Comparative study of cholesteatoma in paediatric and adult patients.

BACKGROUND: The aggressiveness of paediatric cholesteatoma has long been a matter of debate. While much of the evidence is substantiated by data from the Western world, it is further limited by the retrospective nature of most studies. Therefore, this paper presents a comparative analysis of various characteristics of cholesteatoma between paediatric and adult populations seen at our centre. METHODS: A total of 50 patients (25 adults and 25 paediatric) with clinical diagnosis of chronic suppurative otitis media with cholesteatoma underwent canal wall down mastoidectomy over a period of two years. The intra-operative findings were noted and patients were followed up for six months. RESULTS: There was more extensive spread and ossicular erosion in paediatric cases. However, complications such as facial canal dehiscence and lateral semicircular canal dehiscence were more common in adults. CONCLUSION: Paediatric cholesteatoma is more aggressive and invasive than adult cholesteatoma, and the clinical behaviour is consistent with findings from other parts of the world.

The complete mitochondrial genome of the strawberry aphid Chaetosiphon fragaefolii Cockerell, 1901 (Hemiptera: Aphididae) from California, USA.

The aphid Chaetosiphon fragaefolii Cockerell, 1901 is an agricultural pest and known vector of strawberry viruses. To better understand its biology and systematics, we performed a genomic analysis on C. fragaefolii collected from Quinalt strawberry plants from Pacific Grove, Monterey county, California, USA using Oxford Nanopore and Illumina sequencing. The resulting data were used to assemble the aphids complete mitogenome. The mitogenome of C. fragaefolii is 16,108 bp in length and contains 2 rRNA, 13 protein-coding, and 22 tRNA genes (GenBank accession number LC590896). The mitogenome is similar in content and organization to other Aphididae. Phylogenetic analysis of the C. fragaefolii mitogenome resolved it in a fully supported clade in the tribe Macrosiphini. Analysis of the cox1 barcode sequence of C. fragaefolii from California found exact and nearly identical sequences to C. fragaefolii and Chaetosiphon thomasi Hille Ris Lambers, 1953, suggesting the two species are conspecific.

Phylogenetic relationships and genetic polymorphisms in wild Indian mice.

Randomly amplified polymorphic DNA (RAPD) analysis was used to examine the extent of variability in 11 Indian wild derived commensal house mice (Mus musculus) populations and compared with inbred strains of musculus and domesticus subspecies as well as commonly used laboratory inbred strains C57BL/6J and DBA/2J. Arbitrary designed 10 mer oligonucleotide primers with 60-70% (G+C) content were used to amplify DNA template. Out of 52 primers screened initially on the laboratory strains, 20 were selected for analysis on the basis of amplification product in the size range of 200-1400 bp. Among 353 total polymorphic bands, 220 bands (64%) were found to be polymorphic in Indian wild mice, 85 bands (25%) in wild derived inbred strains and 37 bands (11%) in laboratory mice strains. The amplification patterns produced by primers were statistically analysed by Jaccard's similarity coefficient the value of which ranged from 0.56 to 0.80. High level of genetic diversity was seen in the Indian wild mice populations as compared to the controls. The UPGMA phenogram grouped mice population into two major clusters except Bikaner [BIK], Bilaspur [BIL] and Ranikhet [RK] populations which were placed outside the close-knit clusters. Inspite of low values of bootstrap estimates obtained by Wagner and Dollo parsimony analysis, the results were comparable with UPGMA phenogram when constitution of the populations in the major cluster was considered. Indian mice populations appeared to be diverse from laboratory inbred mice strains.

Differential effects of filipin and methyl-beta-cyclodextrin on B cell receptor signaling.

