Fluororuby as a marker for detection of acute axonal injury in rat spinal cord

Axonal damage is a common pathological consequence of spinal cord injury. Previous studies have detected axonal injury with silver stains for degeneration or immunohistochemistry for alterations in components such as beta-amyloid precursor protein, neurofilament or ubiquitin. Fluororuby has recently been introduced as a neuronal tracer in studies of spinal cord injury and regeneration. Our study was carried out to determine whether Fluororuby can be used to identify injured axons and monitor the time course of axonal damage. Adult rats underwent needle puncture injury to the white matter in the midline and lateral spinal cord at T11. At the same time, 0.05 microl of Fluororuby was injected into the cord at the same sites. After survival times ranging from 6 h to 3 weeks, spinal cords were cut into longitudinal frozen sections and examined with confocal microscopy. Fluororuby was found to label key features of axonal injury including axonal swelling, retraction balls and disrupted axons. Damaged axons close to the injury site were consistently labeled within 6 h, with indications of swollen and disconnected axons spreading further from the site during the first week. Fewer injured axons were labeled after 1 week survival, but the marker revealed longer distances of degenerating axons both distal and rostral to the injury site. Our findings indicate that Fluororuby is a quick, sensitive, reliable and technically simple fluorescent marker for early stages of acute axonal injury and degeneration.     

Cyto- and chemoarchitecture of the cerebral cortex of an echidna (Tachyglossus aculeatus). II. Laminar organization and synaptic density

We have examined the distribution and morphology of neurons immunoreactive for nonphosphorylated neurofilament protein (SMI-32 antibody), calcium-binding proteins (parvalbumin, calbindin, calretinin), and neuropeptide Y as well as neurons reactive for NADPH diaphorase in the cerebral cortex of the Australian short-beaked echidna (Tachyglossus aculeatus). We have also studied synaptic morphology and density in S1 somatosensory cortex and assessed parameters associated with metabolic activity of the cerebral cortex (vessel volume density, mitochondrial volume density, and mitochondrial numerical density) in semi- and ultrathin sections. SMI-32 immunoreactivity was found mostly in layer V pyramidal neurons in selected cortical regions (S1, PV, V1, A). These neurons often showed atypical morphology compared with therian cortex. Neurons immunoreactive for calcium-binding proteins were broadly similar in both morphology and distribution to those seen in therian cortex, although calretinin-immunoreactive neurons were rare. Both Gray type I and Gray type II synapses could be identified in echidna S1 cortex and were similar to those seen in therian cortex. Peak synaptic density was in upper layer IV, followed by layer I, lower layer II, and upper layer III. Most synapses were of type I (72%), although types I and II were encountered with similar frequency in lower layer II and upper layer III. The capillary volume fraction values obtained for the echidna (from 1.18% in V1 to 1.34% in S1 cortex) fall within the values for rodent cortex. Similarly, values for mitochondrial volume fraction in echidna somatosensory cortex (4.68% +/- 1.76%) were comparable to those in eutherian cortex.     

Synthesis and activity of substituted 4-(indazol-3-yl)phenols as pathway-selective estrogen receptor ligands useful in the treatment of rheumatoid arthritis

Pathway-selective ligands for the estrogen receptor (ER) inhibit NF-kappaB-mediated inflammatory gene expression causing a reduction of cytokines, chemokines, adhesion molecules, and inflammatory enzymes. SAR development of a series of 4-(indazol-3-yl)phenols has led to the identification of WAY-169916 an orally active nonsteroidal ligand with the potential use in the treatment of rheumatoid arthritis without the classical proliferative effects associated with estrogens.     

UK Food Standards Agency Optimal Nutrition Status Workshop: environmental factors that affect bone health throughout life

The UK Food Standards Agency (FSA) convened a group of expert scientists to discuss and review UK FSA- and Department of Health-funded research on diet and bone health. This research focused on the lifestyle factors that are amenable to change and may significantly affect bone health and the risk of osteoporotic fracture. The potential benefits of fruits and vegetables, meat, Ca, vitamins D and K and phyto-oestrogens were presented and discussed. Other lifestyle factors were also discussed, particularly the effect of physical activity and possible gene-nutrient interactions affecting bone health.     

An abnormal retinal projection to the lateral posterior nucleus in micrencephalic rats

The retinofugal projections of albino rats made micrencephalic by prenatal exposure to the cytotoxic teratogen methylazoxymethanol acetate (MAM Ac) have been examined. The only abnormality noted was an increased projection to the lateral posterior nucleus of the thalamus in rats exposed to MAM Ac on embryonic day 15. The relatively normal retinofugal projections were surprising in view of the extensive damage induced by prenatal exposure to this drug.     

Efficacy of "high-intensity" blue-light and "standard" daylight phototherapy for non-haemolytic hyperbilirubinaemia

We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy.     

双能量X线骨质密度测量仪监测小儿下肢骨延长骨矿物质的变化

目的　在儿童骨延长的患儿中 ,为了能够有效地控制骨延长的速率 ,达到骨延长的目的 ,采用双能量X线骨质密度测量仪 (dualenergyX Rayabsorptiometry ,DEXA)监测延长断端骨矿含量 (bonemineralcontent,BMC)的变化。方法　 30例患儿中有 5 0处下肢作了骨延长术 ,平均年龄10 .9岁 (5～ 17岁 ) ,引起短肢的病因不同。术后 7～ 10d开始行骨延长 ,每次延长 0 .2 5mm ,每天 4次。牵引延长期间每周扫描一次 ,拆除外固定器后每 2周扫描一次到术后 2年。DEXA扫描的分辨率是 1mm× 1mm ,扫描速度 30mm/s。比较不同延长时期中骨矿含量的变化。分析不同病因和不同外固定器之间骨矿含量变化的差别。结果　不同固定器之间骨矿含量的差别无著性意义。根据骨延长区BMC增加速率 ,将患儿分为快速组、一般组和慢速组。快速组每日BMC增加速率为 0 .3%～ 0 .6 % ,新骨生长快速 ;一般组每日BMC增加 0 .1%～ 0 .3% ,新骨中速生长 ;慢速组每日增加 <0 .1% ,新骨生成缓慢。骨矿化速率与原发病因相关。结论　DEXA能动态监测骨延长中新生骨的骨矿含量的变化 ,根据骨矿含量变化的程度 ,能够调整骨延长的速率 ,从而达到预期骨延长的目的。