Loss of neuronal GSK3ß reduces dendritic spine stability and attenuates excitatory synaptic transmission via ß-catenin.

Central nervous glycogen synthase kinase 3ß (GSK3ß) is implicated in a number of neuropsychiatric diseases, such as bipolar disorder, depression, schizophrenia, fragile X syndrome or anxiety disorder. Many drugs employed to treat these conditions inhibit GSK3ß either directly or indirectly. We studied how conditional knockout of GSK3ß affected structural synaptic plasticity. Deletion of the GSK3ß gene in a subset of cortical and hippocampal neurons in adult mice led to reduced spine density. In vivo imaging revealed that this was caused by a loss of persistent spines, whereas stabilization of newly formed spines was reduced. In electrophysiological recordings, these structural alterations correlated with a considerable drop in the frequency and amplitude of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-dependent miniature excitatory postsynaptic currents. Expression of constitutively active ß-catenin caused reduction in spine density and electrophysiological alterations similar to GSK3ß knockout, suggesting that the effects of GSK3ß knockout were mediated by the accumulation of ß-catenin. In summary, changes of dendritic spines, both in quantity and in morphology, are correlates of experience-dependent synaptic plasticity; thus, these results may help explain the mechanism of action of psychotropic drugs inhibiting GSK3ß.

How fit are children and adolescents with haemophilia in Germany? Results of a prospective study assessing the sport-specific motor performance by means of modern test procedures of sports science.

There are a lot of publications on the physical fitness of patients with haemophilia (PWH), however, most studies only reflect individual sport-specific motor capacities or focus on a single fitness ability. They involve small patient populations. In this respect principal objective of this study was to compare the physical fitness in all respects and the body composition of young PWH to healthy peers based on the most valid data we could get. Twenty-one German haemophilia treatment centres were visited from 2002 to 2009. PWH between 8 and 25 years were included. They performed a five-stage fitness test covering the sport-specific motor capacities for coordination, measured by one leg stand, strength, aerobic fitness and mobility as well as body composition. The patients' results were compared with age- and gender-specific reference values of healthy subjects. Two hundred and eighty-five PWH (mean age 13.2 ± 4.5 years, 164 PWH with severe disease) were included prospectively in the study. PWH are significantly below the reference values of healthy subjects in the one-leg stand test, the mobility of the lower extremity, the strength ratio of chest and back muscles and the endurance test. In body composition, the back strength and the mobility of the upper extremity PWH are significantly above the reference values. There are no significant differences in abdominal strength. In conclusion we found specific differences in different fitness abilities between PWH and healthy subjects. Knowing this, we are able to work out exercise programmes to compensate the diminished fitness abilities for our PWH.

Risk perception and psychological morbidity in men at elevated risk for prostate cancer.

OBJECTIVE: As prostate-specific antigen (psa) makes prostate cancer (pca) screening more accessible, more men are being identified with conditions that indicate high risk for developing pca, such as elevated psa and high-grade intraepithelial neoplasia (hgpin). In the present study, we assessed psychological well-being and risk perception in individuals with those high-risk conditions. METHODS: A questionnaire consisting of a psychological symptom survey, a trait risk-aversion survey, and a cancer-specific risk perception survey was administered to 168 patients with early-stage localized pca and 69 patients at high risk for pca (n = 16 hgpin, n = 53 psa > 4 ng/mL). Analysis of variance was used to examine differences in psychological well-being and appraisal of risk between the groups. RESULTS: Compared with the pca group, the high-risk group perceived their risk of dying from something other than pca to be significantly lower (p = 0.007). However, pca patients reported significantly more clinically important psychological symptoms. CONCLUSIONS: The identification of prostate conditions that predict progression to cancer might not result in the psychological symptoms commonly experienced by pca patients, but does appear to be related to a distorted perception of the disease's mortal risk. Patients with pca experience reduced psychological well-being, but better understand the risks of pca recurrence and death. Education on the risks and outcomes of pca can help at-risk men to view health assessments with reduced worry.