Methyl-beta-cyclodextrin and filipin are cholesterol-binding reagents often used interchangeably to investigate functional requirements for lipid rafts in receptor-mediated signal transduction. Recently, contradictory results were reported by two groups using these reagents in different model systems to investigate the role of lipid rafts in BCR signaling. We confirm here that BCR-mediated calcium release is inhibited by filipin and enhanced by cyclodextrin. The inhibitory effect of filipin could not be attributed to raft disruption, however, because its ability to release raft-associated proteins into the detergent-soluble phase of cell lysates was less than that of cyclodextrin. In contrast, we found that filipin profoundly inhibited phosphorylation of the raft-associated adaptor protein Cbp/PAG, whereas the effect of cyclodextrin was minor. Thus, filipin and cyclodextrin modify cholesterol-rich microdomains through different mechanisms with different consequences on receptor signaling. In addition, the enhanced calcium release observed under conditions of maximum raft disruption suggests that rafts have a role in negatively regulating BCR signals.

Transient translocation of the B cell receptor and Src homology 2 domain-containing inositol phosphatase to lipid rafts: evidence toward a role in calcium regulation.

Membrane microdomains (lipid rafts) are enriched in selected signaling molecules and may compartmentalize receptor-mediated signals. Here, we report that in primary human B lymphocytes and in Ramos B cells B cell receptor (BCR) stimulation induces rapid and transient redistribution of a subset of engaged BCRs to lipid rafts and phosphorylation of raft-associated tyrosine kinase substrates. Cholesterol sequestration disrupted the lipid rafts, preventing BCR redistribution, but did not inhibit tyrosine kinase activation or phosphorylation of mitogen-activated protein kinase/extracellular regulated kinase. However, raft disruption enhanced the release of calcium from intracellular stores, suggesting that rafts may sequester early signaling events that down-regulate calcium flux. Consistent with this, BCR stimulation induced rapid and transient translocation of the Src homology 2 domain-containing inositol phosphatase, SHIP, into lipid rafts.

Comparative study of fluoxetine, sibutramine, sertraline and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry.

We compared the effects of treatment with high doses of fluoxetine, sibutramine, sertraline, and dexfenfluramine for 4 days on brain serotonergic nerve terminals in rats. Methylenedioxymethamphetamine (MDMA) and 5,7-dihydroxytryptamine (5,7-DHT) were used as positive controls because both compounds deplete brain serotonin. Food intake and body weight changes were also monitored and yoked, pair-fed animals were used to control for possible changes in morphology due to nutritional deficits. Fluoxetine, sibutramine, sertraline and dexfenfluramine all produced a significant reduction in body weight. Fluoxetine, sibutramine and sertraline treatment resulted in no depletion of brain serotonin but produced morphological abnormalities in the serotonergic immunoreactive nerve network. In contrast, dexfenfluramine and MDMA depleted brain serotonin and produced morphological changes in the serotonin nerve network. These results indicate that even though fluoxetine, sibutramine and sertraline do not deplete brain serotonin, they do produce morphological changes in several brain regions (as identified by serotonin immunohistochemistry). Dexfenfluramine and MDMA, on the other hand, markedly deplete brain serotonin and also produce morphological changes. Collectively, these results lend support to the concept that all compounds acting on brain serotonin systems, whether capable of producing serotonin depletion or not, could produce similar effects on the morphology of cerebral serotonin systems.

Immunohistochemical detection of active transforming growth factor-beta in situ using engineered tissue.

The biological activity of transforming growth factor-beta 1 (TGF-beta) is governed by dissociation from its latent complex. Immunohistochemical discrimination of active and latent TGF-beta could provide insight into TGF-beta activation in physiological and pathological processes. However, evaluation of immunoreactivity specificity in situ has been hindered by the lack of tissue in which TGF-beta status is known. To provide in situ analysis of antibodies to differentiate between these functional forms, we used xenografts of human tumor cells modified by transfection to overexpress latent TGF-beta or constitutively active TGF-beta. This comparison revealed that, whereas most antibodies did not differentiate between TGF-beta activation status, the immunoreactivity of some antibodies was activation dependent. Two widely used peptide antibodies to the amino-terminus of TGF-beta, LC(1-30) and CC(1-30) showed marked preferential immunoreactivity with active TGF-beta versus latent TGF-beta in cryosections. However, in formalin-fixed, paraffin-embedded tissue, discrimination of active TGF-beta by CC(1-30) was lost and immunoreactivity was distinctly extracellular, as previously reported for this antibody. Similar processing-dependent extracellular localization was found with a neutralizing antibody raised to recombinant TGF-beta. Antigen retrieval recovered cell-associated immunoreactivity of both antibodies. Two antibodies to peptides 78-109 showed mild to moderate preferential immunoreactivity with active TGF-beta only in paraffin sections. LC(1-30) was the only antibody tested that discriminated active from latent TGF-beta in both frozen and paraffin-embedded tissue. Thus, in situ discrimination of active versus latent TGF-beta depends on both the antibody and tissue preparation. We propose that tissues engineered to express a specific form of a given protein provide a physiological setting in which to evaluate antibody reactivity with specific functional forms of a protein.

