Anisatin modulation of the gamma-aminobutyric acid receptor-channel in rat dorsal root ganglion neurons.

1. Anisatin, a toxic, insecticidally active component of Sikimi plant, is known to act on the GABA system. In order to elucidate the mechanism of anisatin interaction with the GABA system, whole-cell and single-channel patch clamp experiments were performed with rat dorsal root ganglion neurons in primary culture. 2. Repeated co-applications of GABA and anisatin suppressed GABA-induced whole-cell currents with an EC50 of 1.10 microM. No recovery of currents was observed after washout with anisatin-free solution. 3. However, pre-application of anisatin through the bath had no effect on GABA-induced currents. The decay phase of currents was accelerated by anisatin. These results indicate that anisatin suppression of GABA-induced currents requires opening of the channels and is use-dependent. 4. Anisatin suppression of GABA-induced currents was not voltage dependent. 5. Picrotoxinin attenuated anisatin suppression of GABA-induced currents. [3H]-EBOB binding to rat brain membranes was competitively inhibited by anisatin. These data indicated that anisatin bound to the picrotoxinin site. 6. At the single-channel level, anisatin did not alter the open time but prolonged the closed time. The burst duration was reduced and channel openings per burst were decreased indicating that anisatin decreased the probability of openings.     

Endogenous ATP released by electrical field stimulation causes contraction via P2x- and P2y-purinoceptors in the isolated tail artery of rats

Electrical field stimulation (EFS) caused contraction of isolated tail arteries of rats. The EFS-induced contraction showed frequency-dependence and was entirely abolished by the sodium channel blocker tetrodotoxin (1 x 10(-7) M). The EFS-induced (at 20 Hz) contraction was reduced by about 60% in the presence of phentolamine (1 x 10(-6) M). Therefore, later experiments were carried out in the presence of phentolamine. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (1 x 10(-8)-1 x 10(-6) M) and basilen blue E-3G (3 x 10(-5)-5 x 10(-5) M), P2-receptor antagonists, significantly inhibited the contraction evoked by EFS. In addition, PPADS significantly inhibited the contractions induced by ATP (1 x 10(-4) M) and a selective P2x-receptor agonist, alpha,beta-methylene ATP (1 x 10(-6) M). In contrast, basilen blue E-3G did not inhibit alpha,beta-methylene ATP-induced contraction. The ecto-ATPase activator apyrase (5 and 10 U/ml) significantly reduced the EFS-induced contractions. These findings suggest that endogenous ATP released by EFS causes contractions of rat tail artery via both the P2x-receptors and P2y-receptors.     

An aminopeptidase inhibitor, bestatin, enhances progesterone and oestradiol secretion by porcine granulosa cells stimulated with follicle stimulating hormone in vitro

We examined the presence of cell surface aminopeptidase on culturedporcine granuiosa cells by employing the aminopeptidase assayusing alanine-p-nitroanilide and histochemical staining usingL-leucyl-β-naphthylamide. Porcine granuiosa cells obtainedfrom follicles 4–5 mm in diameter were cultured for 7days. The aminopeptidase assay showed that the porcine granuiosacell culture had aminopeptidase activity and that this activitywas inhibited in a dose-dependent manner by bestatin which bindsto cell surfaces and inhibits cell surface aminopeptidases.Histochemical staining also indicated that cultured granuiosacells had aminopeptidase activity. Porcine granuiosa cells werecultured in the presence or absence of porcine follicle stimulatinghormone (FSH, 3.125 nmol/1) and/or bestatin (0.4, 4.0 and 40.0µ/ml) for 7 days, and the production of progesterone andoestradiol was measured. In the presence of porcine FSH, theproduction of progesterone and oestradiol by granuiosa cellswas increased significantly by 5- and 2-fold respectively. Theseincreases were enhanced further by bestatin (40.0 (µg/ml).In the absence of porcine FSH, progesterone production was enhancedby bestatin (40.0 µg/ml), whereas no significant effectof bestatin on oestradiol secretion was observed. These findingsindicate that the inhibition of membrane-bound amino-peptidase(s)on the cell surfaces affects the steroidogenesis of granuiosacells, and that these aminopeptidase(s) are important regulatorsof granuiosa cell differentiation.     