The allergen Bet v 1 in fractions of ambient air deviates from birch pollen counts.

BACKGROUND: Proof is lacking that pollen count is representative for allergen exposure, also because allergens were found in nonpollen-bearing fractions of ambient air. OBJECTIVE: We monitored simultaneously birch pollen and the major birch pollen allergen Bet v 1 in different size fractions of ambient air from 2004 till 2007 in Munich, Germany. METHODS: Air was sampled with a ChemVol high-volume cascade impactor equipped with stages for particulate matter (PM)>10 microm, 10 microm>PM>2.5 microm, and 2.5 microm>PM>0.12 microm. Allergen was determined with a Bet v 1-specific ELISA. Pollen count was assessed with a Burkard pollen trap. We also measured the development of allergen in pollen during ripening. RESULTS: About 93 +/- 3% of Bet v 1 was found in the PM > 10 microm fraction, the fraction containing birch pollen. We did not measure any Bet v 1 in 2.5 microm > PM > 0.12 microm. Either in Munich no allergen was in this fraction or the allergen was absorbed to diesel soot particles that also deposit in this fraction. Pollen released 115% more Bet v 1 in 2007 than in 2004. Also within 1 year, the release of allergen from the same amount of pollen varied more than 10-fold between different days. This difference was explained by a rapidly increasing expression of Bet v 1 in pollen in the week just before pollination. Depending on the day the pollen is released during ripening, its potency varies. CONCLUSION: In general, pollen count and allergen in ambient air follow the same temporal trends. However, because a 10-fold difference can exist in allergen potency of birch pollen, symptoms might be difficult to correlate with pollen counts, but perhaps better with allergen exposure.

Batrachotoxin block of fast axoplasmic transport in mammalian nerve fibers.

Batrachotoxin (BTX) irreversibly blocks fast axoplasmic transport in nerve in concentrations as low as 0.2 micromolar. The action of BTX was studied in cat sciatic nerves in vitro by measuring the rate of the crest outflow after injection of the L7 dorsal root ganglion with [3-H]leucine. Tetrodotoxin, which in itself does not affect fast axoplasmic transport, inhibited the blocking action of BTX. Unlike the BTX block of nerve and muscle membrane excitability brought about through increased permeability to sodium ion, the BTX block of fast axoplasmic transport occurs with or without sodium ion in the medium. High concentrations of calcium ion protected against the blocking action of BTX, while magnesium ion did not. An action of BTX on the transport mechanism inside the fibers was indicated by the small reduction of adenosine triphosphate plus creatine phosphate, which in itself did not account for the block of axoplasmic transport.

Metabolic dependence of fast axoplasmic transport in nerve.

Fast axoplasmic transport, shown in cat sciatic nerves by a crest of labeled activity after injection of the L7 ganglion with [(3)H]-leucine or [ (3)H]-lysine, was stopped within 15 minutes after death of the animals by bleeding. If the sciatic nerves were removed from the animals and placed in a chamber supplied with oxygen at 38 degrees centigrade, fast transport was sustained. Transport was rapidly blocked in similar in vitro preparations when the nerves were kept in a nitrogen environment. Fast axoplasmic transport is closely dependent upon oxibdative metabolism.

Fast transport system of materials in mammalian nerve fibers.

A fast transport system of materials is shown in cat sensory fibers of sciatic nerve. After injection of tritiated leucine into the lumbar seventh ganglia, the distribution of activity was measured in the sciatic nerves from 2 to 8 hours afterward. The distribution showed a crest of activity advancing down the fibers at a rate of approximately 410 millimeters per day. An intraaxonic locus of the activity was indicated by a block of the downflow induced by local freezing which causes the fibers to close off. Some of the activity in the nerve was due to free tritiated leucine, with most of it incorporated into polypeptide, soluble protein, and subcellular particulates.

Natural abundance carbon-13 nuclear magnetic resonance spectra of the canine sciatic nerve.

