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Medulla
Kinds of Medulla Selected AbstractsINVOLVEMENT OF N -METHYL- d -ASPARTATE RECEPTORS and NITRIC OXIDE IN THE ROSTRAL VENTROMEDIAL MEDULLA IN MODULATING MORPHINE PAIN-INHIBITORY SIGNALS FROM THE PERIAQUEDUCTAL GREY MATTER IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2005Kazem Javanmardi SUMMARY 1.,Supraspinal opioid antinociception is mediated, in part, by connections between the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM). Morphine antinociception from the PAG is decreased by serotonin, N -methyl- d -aspartate (NMDA) and opioid receptor antagonists administered into the RVM. Because the brain isoform of nitric oxide synthase (NOS) is also prominent in the RVM, the present study was designed to evaluate the effects of microinjection of the non-selective NOS inhibitor NG -nitro- l -arginine methyl ester (l -NAME) and the non-competitive NMDA receptor antagonist MK-801 into the RVM on PAG morphine antinociception and their potential interactions, as measured by the tail-flick test. 2.,Rats were anaesthetized with sodium pentobarbital and then special cannulas were inserted stereotaxically into the RVM and PAG. After 1 week recovery, the effects of microinjection of MK-801 and l -NAME into the RVM and their interactions in altering PAG morphine (2.5 µg) antinociception elicited from the PAG were assessed. 3.,Mesencephalic morphine antinociception was significantly reduced after pretreatment with l -NAME (0.6,1.3 µmol) or MK-801 (0.8 nmol). The reduction in mesencephalic morphine antinociception when MK-801 (0.8 nmol) and l -NAME (1 µmol) were microinjected sequentially into the RVM was not significantly different from the effects of MK-801 (0.8 nmol) or l -NAME (1 µmol) administered alone. 4.,These data imply that NMDA receptors and nitric oxide production in the RVM modulate the transmission of opioid pain-inhibitory signals from the PAG. [source] Social Stress Alters Expression of Large Conductance Calcium-Activated Potassium Channel Subunits in Mouse Adrenal Medulla and Pituitary GlandsJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2009O. Chatterjee Large conductance calcium-activated potassium (BK) channels are very prominently expressed in adrenal chromaffin and many anterior pituitary cells, where they shape intrinsic excitability complexly. Stress- and sex-steroids regulate alternative splicing of Slo-,, the pore-forming subunit of BK channels, and chronic behavioural stress has been shown to alter Slo splicing in tree shrew adrenals. In the present study, we focus on mice, measuring the effects of chronic behavioural stress on total mRNA expression of the Slo-, gene, two key BK channel , subunit genes (,2 and ,4), and the ,STREX' splice variant of Slo-,. As a chronic stressor, males of the relatively aggressive SJL strain were housed with a different unfamiliar SJL male every 24 h for 19 days. This ,social-instability' paradigm stressed all individuals, as demonstrated by reduced weight gain and elevated corticosterone levels. Five quantitative reverse transcriptase-polymerase chain assays were performed in parallel, including ,-actin, each calibrated against a dilution series of its corresponding cDNA template. Stress-related changes in BK expression were larger in mice tested at 6 weeks than 9 weeks. In younger animals, Slo-, mRNA levels were elevated 44% and 116% in the adrenal medulla and pituitary, respectively, compared to individually-housed controls. ,2 and ,4 mRNAs were elevated 162% and 194% in the pituitary, but slightly reduced in the adrenals of stressed animals. In the pituitary, dominance scores of stressed animals correlated negatively with , and , subunit expression, with more subordinate individuals exhibiting levels that were three- to four-fold higher than controls or dominant individuals. STREX variant representation was lower in the subordinate subset. Thus, the combination of subunits responding to stress differs markedly between adrenal and pituitary glands. These data suggest that early stress will differentially affect neuroendocrine cell excitability, and call for detailed analysis of functional consequences. [source] Direct Evidence for Imidazoline (I1) Receptor Modulation of Ethanol Action on Norepinephrine-Containing Neurons in the Rostral Ventrolateral Medulla in Conscious Spontaneously Hypertensive RatsALCOHOLISM, Issue 4 2007Guichu Li Background: Enhancement of the rostral ventrolateral medulla (RVLM) presympathetic (norepinephrine, NE) neuronal activity represents a neurochemical mechanism for the pressor effect of ethanol. In this study, we tested the hypothesis that ethanol action on