The effects in vivo of purified preparations of murine macrophage colony stimulating factor-1, recombinant murine granulocyte-macrophage colony stimulating factor and natural and recombinant murine interleukin 3 without and with pretreatment of mice with purified iron-saturated human lactoferrin

The influence of purified natural colony stimulating factor-1 (CSF-1), purified recombinant granulocyte-macrophage (GM)-CSF, purified recombinant interleukin 3 (IL3) and natural IL3 were assessed in mice that were untreated or pretreated with purified iron-saturated human lactoferrin (LF) in order to first suppress myelopoiesis in the mice. S1/S1d mice responded to recombinant GM-CSF and recombinant IL3 in a manner similar to the response of their +/+ littermates. These 4 factors increased the cycling status of hematopoietic progenitors in vivo. The effects were more noticeable if myelopoiesis was first decreased by LF. The effects do not appear to be due to endotoxin contamination. It cannot be discerned from these studies whether the effects are direct ones on the progenitor cells or indirect ones mediated through growth-factor releasing accessory cells. It is possible that effects can be both direct and indirect.     

Recent advances with thyrocalcitonin.

Thyrocalcitonin (TCT) is a 32 amino acid peptide hormone similar, but not identical, in structure from fish to man. Mammals produce the hormone in non-follicular thyroidal "C-cells" which can be identified visually using recently developed immunocytochemical methods. Although TCT exerts effects on the gut and kidney, bone seems to be the primary target tissue. The ability of TCT to restrict calcium fluxes from bone to blood and to inhibit bone resorption explains its utility for treating certain metabolic bone diseases, e.g. Paget's disease. The bone effects also account for the ability of TCT to combat a hypercalcemic challenge. Recent work suggests close relationships and a possible closed-loop feedback system between the gut and thyroid. In animals, gastrin is a potent TCT secretagogue; studies in man indicate that TCT, in turn, can effect gastric acid secretion and intestinal secretion of water and electrolytes. This gastrin-TCT relationship may help control levels of blood calcium during intestinal absorption of calcium following feeding. The ability of gastrin to stimulate TCT release has been applied clinically for the early diagnosis of medullary thyroid carcinoma (MTC), a C-cell tumor. Subclinical or questionable cases of MTC have been identified reliably using a simple, rapid provocative test involving pentagastrin injection and evaluation of blood samples by radioimmunoassay for elevated levels of TCT.     

Smoking Cessation in the Chicago Coronary Prevention Evaluation Program

Quit-rates for cigarette smokers in a lifestyle intervention program aimed at reducing coronary risk were 24 percent for all participants and 34 percent for non-dropouts. Recidivism remained very low during participation in the program. Half of the smokers who quit did so after being in the program more than two years. These data suggest that while engaging in an effort to make other changes in lifestyle, many smokers can be helped to quit. Sustained antismoking efforts in the clinical practice of medicine can be expected to share these same positive aspects. While mass public health programs to eliminate smoking and prevent young people from taking up the habit are being developed, health practitioners can make a significant contribution by including vigorous efforts at smoking cessation as part of routine practice.     

The effect of noradrenaline and 5-hydroxytryptamine injected into a lateral cerebral ventricle, on thermoregulation in the new-born lamb.

1. Respiratory frequency, shivering, ear skin temperatures and rectal temperatures were observed following intraventricular injections of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and saline (NaCl) into new-born lambs exposed to ambient temperatures of 4, 21, or 30 degrees C. 2. Intraventricular NA caused respiratory rate to decrease and body temperature to increase in the 30 degrees C environment. At 21 degrees C, it increased ear skin temperature but did not significantly affect rectal temperature. At 4 degrees C, NA decreased shivering and rectal temperature fell. 3. 5-HT elevated respiratory rate in the 30 degrees C environment and increased ear skin temperature in the 21 and 4 degrees C environments. In the 4 degrees C environment rectal temperature decreased. 4. In general, the change in rectal temperature was related to the dosage of drug administered. Control injections of NaCl had no significant effect on any of the variables measured. 5. The monoaminergic pathways involved in thermoregulation in the new-born lamb appear to be organized in a manner similar to that of the adult sheep and are functional at birth.     

Nicotinic AChR in subclassified capsaicin-sensitive and -insensitive nociceptors of the rat DRG

Nociceptive cells of the dorsal root ganglion (DRG) were subclassified, in vitro, according to patterns of voltage-activated currents. The distribution and form of nicotinic ACh receptors (nAChRs) were determined. nAChRs were present on both capsaicin-sensitive and -insensitive nociceptors but were not universally present in unmyelinated nociceptors. In contrast, all A delta nociceptors (types 4, 6, and 9) expressed slowly decaying nAChR. Three major forms of nicotinic currents were identified. Specific agonists and antagonists were used to demonstrate the presence of alpha7 in two classes of capsaicin-sensitive, unmyelinated nociceptors (types 2 and 8). In type 2 cells, alpha7-mediated currents were found in isolation. Whereas alpha7 was co-expressed with other nAChR in type 8 cells. These were the only classes in which alpha7 was identified. Other nociceptive classes expressed slowly decaying currents with beta4 pharmacology. Based on concentration response curves formed by nicotinic agonists [ACh, nicotine, dimethyl phenyl piperazinium (DMPP), cytisine] evidence emerged of two distinct nAChR differentially expressed in type 4 (alpha3beta4) and types 5 and 8 (alpha3beta4 alpha5). Although identification could not be made with absolute certainty, patterns of potency (type 4: DMPP > cytisine > nicotine = ACh; type 5 and type 8: DMPP = cytisine > nicotine = ACh) and efficacy provided strong support for the presence of two distinct channels based on an alpha3beta4 platform. Studies conducted on one nonnociceptive class (type 3) failed to reveal any nAChR. After multiple injections of Di-I (1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) into the hairy skin of the hindlimb, we identified cell types 2, 4, 6, 8, and 9 as skin nociceptors that expressed nicotinic receptors. We conclude that at least three nicotinic AChR are diversely distributed into discrete subclasses of nociceptors that innervate hairy skin.     

Attenuation of sham feeding by naloxone is stereospecific: evidence for opioid mediation of orosensory reward

The time course of the suppressive action of naloxone on sham feeding was examined in gastric fistulated rats. One hour sham intake of 30% sucrose solution was halved by 1.25 mg/kg IP (-)-naloxone. A maximal 75% reduction was obtained with 2.5 mg/kg. Naloxone's effect appeared to mimic the attenuation of intake rate produced by sucrose dilution. The stereoisomer (+)-naloxone (1.25, 2.5 and 10 mg/kg IP) was ineffective. These data confirm the involvement of opioid receptors in naloxone anorexia and are consistent with opioid involvement in the rewarding aspects of ingestion.