The proton-decoupled natural abundance carbon-13 nuclear magnetic resonance spectrum of the canine sciatic nerve is virtually identical to that of canine adipose tissue and markedly similar to that of liquid triolein. No resonances assignable to cholesterol, glycolipids, or sphingolipids are detectable in the sciatic nerve spectrum despite their abundance in the myelin sheath of this nerve. However, many such resonances are observed in lipid extracts of the nerve. Chronmatographic analysis of specimens of canine and rabbit sciatic nerve has revealed that these contain sufficient triglyceride to account quantitatively for the observed spectrum. Proton nuclear magnetic resonance and spin-labeling results for preparations containing myelin, especially those derived from the peripheral nerve, should be critically examined for experimental artifacts reflecting the triglyceride content.

Three steroid-binding globulins, their localization in the brain and nose, and what they might be doing there.

Steroid-binding globulins (SBGs) such as sex hormone binding globulin, corticosteroid binding globulin, and vitamin-D binding protein are receiving increasing notice as being actively involved in steroid actions. This paper reviews data of all three of these SBGs, focusing on their presence and possible activity in the brain and nose. We have found all three proteins in the brain in limbic areas such as the paraventricular (PVN) and supraoptic nuclei (SON) as well as other areas of the hypothalamus, hippocampus, and medial preoptic area. There is also evidence that all three are made in the PVN and SON, in conjunction with the neuropeptides oxytocin and vasopressin. The localization of these three SBGs is more variable within areas of the main olfactory area and the vomeronasal organ. However, all three are found in the mucus of these areas, suggesting that one of their functions is to sequester aerosol steroids, such as pheromones, and deliver them to sensory cells and then to deeper sensory areas. In this manuscript, we present multiple models of SBG action including: A) SBG binding to a membrane receptor, B) this SBG receptor being associated with a larger protein complex including cytoplasmic steroid receptors, C) when the SBGs binds to their SBG receptors, second messengers within the cells respond, D) after SBG binding to its receptor, it releases its associated steroid into the membrane's lipid bilayer, from which it gains access into the cell only when bound by an internal protein, E) the SBG, possibly with its bound SBG receptor, is internalized into the cell from which it can gain access to numerous organelles and possibly the cell's nucleus or F) associate with intracellular steroid receptors, G) SBGs produced in target cells are released from those cells upon specific stimulation, and H) according to the Free Steroid Hypothesis steroids released from the extracellular SBG passively diffuse across the plasma membrane of the cell. These models move the area of steroid endocrinology forward by providing important paths of steroid activity within many steroid target cells.

The origin and nature of beading: a reversible transformation of the shape of nerve fibers.

Nerve fibers which appear beaded (varicose, spindle-shaped, etc.) are often considered the result of pathology, or a preparation artifact. However, beading can be promptly elicited in fresh normal nerve by a mild stretch and revealed by fast-freezing and freeze-substitution, or by aldehyde fixating at a temperature near 0 degree C (cold-fixation). The key change in beading are the constrictions, wherein the axon is much reduced in diameter. Axoplasmic fluid and soluble components are shifted from the constrictions into the expansions leaving behind compacted microtubules and neurofilaments. Labeled cytoskeletal proteins carried down by slow axonal transport are seen to move with the soluble components and not to have been incorporated into and remain with, the cytoskeletal organelles on beading the fibers. Lipids and other components of the myelin sheath are also shifted from the constrictions into the expansions, with preservation of its fine structure and thickness. Additionally, myelin intrusions into the axons are produced and a localized bulging into the axon termed "leafing". The beading constrictions do not arise from the myelin sheath: beading occurs in the axons of unmyelinated fibers. It does not depend on the axonal cytoskeleton: exposure of nerves in vitro to beta, beta'-iminodipropionitrile (IDPN) disaggregates the cytoskeletal organelles and even augments beading. The hypothesis advanced was that the beading constrictions are due to the membrane skeleton; the subaxolemmal network comprised of spectrin/fodrin, actin, ankyrin, integrins and other transmembrane proteins. The mechanism can be activated directly by neurotoxins, metabolic changes, and by an interruption of axoplasmic transport producing Wallerian degeneration.

