Release and actions of adenosine in the central nervous system

Adenosine is released from active neurons into the extracellular fluid at a concentration of about 1mol/l. Neither the precise cellular origin nor the biochemical form of release has been firmly established, though the nucleotide is probably released partly directly, as a result of raised intracellular levels, and partly as nucleotides, which are subsequently hydrolysed. Once in the extracellular medium, adenosine markedly inhibits the release of excitatory neurotransmitters and modulatory peptides and has direct inhibitory effects on postsynaptic excitability via A₁ receptors. A population of A₂ receptors may mediate depolarization and enhanced transmitter release. Adenosine also modulates neuronal sensitivity to acetylcholine and catecholarnines, all these effects probably contributing to the behavioural changes observed in conscious animals. As a result of their many actions, adenosine analogues are being intensively investigated for use as anticonvulsant, anxiolytic, and neuroprotective agents.     

Haptic localization and the internal representation of the hand in space

As the hand actively explores the environment, contact with an object leads to neuronal activity in the topographic maps of somatosensory cortex. However, the brain must combine this somatotopically encoded tactile information with an internal representation of the hand's location in space if it is to determine the position of the object in three-dimensional space (3-D haptic localization). To investigate the fidelity of this internal representation in human subjects, a small tactual stimulator, light enough to be worn on the subject's hand, was used to present a brief mechanical pulse (6-ms duration) to the right index finger before, during, or after a fast, visually evoked movement of the right hand. In experiment 1, subjects responded by pointing to the perceived location of the mechanical stimulus in 3-D space. Stimuli presented shortly before or during the visually evoked movement were systematically mislocalized, with the reported location of the stimulus approximately equal to the location occupied by the hand 90 ms after stimulus onset. This pattern of errors indicates a representation of the movement that fails to account for the change in the hand's location during somatosensory delays and, in some subjects, inaccurately depicts the velocity of the actual movement. In experiment 2, subjects were instructed to verbally indicate the perceived temporal relationship of the stimulus and the visually evoked movement (i.e., by reporting whether the stimulus was presented before, during, or after the movement). On average, stimuli presented in the 38-ms period before movement onset were more likely to be perceived as having occurred during rather than before the movement. Similarly, stimuli in the 145-ms period before movement termination were more likely to be perceived as having occurred after rather than during the movement. The analogous findings of experiments 1 and 2 indicate that the same inaccurate representation of dynamic hand position is used to both localize tactual stimuli in 3-D space and construct the perception of arm movement.     

Effects of prostaglandin F2α(PGF2α) and prostaglandin I2 (PGI2) on nerve-mediated secretion in guinea-pig colon

We have applied conventional flux-chamber and intracellular recording methods to investigate the effects of the prostaglandins PGF₂ and PGI₂ upon epithelial ion transport and on the electrical behaviour of submucosal neurones in guinea-pig colon. In flux-chamber experiments on segments of colon, both prostaglandins evoked a dose-dependent increase in short-circuit current that was reduced in chloridedepleted Krebs solution and by serosal addition of tetrodotoxin or atropine, but was unaffected by hexamethonium. These results indicate activation of chloride secretion via submucosal neurones. The response to PGF₂ was decreased by piroxicam. Application of PGF₂ or PGI₂ to submucosal neurones evoked depolarization of the membrane potential associated with an enhanced spike discharge. The depolarizing response was tetrodotoxin insensitive, indicating a direct effect of the prostaglandins on the impaled neurones. Membrane depolarization was frequently associated with the occurrence of fast excitatory postsynaptic potentials, suggesting in addition that part of the excitatory effect is mediated by the activation of neural circuits that drive the impaled neurone synaptically. The results of this study indicate that the secretory effects of prostaglandins are mediated in part by submucosal neurones and further suggest that the colonic submucosal plexus may function as an amplifier to enhance the epithelial response to inflammatory mediators.     

Inherited complement deficiency in children surviving fulminant meningococcal septic shock

We evaluated the complement system in 29 children (mean age: 4.5 years) who survived fulminant meningococcal septic shock. No terminal complement deficiencies were found. One patient, who experienced the most dramatic disease course, had a decreased haemolytic activity in the haemolytis-in-gel test for the alternative pathway. The properdin concentration in serum of this patient was < 0.1 g/ml (n = 17.1–27.7 g/ml). Coagulation studies revealed a heterozygeous type I protein C deficiency as well. He was the only patient with aNeisseria meningitidis group Y infection.     