Maturation of brain stem neurons involved in respiratory rhythmogenesis: biochemical, bioelectrical and morphological properties.

Neonatal and adult respiratory-related functions of brain stem were compared using in vivo or in vitro approaches. The control of inspiratory off-switch by glutamate-like neurotransmitters was found active at birth. However, neurons from the nucleus tractus solitarius (NTS) are immature at birth because they present growth cones and the transient potassium current appears progressively during the first week of life in association with modification of the dendritic tree. These data support the hypothesis that the mechanisms of respiratory rhythmogenesis are different at birth and in the adult.

Two distinct phases characterize maturation of neurons in the nucleus of the tractus solitarius during early development: morphological and electrophysiological evidence.

We have used electrophysiology and light microscopy of intracellularly labeled neurons in the nucleus of the tractus solitarius (nTS) in brainstem slices of the newborn rat (P0 to P6) to examine the functional and morphological correlation of their development. Three-dimensional reconstruction of neurons injected intracellularly with biocytin, following electrophysiological recording, revealed a close correspondence between morphological immaturity (appearing as polarization of the dendritic tree) and the absence of a ramp-like voltage trajectory at the offset of hyperpolarizing current injections-IA negativity (8 of the 8 cells examined showed this correlation). These morphologically polarized IA negative neurons showed preferential dendritic sprouting in two diametrically opposite poles of the perikaryon. The orientation of the polarity differed according to the rostrocaudal location of the neuron. The appearance of a polarized dendritic tree during the first (immature) phase was transient and closely coincident with IA negativity. Following the development of adult-like electrophysiological characteristics, i.e., IA positivity, nucleus of the tractus solitarius neurons showed remarkably different morphological features (9 of 10 cells). These included a wide-spread branching of the dendritic tree in all directions, giving it a bushy appearance (cell body to dendrite ratio of 1:40). Numerous dendritic spines, growth cones on both dendrites and axons, and axon collateralization were present during both phases and indicate that nTS neurons during the two phases of early development demonstrate dynamic features of growth and maturation. The development of adult-like electrophysiological characteristics, i.e., IA positivity, progressively increased in the postnatal period. During the later part of the first postnatal week, twice as many neurons showed IA positivity in days P3 to P6 as compared with days P0 to P2. These results reveal the dynamic nature of neurons in the nTS during early development and illustrate the close link between morphology and functional characteristics in this region. We suggest that the establishment of adult-like morphology can be modified by appropriate environmental clues provided to nTS neurons during the initial (immature) phase of early postnatal development.

Early ontogeny of the vagus nerve: an analysis of the medulla oblongata and cervical spinal cord of the postnatal rat.