Cytoskeletal organelles and myelin structure of beaded nerve fibers.

Freshly removed cat peripheral nerves and lumbar spinal cord roots were prepared by freeze-substitution to study the form changes, cytoskeletal alterations and myelin structure in beaded nerve fibers. Fibers of unstretched nerves so prepared were close to cylindrical. When lightly stretched with tensions of 2-10 g before being rapidly frozen, beading appeared as a series of constrictions between the more normally expanded regions of the internodes with the paranodal regions spared. Beading also was seen in the fibers of sciatic and radial nerves fast-frozen in situ with the limbs placed in full extension to cause stretching. The cross-sectional area of the axon in the constrictions of beaded fibers was reduced by as much as 95%. The compaction of the microtubules and neurofilaments in the constructions was accounted for by the movement of axoplasmic fluid from the constrictions axially into the nearby regions where the axon and fiber diameters are close to normal. The electron-lucid area approximately 5 nm thick around the microtubules appeared to hinder their close approach in the constrictions although some microtubules touch. The neurofilaments are generally separated at a mean distance of 8-10 nm and approach to a mean distance of 4 nm in the constrictions. Neither the beading nor the reversal of beading, which occurs on relaxation from stretch, was blocked by periods of anoxia lasting several hours. Deletion of calcium from the incubating medium initiated some small amount of beading and additionally greatly augmented the beading on stretch. Beading also was present in some of the myelinated fibers of the dorsal columns of the spinal cord where stretch would not be present. These findings suggest that beading is due to a contractile process in the axon initiated by stretch and by other changed states of the fiber. Concomitantly with the contraction of the axon in the beading constrictions, the myelin sheath in that region was greatly reduced in circumference, to as much as 1/3 to 1/5 of normal. The decrease of the sheath diameter was not accompanied by a change in its thickness or in its lamellar fine structure. A repeat distance of the dense lines of 14 nm was measured in both the constricted and nonconstricted regions. To account for these findings lipid, and most likely other components of the myelin lamellar membranes, must move longitudinally from the constrictions in the plane of the lamellar membranes, and do this within 5-10 s.(ABSTRACT TRUNCATED AT 400 WORDS)

Myelin intrusions in beaded nerve fibers.

Small intrusions form in the internodes in or near the constrictions of beaded fibers prepared by fast-freezing and freeze-substituting mildly stretched nerves in the cat and rat. They appear as inwardly directed folds of the inner lamellae of the myelin sheath, or regularly formed spheres composed of lamellae with major dense and interperiod lines like those of the myelin sheath. A splitting of the lamellae and separation of the major dense lines may occur with an accumulation of Schwann cell cytoplasm between them, the result of an influx of cytoplasmic fluid from nearby constrictions. Longitudinally oriented microtubules have been observed in the intrusions, in the adaxonal Schwann cell cytoplasm, and in the innermost lamellae of the myelin sheath. The paranodes contain a number of larger intrusions in the form of spurs and globules along with shelve-like folds of the myelin sheath oriented in the longitudinal direction. Axoplasmic fluid driven from the constrictions during beading can enter the paranodes to smooth out their folds leaving the globular and spur-shaped myelin intrusions in isolation. Their wall thickness, measured from the central opening to the surface of the intrusion, is the same as that of the myelin sheath or, in some cases, double, the result of the folding of a spur-like intrusion upon itself. Intrusions unconnected to the sheath are seen in unbeaded fibers with regular, compact lamellae surrounded by axolemma. Others lack a covering axolemma and consist of variably disorganized and irregularly shaped lamellae suggesting that they are undergoing fragmentation and dissolution within the axon. The hypothesis is advanced that the intrusions in the internodes arise from an excess of lipid and other myelin components when the diameter of the sheath is reduced in the beading constrictions. In the paranodes, excess myelin components moved into these regions form the shelf-like folds which may fuse to form intrusions. These, separated from the myelin sheath, undergo fragmentation and dissolution and are carried by retrograde transport to the cell bodies where their constituent components can be reutilized.

