Uptake of tritium-labelled biogenic amines by the prostomium of the polychaete Nereis virens (Sars) (Annelida)

The uptake of tritium-labelled 5-HT, noradrenaline, 5-hydroxytrytophan, DOPA and dopamine by the cerebral ganglion and prostomial nervous system of the polychaete Nereis virens has been examined using radioautography at the level of the light microscope. Pronounced uptake of (3)H-5HT occurred in the antennal, palpal, tegumentary and nuchal nerves as well as in ganglionic nuclei 13, 14, 15, 16, 17, 20, 24 and 25, the mid-brain neuropile, the neurosecretory neuropil and the infracerebral organ; (3)H-NA uptake was observed in small cells in the prostomial epidermis, and the infracerebral organ; (3)H-dopamine only in one of two common types of epidermal mucus cells. Prostomial muscles labelled generally with (3)H-NA and at specific sites with (3)H-5HT. These observations support the concept of an efferent serotonergic system originating in several cerebral ganglionic nuclei and serving prostomial muscle and epidermis. Evidence for an afferent adrenergic system is less substantial. The role of dopamine remains obscure.     

An experimental model of tardive dyskinesias

Rats treated continually and chronically with trifluoperazine (ca 3 mg/kg/day) for six months initially developed mild catalepsy and an inhibition of spontaneous locomotor activity; both effects disappeared by three months. An initial increase in dopamine turnover (as measured by levels of homovanillic acid and dihydroxyphenylacetic acid) also disappeared by three months. Apomorphine-induced stereotypy was completely inhibited in drug-treated animals at two weeks, but progressively returned to normal after three months of drug intake. An exaggerated response to apomorphine developed in animals after six months of drug administration. Inhibition of striatal dopamine-stimulated adenylate cyclase found during the first month of drug intake was reversed at three months, a trend exaggerated after continuous drug administration for six months. Specific striatal ³H-spiperone binding affinity decreased acutely, but was increased after six months drug intake; no change in number of receptor sites occurred.These changes suggest that at least striatal dopamine receptors may become “supersensitive” during chronic neuroleptic treatment.     

Endothelin action on vascular smooth muscle involves inositol trisphosphate and calcium mobilization

Cultured endothelial cells release a potent vasoconstrictor peptide, endothelin. Cumulative addition of synthetic endothelin to isolated rabbit aortic rings elicited a concentration-dependent increase in contractile tension which was endothelium-independent. In cultured rabbit vascular smooth muscle cells loaded with the fluorescent dye fura 2, endothelin induced a concentration-dependent increase in [Ca2+]i over the range of 0.01 to 100 nM. Moreover, in the absence of extracellular Ca2+, endothelin could still induce an increase in [Ca2+]i. In addition, endothelin stimulated 45Ca2+ efflux from preloaded vascular smooth muscle cells in the presence and absence of extracellular Ca2+, as well as stimulating 45Ca2+ influx in a concentration-dependent manner. Measurement of inositol phosphates in [3H]-myoinositol-labelled vascular vascular trisphosphate. Unlabelled endothelin inhibited (125I)-endothelin binding to cultured rabbit vascular smooth muscle cells in a concentration-dependent manner. Binding was not inhibited by other vasoactive hormones or calcium channel ligands, suggesting cell surface receptors specific for endothelin. We conclude that one of the initial membrane events in the action of endothelin is to induce phospholipase C-stimulated PIP2 hydrolysis and that this signalling mechanism is initiated by endothelin/receptor interaction at the plasma membrane.     

Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage

Reduced endothelial nitric oxide synthase (eNOS) function has been linked to secondary complications of subarachnoid hemorrhage (SAH). We previously found that there is increased eNOS function after SAH but that it is uncoupled, leading to secondary complications such as vasospasm, microthromboembolism and neuronal apoptosis. Here we test the hypothesis that recoupling eNOS with simvastatin can prevent these complications. SAH was created in mice that were treated with vehicle or simvastatin starting 2 weeks before or 30 minutes after SAH. SAH increased phosphorylated eNOS which was prevented by pre- or post-treatment with simvastatin. Simvastatin pre-treatment also prevented the increase in eNOS monomer formation that was associated with SAH, decreased superoxide anion radical production and increased NO. These changes were associated with decreased vasospasm, microthromboemboli and neuronal injury. The data suggest that simvastatin re-couples eNOS after SAH, leading to decreased secondary complications such as vasospasm, microthromboemboli and neuronal injury.     