Retrograde transport of cholera toxin conjugated with horseradish peroxidase in the postnatal rat has revealed remarkable features of dendritic fields of vagal motor neurons in the medulla oblongata and cervical spinal cord during the period of early development (0-10 days). At birth, vagal motor neurons in the dorsal motor nucleus of the vagus, nucleus ambiguus, nucleus retroambigualis, nucleus dorsomedials and the spinal nucleus of the accessory nerve are small with relatively few, unbranched processes. The span of the dendritic tree is much smaller than that found in adult animals. By the postnatal Day 2 there are marked changes in the soma as well as in the dendritic tree of these neurons. There is dispersion of the cell bodies within the neuropil as well as an expansion of the total area of the brain stem occupied by these motor neurons and their dendritic processes which show extensive growth and branching. By postnatal Day 3 the most extensive proliferation of these neurons is seen and appears to represent the peak of dendritic growth of vagal motor neurons such that the area occupied by the dendritic tree of a single neuron is three times that seen in an adult rat. This proliferation gradually decreased during the subsequent seven days of early development (i.e. Days 4-10) so that by Day 10 the dendritic span of vagal motor neurons was reduced to about twice the adult size. This growth progressively decreased from Days 10 to 30 at which time adult levels were reached. Ultrastructural examination of these horseradish peroxidase labeled dendrites showed a positive correlation between the number of dendritic processes and the number of axo-dendritic synapses. This was accompanied by an increase in the number of identifiable synaptic junctions. These morphological complexities observed during the period of early development of vagal motor neurons indicate that the vagus nerve undergoes dramatic changes during the period of early development including the establishment of numerous synaptic contacts between vagal afferents and efferents in the brainstem. A number of these changes occur in developing dendritic fields of vagal motor neurons during the first three days of neonatal life. It is reasonable to assume that developmental abnormalities during this "critical period" could produce significant functional changes in the pattern of respiration as well as in the control of airway smooth muscle.

Reversible, short-lasting, and dose-dependent effect of (+)-fenfluramine on neocortical serotonergic axons.

Dextrofenfluramine [+)-fenfluramine) is the dextro-optical isomer of the racemic compound (+/-)-fenfluramine. This compound stimulates the release of serotonin (5-HT) and blocks its re-uptake in serotonergic nerve terminals. (+)-Fenfluramine and its nor metabolite which have been localized in significant amounts in the rat brain are useful anorectic agents in animals. In humans, (+)-fenfluramine is used as an anti-obesity agent when administered orally in doses of 0.25 mg/kg/twice a day. Studies in some animal species (such as the rat and monkey, but not mice) using high doses of (+)-fenfluramine (administered subcutaneously) have shown long-term neurochemical and immunocytochemical effects in selected brain regions. In the present study we used the rat to determine the mechanism underlying the anorectic effect of orally administered (+)-fenfluramine. The rat was selected because long-term effects of (+)-fenfluramine have been previously described in this species. In addition, a variety of other aspects of orally administered (+)-fenfluramine have been addressed in this study. For example, how long does the depletion of 5-HT in the nerve terminals last following cessation of the drug treatment? i.e. is the effect reversible? Is this depletion of 5-HT and the resultant abnormal morphology of 5-HT-immunoreactive nerve terminals seen at high doses dose-dependent? Since some of these questions relate to morphological evaluation of this drug in brain 5-HT systems, we have examined this system as part of our ongoing effort to examine brain monoaminergic systems under perturbed conditions. We have used a morphological (immunocytochemical) approach to answer these questions. The primary function of this study was to evaluate the effects of short-term exposure (4 days) to varying doses of orally administered (+)-fenfluramine on 5-HT-immunoreactive nerve terminals in the frontal cortex of the rat. The frontal cortex was selected because it contains a homogeneous population of nerve fibers and terminals unlike other cortical regions, the hippocampus, striatum and the hypothalamus where a mixed population of coarse and fine fibers has been described. Since the previously reported effect of fenfluramine on 5-HT nerve terminals was the appearance of coarse fibers, the region of cortex selected for this study showed no coarse fibers in the pair-fed control. This essential feature of control regions has not been used in previous studies on this subject. The present study demonstrates that (+)-fenfluramine produces a dose-dependent reduction in 5-HT immunoreactivity of 5-HT nerve terminals in the neocortex of adult rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Monoaminergic and Peptidergic Innervation of the Intermedio-Lateral Horn of the Spinal Cord.