The relation of the beading of myelinated nerve fibers to the bands of Fontana.

The bands of Fontana, appearing as spirals or irregular light and dark strips crossing the surface of unstretched nerves, are due to the wavy disposition of nerve fibers within the epineural-perineural sheaths. A mean tension of 2.7 +/- 0.23 (S.E.M.) g applied to segments of rat tibial nerves straightens the fibers and unbands the nerves causing them to lengthen by 9.35 +/- 0.89%. The nerves cold-fixed in situ at that point showed the myelinated fibers to be beaded. On relaxation the nerves rebanded and the fibers were no longer beaded. The tension at which unbanding occurred was better determined when the epineural-perineural sheaths were slit longitudinally. Under these conditions, unbanding occurred at a mean tension of 0.59 +/- 0.08 g and the nerves lengthened by 8.56 +/- 0.58%. The lengthening was not statistically different from that seen in sheathed nerves. In preparations with the epineural-perineural sheaths removed, banding was lost with tensions of 0.20 +/- 0.03 g and the nerves lengthened by 12.1 +/- 1.04%. The tensions needed were significantly lower than that for the sheathed and slit-sheath nerve groups. When cold-fixed, when banding was lost, the fibers were seen to be beaded. Banding of the desheathed nerves returned on relaxation of the nerves. However, after tensions of 8 g they showed plasticity in which the ends of the nerves needed to be pushed together to initiate rebanding in comparison to sheathed or sheath-slit nerves which rebanded spontaneously following relaxation after even higher tensions of 40 g. At the highest tensions the nerves remained extended and could not be forcibly rebanded.(ABSTRACT TRUNCATED AT 250 WORDS)

Slow transport of freely movable cytoskeletal components shown by beading partition of nerve fibers in the cat.

To account for the transport in nerve fibers of tubulin and neurofilament proteins in slow component a, the Structural Hypothesis holds that these proteins are assembled into microtubules and neurofilaments in the cell bodies and the cytoskeletal organelles then moved down in the fibers as part of an interconnected matrix at a uniform rate of about 1 mm/day. The Unitary Hypothesis, on the other hand, considers these proteins to be carried down within the fibers as soluble components or as freely movable small polymers or subunits turning over locally in the stationary cytoskeleton. To differentiate between the two hypotheses, cat L7 dorsal roots were taken at times from 7 to 25 days after their L7 dorsal root ganglia were injected with [3H]leucine to assess the labeling of the cytoskeleton by the use of beading and autoradiography. Beading was induced by a mild stretch and after fast-freezing and freeze-substitution of the roots for histological preparation, the beads were seen in the fibers as a series of expanded regions alternating with constrictions. In the constrictions the cytoskeleton was compacted into an area as small as 5% that of the normal axon, with the axoplasmic fluid and displaceable (freely movable) components squeezed from the constrictions into the adjoining expansions. Roots taken after 7 and 14 days, times consistent with slow component a downflow, were assessed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and their content of tubulin and neurofilament proteins shown to constitute 40-50% of all the labeled proteins present. In autoradiographs of dorsal roots taken at those times, numerous grains due to radioactivity were located over the non-constricted regions of the fibers. Few or no grains were present over the constrictions after 7 days. The findings are in accord with the labeled tubulins and neurofilament proteins being present in soluble form in the fibers and expressed from the constrictions into the expansions of the beaded fibers. In contrast, a number of fibers in roots taken at 14-20 days after injection showed somewhat higher grain densities over the constrictions, and more so after 25 days, indicating uptake of labeled subunits into the cytoskeletal organelles at later times. The results are consistent with the downflow of tubulin and neurofilament proteins as soluble components which drop off in the axon to turn over locally in their respective cytoskeletal organelles.

