Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors.

The behavioral and cognitive effects of nicotine suggest that nicotinic acetylcholine receptors (nAChRs) participate in central nervous system (CNS) function. Although nAChR subunit messenger RNA (mRNA) and nicotine binding sites are common in the brain, there is little evidence for synapses mediated by nAChRs in the CNS. To test whether, CNS nAChRs might modify rather than mediate transmission, the regulation of excitatory synaptic transmission by these receptors was examined. Nanomolar concentrations of nicotine enhanced both glutamatergic and cholinergic synaptic transmission by activation of presynaptic nAChRs that increased presynaptic [Ca2]i. Pharmacological and subunit deletion experiments reveal that these presynaptic nAChRs include the alpha 7 subunit. These findings reveal that CNS nAChRs enhance fast excitatory transmission, providing a likely mechanism for the complex behavioral effects of nicotine.

GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis.

We have found that, during the early stages of cortical neurogenesis, both GABA and glutamate depolarize cells in the ventricular zone of rat embryonic neocortex. In the ventricular zone, glutamate acts on AMPA/kainate receptors, while GABA acts on GABAA receptors. GABA induces an inward current at resting membrane potentials, presumably owing to a high intracellular Cl- concentration maintained by furosemide-sensitive Cl- transport. GABA and glutamate also produce increases in intracellular Ca2+ in ventricular zone cells, in part through activation of voltage-gated Ca2+ channels. Furthermore, GABA and glutamate decrease the number of embryonic cortical cells synthesizing DNA. Depolarization with K+ similarly decreases DNA synthesis, suggesting that the neurotransmitters act via membrane depolarization. Applied alone, GABAA and AMPA/kainate receptor antagonists increase DNA synthesis, indicating that endogenously released amino acids influence neocortical progenitors in the cell cycle. These results demonstrate a novel role for amino acid neurotransmitters in regulating neocortical neurogenesis.

Serotonin receptors. Genetic insights into serotonin function.

Targeted disruption of the genes for the 5-HT1B and 5-HT2C serotonin receptors and monoamine oxidase A have confirmed pharmacological experiments and revealed unexpected behavioral roles for serotonin.

Intragastric pH measurement using a novel disposable sensor.

An unique disposable pH sensor molded into the end of a nasogastric tube was tested in twelve healthy human volunteers. A Spearman's rank correlation coefficient (rs) of 0.90 was observed for the sensor and an indwelling miniature glass membrane electrode. The sensor did not correlate as well with aspirated stomach fluid (rs = 0.68). No sensor calibration was necessary and the sensors measured +/- 0.1 pH in laboratory pH buffers before and after the clinical study. Both bare and shielded disposable sensors closely agreed with a shielded miniature glass electrode.

The development of the nociceptive responses in neurokinin-1 receptor knockout mice.

An important yet unanswered question is how neonates respond to painful stimuli, given the immaturity of their neural pathways. We examined the development of the neurokinin system using a novel approach, examining changes of this system by observing the pain responses of mice lacking the NK1 receptor at different stages of development We show that the NK1 receptor is not involved in nociception to heat, mechanical or chemical stimuli, at 3 days. In contrast, the NK1 receptor is involved in nociceptive responses to high intensity heat and mechanical stimuli, and mediates the second phase of the formalin response in 21-day-old mice. This indicates that nociception in neonates does not require the NK1 receptor and that the functional maturation of the NK1 receptor allows diversity in both the type of stimuli that activate the pain system and the types of responses elicited by nociceptive stimuli.

Molecules that specify modality: mechanisms of nociception.

Damage-sensing neurons express a unique cohort of genes encoding channels and receptors that play a role in nociception. However, there are redundant pathways involved in, for example, inflammatory pain and many channels and receptors have additional physiologic roles unrelated to nociception. Thus, it is impossible to ascribe a particular sensory modality to the expressions of a single molecular entity. Despite this, the relatively selective expression of a number of channels and receptors in nociceptive neurons provide potentially interesting analgesic drug targets that can be examined through the generation of knockout mice.

An exceptional case of lethal disulfiram-alcohol reaction.

A case of fatal disulfiram-alcohol reaction due to ingestion of ethanol and antabuse is presented. Unusual autopsy findings and toxicological results are described. This case represents a report of corrosion lesion in the lower oesophagus and stomach due to a violent chemical reaction in situ and also the highest blood concentration of acetaldehyde (41 mg/l) ever recorded.

Measurement of 'free' gold in patients receiving disodium aurothiomalate and the association of high free to total gold levels with toxicity.