In the rat the monoaminergic and neuropeptidergic innervation of the sympathetic visceral nuclei of the entire thoracic spinal cord has been analysed in serial horizontal sections using immunocytochemistry. Tyrosine hydroxylase (TH), Phenyl-ethanolamine-N-methyl-transferase (PNMT), 5-hydroxytryptamine (5-HT), substance P (SP) and enkephalin (ENK) immunoreactive (IR) nerve terminals form tufts of plexa with strong IR in the principal part of the intermediolateral nucleus (ILp) with the terminals in an extraperikaryal location. High densities of these strongly IR terminals are also found in the principal part of the intercalated nucleus (ICp) and in the paraependymal part of the intercalated nucleus (ICpe). The various types of IR nerve terminals also form rostro-caudally oriented and latero-medially oriented strands of strongly IR nerve terminals at regular intervals within each segment. Outside these sympathetic nuclei the terminals are absent or only weakly to moderately IR. The similar pattern of monoamine and peptide innervation of the putative preganglionic sympathetic neurons along the entire thoracic spinal cord may be related to the general three dimensional architecture of the preganglionic multipolar neurons. Thus, these inputs tend to cover the entire surface area of the preganglionic neurons in a uniform way. Some heterogeneities have been observed for the TH, PNMT and neuropeptide Y (NPY) innervation which may contribute to a differential control of sympathetic preganglionic neurons. It is suggested that the unique features of the descending monoaminergic or peptidergic neurons to sympathetic spinal nuclei are related to a demand for maintained transmission upon prolonged activation in these cardiovascular systems, allowing the maintenance of cardiovascular homeostasis.

Monoaminergic and Peptidergic Innervation of the Intermedio-Lateral Horn of the Spinal Cord.

In the rat the monoamine and neuropeptide innervation of the sympathetic visceral nuclei has been analysed using retrograde tracing and single and double immunolabelling procedures. When combined with tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT) and enkephalin (ENK) immunocytochemistry, somata and dendrites of many preganglionic sympathetic neurons projecting to the coeliac ganglion visualized by retrograde tracing are found in close association with strands and plexa of strongly TH, 5-HT or ENK immunoreactive (IR) nerve terminals, while others have only a minor association with strong TH, 5-HT and ENK immunoreactivities, suggesting that a differential control of preganglionic sympathetic neurons is possible. Experiments with double immunolabelling procedures give further support to a direct innervation of preganglionic sympathetic neurons by TH, 5-HT and ENK IR nerve terminals. In conclusion, the present results open up the possibility for differential regulation of the preganglionic sympathetic neurons according to the Sherringtonian concept of spatial occlusion and facilitation in a pool of motoneurons.

Comparative evaluation of oral prostaglandin E2 & intravenous oxytocin for induction of labour.

Oral prostaglandin E2 tablets (group I) and iv Oxytocin (group II) were evaluated in 120 randomly selected women subjected to induction of labour. In group I, 60 women received oral prostaglandin E2 tablets in incremental doses from 0.5-1.5 mg hourly, depending upon the parity and Bishop score of the patient. Group II women received oxytocin iv in 5 per cent dextrose, starting at a rate of 2 mU/min and gradually increasing to a maximum of 64 mU/min. Overall success rate in group I (prostaglandin E2) and group II (intravenous oxytocin) was 85 and 93.3 per cent respectively (P greater than 0.05). In the favourable group (Bishop score 6-13) the induction delivery interval (IDI) for group I and group II was 8.86 h and 7.95 h respectively (P greater than 0.05), while in the unfavourable group (Bishop score less than or equal to 5), the IDI for the respective groups were 13.42 h and 10.11 h (P less than 0.05). Side effects with prostaglandin E2 were mostly mild gastrointestinal ones. A significantly higher incidence of foetal distress was observed with intravenous oxytocin (15%) as compared to prostaglandin E2 (3.33%). Oral prostaglandin E2 was thus found to be a better alternative to intravenous oxytocin in multiparous women with favourable Bishop score (greater than 6) and in those in whom fluid retention is to be avoided (e.g., conditions like toxemias, renal disease).

Rapidly adapting pulmonary receptor afferents: II. Fine structure and synaptic organization of central terminal processes in the nucleus of the tractus solitarius.

