BackgroundThe maintenance of the intestinal epithelium is of great importance for the survival of the organism. A possible nervous control of epithelial cell renewal was studied in rats and mice.MethodsMucosal afferent nerves were stimulated by exposing the intestinal mucosa to capsaicin (1.6 mM), which stimulates intestinal external axons. Epithelial cell renewal was investigated in the jejunum by measuring intestinal thymidine kinase (TK) activity, intestinal 3H-thymidine incorporation into DNA, and the number of crypt cells labeled with BrdU. The influence of the external gut innervation was minimized by severing the periarterial nerves.Principal FindingsLuminal capsaicin increased all the studied variables, an effect nervously mediated to judge from inhibitory effects on TK activity or 3H-thymidine incorporation into DNA by exposing the mucosa to lidocaine (a local anesthetic) or by giving four different neurotransmitter receptor antagonists i.v. (muscarinic, nicotinic, neurokinin1 (NK1) or calcitonin gene related peptide (CGRP) receptors). After degeneration of the intestinal external nerves capsaicin did not increase TK activity, suggesting the involvement of an axon reflex. Intra-arterial infusion of Substance P (SP) or CGRP increased intestinal TK activity, a response abolished by muscarinic receptor blockade. Immunohistochemistry suggested presence of M3 and M5 muscarinic receptors on the intestinal stem/progenitor cells. We propose that the stem/progenitor cells are controlled by cholinergic nerves, which, in turn, are influenced by mucosal afferent neuron(s) releasing acetylcholine and/or SP and/or CGRP. In mice lacking the capsaicin receptor, thymidine incorporation into DNA and number of crypt cells labeled with BrdU was lower than in wild type animals suggesting that nerves are important also in the absence of luminal capsaicin, a conclusion also supported by the observation that atropine lowered thymidine incorporation into DNA by 60% in control rat segments.ConclusionEnteric nerves are of importance in maintaining the intestinal epithelial barrier.

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Net fluid transport was measured in denervated jejunal segments of rats infected with larvae of Nippostrongylus brasiliensis. On days 6-9 after nematode inoculation, when the jejunal segment exhibited macroscopic and microscopic signs of inflammation, net fluid absorption was noticeably attenuated compared with control, and in eight of 26 experiments a net fluid secretion was seen. To determine whether enteric nerves participated in the response, intravenous hexamethonium (10 mg/ kg body weight) was given or lidocaine (1% solution) was placed on the serosa of the intestinal segment. Both drugs significantly reduced fluid secretion or increased fluid absorption. The This study was designed to investigate further the relationship between inflammation and fluid transport in the small intestine of the rat. For this purpose rats were inoculated with Nippostrongylus brasiliensis by injecting the parasites subcutaneously. On day 3 the nematodes reach the small intestine and on days 6-8 an inflammatory response in the jejunum is seen. Ten to 12 days after inoculation, the worms are expelled from the small intestine and the inflammatory response fades away. Fluid transport was measured in vivo in rats before and after expulsion of the parasite and the possible involvement of ENS in the response was tested pharmacologically. Methods ANIMALSSprague-Dawley rats (Alab AB, Stockholm, Sweden) weighing 300-400 g were given a subcutaneous injection of 6000 larvae of Nippostrongylus brasiliensis in 0 5 ml saline. Rats were housed in standardised environmental conditions (22°C, 60% humidity, light 6-00-18.00 hours). The animals were studied on days 6-9 or 11-14 after being injected with larvae.ANESTHESIA AND OPERATIVE PROCEDURES Anaesthesia was induced by mebumal (60 mg.kg-1 body weight) and maintained with chloralose (100 mg.kg-1 bw) as a bolus plus 20 mg.h-l.kg-1 body weight as an infusion.A tracheotomy was performed and a tracheal cannula was inserted to maintain a free airway. Catheters were inserted into the femoral artery and vein for blood pressure recordings and drug administration, respectively. To prevent acidosis due to the operative trauma an infusion of a glucose-bicarbonate solution (see below) was given intra-arterially at a rate of 0 03 ml.min-l. A Statham pressure transducer (Model P23AC) was connected to the arterial catheter and arterial pressure was continuously recorded on a Grass polygraph.The abdomen was opened by midline incision. A 5 to 10 cm long segment of the jejunum was selected. In the experiments performed on days 6-9 after injecting the larvae, the part of the jejunum with the most severe signs of inflammation was selected for the experiment. The remainder of the small intestine and the colon were removed. All nerves in the tissues around the superior mesenteric artery were cut, thereby accomplishing denervation of the extrinsic autonomic nervous supply to the intestinal segment.The rat was placed on a thermistor controlled operating table. The rat, except for its head and 1526 on 9 May 20...

D/H isotope-substitution effects on the Jahn-Teller (J-T) distortion of cation radicals of partially deuteriated benzenes; benzene-d 5 , benzene-1,2,4,5-d 4 , benzene-1,4-d 2 , and benzene-1,3,5-d 3 , were investigated by electron spin resonance (EPR) using frozen haloalkanes and porous silicas as matrices. Quantum-chemical calculations using the density functional theory (DFT) method were also performed. The way of distortion of the cation radicals of selectively deuteriated benzenes is unique relative to the deuteriation sites in all the matrices used. The ground state of the distorted cation is 2 B 2g of D 2h symmetry, regardless of the way of isotope labeling. The undeuteriated C-H bonds occupy the specific positions in the distorted form where the higher spin density appears, in agreement with the result of theoretical calculations. The role of the matrix to stabilize the distorted form is also discussed.

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