Serum from patients with rheumatoid arthritis (RA) receiving disodium aurothiomalate was analysed for total gold by atomic absorption spectrometry and for unbound (free) gold by the same method after ultrafiltration by an inert membrane. It was shown that it is possible to obtain reliable free gold concentrations by this method. Good correlations were shown between total and 'free' gold and between total and protein bound gold (PBG) for 54 patients with RA who were stabilised on gold therapy. Significant correlation was also shown between the same parameters for a second group of 15 patients starting gold therapy who were bled at weekly intervals for nine weeks immediately before medication. A single correlation with regression for all patients studied again showed good correlation between total and free gold and between total and PBG. Of the 189 paired values plotted, 182 fell within 2SD of the regression lines for the two plots. Of the seven patients with results outside 2SD of the regression line, six presented with side effects during the study.

Perioperative management of the left ventricular assist device recipient.

An understanding of the unique preoperative, intraoperative, and postoperative considerations of left ventricular assist device implantation is essential for the successful anesthetic management of these challenging cases. This article discusses the different stages of anesthetic care of the left ventricular assist device recipient, including preoperative assessment, lining, induction, separation from cardiopulmonary bypass, and the postbypass period.

Substance P elevates intracellular calcium in both neurons and glial cells from the dorsal horn of the spinal cord.

1. We used microfluorimetric measurement of [Ca2+]i to identify substance P-sensitive cells acutely isolated from the dorsal horn of neonatal rats. We then used morphological, physiological, and immunocytochemical criteria to delineate two distinct populations of substance P-sensitive dorsal horn cells. 2. One population of cells with small-diameter cell bodies and many fine processes responds to substance P by releasing Ca2+ from internal stores. Many of these cells express the O4 surface antigen, and are thus likely to be glial cells, probably from the oligodendrocyte lineage. None of the cells with glial attributes respond to N-methyl-D-aspartate (NMDA), providing further evidence that they are nonneuronal. 3. In a second population of dorsal horn cells, substance P elevates [Ca2+]i by promoting Ca2+ entry. This class of cells is morphologically distinct from substance P-sensitive glial cells in that it exhibits large-diameter cell bodies, has smooth tapering processes, and is sensitive to NMDA. This second class of cells is therefore likely to consist of neurons. 4. Consistent with the identification of different mechanisms of Ca2+ elevation in the two cell types, the kinetics of the substance P-evoked release of Ca2+ in glial cells is very different than the kinetics of the Ca(2+)-entry response evoked in neurons. The glial cell response had a rapid average rate of rise (mean = 260 +/- 105 nM/s) and relatively brief duration (mean = 7.6 +/- 2.2 s) whereas the neuronal response had a much slower rate of rise (mean = 10 +/- 9 nM/s) with a much longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Patterns of urinary excretion of gold in patients with rheumatoid arthritis undergoing chrysotherapy.

Thirty patients receiving gold therapy for rheumatoid arthritis (RA) were studied for the urinary excretion of gold. Statistical analysis of all the urine specimens passed over a period of four days by each patient showed that a definite rhythm of gold excretion exists for each patient which is possibly related to water excretion but not to creatinine excretion. The study indicates possible reasons for the inability of earlier workers to relate gold excretion to the general body gold status of patients and suggests that as the study of 24 hour excretions of gold may be an insensitive marker of gold excretion, closer examination of individual patient rhythms of gold excretion could possibly provide a more useful method of analysis.

Patterns of gold levels in urine, serum, and saliva in patients with rheumatoid arthritis undergoing chrysotherapy.

Twenty patients undergoing treatment with aurothiomalate for rheumatoid arthritis (RA) were studied for the presence of gold in all urine specimens passed over four days and for gold in the serum of blood drawn by venous section at 10.00, 16.00, and 22.00 hours on a single day of the study. Specimens of saliva collected at the same times as the blood specimens were also analysed for (total) gold content. Eighteen patients showed rhythmic urinary gold excretion. Variations were observed in the serum levels for total, free, and protein bound gold at different times of the day and night together with similar variations in the salivary total gold levels. It was established that a possible relation exists between urinary gold, serum gold, and salivary gold such that at times of higher urinary gold excretion the serum gold levels (total, free, and protein bound) and the total salivary gold levels were decreased. Conversely, at times of lower urinary gold excretion serum and salivary gold levels were increased.

Habitability of planets around red dwarf stars.

Recent models indicate that relatively moderate climates could exist on Earth-sized planets in synchronous rotation around red dwarf stars. Investigation of the global water cycle, availability of photosynthetically active radiation in red dwarf sunlight, and the biological implications of stellar flares, which can be frequent for red dwarfs, suggests that higher plant habitability of red dwarf planets may be possible.