The nucleus of the tractus solitarius (nTS) is a site for termination of primary afferents originating from a variety of different visceral sensory endings (Kalia and Mesulam: J. Comp. Neurol. 193:523-553, '80). The light and electron microscopic evaluation of bouton terminals of slowly adapting lung stretch (SAR) afferent fibers originating from the tracheobronchial tree has been described previously (Kalia and Richter: J. Comp. Neurol. 241:503-520, 521-535, '85). The companion article (Kalia and Richter: J. Comp. Neurol. 273:000-000, '88) describes details of the light microscopic organization of a second group of pulmonary afferents, the rapidly adapting receptors (RARs), that are known to signal transient volume changes in airways (Sellick and Widdicombe: J. Physiol. (Lond.) 203: 359-381, '69; Q.J. Exp. Physiol. 55:153-163, '70). Terminals from RAR afferents are concentrated within two specific subnuclear groups of the nTS (dnTS and nI) and are distributed over 4 mm of the medulla oblongata rostrocaudally. Within the nTS, axon collaterals of RAR afferents remain myelinated up to a diameter of 0.4-1.0 microns. Preterminal processes are always unmyelinated and range in diameter from 0.15 to 0.3 microns. Bouton terminals (1.0-2.0 microns) are of both the en passant and end terminal varieties. The synaptic profiles formed by 143 bouton terminals of RAR afferents, were examined in uninterrupted sequential sections and are described in this paper. All the bouton terminals examined under the electron microscope were found to contain clear, round synaptic vesicles. Boutons made synaptic contact with different profiles in each of the two subnuclei (dnTS and nI) examined. Contacts were usually asymmetrical (type I) containing clear, round synaptic vesicles 35-50 nm in diameter. In the dorsal subnucleus of the nTS (dnTS), the synaptic arrangement of RAR boutons did not appear to be complex. The RAR bouton terminal was usually located in juxtaposition to unlabeled axon terminals of similar morphological characteristics. Typically, the RAR bouton terminal made synaptic contact with a medium-sized spiny dendrite. No axosomatic contacts involving RAR afferents were observed in this subnucleus. In the intermediate subnucleus of the nTS (nI), the most common synaptic arrangement of RAR bouton terminals was in the form of a "glomerulus," which was formed by five to seven different types of neuronal profiles surrounding the labeled RAR bouton terminal.(ABSTRACT TRUNCATED AT 400 WORDS)

Rapidly adapting pulmonary receptor afferents: I. Arborization in the nucleus of the tractus solitarius.

The organization of axon collaterals, preterminal processes, and presumptive synaptic boutons of single physiologically identified rapidly adapting receptor (RAR) pulmonary afferent fibers was examined following the intraaxonal application of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP). The RAR axons were injected 200-300 microns lateral to the nucleus of the tractus solitarius (nTS) at a number of different rostrocaudal levels in seven individual experiments. The trajectories of the stained axons were reconstructed from individual 50-microns-thick serial sections. The rostrocaudal extent, as well as the distribution of the trajectory of each RAR afferent, was reconstructed from every section by using a camera lucida attachment. In this first of two papers, we describe the pattern of organization of bouton terminals of RAR afferents related to cytoarchitectonically distinct subnuclei of the nTS. In the companion paper, morphological details of the fine structure of these synaptic boutons and axonal branches are described in different subnuclei in order to illustrate morphological differences in these functionally distinct regions. A number of significant findings have resulted from this light microscopic study. The central process of a single RAR afferent fiber arborized in the medulla oblongata over a considerable distance in the rostrocaudal plane (2.5 mm rostral to 1.4 mm caudal to the obex). A single RAR afferent fiber terminated in numerous bouton terminals (range 500-1,050), and these terminals arose from over 400 segments of branches of the parent injected axon. A small number of en passant bouton terminals were found. There appeared to be a remarkable degree of consistency in the subnuclei of the nTS where these terminals arborized. The dorsal and dorsolateral subnuclei of the nTS received 144-647 bouton terminals. The second-largest concentration of bouton terminals of RAR afferents was found in the intermediate (nI) subnucleus of the nTS. No labeled bouton terminal was found in the ventral and ventrolateral subnuclei of the nTS. This finding is in sharp contrast to the terminations of SAR afferents which terminated predominantly in the ventral and ventrolateral nuclei of the nTS, the interstitial nucleus of the nTS, and the nI. The parent RAR axon could be traced as far rostrally as 2.5 mm, even though the region of terminal arborization could not be followed beyond 0.8 mm. The destination of this rostrally projecting RAR afferent could not be determined in this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuropeptide Y-immunoreactive perikarya and nerve terminals in the rat medulla oblongata: relationship to cytoarchitecture and catecholaminergic cell groups.