Glucose intolerance during prolonged sevoflurane anaesthesia

Purpose

The effects of prolonged sevoflurane anaesthesia on insulin sensitivity were investigated by two successive intravenous glucose tolerance tests (IVGTT) in eight patients who underwent prolonged surgery.

Methods

The first IVGTT was administered (25 g glucose as 20% dextrose in water iv) over two minutes 35 min after initiation of surgery. Arterial blood samples were obtained at 0, 5, 10, 30, 60, and 120 min after glucose administration for blood glucose and plasma insulin determination. A second IVGTT was performed six hours following the initiation of surgery.

Results

The disappearance rate of glucose (k-value) for the first IVGTT was 0.887 ± 0.436 (mean ± SD) % · min^?1, and 0.784 ± 0.289 for the second IVGTT. Both k-values are lower than the normal value. The maximum insulin response to glucose (ΔIRI · ΔBS^?1) of the second IVGTT was lower than the first IVGTT (0.124 ± 0.092 vs 0.071 ± 0.056, P < 0.05). The total insulin output of the first IVGTT was higher than the second IVGTT (1,161 ± 830 vs 568 ± 389 μU · min · ml^?1, P < 0.05).

Conclusion

Glucose intolerance is enhanced by diminished insulin output in response to blood glucose elevation during prolonged anaesthesia and surgery.     

Analysis of orthograde fast axonal transport and nonaxonal transport along the optic pathway of albino rabbits during increased and decreased intraocular pressure

Orthograde fast axonal and nonaxonal transport through the optic disc was studied quantitatively and autoradiographically in albino rabbits during elevated (30 or 50 mmHg), normal (13–15 mmHg) and decreased (0–4 mmHg) intraocular pressure (IOP). In cases of intraocular hypertension up to 50 mmHg, autoradiographic findings of a disturbed orthograde fast axonal transport were seen in the optic disc within 3 hr. The blockage was relatively mild and uniform, and was distributed adjacent to the extension line of sclera. Despite this histological evidence of blockage, a quantitative analysis showed no statistically significant decrease in axonally transferred radioactivity within 3 hr. Decrease in the transferred material was evident at 6 hr, and the extent of decrease was mild (ca. 20% at the most prominent portion). In cases of moderate intraocular hypertension (30 mmHg) for 6 hr, a quantitative analysis showed no decrease in axonal transport. After 3–6 hr of intraocular hypotension (0–4 mmHg), papilledema did not develop and autoradiographically there was no accumulatjon of axonal components. Axonally transferred material remained quantitatively at the same level as in the control animals. Nonaxonal transport along the optic nerve was doubly enhanced in cases of intraocular hypertension up to 50 mmHg, and was reduced to one thrid at level of 0–4 mmHg. Filtration of intraocular fluid through the optic disc appears to be the largest component of the nonoxonal transport.     

A reappraisal of time trends in ulcer disease: factors related to changes in ulcer hospitalization and mortality rates.

There has been a dramatic decline in reported hospitalization and mortality rates for peptic ulcer disease in the past two decades. Data from the National Center for Health Statistics and from the Commission on Professional and Hospital Activities were examined to determine the cause(s) for this decline. Gastric and duodenal ulcer mortality rates decreased by 58 per cent and 68 per cent, respectively, from 1962 to 1978; changes in criteria for selecting the underlying cause of death might account for some of this apparent decrease. Hospitalization rates for duodenal ulcers decreased nearly 50 per cent from 1970 to 1978, but hospitalizations for gastric ulcers did not decrease. During this same time period, hospitalizations for peptic ulcers as one of the "all listed" causes remained stable, and hospitalizations for a closely related diagnosis, gastritis/duodenitis, increased. Changes in coding practices, hospitalization criteria, and diagnostic procedures appear to have contributed to the decline in reported hospitalization and mortality rates for peptic ulcer disease.     

