L/M speed-matching ratio predicts reading in children.

PURPOSE: Many behavioral studies have found impaired perception of dynamic visual stimuli in dyslexia and several neuroimaging studies have found reduced activation of the human motion area MT+ in dyslexia. These results are often interpreted as a magnocellular (MC) deficit in dyslexia. It has also been claimed that colored filters can help dyslexics to read. One defining feature of the MC-pathway is a greater weight for L-cone input than M-cone input, and at most very weak S-cone input. We measured the subjective speed matches between L-, M-, and S-cone isolating stimuli in good and poor readers. METHODS: Subjects performed a speed-matching task with drifting cone-isolating stimuli to find the point of subjective equality between two drifting patterns. Such a task is known to activate cortical area MT+, presumably via the MC-pathway. RESULTS: L- to M-cone speed-match ratios were negatively correlated with single-word (r=-0.46) and irregular-word reading (r=-0.56) but not with non-word reading. CONCLUSIONS: Results suggest that relative L-cone sensitivity within the MC-pathway may limit orthographic reading performance.     

Neridronate prevents bone loss in patients receiving androgen deprivation therapy for prostate cancer.

Today, androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer, although it presents important complications such as osteoporosis. Neridronate, a relatively new bisphosphonate, is able to prevent bone loss in patients with prostate cancer during androgen ablation. INTRODUCTION: Androgen-deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer. This therapy has iatrogenic complications, such as osteoporosis. The aim of our study was to evaluate the efficacy of neridronate, a relatively new bisphosphonate, to prevent bone loss during androgen ablation. MATERIALS AND METHODS: Forty-eight osteoporotic patients with prostate cancer, treated with 3-month depot triptorelina, were enrolled and randomly assigned to two different treatment groups: group A (n = 24) was treated with a daily calcium and cholecalciferol supplement (500 mg of elemental calcium and 400 IU cholecalciferol), and group B (n = 24) received in addition to the same daily calcium and cholecalciferol supplement, 25 mg of neridronate given intramuscularly every month. All patients also received bicalutamide for 4 weeks. Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of therapy; moreover, deoxypyridinoline (DPD) and bone alkaline phosphatase (BALP) were determined at the beginning, midway through, and at the end of the study. RESULTS: After 6 and 12 months, whereas patients treated only with calcium and cholecalciferol (group A) showed a marked bone loss, with increased levels of DPD and BALP compared with baseline values, patients treated also with neridronate (group B) had substantially unchanged levels of these markers. After 1 year of treatment, lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol (group A), whereas it did not change significantly at any skeletal site in patients treated also with neridronate (group B). No relevant side effects were recorded during our study. CONCLUSIONS: Neridronate is an effective treatment in preventing bone loss in the hip and lumbar spine in men receiving ADT for prostate cancer.     

Binding and retrograde transport of leukemia inhibitory factor by the sensory nervous system.

Leukemia inhibitory factor (LIF), a peptide growth factor with multiple activities, has recently been shown to support the generation and survival of sensory neurons in cultures of mouse neural crest and dorsal root ganglia (DRG). We have conducted binding experiments with 125I-LIF on cultures of DRG to determine the receptor distribution for LIF on these cells and found that at least 60% of the sensory neurons in the cultures bound 125I-LIF, all of which could be eliminated by the addition of unlabeled LIF. The other cells in the culture, which morphologically appeared to be Schwann cells, did not bind appreciable quantities of 125I-LIF. In order to investigate whether LIF is retrogradely transported to sensory neurons in vivo, 125I-LIF was injected into the footpads and gastrocnemius muscles of newborn and adult mice, following sciatic nerve ligation. Radioactivity accumulated in the distal portion of the sciatic nerve, indicating retrograde transport of LIF. Subsequent experiments on mice with unligated sciatic nerves showed that 125I-LIF is specifically transported into the sensory neurons of the DRG. There was no apparent transport of 125I-LIF into motor neurons in the spinal cord. These experiments demonstrate that LIF can specifically bind to and be transported by sensory neurons and further support the idea that LIF acts as a target-derived neurotrophic factor, analogous to NGF.     

Effects of antisense mediated inhibition of cathepsin K on human osteoclasts obtained from peripheral blood.

Cathepsin K is a cystein protease that displays a proteolytic activity against Type I collagen and is abundantly and selectively expressed in osteoclasts where it plays a critical role in bone degradation. Its direct role in bone tissue has been defined by knock-out mice studies and inhibiting strategies in animals models. However, direct proof of cathepsin K function in human osteoclast model in vitro is lacking. The aim of this study is to analyze cathepsin K expression and localization in human osteoclasts obtained from peripheral blood and to examine cathepsin K function in these cells by antisense oligodeoxynucleotide (AS-ODN) strategy. AS-ODN was added to the culture of osteoclast precursors induced to differentiate by RANKL and M-CSF. AS-ODN treatment produced a significant down-regulation of cathepsin K mRNA (>80%) and protein expression, as verified respectively by Real-time PCR and by immunocytochemistry or Western blot. The cathepsin K inhibition caused an impairment of resorption activity as evaluated by a pit formation assay ( p = 0.045) and by electron microscopy, while the acidification process was unaffected. We demonstrated that antisense strategies against cathepsin K are selectively effective to inhibit resorption activity in human osteoclasts, like in animal models.     

Transmitter Release Associated with Long-term Synaptic Depression in Rat Corticostriatal Slices

Using a corticostriatal slice preparation, we have recently shown that tetanic stimulation of the corticostriatal pathway produces long-term depression (LTD) of striatal excitatory synaptic transmission. In the present study we have analysed the relationship between LTD and the striatal release of different endogenous transmitters. Samples of perfusate were collected via a small cannula placed just above the surface of the striatal slice close to the recording electrode, and were analysed by HPLC. The high-frequency stimulation (100 Hz, three trains, 3 s duration, 20 s intervals) used to induce LTD caused a significant but transient increase in the release of both excitatory (aspartate and glutamate) and inhibitory (glycine and GABA) amino acid transmitters. Tetanic stimulation also produced a significant, but transient increase in the release of endogenous dopamine. We conclude that the tetanic stimulation of the corticostriatal pathway is able to induce a large but transient release of excitatory amino acids and of dopamine, whose participation in the induction of striatal LTD has been demonstrated previously. Moreover, the maintenance of this form of synaptic plasticity does not seem to require a sustained change in transmitter release.