A novel strategy for the isolation of defined pyrG mutants and the development of a site-specific integration system for Aspergillus awamori

A homologous gene transfer system for Aspergillus awamori for site-specific integration is described, based on two components. First, a defined A. awamori pyrG mutant strain constructed by a selection strategy for gene-replacement in fungi. Second, a vector with a homologous pyrG selection marker containing a defined mutation at a site different from that of the mutations in the pyrG gene of the defined mutant strain. Defined mutation in the A. awamori pyrG gene, isolated from a genomic library by heterologous hybridisation with the A. niger pyrG gene as a probe, were introduced by specifically altering sequences at restriction sites in the coding region of the gene. After transformation of the A. awamori wild-type strain with vectors containing these mutated pyrG genes, and selection for 5-fluoro-orotic acid resistance (5-FOA^R), on the average 60% of the 5-FOA^R colonies originated from replacement of the wild-type pyrG gene by the mutated pyrG allele. After transformation of a mutant strain, carrying a mutation near the 5 end of the pyrG gene with vectors containing a mutation near the 3 end of the pyrG gene, 35% of the resulting transformants contained one copy of the vector at the pyrG locus.     

An expert system to teach troubleshooting of common problems associated with the automated anesthesia recordkeeper

Automated anesthesia recordkeepers have been used to monitor patients during surgery in up to 90% of cases at The Ohio State University. The record-keeping devices are complex and can be difficult to troubleshoot. The 1st-CLASS Fusion Program, an expert system shell-program, has been programmed to allow the resident or nurse anesthetist to solve the two most common types of problems associated with the recordkeeper: printer problems and patient monitor problems. Use of this program allows the resident or nurse anesthetist to troubleshoot the recordkeeper quickly and accurately and promotes in the user a sense of competence and control over the technology.     

Effects of mental state on heart rate and blood pressure variability in men and women

Summary. The effect of different mental states on autonomic modulation of the cardiovascular system was assessed in healthy, normotensive men (n=18) and women (n=12). Heart rate variability (HRV), systolic blood pressure variability (BPV) and arterial baroreflex function were assessed during 4 tests at rest ((10 min+5 min recovery)×4):

• 1 Control (spontaneous breathing, (SB)
• 2 Mental distraction (SB+word puzzle)
• 3 Conscious control of breathing (paced at SB rate) and
• 4 Mental stress (SB+computer quiz).

There were no significant gender differences in the responses to the interventions in terms of arterial (spontaneous) baroreflex (SPBX) control of HR, and indices of time and frequency domains of HRV and BPV, with the exception of the sympathetic indicator of HRV (low frequency power/total power; P<0.01) which was lower in women during control and mental stress tests. Conscious control of breathing at SB did not alter HRV, BPV or SPBX in either men or women. Mental distraction and mental stress led to decreases in indices of time and frequency domains of HRV and BPV in all subjects, as well as increases in HR during distraction and in systolic BP during stress. These findings suggest that in studies of cardiovascular control:

• 1 Paced breathing at SB can be used for individuals with irregular breathing patterns
• 2 The extent of mental stress achieved is intervention-specific and for the most part, independent of gender and
• 3 Resting assessment of HRV, BPV and SPBX can be made by having subjects sit quietly without interventions in a controlled laboratory setting.

     

Nursing home residents' perceptions of relocation

Summary

• ? The lived experience of relocating to a nursing home is explored from the perspective of 19 residents of Australian nursing homes.
• ? The interpretative research methodology is informed by hermeneutic phenomenology.
• ? In-depth interviews were conducted with 19 nursing home residents living in nursing homes in NSW. Interviews were audiotaped, transcribed and analysed to identify emergent themes.
• ? The themes are described and interpreted to provide an understanding of the relocation experience.

     

Endothelial lipopigment as an indicator of α-tocopherol deficiency in two equine neurodegenerative diseases

Two spontaneous neurodegenerative diseases of the horse, equine motor neuron disease (EMND) and equine degenerative myeloencephalopathy (EDM), have been associated with -tocopherol deficiency, and both were characterized by prominent accumulations of endothelial lipopigment in the small vessels of the spinal cord. These endothelial pigment deposits appear to be reversible. In EMND horses pasture-supplemented for 9 months or more after the progression of weakness and wasting had arrested, there was very little endothelial lipopigment. The origin and the potential effects of these endothelial lipopigment accumulations are discussed.     

Intracisternal injection of TRH antibody blocks gastric emptying stimulated by 2-deoxy-d-glucose in rats

We evaluated the effect of 2-deoxy-d-glucose (2-DG) on gastric emptying of a non nutrient solution in conscious rats using a Phenol red method. Intravenous injection of 2-deoxy-d-glucose dose-dependently increased the rate of gastric emptying. This stimulatory action of 2-DG was abolished by subdiaphragmatic vagotomy. Intracisternal injection of thyrotropin-releasing hormone (TRH) antibody blocked intracisternal TRH and intravenous 2-DG-induced enhancement of gastric empyting but not the stimulation of gastric emptying induced by intracisternal pancreatic polypeptide. The TRH antibody injected intraperitoneally had no effect. These results suggest that endogenous TRH in the brain is involved in vagal-dependent stimulation of gastric emptying by 2-DG.