Fabry disease - current data and therapeutic approaches.

Fabry disease represents an X-linked inherited disorder resulting in the accumulation of globotriaosylceramide (Gb3). This review explains the clinical manifestations and the possible therapies for this condition. Fabry disease is considered the second most frequent lysosomal storage disease. More than 1000 mutations of the galactosidase alpha (GLA) gene associated with this disorder have been identified. Pain, either episodic crises or chronic pain, is one of the earliest symptoms in Fabry disease. Gastrointestinal, ocular, ear or skeletal manifestations may complete the clinical picture. Cardiac and renal involvements are the most severe complications leading to organ failure and death. The cerebrovascular lesions may result in severe symptoms including stroke at younger ages. The diagnosis of Fabry disease may be put by enzymatic assays of the α-galactosidase A (AGAL-A) activity in plasma or leukocytes but genetic analysis remains the "gold standard" in identifying the precise mutation and even guiding the treatment. Enzyme replacement therapy (ERT) was the first step in treating subjects with Fabry disease. It proved important decrease of the number of sever clinical events and reduction of symptoms. Chemical chaperone therapy has many advantages including oral administration and was already approved in Europe and US, but it is suitable only for subjects with amenable mutations. Gene therapies (either ex vivo or in vivo) promise to represent a new era for many disorders including Fabry disease, the preliminary data being encouraging. Although many steps were taken in understanding the pathogeny of Fabry disease, future research is needed especially in the field of therapeutic approaches.

Investigating the association between anxiety symptoms and mood disorder in high-risk offspring of bipolar parents: a comparison of Joint and Cox models.

BACKGROUND: Anxiety is associated with mood disorders including bipolar disorder. Two statistical modelling frameworks were compared to investigate the longitudinal relationship between repeatedly measured anxiety symptoms and the onset of depression and bipolar disorder in youth at confirmed familial risk. METHODS: Prospectively collected data on 156 offspring of a parent with confirmed bipolar disorder participating in the Canadian Flourish high-risk offspring longitudinal cohort study were used for this analysis. As part of the research protocol at approximately yearly visits, a research psychiatrist completed the HAM-A and a semi-structured diagnostic research interview following KSADS-PL format. Diagnoses using DSM-IV criteria were made on blind consensus review of all available clinical information. We investigated two statistical approaches, Cox model and Joint model, to evaluate the relationship between repeated HAM-A scores and the onset of major depressive or bipolar disorder. The Joint model estimates the trajectory of the longitudinal variable using a longitudinal sub-model and incorporates this estimated trajectory into a Cox sub-model. RESULTS: There was evidence of an increased hazard of major mood disorder for high-risk individuals with higher HAM-A scores under both modelling frameworks. After adjusting for other covariates, a one-unit increase in log-transformed HAM-A score was associated with a hazard ratio of 1.74 (95% CI (1.12, 2.72)) in the Cox model compared to 2.91(95% CI (1.29, 6.52)) in the Joint model. In an exploratory analysis there was no evidence that family clustering substantially affected the conclusions. CONCLUSIONS: Estimated effects from the conventional Cox model, which is often the model of choice, were dramatically lower in this dataset, compared to the Joint model. While the Cox model is often considered the approach of choice for analysis, research has shown that the Joint model may be more efficient and less biased. Our analysis based on a Joint model suggests that the magnitude of association between anxiety and mood disorder in individuals at familial risk of developing bipolar disorder may be stronger than previously reported.

Diagnóstico de obstrucción de catéter peritoneal mediante peritoneografía fluoroscópica / Diagnosis of obstruction peritoneal catheter by fluoroscopic peritoneography

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Peritonitis causada por Pantoea agglomerans en diálisis peritoneal / Peritonitis caused by Pantoea agglomerans in peritoneal dialysis

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Factores de riesgo asociados a hernias en diálisis peritoneal / Risk factors associated with hernias on peritoneal dialysis

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Peritonitis causada por Paracoccus yeei en diálisis peritoneal / Paracoccus yeei peritonitis in peritoneal dialysis

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Interrelations between hepatic stellate cells and immune system cells in patients with hepatocellular carcinoma.

OBJECTIVE: Our aim was to identify potential correlations between activated hepatic stellate cells (HSCs) and immune system's cells in patients with viral C hepatocellular carcinoma, by quantifying the percentage of activated HSCs, T-lymphocytes, natural killer cells and B-lymphocytes, in three distinct regions: tumor, transition area and the vicinity tissue (2-5 mm). PATIENTS AND METHODS: We prospectively included 20 samples prelevated at necropsy from patients with HCC and C viral infection. We assessed the percentage of alpha-smooth muscle actin (α-SMA), CD45RO, NK1 and CD20 expression using immunohistochemistry and a semi-quantitative scoring method. RESULTS: We found an inverse correlation between the number of α-SMA-positive HSCs and the number of NK1-positive cells in tumor (p=0.0007), in the transition area/tumor capsule (p=0.024) and in the vicinity tissue (p=0.038). Regarding T-lymphocytes, we have also identified an inverse correlation with the number of α-SMA-positive HSCs in tumor (p=0.0036), in the transition area/tumor capsule (p=0.034) and in the vicinity tissue (p=0.047). We found no correlation between the number of activated HSCs and the number of CD20-positive cells in all three examined areas. CONCLUSIONS: The analysis of HSCs activity within specified areas of tumoral liver tissue may lead to new perspectives in early diagnosis of relapses and in the development of future neoadjuvant therapies.

