Multi-system neurological disease is common in patients with OPA1 mutations

Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal ‘dominant optic atrophy plus’ variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44–6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08–4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment

Eco-friendly aqueous core surface-modified nanocapsules

In this work, positively charged nanocapsules have been developed for potential ocular delivery exploiting the deposition of PLA onto the droplet surface of a W/O nanoemulsion prepared by the reversed procedure of the PIT method. PLA in combination with different amounts of various oils and surfactants have been studied in order to select the best formulation for polymeric nanocapsule preparation. The traditional visual observation together with the Turbiscan® technology were exploited in order to identify the best combination of polymer/oil for nanocapsule preparation. Two different primary surfactants (Span® 60 and Span® 80) have been tested to select their influence on the field of existence of the nanoemulsion by the construction of the pseudoternary phase diagrams. Cationic hybrid NC have been prepared by the addition of a coating layer of DDAB. The physico-chemical and morphological properties of all the prepared nanocapsules have been evaluated and compared by PCS, DSC and AFM. Therefore, positively charged nanocapsules can be easily prepared by a simple eco-friendly technique that exploits biocompatible materials avoiding a large input of mechanical energy as a potential ocular delivery systems for hydrophilic compounds or gene materials

Formacao e Biodisponibilidade de Residuos de Piretroides- 14C Ligados ao Solo.

Observou-se a degradacao de cipermetrina-14C e de permetrina-14C em amostras de solo Gley Humico e Latossolo Vermelho-Amarelo, em condicoes de laboratorio. A degradacao a 14CO2 foi principalmente biologica, pois foi muito reduzida em amostras de solos esterilizados, analisadas durante 35 dias de incubacao dos piretroides nos solos. A formaçao de resíduos nao-extraiveis de cipermetrina-14C ou de seus metabolitos nos solos representou, apos 120 dias, 47% do radiocarbono recuperado no solo Gley Humico, e 91% no solo Latossolo Vermelho-Amarelo. Parte desses residuos foram liberados sob forma de 14CO2 apos adicao de solo nao-tratado, que serviu de fonte de inoculo, indicando biodisponibilidade do residuo ligado pela acao microbiana do solo.Made available in DSpace on 2011-04-09T12:14:29Z (GMT). No. of bitstreams: 1 pab08fev92.pdf: 252909 bytes, checksum: 698c8ed0504c2c530b1c1e5efd6de1ad (MD5) Previous issue date: 2001-08-23199

Risk of sudden death and outcome in patients with hypertrophic cardiomyopathy with benign presentation and without risk factors

Patients with hypertrophic cardiomyopathy (HC) are reported to have a mortality rate of about 1.0% per year, and those patients without sudden death risk factors and with no or mild symptoms are generally considered to have a benign clinical presentation. However, the risk of sudden death and the outcome in this latter subgroup have not been investigated systematically and remain unresolved. We assessed the risk of sudden death and outcome in 653 consecutive patients with HC without risk factors and with no or mild symptoms. Over a median follow-up of 5.3 years, 35 patients (5.4%) died of HC-related causes. Mean age at death was 46 \ub1 20 years in patients who died suddenly and 66 \ub1 15 and 72 \ub1 9 years, respectively, in patients who died of heart failure or stroke. Event rate was 0.6% per year for sudden death, 0.2% per year for heart failure death, and 0.1% per year for stroke-related death. Sudden death risk was independently and inversely related to age, and risk of heart failure or stroke death was directly related to age (p = 0.020). At 10 years after the initial evaluation, sudden death risk was 5.9%, with sudden death rate being the lowest (0.3% per year) in patients with normal left atrial dimension ( 6440 mm). In conclusion, in patients with HC without conventional risk factors and with no or mild symptoms, the risk of sudden death was not negligible, with an event rate of 0.6% per year. Heart failure and stroke-related death were less common and largely confined to older patients. These results underscore the need for a more accurate assessment of the sudden death risk in patients with HC. \ua9 2014 Elsevier Inc. All rights reserved