"Real world effectiveness of cerliponase alfa in classical and atypical patients. A case series".

INTRODUCTION: Late infantile neuronal ceroid lipofuscinosis is an autosomal recessive disease caused by mutations in the CLN2/TPP1 gene, with secondary enzyme deficiency. In classical phenotypes, initial symptoms include seizures and delayed language development between 2 and 4 years of age. This article describes the presentation of CLN2 disease in a cohort of Colombian patients, as well as the impact of treatment on the course and progression of the disease. METHODS: Case series report of 8 patients with a confirmed diagnosis of neuronal ceroid lipofuscinosis treated with cerliponase alfa who remained on clinical and paraclinical follow-up for up to 24 months before and after treatment. RESULTS: An atypical phenotype, associated with initial symptoms and late diagnosis, was present in 5/8 patients. The most frequent symptoms were seizures and developmental delay, with age of onset at 24 months (classical phenotype) and 48 months (atypical phenotype). A novel mutation (c.1438G > A) was found in two siblings. All of the patients received cerliponase alfa, and there were no serious adverse events. No decline in the clinical status greater than 2 points on Hamburg, Weill Cornell and CNL2 clinical assessment scale was observed during follow-up after treatment initiation. CONCLUSION: This is the first case series reported for neuronal ceroid lipofuscinosis patients in Colombia. In contrast with other reports, the majority of cases reported here displayed an atypical phenotype. Our study highlights the importance of early diagnosis and timely initiation of therapy, which is a feasible therapy, well tolerated by patients and accepted by caregivers in this country, generating a positive impact in the quality of life of CLN2 patients and on disease outcome.

Neodymium nanoparticles: biosynthesis and structural analysis.

Small metallic nanoparticles of neodymium are obtained by a facile route based on the biosynthesis and the pH conditions that demonstrate the possibility of obtaining particles of 1-8 nm. The size is controlled by synthesis conditions. Smaller clusters were obtained with pH = 5, while for pH = 10 evidences of nanorods productions are found and this opens the perspective to use this rare-earth element for zero and one dimensional based applications. Using transmission electron microscopy techniques, the size distribution and structure are studied. Density functional theory-based calculations allow the determination of the lowest energy configuration, which is based on the hexagonal bulk symmetry. Theoretical models are used to simulate the high resolution transmission electron microscopy to identify the experimental image, determining that the synthesized nanoparticles reach the lowest energy hexagonal configurations.

Dosimetric assessment of radon in a vegetable system.

An alpha-dose calculation due to radon uptake in anthers of Tradescantia, clone 4430, has been performed. Probability distribution density of the dose in the pollen mother cells was calculated by means of a model that simulates the interaction of separate alpha-particles with these cells. It is shown that alpha-radiation from either radon or its decay products surrounding the buds does not reach pollen mother cells because of the short-range alpha-particles. However, it is suggested that radon diffuses through the gap structure of the bud to the anther from which a radon-gas adsorption process takes place. Absorbed-dose calculations in the anther are discussed as well as their relationship to the experimental results of micronucleus induction in pollen mother cells. The radon concentration interval used (0.85 kBq m(-3)-98.16 kBq m(-3)) is equivalent to the exposure to an average environmental radon concentration (40 Bq m(-3)) for 2.3 months or 22.1 years, respectively. The lowest radon concentration to induce micronuclei was 12.1 kBq m(-3), which is 15 times in excess of that adopted for old buildings in Canada.

Genetic effects observed in tetrads of Tradescantia induced by radon.

Inflorescences of Tradescantia clone 4430 were exposed to different concentrations of radon (Rn) gas (0.85, 12.10, 36.50 and 98.16 kBq/m3) from plants placed in an acrylic chamber that received radon from a container with pitchblende (containing uranium mineral). The exposure time was 24 h, afterwards the plants were left for 6 h in water and constantly aerated. Positive control plants were irradiated with gamma rays (0.8 Gy) and negative control plants received ambient air only (the background measurement had a mean of 0.38 kBq/m3). Micronuclei (MCN) in the tetrads induced by alpha particles emitted from Rn were tabulated and a linear concentration response was obtained. The potency of radon to induce MCN from the slope of the regression line was 0.13 MCN/kBq/m3 of alpha-radiation. Radon could reach the anthers by diffusion through the aerial spaces within the buds.

Evidence for an effect of exposure to low levels of alpha particle irradiation in larval cells of Drosophila as measured in the wing-spot test.

Larvae of Drosophila were exposed to a range of concentrations of alpha particles from 3 to 318 mRad, and genetic effects measured in the wing-spot test. The results were positive, and evidence of a linear relationship between exposure and response observed. The induction of chromosome breakage is suggested by the significantly higher frequency of twin spots in the treated series compared with controls.

SOS induction by low activity alpha sources: microdosimetric considerations.

The SOS response to alpha-radiation was measured using two Escherichia coli strains with differential repair capabilities. Monolayers of exponentially growing cells, placed on cellulose acetate filters, were exposed to an electrodeposited 252Cf alpha source to total doses from 46 to 165 cGy at a dose-rate of 0.8 cGy/min. A mean alpha energy of 2.9 MeV, with a corresponding LET of 133 keV/micrometer (for water) was attained by means of a filter placed between the bacterial culture and the radioactive source. Owing to the low fluences ranging from 0.013 to 0.037 alpha-particles/cell and short irradiation times, calculations of the estimated number of irradiated cells were done to obtain the total absorbed doses by the culture. The results show that in spite of the low doses, the damage was sufficient to induce the SOS function in one of the strains used (PQ37). Nevertheless in another strain IN88, lacking double strand break repair and which should be more sensitive, SOS induction could not be observed, probably due to the killing effect of the high LET radiation.