Background & aims: Protein-energy wasting (PEW) is increasingly becoming a clinical problem in maintenance hemodialysis patients and guidelines call for nutritional interventions. Serum prealbumin (transthyretin) represents a critical nutritional marker positively correlated with patient survival and negatively correlated with morbidity. Nutritional counseling, oral supplementation as well as intradialytic parenteral nutrition (IDPN) are recommended to fight PEW, however clinical trials on their use are scarce. Methods: We conducted a prospective, multicenter, randomized, open-label, controlled, parallel-group Phase IV clinical trial in 107 maintenance hemodialysis patients suffering from PEW to assess the impact of IDPN on prealbumin and other biochemical and clinical parameters reflecting nutritional status. Patients randomized to the intervention group received standardized nutritional counseling plus IDPN three times weekly over 16 weeks followed by a treatment-free period of 12 weeks. The control group received standardized nutritional counseling only. Main trial inclusion criteria included moderate to severe malnutrition (SGA score B or C), maintenance hemodialysis therapy (3 times per week) for more than six months, and presence of two out of the following three criteria: albumin <35 g/L, prealbumin <250 mg/L, phase angle alpha <4.5 assessed by bioelectrical impedance analysis (BIA). Changes in serum prealbumin, albumin, transferrin, phase angle alpha, subjective global assessment (SGA) score and health-related quality of life using the 12-item short form health survey (SF-12) were investigated. Results: IDPN significantly increased prealbumin (p < 0.05), showing rapid rise within 16 weeks of treatment and sustained response thereafter. In the full analysis set (n ¼ 83), 41.0% of 39 patients receiving IDPN achieved a relevant (i.e., at least !15%) increase in prealbumin over baseline at week 4 compared to 20.5% of 44 patients in the control group. Considerably more patients with IDPN therapy achieved an increment of prealbumin >30 mg/L at week 16 (48.7% vs. 31.8%). Prealbumin response to IDPN therapy was more prominent in patients suffering from moderate malnutrition (SGA score B) compared to patients with severe malnutrition (SGA score C). Conclusions: The results of this trial demonstrate for the first time that IDPN therapy, given three times weekly in a 16-week short-term intervention, results in a statistically significant and clinically relevant

The administration of neurotrophins affects neuronal survival and growth, but less is known about their ability to modify the expression of growth associated genes following injury to CNS neurons. Here we characterize the effect of brain‐derived neurotrophic factor (BDNF) on mRNA levels for Tα1 α‐tubulin, and for GAP‐43, two genes whose expression levels in retinal ganglion cells (RGC) tend to correlate with growth. We first determined that most adult rat RGCs can retrogradely transport BDNF by injecting 125I‐BDNF into RGC target sites in vivo. We then used quantitative in situ hybridization to characterize the effect of axotomy, or axotomy and BDNF administration on mRNA levels for GAP‐43 and Tα1. Axotomy alone resulted in a general decrease in Tα1 α‐tubulin mRNA levels by 2 weeks, and elicited an increase in GAP‐43 mRNA levels in an average of 30% of surviving RGCs. The intravitreal administration of a single dose of BDNF (5 μg) to axotomized RGCs on the day of injury did not affect Tα1 α‐tubulin mRNA levels, but was followed by a moderate (approximately 80%), and short‐lasting enhancement of GAP‐43 mRNA levels in most RGCs during the first week after axotomy. No significant increase in GAP‐43 mRNA levels was observed when BDNF was injected into the uninjured eye. We conclude that BDNF specifically enhances GAP‐43 but not Tα1 mRNA levels in injured RGCs. Because BDNF is known to stimulate branch length of injured RGCs, we suggest that changes in the expression of GAP‐43, but not Tα1 tubulin, correlate with branching of injured neurons as opposed to long distance regrowth. J. Neurosci. Res. 47:561–572, 1997. © 1997 Wiley‐Liss, Inc.

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We describe the results of cell transplantation experiments performed to investigate mesodermal lineages in Drosophila melanogaster, particularly the lineages of the somatic muscles, the visceral muscles and the fat body. Cells to be transplanted were labelled by injecting a mixture of horseradish peroxidase (HRP) and fluorescein-dextran (FITC) in wild-type embryos at the syncytial blastoderm stage. For transplantation cells were removed from the ventral furrow, 8-12 min after the start of gastrulation, and individually transplanted into homotopic or heterotopic locations of unlabelled wild-type hosts of the same age. HRP labelling in the resulting cell clones was demonstrated histochemically in the fully developed embryo; histotypes could be distinguished without ambiguity. Mesodermal cells were already found to be committed to mesodermal fates at the time of transplantation. They developed only into mesodermal derivatives and did not integrate in non-mesodermal organs upon heterotopical transplantation. No evidence was found for commitment to any particular mesodermal organ at the time of transplantation. The majority of somatic muscle clones contributed cells to only one segment. However, clones were not infrequently distributed through two or even three segments. Clones of fat body cells were generally restricted to a small region. However, cells of clones of visceral musculature were widely distributed. With respect to the proliferative abilities of transplanted cells the clones were difficult to interpret due to the syncytial character of the somatic musculature and the fact that the organization of the other organs is poorly understood. Evidence from histological observations of developing normal embryos indicates only three mitoses for mesodermal cells. Clones larger than seven cells were not found when embryos were fixed previous to germ-band shortening; larger clones were found in the fat body and visceral musculature after fixing the embryos at the end of organogenesis. Quantitative considerations suggest that a few mesodermal cells might perform more than three mitoses.