Complexation of polyvalent cyclodextrin ions with oppositely charged guests: entropically favorable complexation due to dehydration.

Thermodynamic parameters for complexation of polyvalent cyclodextrin (CD) cation and anion with oppositely charged guests have been determined in D2O containing 0.02 M NaCl by means of 1H-NMR spectroscopy. Protonated heptakis(6-amino-6-deoxy)-beta-CD (per-NH3+-beta-CD) forms stable inclusion complexes with monovalent guest anions. The enthalpy (deltaH) and entropy changes (deltaS) for complexation of per-NH3+-beta-CD with p-methylbenzoate anion (p-CH3-Ph-CO2-) are 3.8 +/- 0.7 kJ mol(-1) and 88.6 +/- 2.2 J mol(-1) K(-1), respectively. The deltaH and deltaS values for the native beta-CD-p-CH3-Ph-CO2- system are -8.6 +/- 0.1 kJ mol(-1) and 15.3 +/- 0.7 J mol(-1) K(-1), respectively. The thermodynamic parameters clearly indicate that dehydration from both the host and guest ions accounts for the entropic gain in inclusion process of p-CH3-Ph-CO2- into the per-NH3+-beta-CD cavity. The fact that the neutral guests such as 2,6-dihydroxynaphthalene and p-methylbenzyl alcohol hardly form the complexes with per-NH3+-beta-CD exhibits that van der Waals and/or hydrophobic interactions do not cause the complexation of the polyvalent CD cation with the monovalent anion. The acetate anion is not included into the per-NH3+-beta-CD cavity, while the butanoate and hexanoate anions form the inclusion complexes. The complexation of the alkanoate anions is entropically dominated. Judging from these results, it may be concluded that Coulomb interactions cooperated with inclusion are required for realizing the large entropic gain due to extended dehydration. Entropically favorable complexation was also observed for the anionic CD-cationic guest system. The present study might present a general mechanism for ion pairing in water.

Acute performance of steroid-eluting screw-in leads for atrial free wall pacing.

The aim of this study was to clarify the acute performance of steroid-eluting screw-in leads in comparison with that of nonsteroid screw-in leads for atrial free wall pacing. In 114 cases (68 males, 46 females, average age 70 years) with atrial free wall pacing by screw-in leads, pacing thresholds and P-wave amplitudes were compared at the time of implantation and 1 week later between 68 cases of nonsteroid and 46 cases of steroid-eluting screw-in leads. No significant differences were seen between the 2 groups at implantation in either voltage or current thresholds measured at pulse widths of 0.1, 0.3, 0.6, 1.0, 2.0 ms, or P-wave amplitudes. Pulse width thresholds at outputs of 2.5 V and 5.0 V were significantly lower for steroid leads 1 week after implantation (2.5 V: 0.34+/-0.27 ms nonsteroid vs. 0.12+/-0.08 ms steroid, p<0.001; 5.0 V: 0.12+/-0.08 ms nonsteroid vs. 0.06+/-0.02 ms steroid, p<0.01). P-wave amplitudes after 1 week were significantly higher for steroid leads (2.6+/-0.7 mV nonsteroid vs 3.0+/-1.2 mV steroid, p<0.001). Threshold rise, including pacing failure, was observed in 15 (22%) of the non-steroid leads, but in only 1 (2%) of the steroid leads. In conclusion, steroid-eluting screw-in leads suppress the acute rise of pacing thresholds in the right atrial free wall and their acute performance is better than that of non-steroid leads. These results suggest that appropriate low-output atrial pacing is feasible immediately after implantation.

Immunocytochemical study of parvalbumin, calbindin D-28k, and calretinin in the superficial dorsal horn of the rat spinal cord following unilateral hindpaw inflammation.

The effect of noxious stimulation on the immunore-activity of the calcium-binding proteins parvalbumin (PV), calbindin-D-28k (CB) and calretinin (CR) was investigated in the superficial dorsal horn of lumbar levels L5-L3 of the rat spinal cord. Freund's adjuvant was injected unilaterally into the hindpaw to induce inflammation. Immunohistochemical techniques were utilized to investigate changes in the calcium-binding proteins 2h and 1, 2, 4, and 7 days after injection. At 24h after injection, a decrease in the intensity of fluorescence of PV-immunoreactive (IR) fibers was observed in the superficial layer (substantia gelatinosa) of the ipsilateral dorsal horn (L5-L3) in most animals. Comparatively fewer animals exhibited changes in the CB- and CR-IR fibers, except at the L3 level 2 days after, and at the L4 level 7 days after the hindpaw injection. After the peak response, at 24h in most animals, there was a decline in the number of responders at 2 days and no differences were noted at 4 days. However, at 7 days, there was again an increase in the number of animals revealing diminished fluorescence intensity in the ipsilateral substantia gelatinosa. Changes in immunoreactivity of calcium binding proteins in the interneurons of the superficial lumbar dorsal horn may reflect hyperactivity within these neurons following noxious stimulation.

Distribution of Fos-like immunoreactivity in the caudal medullary reticular formation following noxious facial stimulation in the rat.

To investigate the topographic organization of nociceptive neurons in the caudal medullary reticular formation, the distribution of cells that exhibit c-fos expression was examined following a unilateral noxious facial stimulus: subcutaneous injection of formalin into the vibrissal pad of awake rats. Labelling for Fos-like immunoreactivity was present in a somatotopic distribution in a region of the lateral reticular formation adjacent to trigeminal nucleus caudalis, which corresponds approximately to lamina V of the medullary dorsal horn. Labelling in adjacent regions of the reticular formation showed no somatotopy but was predominantly ipsilateral. Contralateral labelling was concentrated ventrolaterally around the lateral reticular nucleus and dorsally near the nucleus of the solitary tract.