The aim of this study was to examine details of the distribution of neuropeptide Y (NPY)-immunoreactive perikarya and nerve terminals in the medulla oblongata in relation to cytoarchitectonically and functionally distinct catecholaminergic regions. The immunoperoxidase method was combined with Nissl staining to determine nuclear boundaries of transmitter-identified nerve cell bodies and to examine the relationship between populations of NPY-immunoreactive neurons and catecholaminergic cell groups (A1, A2, C1, C2, and C3) in serial sections. Previous studies using immunofluorescence have described the existence of NPY catecholaminergic immunoreactive nerve cell bodies in the brainstem. No information is currently available with regard to details of the distribution of these peptidergic neurons and nerve terminals in the functional subnuclear units of the medulla oblongata. In this study we have delineated the anatomical association of NPY immunoreactivity with cardiovascular function. Neuropeptide Y-immunoreactive neurons were found located in close association with noradrenergic neurons of the A1 cell group in the caudal ventrolateral medulla oblongata, where they were usually found located dorsal to the lateral reticular nucleus (LRt). A second population of NPY-immunoreactive neurons was found located medial to the A1 cell group in the ventral subdivision of the reticular nucleus of the medulla (MdV). Neuropeptide Y-immunoreactive neurons in the rostral medulla were found located in regions corresponding to the principal distribution of adrenergic neurons in the C1, C2, and C3 cell groups. In the dorsomedial medulla (A2 region) NPY-immunoreactive neurons were localized in the area postrema (ap) and in a number of subnuclei of the nucleus of the tractus solitarius (nTS), i.e., the dorsal parasolitary region (dPSR), the dorsal strip (ds), the periventricular region (PVR), and the ventral parasolitary region (vPSR). The location of NPY-immunoreactive perikarya and nerve terminals in the dorsal subnuclei of the nTS, i.e., the dPSR and ds, is of particular significance, since this distribution corresponds with the location of small adrenergic neurons as well as with the site of termination of aortic and carotid sinus nerve afferent fibers. NPY-immunoreactive neurons in the dorsomedial medulla are ideally situated for receiving monosynaptic input from baroreceptor afferents and could play a key role in the central integration of cardiovascular reflexes.

Evidence for discrete alterations in central cardiovascular catecholamine and neuropeptide Y immunoreactive neurons in aged male rats and in genetically hypertensive male rats of the Lyon strain.

A computer-assisted morphometrical and microdensitometrical analysis has been performed on cardiovascular noradrenaline (NA), adrenaline (A) and neuropeptide (Y (NPY) neurons in adult and 24-month-old male rats and on hypotensive (LL), normotensive (LN) and hypertensive (LH) male rats of the Lyon strain using the indirect immunoperoxidase procedures. It was found that in NPY/phenylethanolamine-N-methyltransferase (PNMT) costoring neurons of the CI area of the rostral medulla oblongata NPY-like immunoreactivity showed a more marked reduction than the PNMT immunoreactivity. Furthermore, within the parvocellular part of the paraventricular hypothalamic nucleus. NPY immunoreactive nerve terminal profiles were much more affected than the PNMT immunoreactive profiles during aging as revealed by a marked reduction in the number of profiles and by a marked reduction of absorbency values in the microdensitometrical analysis. Thus, in the NPY/PNMT costoring neurons of the A C1 group of the ventrolateral medulla projecting, for example, to the hypothalamus, the peptide transmission line may have a special vulnerability to the aging processes which may contribute to the development of hypertension in old people in view of a vasodepressor role of many central NPY/PNMT neurons. An extensive morphometrical and microdensitometrical analysis of the various catecholamine (CA) cell groups of the medulla oblongata of the LL, LN and LH rats of the Lyon strain was performed. In a comparison between LL and LH rats the A2 cell group of the LH strain showed a trend for an increase in the mean tyrosine hydroxylase (TH) immunoreactive cell body area and the C3 group showed a significant increase in the number of PNMT immunoreactive profiles.(ABSTRACT TRUNCATED AT 250 WORDS)