Dietary beauvericin and enniatin B exposure cause different adverse health effects in farmed Atlantic salmon.

The extensive use of plant ingredients in novel aquafeeds have introduced mycotoxins to the farming of seafood. The emerging enniatin B (ENNB) and beauvericin (BEA) mycotoxins have been found in the novel aquafeeds and farmed fish. Little is known about the potential toxicity of ENNs and BEA in farmed fish and their feed-to-organ transfer. Atlantic salmon (Salmo salar) pre-smolt (75.3 ± 8.10 g) were fed four graded levels of spiked chemical pure ENNB or BEA feeds for three months, in triplicate tanks. Organismal adverse health end-point assessment included intestinal function (protein digestibility), disturbed hematology (red blood cell formation), bone formation (spinal deformity), overall energy use (feed utilization), and lipid oxidative status (vitamin E). Both dietary BEA and ENNB had a low (<∼0.01%) transfer to organs (kidney > liver > brain > muscle), with a higher transfer for ENNB compared to BEA. BEA caused a growth reduction combined with a decreased protein digestion and feed conversion rate- ENNB caused a stunted growth, unrelated to feed utilization capacity. In addition, ENNB caused anemia while BEA gave an oxidative stress response. Lower bench-mark dose regression assessment showed that high background levels of ENNB in commercial salmon feed could pose a risk for animal health, but not in the case of BEA.

"The fact that I can be in front of others, I am used to being a bit behind": how assistive activity technology affects participation in everyday life.

PURPOSE: This article explores the experiences of mobility-impaired individuals participating in leisure-time physical activities through the use of assistive activity technology (AAT). Its purpose is to highlight how these experiences affect participation in everyday life. This article provides new knowledge about the participation of this population in leisure-time physical activities. METHODOLOGY: Qualitative, semi-structured interviews were analysed according to the stepwise-deductive-inductive approach. During the analysis, self-determination theory (SDT) emerged as a theoretical tool for understanding how social context affects motivation as an interacting concept in the participation of leisure-time physical activity (LTPA). FINDINGS: Individuals with mobility impairments who use AAT for leisure-time physical activities experience opportunities to participate in ordinary and valued activities that allow them to improve their social positions. Further, use of AAT provided the informants with opportunities to alter their daily routines, enjoy time on their own and enhance their personal awareness. Having opportunities to use AAT independently is experienced as a recognition of their individuality. Thus, this article highlights a new aspect of participation as performing a socially valued activity in solitude. CONCLUSIONS: How technology provides opportunities for social interaction influences the informants' experiences and motivation to use technology. LTPA through the use of AAT promotes mastery and personal dignity, thereby revealing a new aspect of participation as being involved in an independent activity. IMPLICATIONS FOR REHABILITATION The allocation system for assistive activity technology requires knowledge about personal motivation for assistive activity technology use and the connection between leisure-time physical activity and social participation. Additional education about and understanding of motivational factors for assistive technology use is needed.

Day activity centres - work for people with intellectual disabilities: a norwegian perspective.

BACKGROUND: Although there is a broad political consensus in Norway that the government should uphold the principles of "full employment" and "work for all", the majority of people with intellectual disabilities in Norway spend their days in segregated work arrangements or at day activity centres. OBJECTIVE: The aim of the current study was to explore what constitutes work and work roles for people with intellectual disabilities and severely limited verbal communication abilities who attend a day activity centre. METHOD: A qualitative ethnographic research design was adopted, and the data were gathered through observing the participants and through conducting conversational interviews with the staff members and the participants with intellectual disabilities. Data were analysed with a hermeneutic approach. RESULTS: The findings showed that even though participants with intellectual disabilities engaged in specific work roles at the day activity centre, these work roles did not constitute work as it is ordinarily conceptualised and valued in society. CONCLUSION: Despite the very real enjoyment that the participants derive from participating in organised occupation, the work that they do has little status or value, and the activity centre itself is not a satisfactory workplace for people with intellectual disabilities.

Preload changes by positive pressure ventilation can be used for assessment of left ventricular systolic function.

