In search of the central respiratory neurons: II. Electrophysiologic studies of medullary fetal cells inherently sensitive to CO2 and low pH.

Although extensively pursued, the central respiratory neurons have remained elusive. We departed from the more conventional physiologic and morphologic methods of system and tissue examination and cultured dissociated fetal rat cells (Fitzgerald et al., J Neurosci Res 33:579-589, 1992) from the area of the nucleus ambiguus and the nucleus tractus solitarius located within the 2 mm rostral to the obex. Pacemaker-like cells, with a regular single or bursting activity, studied at 3-5 weeks of age, responded to very small pulses of CO2 (50 ms) and low pH with an increase in spike frequency and a decrease in spike amplitude. Other irregularly beating or silent cells did not respond or else required very large pulses (> 200 ms) to do so. The pacemaker cells also responded to hypoxia induced by administration of sodium hydrosulfite with an increase in spike frequency and amplitude; high oxygen (> 600 torr) and adenosine produced a decrease in electrical activity. Most of these cells were multipolar after staining with antibodies to neuron-specific enolase (NSE) and Fragment C of tetanus toxin. They did not stain for choline acetyltransferase (ChAT). The results suggest that these cultured cells, expressing a phenotype inherently responsive to CO2 and low pH, have the characteristics of central respiratory chemoreceptors, and may be involved in the generation of the respiratory rhythm.     

Coping with gastrointestinal endoscopy: self-efficacy enhancement and coping style.

Forty-eight men scheduled for endoscopy were assessed for preferred coping style and assigned to one of four preparation conditions: (a) relaxation plus coping self-efficacy (SE) enhancement, (b) relaxation only, (c) procedural information, and (d) no preparation. It was hypothesized that increases in SE would be associated with better behavioral and self-report assessments of coping with endoscopy, and that coping style would moderate effects of SE enhancement. Hypotheses were largely confirmed. Ss in SE enhancement preparation experienced greater increases in coping SE and greater decreases in distress before and during endoscopy than did other Ss. Changes in coping SE were negatively correlated with changes in anticipatory anxiety, and SE ratings were significantly related to distress during endoscopy. Ss classed as monitors fared most poorly with no-preparation, whereas blunters did most poorly with procedural information.     

Essential Nature of Choline with Implications for Total Parenteral Nutrition

Choline is known to be important in many metabolic pathways; at this time, however, it is not considered an essential nutrient for human beings. Current evidence strongly suggests that choline is “conditionally essential,” particularly for patients receiving total parenteral nutrition (TPN). Studies in patients receiving long-term TPN have shown that low levels of plasma choline are common and can be associated with hepatic steatosis. Treatment of these patients with oral administration of choline improved plasma levels and decreased hepatic fat content; however, oral choline supplements are associated with poor compliance. More recently, investigators have evaluated intravenous administration of choline as a treatment for TPN-associated hepatic steatosis in patients with documented subnormal plasma free-choline levels. Initial results indicate that intravenous administration of choline may be an effective treatment for TPN-associated hepatic dysfunction.     

Mucolytic agents and otitis media with effusion

Middle ear effusion was obtained from children with otitis media with effusion and separated into thick (mucoid) and thin (serous) pools. Both effusion types contained similar amounts of non-dialysable solids. However, the thick effusions contained more mucus glycoprotein than the thin effusions, 25% and 8.2% respectively. Amino acid and carbohydrate analysis of the CsCl purified mucus glycoproteins demonstrated that the glycoprotein from the thick and thin effusions differed in their protein core, those from the thick effusions possessing a higher percentage of serine and threonine, the amino acids to which the sugar side-chains attach. They are also more glycosylated. N-acetyl cysteine and mercaptoethanol caused a fall in the viscosity of solutions of purified middle ear glycoprotein and effusion homogenate. However, longer term incubation caused a rise above the starting viscosity. This effect was concentration-dependent, and was mediated by low molecular weight components in the effusion and not the mucus glycoprotein. S-carboxymethyl cysteine had no effect on the viscosity of either the purified mucus glycoprotein or the effusion homogenate. Therefore, to produce a decrease in effusion viscosity in vivo, the concentration of mucolytic reaching the middle ear and the time it remains there are critical factors.     

