A comparison of the antimuscarinic effects of pirenzepine and N-methylatropine on ganglionic and vascular muscarinic receptors in the rat

The antimuscarinic properties of pirenzepine and N-methylatropine were evaluated in two intact preparations by measuring A) the inhibition of increase in mean arterial pressure evoked by McN-A-343 in pithed rats through activation of ganglionic muscarinic receptors and B) the inhibition of fall in arterial pressure evoked by methacholine in anaesthetized rats through activation of vascular muscarinic receptors. To characterize the antimuscarinic potencies of pirenzepine and N-methylatropine, for both antagonists doses were calculated that produce a 10-fold shift to the right of the dose-response curves for A) the pressor response to McN-A-343 (i.v. administration) in pithed rats (D10-p.r.) and B) for the depressor effect to methacholine (i.v. administration) in anaesthetized rats (D10-an.r.), respectively. Whereas N-methylatropine was virtually equieffective in blocking both muscarinic responses (D10-an.r./D10-p.r. approximately equal to 1), pirenzepine, however, was considerably more potent at ganglionic than at vascular muscarinic receptors (D10-an.r./D10-p.r. approximately equal to 16). These data confirm the existence of excitatory ganglionic muscarinic receptors with high affinity for pirenzepine (M1) and provide evidence for the presence of M2 receptors - receptors which show a low sensitivity to pirenzepine - on vascular smooth muscle cells. To further characterize the anticholinergic properties of pirenzepine, its effect on the pressor response to DMPP, a nicotinic ganglionic stimulant, was investigated in pithed rats. A high dose of pirenzepine (1.13 mumol/kg), given i.v., did not affect nicotinic ganglionic transmission.     

COMPARISON OF DNA RENEWAL IN GERM-FREE AND CONVENTIONAL MICE USING [125I]IODODEOXYURIDINE AND [3H]THYMIDINE

Germ-free (GF) and conventional (CV) C3H mice received a single injection of 1 μCi [³H]thymidine and 3 μCi [¹²⁵I]iododeoxyuridine to provide simultaneous labeling of DNA with the two precursors. Thymus, spleen, mesenteric lymph nodes, bone marrow (femora), small intestine, colon and skin were examined for total organ activity and rate of DNA renewal 1–8 days after injection. Precursor incorporation, assayed on day 1, was lower in the thymus, mesenteric lymph nodes and femora (and, to a lesser extent, in the spleen and colon) of GF mice as compared to CV animals. The opposite was observed in the small intestine and skin, i.e. total organ activity was higher in GF animals. Differences in precursor incorporation were partly due to differences in organ weights between the two groups of mice. In comparison to CV animals, DNA renewal rates were diminished in the mesenteric lymph nodes, bone marrow, colon (following a 3-day plateau) and spleen of GF mice. Little, if any, difference was observed between the two groups with respect to the rate of DNA turnover in the thymus and skin. Radioactivity of the small intestine remained constant for 2 days. Thereafter intestinal activity in GF mice declined at an initial slow rate between days 2 and 5 followed by a rapid decrease between days 5 and 8. In CV mice the first phase of activity loss was short with the rapid decline in intestinal activity beginning on day 3. From the slopes of the regression lines, the percentage thymidine reutilization was estimated. Reutilization varied from 0 to 63% in the various organs examined, with the greatest difference between GF and CV mice occurring in the mesenteric lymph nodes.     

Cortical mechanisms and cues for action

Monkeys have more highly developed brains and are more intelligent than rats; yet rats learn some tasks as efficiently as monkeys. For example, rats are as quick at discovering which of two doors hides food or how to open the doors. Presumably tasks of this sort do not greatly tax cortical associative mechanisms since the animals have only to cumulate facts about objects. It is argued that cortical mechanisms are crucial for the ability to relate together information that is presented at different times or in different places. After removal of parts of frontal cortex monkeys can still associate cues that are presented together but they are poor at relating cues that are presented apart.     

NAD+ kinase: molecular weight determination by low-angle laser-light scattering

Low-angle laser-light scattering (LALLS) was employed to measure the absolute molecular weight of chicken liver NAD+ kinase (NADK). The weight-average molecular weight (Mw) was found to be 275 000 +/- 15 000. The corresponding value for the second virial coefficient was -1.65 X 10(-3) ml X mol X g2. The value for Mw is in close accord with estimates reported for pigeon liver (270 000) and C. utilis (260 000) NADK. If the active enzyme is a dimer, the weight difference between pigeon/chicken liver and rabbit liver (136 000) NADK would indicate that the latter enzyme is an active monomer unit.     

Separation of peptides by reverse-phase high-performance liquid chromatography using propyl- and cyanopropylsilyl supports

The separation of peptides and proteins by reverse-phase high-performance liquid chromatography with cyanopropylsilyl and large-pore propylsilyl supports, together with aqueous trifluoroacetic acid/acetonitrile gradients, was studied. Operating parameters (trifluoroacetic acid concentration, flow rate, and gradient slope) were evaluated using different enzymatic digests of horse cytochrome c and bovine serum albumin. Peptides ranging in size from five amino acids to 68 kDa could be separated on the propylsilyl column in a single chromatographic run. The cyanopropylsilyl column is suitable as a supplement to the use of the large-pore column for medium size (5-20 amino acids) peptides. The chromatographic supports and conditions presented here offer a simple, sensitive, and rapid separation system for a wide size range of peptides and proteins. They extend the versatility of separation methodology for these molecules.     

Tolerance induction by the peroral administration of protein antigens

The possibility of inducing systemic tolerance in animals by feeding them with ovalbumin and human serum was studied on mice, rats and rabbits. Antibodies to ovalbumin, human serum albumin and immunoglobulins (IgG, IgA, IgM) were determined by the passive hemagglutination test in the sera of the test and control animals after the second immunization made through a parenteral route. Tolerance to all the antigens under study was obtained in mice and rats, while in rabbits such feeding was found to produce the priming effect. The degree of tolerance was the greater, the more was the dose of the antigen and the longer was the period of feeding. Different proteins showed varying tolerogenic activity; the same degree of tolerance in mice was obtained by feeding them with IgG in a dose of 0.3-0.5 mg and with ovalbumin or human serum albumin in a dose of 6-12 mg (per gram of body weight). Tolerance was determined on day 3 after the course of feeding was over; in 3 weeks tolerance essentially decreased, and in 1.5-2 months it was replaced by normal reactiveness. Tolerance induced by the oral administration of antigens proved to be immunologically specific.     

The Coccidian Genus Calyptospora n. g. and Family Calyptosporidae n. fam. (Apicomplexa), with Members Infecting Primarily Fishes1

Calyptospora n. g. was erected for Eimeria funduli because the sporocyst of that species lacks Stieda and sub-Stieda bodies, has a veil supported by sporopodia, and has an anterior apical opening. A suture may be present, but it does not completely divide the sporocyst into two valves. Because C. funduli has an obligatory invertebrate intermediate host, we established Calyptosporidae n. fam. to accommodate Calyptospora and tentatively to accept Goussia. A new subgenus, Plagula, is erected for species of Goussia with a sporocystic veil not supported by sporopodia. We consider the family more primitive than Eimeriidae, Sarcocystidae, and possibly Lankesterellidae.     

Some dermatoglyphic traits in breast carcinoma

The finger and palmar prints of 60 women with breast carcinoma were studied. The results were compared with two groups of healthy women, the first consisted of old women and the second of young women. The dermatoglyphics seem to be of little use in the diagnosis of cancers of ectodermic origin. Supported by M.P.I. 60%, 1983