Origin of beading constrictions at the axolemma: presence in unmyelinated axons and after beta,beta'-iminodipropionitrile degradation of the cytoskeleton.

Myelinated nerve fibres become beaded when nerves are subjected to a mild stretch; the beading is seen as varicosities, a series of alternating constrictions and enlargements, when using freeze-substitution or cold-fixation to hold this labile form change in place during fixation. One possibility for how this form change comes about is that the myelin sheath or its Schwann cell initiates beading. We now report, however, that a similar beading is seen in the axons of unmyelinated fibres. In electron micrographs, longitudinal sections of axons show the series of constrictions and expansions typical of beading. In cross-sections, axons with unusually small diameter, corresponding to the constrictions, are seen to contain closely packed microtubules and neurofilaments while neighbouring swollen axons with widely dispersed microtubules correspond to the beading expansions. Another possibility for the form change is that the cytoskeleton is responsible for beading. We discovered that direct exposure of nerves to beta, beta'-iminodipropionitrile in vitro for 1-6 h causes both axonal microtubules and neurofilaments to become degraded and replaced by an amorphous residue. Nevertheless, beta,beta'-iminodipropionitrile-treated nerves show constrictions in myelinated fibres when stretched. An even greater degree of beading with narrower and longer constrictions appears in some fibres, with the expanded regions having oblate ends giving the appearance of a string of sausages. In cross-sections taken through the constrictions, a greater than usual reduction of axonal area was seen, this was due to the loss of cytoskeletal organelles which would act to limit the degree of constriction. With longer exposure to beta, beta'-iminodipropinitrile more fibres show complete degeneration of the cytoskeleton and form ovoids typical of Wallerian degeneration. Unmyelinated axons of beta, beta'-iminodipropionitrile-treated nerves which showed degeneration of their cytoskeleton with its replacement by amorphous material still demonstrated beading. As neither the myelin sheath nor the intact cytoskeleton within the axon is necessary for beading, by exclusion, we consider beading constrictions to be initiated at the level of the axolemma. In our hypothesis the membrane skeleton is responsible; namely, the spectrin, actin and other molecular species lining the inside of the axolemma and binding to transmembrane proteins. The membrane skeleton may be activated by stretch via transmembrane proteins (e.g. beta 1-integrins). The membrane skeleton mechanism may also be directly engaged in the production of Wallerian degeneration or be induced by neurotoxic agents.

The beaded form of myelinated nerve fibers.

When the nerves are lightly stretched and fixed by freeze-substitution, their fibers show the form-change termed "beading" which consists of a series of undulating constrictions and swellings in the internodes. This form change has not ordinarily been seen in chemically fixed nerves, or when it has, it has been ascribed to a pathological change or an artifact. We now report that beading is also retained in normal nerves when, following a light maintained stretch, they are fixed with aldehydes at a temperature close to 0 degrees C. The degree of beading in single fibers teased from the aldehyde fixed nerves was graded and found to be maximal at 0 degrees C, falling off with increased temperature until, at temperatures above 16 degrees C, most fibers showed no beading or a very mild beading. The fibers of nerves cold-fixed at 0 degrees C displayed the characteristics as freeze-substituted fibers, but with a somewhat smaller number of maximally beaded fibers and an 18% reduction in microtubule numbers in the axons. Desheathing or slitting the sheaths of the nerves before cold-fixation increased the probability of retaining beading. Exposure of stretched nerves to the aldehyde fixative at room temperatures for times as short as 3-5 min before they were cold-fixed showed a diminished degree of beading, indicating that aldehydes can have a deleterious effect on the beading mechanism which we hypothesize to be present in the fiber. This action is distinct from the general cross-linking action of aldehydes.

Developments in neurochemistry related to axoplasmic transport.

