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61.
While inhaled polycyclic aromatic hydrocarbons have long been suspected to
induce lung cancer in humans, their dosimetry has not been fully
elucidated. A key question is whether the critical exposure occurs during
absorption in the lungs, or if toxicants in the systemic circulation
contribute significantly to lung cancer risk. In particular, data are
needed to determine how the physical properties of inhalants affect local
dosimetry in the respiratory tract. Pyrene, a tobacco smoke component, was
selected for study because it has physical properties between those of
highly lipophilic benzo[a]pyrene and water- soluble nitrosamines. Aliquots
of 5 ng of pyrene dissolved in a phospholipid/ saline suspension were
instilled as a single-spray bolus in the posterior trachea of the dog just
anterior to the carina. For 3 h after instillation, blood was repeatedly
sampled from the azygous vein, which drains the mucosa around the point of
instillation, and from both sides of the systemic circulation. At 3 h
post-instillation, tissue samples were taken. Autoradiography was used to
determine the depth distribution of pyrene in the tracheal mucosa. The
concentration of pyrene-equivalent radioactivity in the azygous vein peaked
9 min after the instillation. At approximately 30 min after instillation, a
rapid early clearance phase shifted into a distinctly slower second
clearance phase. Rates of rapid clearance were, however, sufficiently slow
to indicate diffusion-limited absorption of pyrene in the trachea. This
finding was corroborated by high concentrations of pyrene in the epithelium
as determined by autoradiography. High epithelial concentration of pyrene
combined with a slow penetration into the circulating blood allowed
substantial first-pass metabolic conversion of pyrene in the tracheal
mucosa. A total of 13% of the instilled pyrene was retained in the tracheal
mucosa 3.2 h after instillation; of this, 29% was parent compound, 52% was
organic-extractable metabolites, 14% was water-soluble metabolites and 6%
(approximately 1% of the instilled amount) was covalently bound to tracheal
tissues. Results support the inference that lipophilic protoxicants,
because of slow, diffusion-limited absorption, are more likely than
water-soluble protoxicants to be bioactivated in the lining epithelium and,
in turn, induce first-pass toxicity at the site of entry. In addition,
limitations were identified in the use of systemically distributed
biomarkers of PAHs, such as urinary hydroxypyrene levels, as indicators of
the biologically effective dose in airway target cells.
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The function of cortical circuits depends critically on the balance between excitation and inhibition. This balance reflects not only the relative numbers of excitatory and inhibitory synapses but also their relative strengths. Recent studies of excitatory synapses in visual and somatosensory cortices have emphasized that synaptic strength is not a fixed quantity but is a dynamic variable that reflects recent presynaptic activity. Here, we compare the dynamics of synaptic transmission at excitatory and inhibitory synapses onto visual cortical pyramidal neurons. We find that inhibitory synapses show less overall depression than excitatory synapses and that the kinetics of recovery from depression also differ between the two classes of synapse. When excitatory and inhibitory synapses are stimulated concurrently, this differential depression produces a time- and frequency-dependent shift in the reversal potential of the composite postsynaptic current. These results indicate that the balance between excitation and inhibition can change dynamically as a function of activity. 相似文献
64.
BE Kelly FRCS GG Cooper MD FRCS JOM Mills FRCR 《International journal of clinical practice》1993,47(5):272-272
SUMMARY Although pneumatosis cystoides intestinalis (PCI) is a well-recognised condition, an individual surgeon is unlikely to encounter it often. The collected experience of two surgical units in Glasgow teaching hospitals over a 15-year period consisted of five patients.1 Surgical and radiological trainees may therefore have little or no exposure to the diagnostic difficulties this condition can cause. We report an illustrative case. 相似文献
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