Screening for health-related quality of life and its determinants in Fabry disease: A cross-sectional multicenter study

BACKGROUND Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by α-galactosidase A (α-Gal A) deficiency. The progressive accumulation of globotriaosylceramide results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. In order to improve health care of FD-patients, knowledge of its predictors is important. The aim of our study was to evaluate health-related quality of life (HrQol) in FD and to identify its independent determinants by exploring a wide range of demographic, social and clinical parameters. RESULTS In this cross-sectional multicenter study, 135 adult patients with FD were recruited at three specialized European centers in Germany and Switzerland. Demographics, social status and clinical parameters as well as data on HrQol (EQ5D, EQ VAS) and depression were collected by means of self-reporting questionnaires and confirmed by medical records. HrQol and its predictors were evaluated by univariate and multivariate regression analyses. The study population consisted of 78 female and 57 male FD patients (median age 48 yrs) of whom 80.7% (N = 109) were on enzyme replacement therapy (ERT) and 10.4% (N = 14) were on chaperone treatment. Univariate analysis revealed various factors reducing HrQol such as age > 40 years, classic phenotype, organ involvement (kidney and heart disease, stroke/transient ischemic attack (TIA), gastrointestinal disturbances), depression, and burning limb pain. However, only the following factors were identified as independent predictors of decreased HrQol: classic phenotype, kidney and heart disease, stroke/TIA, depression, and burning limb pain. ERT and chaperone therapy were independent determinants of increased HrQol. CONCLUSIONS Modifiable factors, such as burning limb pain and depression, identified as independent predictors of HrQol-deterioration should be addressed in programs aiming to improve HrQol in FD. A multidisciplinary approach is essential in FD-patients since diverse organ involvement prominently compromises HrQol in affected patients. Our findings showed that the classic phenotype is a strong predictor of worsening HrQol

Lyso-GM2 Ganglioside: A Possible Biomarker of Tay-Sachs Disease and Sandhoff Disease

To find a new biomarker of Tay-Sachs disease and Sandhoff disease. The lyso-GM2 ganglioside (lyso-GM2) levels in the brain and plasma in Sandhoff mice were measured by means of high performance liquid chromatography and the effect of a modified hexosaminidase (Hex) B exhibiting Hex A-like activity was examined. Then, the lyso-GM2 concentrations in human plasma samples were determined. The lyso-GM2 levels in the brain and plasma in Sandhoff mice were apparently increased compared with those in wild-type mice, and they decreased on intracerebroventricular administration of the modified Hex B. The lyso-GM2 levels in plasma of patients with Tay-Sachs disease and Sandhoff disease were increased, and the increase in lyso-GM2 was associated with a decrease in Hex A activity. Lyso-GM2 is expected to be a potential biomarker of Tay-Sachs disease and Sandhoff disease

Indução do crescimento ovariano em Aegla uruguayana (Crustacea, Anomura, Aeglidae) mediante a incorporação de neuroreguladores ao alimento