Biochemical actions of chronic ethanol exposure in the mesolimbic dopamine system

In previous studies, we have demonstrated that chronic administration of morphine or cocaine produces some common biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc), components of the mesolimbic dopamine system implicated in the reinforcing actions of these and other drugs of abuse. Since this neural pathway is also implicated in the reinforcing actions of ethanol, it was of interest to determine whether chronic ethanol exposure results in similar biochemical adaptations. Indeed, as seen for chronic morphine and cocaine treatments, we show here that chronic ethanol treatment increased levels of tyrosine hydroxylase and glial fibrillary acidic protein immunoreactivity, and decreases levels of neurofilament protein immunoreactivity, in the VTA. Also like morphine and cocaine, ethanol increases levels of cyclic AMP-dependent protein kinase activity in the NAc. These actions of ethanol required long-term exposure to the drug, and were in most cases not seen in the substantia nigra or caudate-putamen, components of the nigrostriatal dopamine system studied for comparison. Altered levels of tyrosine hydroxylase in catecholaminergic cells frequently reflect altered states of activation of the cells. Moreover, increasing evidence indicates that ethanol produces many of its acute effects on the brain by regulating NMDA glutamate and GAB_A receptors. We therefore examined the influence of chronic ethanol treatment on levels of expression of specific glutamate and GABA receptor subunits in the VTA. It was found that long-term, but not short-term, ethanol exposure increased levels of immunoreactivity of the NMDARl subunit, an obligatory component of NMDA glutamate receptors, and of the Glu Rl subunit, a component of many AMPA glutamate receptors; but at the same time, long-term ethanol exposure decreased immunoreactivity levels of the α1 subunit of the GABA_A receptor complex. These changes are consistent with an increased state of activation of VTA neurons inferred from the observed increase intyrosine hydroxylase (TH) expression. These results demonstrate that chronic ethanol exposure results in several biochemical adaptations in the mesolimbic dopamine system, which may underlie prominent changes in the structural and functional properties of this neural pathway related to alcohol abuse and alcoholism. © 1995 Wiley-Liss, Inc.     

Day-to-Day Variation in Iron Status Indexes is Similar for Most Measures in Elderly Women With and Without Rheumatoid Arthritis

Objective To determine the day-to-day variation in biochemical measures of iron status in a group of elderly women with rheumatoid arthritis compared with a group of healthy elderly women.Design Venous blood samples were collected from each subject on 3 nonconsecutive days during a 2-week study period; subjects had fasted overnight. Variability in hemoglobin level, hematocrit value, serum iron concentration, total iron-binding capacity, transferrin saturation, serum ferritin concentration, and plasma transferrin receptor level was determined.Subjects Two groups of women, one with rheumatoid arthritis (n=10) and another that was apparently healthy (n=10).Statistical analyses Variance component analysis was used to estimate the biological variation (σ²_day) and analytic variation (σ²_rep) for each iron index. The coefficient of variation (CV) for each variance component was calculated: coefficient of biological variation = CV_day, coefficient of analytic variation = CV_rep, and coefficient of a single future determination = CV_fd.Results The CV_rep for all iron indexes was smaller than the CV_day in both groups. The CV_day was considerably higher for serum iron concentration and for transferrin saturation than for the other indexes in both groups (16.6% arid 16.6% in healthy subjects and 33.6% and 28.2%, respectively, in subjects with rheumatoid arthritis). The higher CV_day for serum iron concentration and transferrin saturation translated into a higher CV_fd for these indexes. Because of the higher variance for these two indexes, more sampling days were required for reliable estimates. CV_da and CV_fd for plasma transferrin receptor level were relatively low.Conclusions These findings corroborate our previous finding that variation of serum ferritin concentration in the elderly is lower than that demonstrated in younger populations. This aging effect persists in the presence of rheumatoid arthritis. Fasting appeared to improve reliability in the determinations for serum iron concentration and transferrin saturation. Variability estimates for the indexes other than serum iron concentration and transferrin saturation were not altered by the inflammation of rheumatoid arthritis. Plasma transferrin receptor level is a reliable index for assessing iron status in populations with rheumatoid arthritis. J Am Diet Assoc. 1996; 96:247-251.