Fast transport of labeled proteins in vertebrate nerve and the particle movement seen in the axoplasm of giant fibers with video microscopy share basic properties. They are both dependent on oxidative metabolism providing ATP to drive transport with the microtubules acting as the "rails" for transport. Glucose is the usual metabolite but when glucose is deleted from an in vitro medium some other endogenous metabolite(s) present in vertebrate nerve can temporarily provide ATP to carry on transport for several hours. The transport filament hypothesis was proposed to account for fast transport in vertebrate nerve. Carriers were pictured to which the various components transported are bound and these moved along the microtubules with the needed energy supplied by ATP utilized by a calmodulin activated Ca-Mg ATPase. Analogous models based on video visualization of particle movement have been proposed. While these models can in general account for fast transport, we require a better understanding of the wide range of slower and intermediate rates of transport seen in vertebrate nerve. The large component of cytoskeletal proteins moved down as slow component a (SCa) at a rate close to 1 mm/d has been accounted for by two different models. In the Structural Hypothesis the microtubules and neurofilament cytoskeletal organelles are considered to be assembled in the cell bodies and then moved down within the axon as an assembled matrix. In the Unitary Hypothesis the cytoskeletal proteins are moved down as soluble proteins on carriers as in the case of fast transport, but these slow transported proteins are more rapidly dropped off in the axon for turnover in the stationary cytoskeleton. Other slow and intermediate rates can similarly be accounted for on the basis of this one mechanism. Experimental evidence in support of the Unitary Hypothesis is presented based on the use of the beading phenomenon to partition the assembled cytoskeleton from the soluble components. Additional evidence is given for a distal assembly of the cytoskeleton in regenerating fibers which further supports Unitary Hypothesis. The Unitary Hypothesis not only best fits with the known properties of transport, it offers new approaches to an understanding of the action of neurotoxins and the genesis of neuropathological changes.

Slow axoplasmic transport of mitochondria (MAO) and lactic dehydrogenase in mammalian nerve fibers.

The axoplasmic transport of the enzyme monoamine oxidase (MAO) (monoamine:O2 oxidoreductase, (deaminating) EC 1.4.3.4), a marker for mitochondria, and lactic dehydrogenase (LDH) (L-lactate:NAD oxidoreductase, EC 1.1.1927), a soluble component of axoplasm, was studied in cat sciatic nerve. For both these enzymes a linear accumulation was found in the nerve proximal to ligations over a period of at least 20 h. In double-ligation experiments no evidence of a depletion of enzymes within the nerve segment was found over this period of time as would be the case if some portion of the enzymes was carried by fast axoplasmic transport. Both the soluble protein enzyme LDH and the mitochondria, shown by MAO, are thus considered to be moved down the nerve by slow axoplasmic transport. Some differences in the two materials were seen in the greater fall in the level of MAO compared to LDH within the double-ligated segment over the succeeding period from 20 to 48 h. These changes are considered with respect to the transport filament model as modified to take into account slow axoplasmic transport.

[Curricula oriented inclusion of children and adolescents with haemophilia in school sports--a new approach within the project "fit for life"]. / Lehrplanorientierte Inklusion hämophiler Kinder und Jugendlicher im Sportunterricht. Ein neuer Ansatz innerhalb des Projekts "fit for life"

Inclusive paedagogic thinking and acting is a modern and increasingly important topic in school sports. It will affect teachers as well as parents and students. The new international guidelines and national curricula enable new ways of inclusion especially for students with chronic illnesses like haemophilia. Special help from the sport teachers is of vital importance. In our project "fit for life" where we advice children and young adults with haemophilia to find their appropriate sport, we developed a new approach for an optimised inclusion of children with haemophilia into sport lessons. The whole project is running in corporation with the German Sport Teachers Association/Hessen. We analysed and rated the actual curricula of the different school years and looked at the specific needs, risks and necessary abilities for persons with haemophilia. By this means we gathered about 600 typical movements and/or exercises for school sports and developed individual advice and adapted exercise solutions for sport lessons.