BACKGROUND: Assessment of preload independent left ventricular function with conductance volumetry is traditionally accomplished by inflating a balloon in the inferior caval vein. Our aim was to investigate if a similar change in preload could be achieved by positive pressure ventilation with large tidal volume. METHODS: Conductance volumetry generating left ventricular pressure-volume loops was used in seven pentobarbital-anesthetized pigs. Changes in preload recruitable stroke work were studied, comparing the effects of inferior vena cava occlusion (IVCO) or large tidal volume (LTV). Cardiodepression was induced by halothane anesthesia and halothane + phenylephrine, and stimulation by epinephrine infusion. RESULTS: Although the decreasis in left ventricular end diastolic volume was slightly less with LTV (16.5 +/- 1.7 ml, mean +/- SEM) than with IVCO (22.4 +/- 1.7 ml) (P < 0.0001) the PRSW-slopes showed a high degree of correlation (r=0.80, P < 0.0001). Although peak tracheal pressures increased significantly to 27.8 +/- 0.9 mmHg during LTV, esophageal pressures (used as an indicator of pericardial pressure) were unchanged. CONCLUSIONS: Positive pressure ventilation with LTV is similar to IVCO in creating transient changes in preload, necessary for assessment of left ventricular systolic function. This observation was valid also during drug-induced cardiac depression and stimulation. The preload recruitable stroke work used for this validation was shown to be a reliable and stable method.

Interpretation of radial pulse contour during fentanyl/nitrous oxide anesthesia and mechanical ventilation.

BACKGROUND: Peripheral arterial blood pressure is not a reliable substitute for proximal aortic pressure. Recognition of this phenomenon is important for correct appreciation of cardiac afterload. Our aim was to evaluate the utility of the radial pulse wave to better understand ventriculo-vascular coupling during anesthesia. METHODS: We observed the differences between aortic systolic pressure (AoSAP, tipmanometry) and radial systolic pressure in 15 patients, (including two women) aged 53-78 years, before coronary artery bypass surgery. We studied the induction of anesthesia with fentanyl (20 microg kg-1), moderate volume loading, and thereafter the addition of 70% nitrous oxide. The circulatory effects of mechanical ventilation were studied by doubling the tidal volumes. Pulse wave contours were assessed by calculation of radical and aortic augmentation indices (AI), which measure the second systolic pressure peak. RESULTS: Radial systolic pressure was higher than AoSAP in the control situation (8+/-2 mmHg), and this SAP gradient increased further with fentanyl (12+/-2 mmHg). The gradient persisted throughout the study, but was partially reduced by volume loading and nitrous oxide, respectively. Radial augmentation index was the only parameter remaining in a stepwise multivariate model to explain the variance in the SAP gradient (r2=0.48). Radial augmentation index also correlated with aortic pulse pressure (r2=0.71). Mechanical ventilation had significant and similar effects on pulse wave augmentation both in the aorta and in the radial artery, and did not affect the radial to aortic SAP gradient. CONCLUSION: These elderly coronary patients had stiff vasculature (high aortic AI) and considerable pulse wave reflection, which was beneficially delayed by fentanyl. Changes in the radial pulse wave augmentation during mechanical ventilation were mainly a result of cyclic changes in the stroke volume, and were seldom associated with an increased systolic pressure gradient from the aorta to the radial artery.

Can a clinically useful aortic pressure wave be derived from a radial pressure wave?

BACKGROUND: The information contained in arterial pressure waveforms is probably underused by most clinicians who manage critically ill patients. It is not generally known that an aortic pressure wave can be synthesized by applying a generalized transfer function to the radial arterial pressure wave. We validated a commercially available system, SphygmoCo (PWV Medical, Sydney). METHODS: Ascending aortic pressure waves were synthesized and comparisons were made between the synthesized aortic waveforms, the measured aortic and radial arterial waveforms. Ascending aortic pressure waves (catheter-tip manometer) and radial artery pressure waves (short fluid-filled catheter) were recorded simultaneously in 12 patients with angina pectoris (age 62-76 years) undergoing cardiac catheterization. Patients were studied at rest, following midazolam, sublingual nitroglycerin and during Valsalva manoeuvres. RESULTS: Both midazolam and nitroglycerin lowered mean arterial pressure but nitroglycerin caused a more selective decrease in the measured and synthesized aortic systolic pressures than in the radial artery pressure. The synthesized aortic systolic pressure was less, by 6-8 mm Hg (SD 2-3) and the synthesized aortic diastolic pressure greater, by 4 mm Hg (SD 2). Despite these differences in pulse pressure, the synthesized waveform tracked the measured waveform before and during interventions. CONCLUSIONS: By deriving an aortic waveform from the radial pulse, monitoring of left ventricular afterload can improve without more invasive means.

NGF, NT-3 and Trk C mRNAs, but not TrkA mRNA, are upregulated in the paraventricular structures in experimental hydrocephalus.