Distribution of cadmium and zinc in tissues and organs,and their age-Related changes in striped dolphins,Stenella coeruleoalba

Cadmium and zinc concentrations were determined in the tissues and organs, including the fetus, of striped dolphins. The kidney showed the highest cadmium concentration and the hepatic cadmium concentration was also relatively high. A similar distribution pattern among soft tissues was also observed with zinc, where its concentration varied less than that of cadmium. A significant positive correlation between zinc and cadmium was found in both the kidney and the liver; the increase of zinc concentration with cadmium was more marked in the liver (Zn:Cd 3∶1 on molar basis) than kidney (Zn:Cd 1∶1). Negligible cadmium concentration in the fetus suggested that cadmium is not transferred to the fetus via the placenta from the mother. Organ-specific age trends of cadmium and zinc concentrations were presented in detail for muscle, liver, kidney, pancreas, brain, and blood. Both metals showed rapid change during the periods of the fetus and weaning.     

Preservation of nerve fiber layer by retinal vessels in glaucoma.

The authors evaluated the correlation between various parameters and the local preservation of the retinal nerve fiber layer in 156 glaucomatous eyes. A vessel-associated preservation of the nerve fiber layer was observed in 45 of the 156 glaucomatous eyes. The presence of "straight" retinal vessels (either arterioles or large venules) and "tortuous" retinal vessels (large or small venules) inside of the scleral ring was correlated with the local preservation of the nerve fiber layer (P less than 0.001 and P less than 0.05, respectively). A local elevation of the floor of the cup was also correlated with the preservation of the nerve fiber layer (P less than 0.01). However, no correlation existed between either the preservation of the nerve fiber layer and the type of glaucoma, sex or age of patient, tilting of the disc, cilioretinal vessel, vertical cup-to-disc ratio, refractive error, disc size, distance between the disc and foveola, or the index of ovalness of the disc. These results suggest that retinal vessels in the disc significantly influence the vulnerability of the nerve fibers to glaucomatous damage.     

Time course of satisfaction of search

"Satisfaction of search" (SOS) refers to the effect in which a second lesion remains undetected after detection of another lesion on the same radiograph. The objective of this study was to clarify our understanding of SOS by relating it to total time of inspection and time intervals before, between, and after discovery of lesions. Detection accuracy of native lesions in chest radiographs, before and after the addition of a simulated nodular lesion, was measured for ten observers. Analysis of data from this and a previous experiment showed that average perceptual accuracy of individual receiver operating characteristic curves was significantly reduced with the addition of the nodules. Plots and analyses of search time revealed that, on average, during a typical 46-second inspection of a case, simulated nodules were found at 18 seconds, native abnormalities at 25 seconds, and false positives occurred at 33 seconds. Time needed to find nodules did not depend on whether native lesions were present; time to find native lesions did not change with addition of nodules; and total search time was the same for images with one, two, or no lesions. The detection results show that the SOS effect was obtained, but that interrupting search in order to measure it also diminishes accuracy. Analysis of the time course data relates SOS to perceptual capture and strategic halting of search.     

Attentional modulation of parieto-occipital cortical responses: implications for hemispatial neglect

Functional magnetic resonance imaging (fMRI) was used to examine whether preattentive and attentive visual processing, the cognitive psychological dichotomy on normal vision, indeed activate the parieto-occipital systems differentially as suggested by recent neuropsychological research. The activation paradigms consisted of feature detection and discrimination of line orientation, and visual fixation, which corresponded to preattentive, attention-requiring, and baseline conditions, respectively. The detection versus fixation contrast revealed activation sites in the right lateral prefrontal cortex and bilateral occipital lobes, whereas the discrimination versus fixation contrast showed broader bilateral activations extending from the occipital lobes through the parietal lobes, prefrontal cortex, thalamus, basal ganglia and upper brainstem. In the discrimination versus detection contrast, significant activations were observed in the right superior and inferior parietal lobules as well as in the subcortical structures. These findings were consistently demonstrated both at intra- and inter-subject levels. The present study provides further evidence to delineate neural substrate for the two distinct modes of visual processing and helps us to understand the neuropsychological mechanism underlying visual attention disorders.