RVLM presympathetic neurons is selectively influenced by the signaling of the local imidazoline (I1) receptor. To support a neuroanatomical and an I1 -signaling selectivity of ethanol, and to circumvent the confounding effects of anesthesia, the dose-related neurochemical and blood pressure effects of ethanol were investigated in the presence of selective pharmacological interventions that cause reduction in the activity of RVLM or nucleus tractus solitarius (NTS) NE neurons via local activation of the I1 or the ,2 -adrenergic receptor in conscious spontaneously hypertensive rats. Results: Local activation of the I1 receptor by rilmenidine (40 nmol) or by the I1/,2 receptor mixed agonist clonidine (1 nmol), and local activation of the ,2 -adrenergic receptor (,2AR) by the pure ,2AR agonist , -methylnorepinephrine (, -MNE, 10 nmol) caused reductions in RVLM NE, and blood pressure. Intra-RVLM ethanol (1, 5, or 10 ,g), microinjected at the nadir of the neurochemical and hypotensive responses, elicited dose-dependent increments in RVLM NE and blood pressure in the presence of local I1,but not ,2 -receptor activation. Only intra-NTS , -MNE, but not rilmenidine or clonidine, elicited reductions in local NE and blood pressure; ethanol failed to elicit any neurochemical or blood pressure responses in the presence of local activation of the ,2AR within the NTS. Conclusion: The findings support the neuroanatomical selectivity of ethanol, and support the hypothesis that the neurochemical (RVLM NE), and the subsequent cardiovascular, effects of ethanol are selectively modulated by I1 receptor signaling in the RVLM. [source] Morphology and Histology of the Atlantic Bottlenose Dolphin (Tursiops truncatus) Adrenal Gland with Emphasis on the MedullaANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2 2005L. S. Clark Summary This study provides the first detailed description of the Atlantic bottlenose dolphin (Tursiops truncatus) adrenal gland with emphasis on the medulla. Thirty-one dolphins of varying age and sex were used in this study. No statistical differences were found between the right and left gland mass, however, the left was typically greater. Mean mass for the right and left adrenal glands were 4.99 ± 0.513 and 5.36 ± 0.558 g, respectively. No statistical differences were found between average gland mass and sexual maturity or sex. The average cortex/medulla ratio was 1.22 ± 0.060 meaning approximately 48% is cortex, 41% is medulla, and 11% was categorized as other (i.e. blood vessels, connective tissue, etc.). The cortex contained pseudolobules and the typical zonation. A medullary band, consisting of highly basophilic staining cells was found at the periphery of the medulla. Projections of the medulla to the gland capsule were noted. Immunolabelling with polyclonal antibodies against the enzymes dopamine , hydroxylase and phenylethanolamine N-methyl transferase indicated that noradrenaline producing cells are found throughout the medulla including the medullary band while adrenaline producing cells are only found within the medullary band. Transmission electron microscopy confirmed the presence of two distinct cell populations within the medullary band and a single cell population throughout the medulla. [source] Reactive oxygen species in rostral ventrolateral medulla modulate cardiac sympathetic afferent reflex in ratsACTA PHYSIOLOGICA, Issue 4 2009M.-K. Zhong Abstract Aim:, The aim of the present study was to investigate whether reactive oxygen species (ROS) in rostral ventrolateral medulla (RVLM) modulate cardiac sympathetic afferent reflex (CSAR) and the enhanced CSAR response caused by microinjection of angiotensin II (Ang II) into the paraventricular nucleus (PVN). Methods:, Under urethane and ,-chloralose anaesthesia, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic-denervated and cervical-vagotomized rats. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin (1.0 nmol). Results:, Bilateral RVLM microinjection of tempol (a superoxide anion scavenger) or polyethylene glycol-superoxide dismutase (PEG-SOD, an analogue of endogenous superoxide dismutase) attenuated the CSAR, but did not cause significant change in baseline RSNA and MAP. NAD(P)H oxidase inhibitors apocynin or phenylarsine oxide (PAO) also showed similar effects, but SOD inhibitor diethyldithio-carbamic acid (DETC) enhanced the CSAR and baseline RSNA, and increased the baseline MAP. Bilateral PVN microinjection of Ang II (0.3 nmol) enhanced the CSAR and increased RSNA and MAP, which was inhibited by the pre-treatment with RVLM administration of tempol, PEG-SOD, apocynin or PAO. The pre-treatment with DETC in the RVLM only showed a