Heart failure in patients is associated with downregulation of mitochondrial quality control genes.

BACKGROUND: Mitochondrial dysfunction is one of key factors causing heart failure. We performed a comprehensive analysis of expression of mitochondrial quality control (MQC) genes in heart failure. METHODS: Myocardial samples were obtained from patients with ischemic and dilated cardiomyopathy in a terminal stage of heart failure and donors without heart disease. Using quantitative real-time PCR, we analysed a total of 45 MQC genes belonging to mitochondrial biogenesis, fusion-fission balance, mitochondrial unfolded protein response (UPRmt), translocase of the inner membrane (TIM) and mitophagy. Protein expression was analysed by ELISA and immunohistochemistry. RESULTS: The following genes were downregulated in ischemic and dilated cardiomyopathy: COX1, NRF1, TFAM, SIRT1, MTOR, MFF, DNM1L, DDIT3, UBL5, HSPA9, HSPE1, YME1L, LONP1, SPG7, HTRA2, OMA1, TIMM23, TIMM17A, TIMM17B, TIMM44, PAM16, TIMM22, TIMM9, TIMM10, PINK1, PARK2, ROTH1, PARL, FUNDC1, BNIP3, BNIP3L, TPCN2, LAMP2, MAP1LC3A and BECN1. Moreover, MT-ATP8, MFN2, EIF2AK4 and ULK1 were downregulated in heart failure from dilated, but not ischemic cardiomyopathy. VDAC1 and JUN were only genes that exhibited significantly different expression between ischemic and dilated cardiomyopathy. Expression of PPARGC1, OPA1, JUN, CEBPB, EIF2A, HSPD1, TIMM50 and TPCN1 was not significantly different between control and any form of heart failure. TOMM20 and COX proteins were downregulated in ICM and DCM. CONCLUSIONS: Heart failure in patients with ischemic and dilated cardiomyopathy is associated with downregulation of large number of UPRmt, mitophagy, TIM and fusion-fission balance genes. This indicates multiple defects in MQC and represents one of potential mechanisms underlying mitochondrial dysfunction in patients with heart failure.

Reconstruction of the hand in Apert syndrome: two case reports and a literature review of updated strategies for diagnosis and management.

BACKGROUND: Apert syndrome is a set of complex malformations of the first brachial arch, with manifestations on the skull, face, hands and feet. At the level of the hand, the following signs are always present: complex syndactyly of the second, third and fourth digits with distal bone fusion; simple syndactyly of the fifth digit; foreshortened thumb with radial clinodactily; and symphalangism excluding the fifth digit. METHODS: The digital separation of an Apert hand should begin at 9 months of age and should be completed by 2 to 4 years of age. Our simplified approach consists of early bilateral surgery on border digits followed by unilateral separation of middle syndactily combined with thumb and digit osteotomies and bone grafting as required. RESULTS: Between 1995 and 2010 seven patients with Apert syndrome underwent reconstructive surgery of the complex hand syndactyly. The main target in our surgical strategy involved early bilateral separation of border digits, which started between 1 and 2 years of age. The unilateral middle syndactyly mass division with osteotomy of the thumb and other digits and bone grafting (as required) was carried out in later surgeries, which are usually completed by 4 years of age. The evaluation of the results was performed based on the functional results of the hand, morbidity, flap necrosis, skin graft lysis, postoperative range of motion in the small joints, gross grasp, pincer grasp, scar appearance, contractures of digits, and aesthetic outcome. CONCLUSION: As intended, this study proves the need for a complex surgical approach as early as possible with low revision rate, and acceptable functional and aesthetic outcome.