Egg and cows' milk hypersensitivity in exclusively breast fed infants with eczema,and detection of egg protein in breast milk.

Forty nine eczematous infants who were still solely and exclusively breast fed and who had never received anything but breast milk were studied for evidence of sensitisation to foods. Thirty four similar infants without eczema formed a control group. The eczematous infants were divided into three groups according to clinical criteria: (1) definite atopic eczema; (2) possible atopic eczema; (3) atopic eczema unlikely. Twenty three infants showed cutaneous hypersensitivity to foods, usually egg and cows'' milk. Seven of 14 infants in group 1 and nine of 20 in group 2 were sensitised compared with four of 15 in group 3 and three of 34 controls (p less than 0.01). Ovalbumin was detected in breast milk from 14 of 19 mothers tested after ingestion of egg, the concentrations being the same for mothers feeding eczematous and normal infants. Breast fed babies developing eczema may be sensitised by foods eaten by their mothers.     

Transmissible and nontransmissible complex chromosome aberrations characterized by three-color and mFISH define a biomarker of exposure to high-LET alpha particles

Insertions have been proposed as potential stable biomarkers of chronic high-LET radiation exposure. To examine this in vitro, we irradiated human peripheral blood lymphocytes in G(0) with either 50 cGy (238)Pu alpha particles (LET 121.4 keV/microm) or 3 Gy 250 kV X rays and stimulated their long-term culture up to approximately 22 population doublings postirradiation. Mitotic cells were harvested at regular intervals throughout this culture period and were assayed for chromosome aberrations using the techniques of three-color and 24-color mFISH. We observed the stable persistence of transmissible-type complex rearrangements, all involving at least one insertion. This supports the hypothesis that insertions are relevant indicators of exposure to high-LET radiation. However, one practical caveat of insertions being effective biomarkers is that their frequency is low due to the complexity and cell lethality of the majority of alpha-particle-induced complexes. Therefore, we propose a "profile of damage" that relies on the presence of insertions, a low frequency of stable simple reciprocal translocations (2B), and, significantly, the complexity of the damage initially induced. We suggest that the complexity of first- and second-division alpha-particle-induced nontransmissible complex aberrations reflects the structure of the alpha-particle track and as a consequence adds radiation-quality specificity to the biomarker, increasing the signal:noise ratio of the characteristic 2B:insertion ratio.     

The use of dynamic elastomeric fabric orthosis suits as an orthotic intervention in the management of children with neuropathic onset scoliosis: A retrospective audit of routine clinical case notes

Background

To date the main treatment approach for neuropathic onset scoliosis has utilised thoracic lumbar sacral orthoses (TLSO) to stabilize the spine and enable stable sitting. Dynamic elastomeric fabric orthoses (DEFOs) may achieve both of these aims if used as an early intervention. Due to a lack of evidence in this area, a retrospective audit of case notes was undertaken to understand current orthotic practice investigating the usage, outcomes and clinical characteristics of treated children with neuropathic onset scoliosis. Clinical notes of 180 children at risk for, or identified with, scoliosis were audited using a search matrix to identify diagnostic group, spinal muscle tone, Gross Motor Functional Classification Scale (GMFCS) level, orthotic treatment modalities, scoliosis specific data, surgical interventions, adaptive technologies used, and outcome measurements reported.

Results

Of the 180 notes examined, 85 were male; mean age nine years one month [SD four years seven months]. Spinal muscle tone was reported in 137 cases: 122/137 presented as low tone, 4/137 high tone, 6/137 fluctuating tone and 5/137 typical tone. Scoliosis was confirmed in (77/180) of whom (39/77) used a DEFO. Another (43/180) had a spinal curve developing, of whom (22/43) used a DEFO. The remaining (60/180) had no report of spinal curvature, but used a DEFO as a preventative measure. GMFCS scores were reported for 49 children of whom 14/49 were graded as level 4 and 17/49 level 5. Of the children with scoliosis who had spinal curve shapes reported, 48/60 had a C-shape presentation and 12/60 had an S-shape.

Conclusions

The findings confirm previously reported papers in children with neuropathic onset scoliosis in relation to curve shape and GMFCS levels. It provides some evidence of the role DEFOs may have in the management of these children, and highlights the need for further research in this area due to the lack of peer-reviewed publications.