glucose, lipids, insulin, and leptin were performed in all CGL patients. RESULTS: In the CGL group the mean age was 14.6±10.7 years where 68.2% (n=15) were younger than 18 years old. All the patients had hypoleptinemia, 95.4% (21/22) low HDL-c, 86.4% (19/22) hypertriglyceridemia, 68.2% (15/22) diabetes, 50% (11/22) hepatic steatosis, 41% (9/22) insulin resistance, 41% (9/22) hypercholesterolemia, and 18.2% (4/22) hypertension. ECHO showed that 36.6% (8/22) of CGL patients presented diastolic dysfunction, 31.8% (7/22) left ventricular hypertrophy (LVH), 27.3% (6/22) increased left atrial volume index (LAVI), and 18.2% (4/22) increased left ventricular systolic diameter (LVDS) but normal ejection fraction (EF), whether using 2D-STE, 68.2% (15/22) of CGL patients showed abnormal global longitudinal strain (GLS) (p<0.01), and in almost LV segments. Positive association between abnormal GLS and A1c (r=0.57, p=0.005), glucose (r=0.5, p=0.018) and basal insulin (r= 0.69, p= 0.024), and negative association with leptin (r = -0.51, p = 0.005) were found in these patients. CONCLUSION: The 2D-STE revealed precocious left ventricular systolic dysfunction in a young CGL population with normal systolic function by ECHO. Early exposure to common metabolic abnormalities as insulin resistance, hyperglycemia, and hypoleptinemia must be involved in myocardial damage in these patients.

Anti-Candida albicans Activity of Thiazolylhydrazone Derivatives in Invertebrate and Murine Models.

Candidiasis is an opportunistic fungal infection with Candida albicans being the most frequently isolated species. Treatment of these infections is challenging due to resistance that can develop during therapy, and the limited number of available antifungal compounds. Given this situation, the aim of this study was to evaluate the antifungal activity of four thiazolylhydrazone compounds against C. albicans. Thiazolylhydrazone compounds 1, 2, 3, and 4 were found to exert antifungal activity, with MICs of 0.125⁻16.0 µg/mL against C. albicans. The toxicity of the compounds was evaluated using human erythrocytes and yielded LC50 > 64 µg/mL. The compounds were further evaluated using the greater wax moth Galleria mellonella as an in vivo model. The compounds prolonged larval survival when tested between 5 and 15 mg/kg, performing as well as fluconazole. Compound 2 was evaluated in murine models of oral and systemic candidiasis. In the oral model, compound 2 reduced the fungal load on the mouse tongue; and in the systemic model it reduced the fungal burden found in the kidney when tested at 10 mg/kg. These results show that thiazolylhydrazones are an antifungal towards C. albicans with in vivo efficacy.

In vivo and in vitro activity of a bis-arylidenecyclo-alkanone against fluconazole-susceptible and -resistant isolates of Candida albicans.

OBJECTIVES: Candida albicans is a commensal organism and opportunistic pathogen associated both with superficial (mucosal and cutaneous) and systemic infections. Extensive use of antifungal agents has led to reduced susceptibility to the few existing drugs, which has encouraged the search for novel antifungal agents. Therefore, the present study investigated the antifungal activity of 2,6-bis[(E)-(4-pyridyl)methylidene]cyclohexanone (PMC) against C. albicans. METHODS: The in vitro activity of PMC was evaluated against C. albicans. Additionally, an invertebrate infection model in Caenorhabditis elegans as well as two infected murine models of oral and systemic candidiasis were used to determine the antifungal efficacy of PMC in vivo. RESULTS: Minimum inhibitory concentrations (MICs) of PMC ranged from 4-32µg/mL against nine clinical and two reference C. albicans isolates. Interestingly, PMC inhibited filamentation in vitro at subinhibitory concentrations similar to fluconazole. PMC also showed low toxicity against murine macrophages and human erythrocytes. In the invertebrate infection model, PMC was efficient in prolonging survival of C. elegans infected with C. albicans SC5314. Treatment with PMC was efficient both in murine models of systemic and oral candidiasis and was similar to that observed with conventional drug treatments (nystatin and fluconazole). CONCLUSIONS: The results of this study indicate the therapeutic potential of PMC as it was able to inhibit filamentation of C. albicans in vitro. These alterations to the fungi by PMC resulted in a reduction of oral and systemic infection in mice. In conclusion, we present promising evidence of the anticandidal activity of PMC in vitro and in vivo.