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PubMed1986

The lymphatic route. 1) Albumin and hyaluronidase modify the normal distribution of interferon in lymph and plasma.

When human recombinant interferon-alpha 2 diluted in saline was injected s.c. into rabbits, the total amount recovered in thoracic lymph was less than 0.4%. Recoveries increased from 2- to 8-fold if interferon was injected in 4% albumin or with hyaluronidase, respectively. Albumin added to interferon acts as an interstitial fluid expander, thus favoring interferon absorption through lymphatics rather than blood capillaries. This strategy may increase the therapeutic index of interferon.

Animals↗
PubMed1987

Acetylcholine in the interpeduncular nucleus of the rat: normal distribution and effects of deafferentation.

We studied the cholinergic projection to the interpeduncular nucleus (IPN) by examining localization of choline acetyltransferase (ChAT) in the habenula, fasciculus retroflexus (FR) and among the subnuclei of the IPN of the rat, using and antibody raised against ChAT. ChAT-containing neurons were present in the ventral portion of the medial habenula, ChAT-stained axons were present in the FR and ChAT-stained axons and terminals were present in the rostral, central and intermediate subnuclei of the IPN. No ChAT staining was seen in the lateral or dorsal subnuclei. The pattern of ChAT localization was thus complementary to the pattern of the habenular substance P projection to the IPN. Lesions of the FR eliminated all ChAT from the IPN while lesions of the stria medullaris produced a modest decrease. Unilateral FR lesions indicated that the FR projection to the central and rostral subnuclei is largely bilateral and symmetrical and that to the intermediate subnuclei is largely ipsilateral. We found no evidence of lesion-induced plasticity, i.e. replacement of ChAT immunoreactivity, by surviving FR axons in these adult brains.

Acetylcholine↗
PubMed1987

Norepinephrine in the interpeduncular nucleus of the rat: normal distribution and the effects of deafferentation.

We used correlative biochemical and histochemical methods to examine (1) the norepinephrine (NE) projection from the paired locus coeruleus (LC) to the midline interpeduncular nucleus (IPN) of the adult rat and (2) the ability of the LC to respond to denervation of their target following removal of noradrenergic afferents (6-hydroxydopamine lesions of the LC) or non-noradrenergic afferents (lesion of the paired fasciculi retroflexi(FR]. Histofluorescence revealed that the NE innervation from the two LC to the IPN is symmetric and overlapping. This projection is confined to rostral, central, and intermediate subnuclei and is absent from lateral and dorsal subnuclei. We found no evidence for homotypic collateral sprouting of undamaged LC neurons into the IPN following unilateral LC lesion. Bilateral LC lesions also did not induce sprouting by NE-containing neurons from other systems (e.g. the superior cervical ganglion or the lateral tegmental group) or from those LC neurons that survived the 6-hydroxydopamine lesion. Histofluorescence following bilateral FR lesions confirmed an earlier observation that apparent hyperinnervation of the IPN by LC afferents is elicited following removal of non-noradrenergic afferents. Measurements of the turnover rate of NE in the IPN of control animals and those that received bilateral FR lesions indicate an increased NE content and increased turnover rate of NE in the IPN of lesioned animals. Taken together these results suggest an increased number of NE terminals and an increase in the activity of tyrosine hydroxylase. No change in NE content or turnover rate was seen in the frontal cortex from these same animals. This is consistent with a target-dependent regulation of heterotypic collateral sprouting.

Animals↗
PubMed1988

Tachykinin binding sites in the interpeduncular nucleus of the rat: normal distribution, postnatal development and the effects of lesions.

Tachykinin binding sites in the basal midbrain were labeled in adult and neonatal rats using 125I-Bolton Hunter (BH) substance P (SP) and 125I-BH eledoisin as ligands. In the adult, binding was very low in the tegmentum and raphe adjacent to the interpeduncular nucleus (IPN). Within the IPN, no binding with either ligand was seen in the target subnuclei of the habenular SP and substance K projections, the lateral subnuclei and the cap of the rostral subnucleus. Labeling with 125I-BH-SP was very light and was restricted primarily to the central subnucleus of the IPN while 125I-BH-eledoisin labeling was very dense over the dorsal, the ventral sector of the rostral, the intermediate and the central subnuclei. Lesions of major afferents to the IPN, the fasciculus retroflexus or the locus coeruleus, had no effect on the distribution or density of the binding of either ligand. In rats 0, 4 or 7 days or age, 125I-BH-SP binding was very dense in the ventral tegmental region, the raphe and in the dorsal, rostral and central subnuclei. 125I-BH-eledoisin binding was extremely dense in the raphe and in the dorsal, rostral, intermediate and central subnuclei but was less dense in the ventral tegmentum. Adult levels of binding in the midbrain were established by 11 days of age. Neonatal lesions restricted to the fasciculus retroflexus had no effect on the density of labeling with either ligand in animals allowed to reach adulthood.