OBJECTS: This study was designed to detect possible alterations in the expression of neurotrophins and trks in kaolin-induced hydrocephalus by in situ hybridization. METHODS AND RESULTS: Sixteen rats were treated by injection of 25 mg kaolin suspended in 0.1 ml of physiological saline into the cisterna magna. Four rats were injected with saline and served as controls. The kaolin-treated rats were divided into two groups studied 1 and 4 weeks after treatment. Rats were anesthetized and killed, and their brains were rapidly dissected and frozen. DNA oligonucleotide probes for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and trkA, trkB, and C were labeled with [(35)S]dATP using terminal deoxyribonucleotidyl transferase for in situ hybridization. Hydrocephalic brains were also classified according to the degree of ventricular enlargement. The results observed were as follows. (1) The medial septal and striatal NGF mRNA levels increased with severity in animals. (2) Hippocampal trkB and BDNF mRNA levels increased with time in animals with moderate ventricular enlargement. (3) Expression of hippocampal trkB, trkC, and NT-3 mRNA increased in animals with moderate ventricular enlargement, while it apparently decreased in the large ventricular enlargement group reaching normal ranges. (4) In the corpus callosum there was an apparent increase in NGF, NT-3 and trkC mRNA, but not in trkA, in hydrocephalic animals. NT-3 EIA confirmed the presence of NT-3 protein increases in corpus callosum. It is therefore possible that simultaneous NGF, NT-3, and trkC receptor upregulation occurred in glial elements of the white matter. CONCLUSIONS: These results demonstrate that neurotrophins and their receptors are overexpressed in many damaged structures of the severely hydrocephalic brain. There were discrepancies in the distribution of NGF and trkA mRNA, and we hypothesize that NGF mRNA in the damaged white matter structure might be due to the reduced availability of other receptors, such as the low-affinity NGF receptors.

Mutual induction of TGFbeta1 and NGF after treatment with NGF or TGFbeta1 in grafted chromaffin cells of the adrenal medulla.

Chromaffin cells have been recognized for their ability to transform into sympathetic ganglion-like cells in response to nerve growth factor (NGF) or to stimulation of other neurotrophic factors. Transforming growth factor beta (TGFbeta) family members have been shown to potentiate the effect of different trophic factors. The aim of this study was to investigate if TGFbeta may influence NGF-induced neuronal transformation and regulation of NGF, TGFbeta1, and their receptors in the adult rat chromaffin tissue after grafting. Intraocular transplantation of adult chromaffin tissue was employed and grafts were treated with TGFbeta1 and/or NGF. Graft survival time was 18 days after which the grafts were processed for TGFbeta luciferase detection assay, NGF enzyme immunoassay, or in situ hybridization. In grafts stimulated with NGF, increased levels of TGFbeta1 and TGFbeta1 mRNA were detected. When grafts instead were treated with TGFbeta1, enhanced levels of NGF protein were found. Furthermore, a positive mRNA signal corresponding to the transforming growth factor II receptor (TbetaRII) was found in the chromaffin cells of the normal adrenal medulla as well as after grafting. No increase of TbetaRII mRNA levels was detected after transplantation or after TGFbeta1 treatment. Instead a reduction of TbetaRII mRNA expression was noted after NGF treatment. NGF stimulation of grafts increased the message for NGF receptors p75 and trkA in the chromaffin transplants. Grafts processed for evaluations of neurite outgrowth were allowed to survive for 28 days and were injected weekly with NGF and/or TGFbeta1. NGF treatment resulted in a robust innervation of the host irides. TGFbeta1 had no additive effect on nerve fiber formation when combined with NGF. Combined treatment of NGF and anti-TGFbeta1 resulted in a significantly larger area of reinnervation. In conclusion, it was found that NGF and TGFbeta1 may regulate the expression of each other's protein in adult chromaffin grafts. Furthermore, TbetaRII mRNA was present in the adult rat chromaffin cells and became downregulated as a result of NGF stimulation. Although no synergistic effects of TGFbeta1 were found on NGF-induced neurite outgrowth, it was found that TGFbeta1 and NGF signaling are closely linked in the chromaffin cells of the adrenal medulla.

External ventricular drainage catheters: effect of surface heparinization on bacterial colonization and infection.