tendency in potentiating the CSAR response of Ang II in the PVN, but significantly potentiated the RSNA and MAP responses of Ang II. Conclusion:, These results suggest that the NAD(P)H oxidase-derived ROS in the RVLM modulate the CSAR. The ROS in the RVLM is necessary for the enhanced CSAR response caused by Ang II in the PVN. [source] Prolonged exposure to inhaled nitric oxide transiently modifies tubular function in healthy piglets and promotes tubular apoptosisACTA PHYSIOLOGICA, Issue 4 2009W. Go, dzik Abstract Aim:, Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator. We hypothesized that those piglets exposed to prolonged iNO react with a modified renal function. Methods:, Randomized, placebo-controlled exposure to 40 p.p.m. iNO (30 h) in piglets (n = 20). Plasma and urine were sampled during three periods (first and second 12 h periods, and finally a 6 h period). We measured urine volumes, plasma and urine electrolytes (UNa, UK, UCl), plasma creatinine and urea. We calculated creatinine clearance (Ccr), and fractional excretions of sodium and potassium (FENa, FEK) and urinary excretions of electrolytes (UENa, UEK, UECl). Haemodynamic data were recorded and renal tubular apoptosis detected. Results:, For the first 12 h, certain parameters significantly increased in the iNO group (mean ± SD): UNa (mmol L,1), 87.7 (±35.0) vs. 39.3 (±22.9), UCl (mmol L,1) 80.4 (±32.8) vs. 48.0 (±26.7), FENa (%) 2.1 (±0.8) vs. 0.7 (±0.5), FEK (%) 31.7 (±7.0) vs. 20.7 (±12.3), as well as UENa (mmol) 61.0 (±21.1) vs. 27.6 (±17.9) and UECl (mmol) 57.3 (24.5) vs. 37.6 (29.0). These changes were absent in the second and third periods of the study. Significant differences in percentage of apoptotic cell nuclei in the renal cortex and medulla were found after iNO exposure: 39% vs. 15%. Conclusion:, Exposure to 40 p.p.m. iNO in healthy anaesthetized piglets has a transient natriuretic effect that disappears after 12 h. We also found evidence of renal tubular apoptosis promotion after 30 h of iNO. [source] Endothelin regulates NOS1 and NOS3 isoforms in the renal medullaACTA PHYSIOLOGICA, Issue 4 2007Erik Persson No abstract is available for this article. [source] EndothelinA (ETA) and ETB receptor-mediated regulation of nitric oxide synthase 1 (NOS1) and NOS3 isoforms in the renal inner medullaACTA PHYSIOLOGICA, Issue 4 2007J. C. Sullivan Abstract Aim:, Our laboratory and others have shown that endothelin (ET)-1 directly stimulates nitric oxide (NO) production in inner medullary collecting duct (IMCD) cells. The goal of this study was to determine which NO synthase (NOS) isoforms in IMCD are sensitive to ET-1, and the role of ETA and ETB receptor activation in vivo and in vitro. Methods:, NOS enzymatic activity and NOS isoform protein expression were examined in cultured IMCD-3 cells and isolated renal inner medulla. ETB receptor-deficient homozygous rats (sl/sl) have elevated levels of circulating ET-1 and lack a functional ETB signalling pathway in kidneys, and furthermore provides a unique model to study ETA receptor signalling in the renal inner medulla in vivo. Results:, Incubation of IMCD-3 cells with exogenous ET-1 (50 nm) resulted in ETA -dependent increased NOS1 protein expression in IMCD-3 cells with no effect on NOS2 or NOS3 expression. ETB receptor antagonism has no effect on NOS expression in IMCD-3 cells. Consistent with in vitro results, cytosolic NOS1 protein expression was significantly greater in the renal inner medulla of sl/sl rats compared with heterozygous (sl/+) controls, with no alteration in NOS3 expression. In contrast to protein expression data, NOS1- and NOS3-specific enzymatic activities decreased in the cytosolic fraction from the renal inner medulla of sl/sl compared with sl/+. Conclusion:, These results provide evidence that both ETA and ETB receptors regulate NOS isoform activity in the renal inner medulla and specifically support the hypothesis that ETA receptor activation increases NOS1 expression. [source] Vacuolar H+ -ATPase expression is increased in acid-secreting intercalated cells in kidneys of rats with hypercalcaemia-induced alkalosisACTA PHYSIOLOGICA, Issue 4 2007W. Wang Abstract Aims:, Hypercalcaemia is known to be associated with systemic metabolic alkalosis, although the underlying mechanism is uncertain. Therefore, we aimed to examine whether hypercalcaemia was associated with changes in the expression of acid,base transporters in the kidney. Methods:, Rats were infused with human parathyroid hormone (PTH, 15 ,g kg,1 day,1), or vehicle for 48 h using osmotic minipumps. Results:, The rats treated with PTH developed hypercalcaemia and exhibited metabolic alkalosis (arterial HCO: 31.1 ± 