Distribution of fos-like immunoreactivity in the medullary and upper cervical dorsal horn produced by stimulation of dural blood vessels in the rat.

Neurophysiological studies have generally failed to find evidence of a specific ascending pathway for visceral nociception. However, pain that arises from deep or visceral tissues typically differs from cutaneous pain, particularly in its diffuse, poorly localized quality. In this study, the c-fos mapping technique was used in order to investigate possible differences in the distribution of central neurons activated by afferent pathways from cutaneous and deep tissues that may be related to the differing quality of the sensations they evoke. The distribution of neurons in the upper cervical and medullary dorsal horn that displayed fos-like immunoreactivity (fos-LI) was examined following mechanical stimulation of dural blood vessels (transverse and superior sagittal sinuses), and was compared to that found following mechanical, thermal, and chemical stimulation of facial sites. Dural stimulation was carried out Brevital anesthesia in rats that had received a chronic surgical exposure of the transverse and superior sagittal sinuses 2 d earlier. Localized mechanical stimulation of the dural surface of the transverse sinus produced a predominantly ipsilateral increase in the number of fos-LI neurons in the medullary and upper cervical dorsal horn (primarily laminae I and V), and in the transition region between the trigeminal nucleus caudalis and interpolaris. Stimulation of the superior sagittal sinus produced increases in fos-LI labeling that were generally smaller than those produced by transverse sinus stimulation. The distribution of fos-LI labeling in the dorsal horn induced by dural stimulation differed from that induced by facial stimulation in two ways. (1) Dural stimulation produced a more diffuse distribution of fos-LI than facial stimulation in the dorsal horn. Whereas facial stimulation produced a dense, localized zone of fos-LI labeling in the dorsal horn, dural stimulation produced fos-LI labeling that extended from the midlevel of caudalis to C2/C3, and also extended across a large portion of the ventrolateral-to-dorsomedial axis of the dorsal horn. This distribution roughly corresponds to the representation of most of the dorsal half of the head and face. (2) Dural stimulation produced a more restricted laminar distribution of fos-LI labeling than facial stimulation, in that the dural-induced labeling in the superficial dorsal horn was primarily restricted to lamina I, whereas facial stimulation typically induced substantial labeling in both lamina I and the outer part of lamina II. These differences in the central organization of the afferent pathways from dural and facial sites may contribute to the differences in the quality of sensations evoked by these pathways.

Fos-like immunoreactivity in the superficial medullary dorsal horn induced by noxious and innocuous thermal stimulation of facial skin in the rat.

1. To examine further the ability of different classes of nociceptive and nonnociceptive primary afferent neurons to induce c-fos expression in central neurons, fos-like immunoreactivity was examined in the medullary dorsal horn (laminae I-IV) of the rat after facial application of a range of warming and cooling thermal stimuli. Urethan-anesthetized rats received 15 30-s thermal pulses (53, 50, 47, 41, 25, or 10 degrees C) applied to the vibrissal pad over a period of 30 min and were perfused 2 h after the end of stimulation. 2. Stimulation of 41 degrees C produced no significant increase in the number of fos-LI-labeled cells in lamina I or II compared with control (35 degrees C) animals. 3. Stimulation of 47 degrees C produced a significant increase in the number of fos-LI-labeled cells in both laminae I and II. Stimulation of 50 degrees C produced a significant increase in labeling, compared with that produced by 47 degrees C, which was primarily in lamina II. Stimulation of 53 degrees C produced no further increase in the number of labeled cells, compared with that produced by 50 degrees C, in lamina I or II. 4. In the cooling direction, 25 degrees C produced a significant increase in labeling above control levels in both lamina I and II, whereas 10 degrees C produced a further increase compared with 25 degrees C, which was restricted to lamina I. 5. None of the stimuli produced a significant increase in labeling in laminae III-IV. 6. The results are interpreted as providing evidence that low-threshold cold receptors, high-threshold cold receptors, and nociceptors are capable of inducing fos expression in dorsal horn neurons, whereas warm receptors are relatively ineffective. The results also provide evidence that neurons that receive input from C polymodal nociceptors are present in both laminae I and II, as are neurons that receive input from low-threshold cold receptors. Neurons that receive input from high-threshold cold receptors, but not from low-threshold cold receptors, appear to be located preferentially in lamina I. The shape of the curve relating fos-LI labeling to stimulus temperature in the warming direction is consistent with the expected pattern of recruitment of primary afferent nociceptors.

[Sympathetic postganglionic innervation of external carotid artery, internal carotid artery, common carotid artery and aorta in the dog--experimental study using HRP and WGA-HRP].

The sympathetic postganglionic innervation of the external carotid artery, internal carotid artery, common carotid artery (CCA) and aorta was studied by using retrograde axonal transport of the horseradish peroxidase (HRP) and wheat germ agglutinin-HRP conjugates (WGA-HRP). When the powder of HRP was applied to the sheaths of internal and external carotid arteries, labeled cells were found only in the ipsilateral superior cervical ganglion (SCG). After injection of WGA-HRP into the walls of the (1) distal, (2) middle, and (3) proximal parts of the CCA, labeled cells were observed in the following ganglia, respectively; (1) the SCG and middle cervical ganglion (MCG), (2) the SCG, MCG and stellate ganglion (SG), and (3) the MCG and SG. These labeled cells were seen in these ganglia of both sides, but they were more marked ipsilaterally. Following injections of WGA-HRP into the walls of ascending and descending aortae, labeled cells were found in the bilateral MCG and SG. These results suggest that the vasodilation of the head and neck after stellate ganglion block using local anesthetic agents is caused by neuronal block of preganglionic sympathetic fibers passing through the stellate ganglion and terminating in the superior cervical ganglion.