Surface heparinization of central venous catheters has earlier been shown to reduce the frequency of bacterial colonization and septicaemia. The present study was undertaken to investigate the benefit of surface heparinization of external ventricular drainage (EVD) catheters in relation to bacterial colonization, as measured by bacterial growth and examination by a 16S-rRNA PCR assay, of catheters and of samples of cerebrospinal fluid (CSF). Ninety-eight heparinized and one hundred unheparinized EVD catheters from the same batch of catheters were used. Twenty point five percent of the heparinized and 22.8% (p = 0.63) of the unheparinized EVD catheters were colonized with bacteria. Culture of CSF, which is the definition of clinical infection in this study, yielded growth in 10.3% of patients with heparinized and in 6.3% (p = 0.18) of those with unheparinized catheters. PCR examination yielded positive signal in 31.3% of patients with heparinized catheters and in 37.7% (p = 0.061) of patients without (CSF and catheters). In the subgroup of patients with subarachnoid haemorrhages, there was a tendency, though not statistically significant, towards a lowered frequency of colonization with 23.1% for heparinized and 33.3% (p = 0.31) for unheparinized catheters. PCR examination did not contribute any further to the diagnostic procedure in the patients concerned. The EVD catheters are skin-penetrating devices and contamination from the skin flora is common. Skin cultures, obtained after skin disinfection and insertion of catheters, showed growth of bacteria in 62% of the patients.

Changes in brain nerve growth factor levels and nerve growth factor receptors in rats exposed to environmental enrichment for one year.

This study examined the effects of long-term differential rearing on levels of brain nerve growth factor, its receptors, and their relationships to cognitive function. Adult rats (two months old) were placed into either enriched or standard housing conditions where they remained for 12 months. Animals from the enriched condition group had significantly higher levels of nerve growth factor in hippocampus, visual and entorhinal cortices compared with animals housed in isolated condition. Immunohistochemical analysis of brain tissue from the medial septal area revealed higher staining intensity and fibre density with both the low-affinity and the high-affinity nerve growth factor receptors. Enriched rats performed better than isolated rats in acquisition of spatial learning and had lower locomotion scores in the open field. These results provide further evidence that experimental stimulation results in increased production of trophic factors and structural reorganization in specific brain regions known to be involved in cognitive function.

Effects of environmental enrichment on cognitive function and hippocampal NGF in the non-handled rats.

In this study we examine whether exposure to differential housing after weaning would counteract the effects of postnatal handling (H) or nonhandling (NH) treatment by affecting learning and memory processes in young rats. In addition, we seek to determine if experience in enriched environment would alter hippocampal nerve growth factor (NGF) levels which is one of the factors known to be involved in the regulation of the survival and differentiation of developing basal forebrain neurones. Rats were either exposed to handling treatment, or left undisturbed starting day 1 after birth through day 21. After weaning on day 22, we exposed half of the H rats and half of the NH rats to environmental enrichment for 60 days. The other respective half of the rats was housed in isolated environmental condition (IC). Behavioural measures were taken in open field test, and spatial water maze test. Exposure to enriched environment following postnatal handling and nonhandling increased hippocampal NGF levels, and improved cognitive function in the both groups, with NH rats being more responsive to the effects of enrichment. Our results suggest that environmental enrichment has the potential to prevent or reduce the cognitive and neurochemical deficits in the adult animals associated with nonhandling.

Aortic and radial pulse contour: different effects of nitroglycerin and prostacyclin.

UNLABELLED: Through vasorelaxation, nitroglycerin is considered to reduce arterial wave reflection and to cause a more pronounced decrease in systolic pressure in the aorta (AoSAP) than in the radial artery (RaSAP). Our aim was to study how radial and aortic pulse wave configurations and the gradient (RaSAP-AoSAP) were affected by nitroglycerin and by prostacyclin, and how these changes correlated to stroke volume, vascular resistance/impedance, and wave reflection. Prostacyclin has not been studied in this context and was chosen because, in contrast to nitroglycerin, it does not reduce stroke volume and reduces afterload by arteriolar dilation. In 18 patients (53-81 yr old; heavily premedicated before coronary artery surgery), blood pressure was measured in both the radial artery and the ascending aorta (tipmanometry), and cardiac output was measured by thermodilution. Mean arterial pressure was reduced stepwise with each drug (mean total decrease 10-12 mm Hg). The initial RaSAP-AoSAP gradient (6 mm Hg) was increased 10 mm Hg by nitroglycerin and was not affected by prostacyclin. The nitroglycerin-induced increase in systolic gradient RaSAP-AoSAP correlated to decreases in stroke volume index, mean arterial pressure, and arterial elastance, but not to decrease in pulse wave augmentation. Thus, decreases in stroke volume index, not wave reflection, seem to be the main reason for an increased RaSAP-AoSAP when nitroglycerin is used in the elderly, hypertensive patient. IMPLICATIONS: We studied ascending aortic and radial pulse contours in patients scheduled for coronary artery surgery. The radial pulse wave can be used for interpretation of central hemodynamic changes during nitroglycerin-, but not prostacyclin-, induced hypotension.