Cysteine protease and cystatin expression and activity during soybean nodule development and senescence.

BACKGROUND: Nodules play an important role in fixing atmospheric nitrogen for soybean growth. Premature senescence of nodules can negatively impact on nitrogen availability for plant growth and, as such, we need a better understanding of nodule development and senescence. Cysteine proteases are known to play a role in nodule senescence, but knowledge is still fragmented regarding the function their inhibitors (cystatins) during the development and senescence of soybean nodules. This study provides the first data with regard to cystatin expression during nodule development combined with biochemical characterization of their inhibition strength. RESULTS: Seventy nine non-redundant cysteine protease gene sequences with homology to papain, belonging to different subfamilies, and several legumain-like cysteine proteases (vacuole processing enzymes) were identified from the soybean genome assembly with eighteen of these cysteine proteases actively transcribed during nodule development and senescence. In addition, nineteen non-redundant cystatins similar to oryzacystatin-I and belonging to cystatin subgroups A and C were identified from the soybean genome assembly with seven actively transcribed in nodules. Most cystatins had preferential affinity to cathepsin L-like cysteine proteases. Transcription of cystatins Glyma05g28250, Glyma15g12211, Glyma15g36180 particularly increased during onset of senescence, possibly regulating proteolysis when nodules senesce and undergo programmed cell death. Both actively transcribed and non-actively transcribed nodule cystatins inhibited cathepsin-L- and B-like activities in different age nodules and they also inhibited papain and cathepsin-L activity when expressed and purified from bacterial cells. CONCLUSIONS: Overlap in activities and specificities of actively and non-actively transcribed cystatins raises the question if non-transcribed cystatins provide a reservoir for response to particular environments. This data might be applicable to the development of strategies to extend the active life span of nodules or prevent environmentally induced senescence.

Burial survival of benthic macrofauna following deposition of simulated dredged material.

In many coastal regions, the disposal of dredged material constitutes the largest (albeit often localised) anthropogenic disturbance to the seabed. Impacts can be minimised by reducing the amount of sediment overburden on the bed at any one time allowing short-term recovery to proceed via the vertical migration of resident species. However, there is currently a limited understanding of the ability of such species to successfully vertically migrate. This study presents the findings of a field experiment to investigate the vertical migratory capability of temperate macroinvertebrate species following the placement of simulated dredged material. The relationships between vertical migration success with sediment characteristics (organic carbon and sand content) and placement depth were explicitly examined. While the polychaete worms Tharyx sp. A. and Streblospio shrubsolii showed poor vertical migration with only 6 cm of sediment overburden, the oligochaete Tubificoides benedii showed some recovery while the gastropod mollusc Hydrobia ulvae exhibited good migratory success, even with 16 cm of sediment overburden. While increases in sand content from 16% to 38% had no noticeable effect on vertical migration, increased sediment organic content from 0.8% to 3.3% detrimentally affected vertical migratory activity. The results support the theory that species' survival following sediment burial is trophic group-related. The relevance of these findings with respect to dredged material disposal management is discussed.

Macrofaunal recolonisation following the intertidal placement of fine-grained dredged material.

Dredged material is increasingly being regarded as a potential resource, and one of its many uses is to create and/or improve intertidal habitats (i.e. beneficial use). However, uncertainties over the longer-term environmental consequences of such schemes have, to date, limited the practice to small-scale applications in UK waters. This paper studies the macrofaunal recolonisation of fine-grained dredged material recharged concurrently at four adjacent recharge areas along the south-east coast of the UK in order to facilitate predictions regarding the recolonisation of comparable schemes and, thereby, to promote effective environmental management. During the 2-year study period, the four recharge areas were distinctly different in terms of their environmental characteristics, primarily wave exposure and bed level. These conditions resulted in different macrofaunal recolonisation rates and community structures. While the low-level, wave-sheltered area experienced rapid recolonisation, the process was delayed until 12 months post-recharge at the relatively wave-exposed areas. Bed level differences resulted in distinctly different communities in wave-sheltered areas but not under wave-exposed conditions. While we are unable to separate the effects of individual environmental variables on recolonisation, these results provide general conclusions as to the importance of environmental conditions on resulting macrofaunal communities.