O efeito estimulante da spiperona e da naloxana sob a maturação ovariana foram avaliados em fêmeas de Aegla uruguayana Schmitt, 1942 e, para isto, tais neuroreguladores foram incorporados ao alimento e administrados a uma dose de 10-8 mol/animal a cada sessão de alimentação. Fêmeas adultas foram coletadas com puçá em um arroio próximo à cidade de Salto, Província de Buenos Aires, Argentina. Dez fêmeas foram sacrificadas, medidas, pesadas e os seus ovários foram retirados e pesados para a determinação do índice gonadossomático (IG). As demais fêmeas (30) foram divididas em três grupos experimentais - (a) controle: alimentadas com pellets controle composto por ração para peixe - 34% de proteína e 43% de proteína; (b) spiperona: alimentadas com pellets controle enriquecidos com spiperona; (c) naloxana: alimentadas com pellets controle enriquecidos com naloxana. Após 7 semanas as fêmeas foram sacrificadas e avaliado o IG. Os ovários e o hepatopâncreas foram quantificados quanto aos níveis de lipídeos totais e colesterol. A naloxana produziu um aumento significativo nos níveis de lipídeos tanto nas gônadas como no hepatopâncreas em relação ao grupo controle. A spiperona produziu aumento significativo nos níveis de lipídeos nas gônadas e no hepatopâncreas e de colesterol no hepatopâncreas quando comparados ao controle. Os níveis de lipídeos foram significativamente menores na hemolinfa das fêmeas que foram alimentadas com pellets com spiperona e maiores nas fêmeas tratadas com naloxana quando comparadas as fêmeas que foram alimentadas apenas com ração. A spiperona e a naloxana, ao inibir os efeitos da dopamina e dos opióides endógenos, provavelmente causaram a secreção do hormônio estimulante das gônadas e a inibição do hormônio inibidor das gônadas, causando, portanto indução do desenvolvimento ovariano. Tal hipótese é reforçada pelos aumentos do índice gonadossomático verificado nestes grupos experimentais.The stimulatory effect of the spiperone and naloxone on the ovarian growth was evaluated in females of Aegla uruguayana Schmitt, 1942, being that these neuroregulators were incorporated to food and administrated at a dose of 10-8 mol/animal to each session food. Adult females were sampled with nets in a stream near the municipality of Salto, Province of Buenos Aires, Argentina. At the beginning of the experiment, 10 females were randomly selected, sacrificed, weighed and their ovaries were quickly dissected and weighed to serve as the initial control for evaluating the degree of ovarian growth (gonadosomatic index -GI). Others females (30) were divided in three experimental groups - (a) control: females fed on control pellets composed by fish food - 34% protein and 43% protein; (b) spiperone: females fed on pellets enriched with the dopaminegic antagonist spiperone; (c) naloxone: females fed on pellets enriched with the enkephalinergic antagonist naloxone. After seven week of experiment the females were sacrificed and evaluated the GI. The lipids and cholesterol levels of ovaries and hepatopancreas were quantified. Naloxone produced a significant increase of lipids levels in both ovaries and hepatopancreas in relation to control group. Spiperone caused significant increase of lipids levels at the gonads and hepatopancreas and cholesterol in hepatopancreas when compared with the control. The lipids levels were significantly lower in hemolymph of the females that were fed with pellets with spiperone and higher at the females treated with naloxone when compared to females that were fed only fish food. The spiperone and naloxone when inhibited the effect of the dopamine and endogenous opioids, probably caused the secretion of the gonad stimulating hormone and the inhibition of the gonad inhibiting hormone, therefore induction of the ovarian development. Such hypothesis can be strengthened for the increases of gonadosomatic indices in these experimental groups

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Not AvailableThe effect of methyl farnesoate (MF) administration on the vitellogenesis of the penaeoidean shrimp, Sicyonia ingentis, was studied. The short- and long-term treat ment e¡ects as well as the e¡ect of two MF injection re gimens (0.1 and 1.0 mg MF/injection) were evaluated. The studies were also carried out to understand the pat tern of vitellogenesis in eyestalk ablated adult and juve nile shrimps. Acombination of endpoints, haemolymph vitellogenin (Vg) levels, gonadosomatic index (GSI) and histology, was used to study the e¡ect of these treat ments. The GSI increased in all the MF-treated shrimp compared with the control shrimps. Although haemo lymphVg levels declined over the experimental period in all the treatments, the Vg levels decreased signi¢- cantly only in the short-term treatment with1.0 mg MF. Similarly, haemolymph protein level also declined over the experimental period in all the treatment groups. However, except in the long-term treatment with 0.1 mg MF, all treatments showed a signi¢cant decrease in haemolymph protein level. Conversely, in all eyestalk ablated adults and juveniles, haemolymphVg, total pro tein and GSI increased over the experimental period, all of which were higher than the concurrent control. The discrepancy in the vitellogenic pattern between MF treated and eyestalk ablated shrimp was possibly due to the di¡erence in the ovarian phase of the initial con trol. Although unilateral eyestalk ablation failed to in duce vitellogenesis in juveniles, bilateral ablation induced vitellogenesis, which indicates that juveniles are competent to undergo vitellogenesis.Not Availabl

Regional Differences in Methyl Farnesoate Production by the Lobster Mandibular Organ

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