Presence of vitronectin and activated complement factor C9 on ventriculoperitoneal shunts and temporary ventricular drainage catheters.

OBJECT: The pathogenesis of cerebrospinal fluid (CSF) shunt infection is characterized by staphylococcal adhesion to the polymeric surface of the shunt catheter. Proteins from the CSF--fibronectin, vitronectin, and fibrinogen--are adsorbed to the surface of the catheter immediately after insertion. These proteins can interfere with the biological systems of the host and mediate staphylococcal adhesion to the surface of the catheter. In the present study, the presence of fibronectin, vitronectin, and fibrinogen on CSF shunts and temporary ventricular drainage catheters is shown. The presence of fragments of fibrinogen is also examined. METHODS: The authors used the following methods: binding radiolabeled antibodies to the catheter surface, immunoblotting of catheter eluates, and scanning force microscopy of immunogold bound to the catheter surface. The immunoblot showed that vitronectin was adsorbed in its native form and that fibronectin was degraded into small fragments. Furthermore, the study demonstrated that the level of vitronectin in CSF increased in patients with an impaired CSF-blood barrier. To study complement activation, an antibody that recognizes the neoepitope of activated complement factor C9 was used. The presence of activated complement factor C9 was shown on both temporary catheters and shunts. CONCLUSIONS: Activation of complement close to the surface of an inserted catheter could contribute to the pathogenesis of CSF shunt infection.

Localized expression of BMP and GDF mRNA in the rodent brain.

Expression of BMP- and GDF-related factors within the transforming growth factor-beta (TGF-beta) superfamily was examined in the rat and mouse brain by in situ hybridization. Strong signals were obtained in neurons for GDF-1 and GDF-10. GDF-1 is expressed at postnatal day 6 in the cerebral cortex, hippocampal CA1 through CA3 neurons, while only weakly expressed by cells in the dentate gyrus. Granule cells and neurons in the polymorph layer of the dentate gyrus are GDF-1-positive, as are the majority of neurons in the cortex. GDF-10 shows a distinct pattern of expression: At P6, strong labelling was seen in the superficial layers of cortex, notably in the posterior cingulate cortex, and in CA3 and dentate gyrus. From postnatal day 21, GDF-1 expression is strong in the hippocampus, cortex, and thalamic nuclei, while GDF-10 expression becomes restricted to the granule cell layer in the dentate gyrus. In contrast, OP-1 expression is restricted throughout development to cells of the medial habenular nucleus, choroid plexus, and leptomeninges. The markedly different expression patterns of these BMPs suggest they serve separate functions in the brain.

Aspects on the optimal photon beam energy for radiation therapy.

The selection of optimal photon beam energy is investigated both for realistic clinical bremsstrahlung beams and for monoenergetic photon beams. The photon energies covered in this investigation range from 60Co to bremsstrahlung and monoenergetic beams with maximum energies up to 50 MeV. One head and neck tumor and an advanced cervix tumor are investigated and the influence of beam direction is considered. It is shown that the use of optimized intensity modulated photon beams significantly reduces the need of beam energy selection. The most suitable single accelerator potential will generally be in the range 6-15 MV for both superficially located and deep-seated targets, provided intensity-modulated dose delivery is employed. It is also shown that a narrow penumbra region of a photon beam ideally should contain low-energy photons (< or =4 MV), whereas the gross tumor volume, particularly when deep-seated targets are concerned, should be irradiated by high-energy photons. The regions where low photon energies are most beneficial are where organs at risk are laterally close to the target volume. The situation is completely changed when uniform or wedged beams are used. The selection of optimal beam energy then becomes a very important task in line with the experience from traditional treatment techniques. However, even with a large number of uniform beam portals, the treatment outcome is substantially lower than with a few optimized intensity-modulated beams.

Optimal electron and combined electron and photon therapy in the phase space of complication-free cure.