Aging↗
PubMed1986

Esophageal blood flow in the cat. Normal distribution and effects of acid perfusion.

The radioactive microsphere technique was used to estimate blood flow to different regions of the esophagus and to adjacent regions of the stomach before and after perfusion of the esophagus with hydrochloric acid (pH 1.5) for 5 min. Under resting conditions total blood flow, as well as blood flow to the mucosal-submucosal layer and the muscular layer, to both sphincters was significantly higher than to the esophageal body. Blood flow to the adjacent regions of the stomach was significantly higher than esophageal blood flow. Acid perfusion resulted in a large increase in total blood flow in both sphincters and the lower esophageal body. Gastric blood flow was not altered by acid perfusion. The esophageal hyperemia resulted primarily from an increase in blood flow to the muscular layer; mucosal-submucosal blood flow was increased only in the lower esophageal sphincter. The present study indicates that short periods (5 min) of gastroesophageal reflux may increase esophageal blood flow.

Animals↗
PubMed1987

Opiate binding sites in the interpeduncular nucleus of the rat: normal distribution and the effects of fasciculus retroflexus lesions.

Opiate receptors have been localized autoradiographically to many regions of the rat central nervous system. The interpeduncular nucleus has an especially high concentration of these receptors. We used [3H]naloxone and [125I] [D-Ala2,MePhe4,Glyol5]enkephalin as ligands to map the distribution of opiate receptors among the subnuclei of the interpeduncular nucleus. The rostral subnucleus contains label that is densest dorsally. More caudally, high densities of opiate binding sites are found in the lateral, rostral, and central subnuclei. The dorsal subnucleus contains a moderate density of binding sites and the intermediate subnuclei contain almost none. Opiate receptors have also been localized to the medial habenulae and the fasciculi retroflexi, which provide a major afferent input to the interpeduncular nucleus. Lesions of the fasciculi retroflexi decreased the density of opiate binding sites in the rostral and lateral subnuclei of the interpeduncular nucleus. There were no changes seen in the dorsal, intermediate or central subnuclei. These results suggest that a minority of opiate receptors in the interpeduncular nucleus are located presynaptically on fasciculi retroflexi axons. Immunocytochemical studies have demonstrated that the rat interpeduncular nucleus contains substance P, serotonin and enkephalin, and each has a distinct subnuclear distribution. Although the opiate binding sites have a wider distribution than substance P, serotonin, or enkephalin individually, the pattern of opiate binding most closely parallels substance P distribution. The combined distribution of substance P, serotonin, and enkephalin is equivalent to that of the opiate binding sites.

Animals↗
PubMed1986

Normal distribution of regional cerebral blood flow measured by dynamic single-photon emission tomography.

Regional CBF (rCBF) was measured quantitatively using the inert-gas washout technique with xenon-133 and single-photon emission computed tomography. Tomographic data were reconstructed by filtered back projection, and flow was calculated according to the double-integral method. Ninety-seven subjects ranging in age from 20 to 59 years received a single examination; eight of these received a second examination within 1 h of the first; seven others received a second examination separated from the first by 1-10 days. Transverse-section images were obtained at 2, 6, and 10 cm above and parallel to the canthomeatal line (CML). Cortical gray matter flows were obtained from 12 brain regions in the slice 6 cm above the CML, and cerebellar and inferior cerebral gray matter flows were obtained from 4 regions in the slice 2 cm above the CML. Mean gray matter flow was 72 +/- 12 ml/min/100 g, with highest flows in the parietal lobes and visual cortex. No significant differences in rCBF occurred when a second study followed the first by 30 min to 10 days. Right-sided rCBF was slightly higher than left in all regions except frontal and parietal lobes where there was no difference. Flow was higher in women than in men and declined mildly with age for both sexes (slope = -0.33 ml/min/100 g/year; p less than 0.05).

Adult↗