The possibility of using intensity-modulated high-energy electrons beams alone or in combination with photon beams to treat tumours located at depths from 5 cm to 25 cm has been investigated. A radiobiologically based optimization algorithm using the probability of complication-free tumour control has been used to calculate the optimal dose distributions. Two different target volumes have been used; one advanced cervical cancer with locally involved lymph nodes and one astrocytoma in the upper brain hemisphere. Treatments with only electron beams and also combinations between electron and photon beams have been investigated. The dependence of the expected treatment outcome on the beam energy and directions was investigated, and to some extent on the number of beam portals. It is shown that the beam direction intervals resulting in a high expected treatment outcome increase with increasing electron energy and also with some electron-photon combinations. For an eccentrically placed, not too deeply situated tumour surrounded by sensitive normal tissue it is shown that the expected treatment outcome can be improved by using electron beams in combination with photon beams compared with using two photon beams, and using two electron beams results in almost as high an expected treatment outcome. The possibility of improving the dose conformity from electron beams by adding photon fields parallel or orthogonal to the electron beams is demonstrated.

Potentiating interactions between morphogenetic protein and neurotrophic factors in developing neurons.

mRNA for bone morphogenetic protein receptor type II (BMPR-II) was mapped to different neurons in peripheral ganglia and spinal cord of the chicken embryo. The expression of this serine/threonine kinase receptor partially overlaps with that of tyrosine kinase receptors Trk and Ret. Biological activities of osteogenic protein-1 (OP-1), a documented ligand for BMPR-II, were tested in explanted embryonic chicken ganglia and dissociated ganglionic neurons. OP-1 had only a limited stimulatory effect on neuronal survival. However, OP-1 combined with either neurotrophin-3 (NT-3, a relative of nerve growth factor) or glial cell line-derived neurotrophic factor (GDNF) potentiated neuronal survival three- to fourfold. We also show that OP-1 strongly potentiates nerve fiber outgrowth from ganglia stimulated with NT-3 or GDNF. Signaling by BMPR-II in neurons may potentiate the tyrosine kinase pathway activated by NT-3 and GDNF. The data suggest that morphogenetic proteins may modulate neurotrophic activities during neuronal development and plasticity.

A non-invasive system for delivering neural growth factors across the blood-brain barrier: a review.

Intraventricular administration of nerve growth factor (NGF) in rats has been shown to reduce age-related atrophy of central cholinergic neurons and the accompanying memory impairment, as well as protect these neurons against a variety of perturbations. Since neurotrophins do not pass the blood-brain barrier (BBB) in significant amounts, a non-invasive delivery system for this group of therapeutic molecules needs to be developed. We have utilized a carrier system, consisting of NGF covalently linked to an anti-transferrin receptor antibody (OX-26), to transport biologically active NGF across the BBB. The biological activity of this carrier system was tested using in vitro bioassays and intraocular transplants; we were able to demonstrate that cholinergic markers in both developing and aged intraocular septal grafts were enhanced by intravenous delivery of the OX-26-NGF conjugate. In subsequent experiments, aged (24 months old) Fischer 344 rats received intravenous injections of the OX-26-NGF conjugate for 6 weeks, resulting in a significant improvement in spatial learning in previously impaired rats, but disrupting the learning ability of previously unimpaired rats. Neuroanatomical analyses showed that OX-26-NGF conjugate treatment resulted in a significant increase in cholinergic cell size as well as an upregulation of both low and high affinity NGF receptors in the medial septal region of rats initially impaired in spatial learning. Finally, OX-26-NGF was able to protect striatal cholinergic neurons against excitotoxicity and basal forebrain cholinergic neurons from degeneration associated with chemically-induced loss of target neurons. These results indicate the potential utility of the transferrin receptor antibody delivery system for treatment of neurodegenerative disorders with neurotrophic substances.

Overstimulation of nerve growth factors in postinfectious and autoimmune diseases.

Nerve growth factor (NGF) in cerebrospinal fluid was measured by ELISA in ten children with postinfectious diseases and in five children with diseases suggested to be of autoimmune etiology. Three groups of patients were studied: (1) those with moderately elevated concentrations (50.67 +/- 17.02 pg/mL, mean and SEM), (2) those with high concentrations (mean 424.25 +/- 125.41 pg/mL, mean and SEM), and (3) those with enormously high concentrations (mean 2,745 +/- 1,819.46 pg/mL, mean and SEM). We suggest that CSF-NGF could be used as an immunologic marker of an ongoing CNS process. Uncontrolled signaling of NGF receptors may lead to long-term inflammatory and autoimmune responses, which in turn can lead to disease.