0.8 vs. 28.1 ± 0.8 mmol L,1 in controls, P < 0.05, n = 6), whereas the urine pH of 6.85 ± 0.1 was significantly decreased compared with the pH of 7.38 ± 0.1 in controls (P < 0.05, n = 12). The observed alkalosis was associated with a significantly increased expression of the B1-subunit of the H+ -ATPase in kidney inner medulla (IM, 233 ± 45% of the control level). In contrast, electroneutral Na+ -HCO cotransporter NBCn1 and Cl,/HCO anion exchanger AE2 expression was markedly reduced in the inner stripe of the outer medulla (to 26 ± 9% and 65 ± 6%, respectively). These findings were verified by immunohistochemistry. Conclusions:, (1) hypercalcaemia-induced metabolic alkalosis was associated with increased urinary excretion of H+; (2) the increased H+ -ATPase expression in IM may partly explain the enhanced urinary acidification, which is speculated to prevent stone formation because of hypercalciuria and (3) the decreased expression of outer medullary AE2 suggests a compensatory reduction of the transepithelial bicarbonate transport. [source] Developmental changes in cell proliferation in the auditory midbrain of the bullfrog, Rana catesbeianaDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2006Andrea Megela Simmons Abstract We examined patterns of cell proliferation in the auditory midbrain (torus semicircularis) of the bullfrog, Rana catesbeiana, over larval and early postmetamorphic development, by visualizing incorporation of 5-bromo-2,-deoxyuridine (BrdU) in cycling cells. At all developmental stages, BrdU-labeled cells were concentrated around the optic ventricle. BrdU-labeled cells also appeared within the torus semicircularis itself, in a stage-specific manner. The mitotic index, quantified as the percent of BrdU-positive cells outside the ventricular zone per total cells available for label, varied over larval development. Mitotic index was low in hatchling, early larval, and late larval stages, and increased significantly in deaf period, metamorphic climax, and froglet stages. Cell proliferation was higher in metamorphic climax than at other stages, suggesting increased cell proliferation in preparation for the transition from an aquatic to an amphibious existence. The change in mitotic index over development did not parallel the change in the total numbers of cells available for label. BrdU incorporation was additionally quantified by dot-blot assay, showing that BrdU is available for label up to 72 h postinjection. The pattern of change in cell proliferation in the torus semicircularis differs from that in the auditory medulla (dorsal medullary nucleus and superior olivary nucleus), suggesting that cell proliferation in these distinct auditory nuclei is mediated by different underlying mechanisms. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 1212,1224, 2006 [source] Cell proliferation in the Rana catesbeiana auditory medulla over metamorphic developmentDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2006Judith A. Chapman Abstract During metamorphic development, bullfrogs (Rana catesbeiana) undergo substantial morphological, anatomical, and physiological changes as the animals prepare for the transition from a fully-aquatic to a semi-terrestrial existence. Using BrdU incorporation and immunohistochemistry, we quantify changes in cell proliferation in two key auditory brainstem nuclei, the dorsolateral nucleus and the superior olivary nucleus, over the course of larval and early postmetamorphic development. From hatchling through early larval stages, numbers of proliferating cells increase in both nuclei, paralleling the overall increase in total numbers of cells available for labeling. Numbers of proliferating cells in the superior olivary nucleus decrease during the late larval and deaf periods, and significantly increase during metamorphic climax. Proliferating cells in the dorsolateral nucleus increase in number from hatchling to late larval stages, decrease during the deaf period, and increase during climax. In both nuclei, numbers of proliferating cells decrease during the postmetamorphic froglet stage, despite increases in the number of cells available for label. Newly generated cells express either glial- or neural-specific phenotypes beginning between 1 week and 1 month post-BrdU injection, respectively, while some new cells express ,-aminobutyric acid within 2 days of mitosis. Our data show that these auditory nuclei dramatically up-regulate mitosis immediately prior to establishment of a transduction system based on atmospheric hearing. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005 [source] Evidence for species differences in the pattern of androgen receptor distribution in relation to species differences in an androgen-dependent behaviorDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2002Brian K. Shaw Abstract Chickens (Gallus gallus domesticus) and Japanese quail (Coturnix japonica), two closely related gallinaceous bird species, exhibit a form of vocalization,crowing,which differs between the species in two components: its temporal acoustic pattern and its accompanying postural motor pattern. Previous work utilizing the quail-chick chimera technique demonstrated that the species-specific characteristics of the two crow components are determined by distinct brain structures: the midbrain confers the acoustic pattern, and the caudal hindbrain confers the postural pattern. Crowing is induced by androgens, acting directly on androgen receptors. As a strategy for identifying candidate neurons in the midbrain and caudal hindbrain that could be involved in crow production, we performed immunocytochemistry for androgen receptors in these brain regions in both species. We also investigated midbrain-to-hindbrain vocal-motor projections. In the midbrain, both species showed prominent androgen receptor immunoreactivity in the nucleus intercollicularis, as had been reported in previous studies. In the caudal hindbrain, we discovered characteristic species differences in the pattern of androgen receptor distribution. Chickens, but not quail, showed strong immunoreactivity in the tracheosyringeal division of the hypoglossal nucleus, whereas quail, but not chickens, possessed strong immunoreactivity in a region of the ventrolateral medulla. Some of these differences in hindbrain androgen receptor distribution may be related to the species differences in the postural component of crowing behavior. The results of the present study imply that the spatial distribution of receptor proteins can vary even between closely related species. Such variation in receptor distribution could underlie the evolution of species differences in behavior. © 2002 Wiley Periodicals, Inc. J Neurobiol 52: 203,220, 2002 [source] Ultrastructure of spermatozoa of lizards in the genus Mabuya from Central BrazilACTA ZOOLOGICA, Issue 1 2009S. M. De Sá Mandel Abstract This is the first description of spermatozoal ultrastructure of Mabuya skinks. The spermatozoa of the species studied are filiform, consisting of a head region, a midpiece and a tail. The head is characterized by the following features: a depressed acrosome anteriorly, an acrosome vesicle divided into cortex and medulla, paracrystalline subacrosomal material, a pointed tip perforatorium, a circular perforatorium base plate inside the subacrosomal cone, an epinuclear lucent zone separated from the subacrosomal cone by a membrane, a large nuclear rostrum, and round nuclear shoulders. The midpiece presents a bilateral stratified laminar structure, a distal centriole, peripheral fibres 3 and 8 grossly enlarged, columnar mitochondria with linear cristae, dense body rings and a triangular annulus. Finally, the tail is composed of a principal piece and an end piece. An axoneme and a fibrous sheath characterize the principal piece, and the end piece is formed only by an axoneme, which loses its pattern in the last portion. Comparisons with members of Teiidae revealed differences in the numbers of dense rings. A well-developed epinuclear lucent zone in Mabuya is less prominent among teiids. In the spermatozoa of Mabuya, the first ring of dense bodies is very large, uniquely resembling the condition present in snakes. [source] Nucleoside transporter and nucleotide vesicular transporter: Two examples of mnemonic regulationDRUG DEVELOPMENT RESEARCH, Issue 1-2 2001Raquel P. Sen Abstract According to their relevant roles in the regulation and availability of extracellular levels of purinergic signals, the nucleoside transporter and the nucleotide vesicular transporter are subject to acute regulation. The plasma membrane nucleoside transporter has been shown to exhibit several regulatory mechanisms, such as regulation by long-term signals, phosphorylation/dephosphorylation processes, and allosteric modulation. The present work reviews studies concerning allosteric modulation of nucleoside and nucleotide vesicular transporters, as the first reported examples of mnemonic behavior in transporter proteins, presenting kinetic and allosteric cooperativity. This fact implies that the protein can exhibit different conformations, each one with specific kinetic parameters. Transport substrates are able to induce slow conformational changes between the different forms of the transporter. This kinetic mechanism can provide several physiological advantages, since it allows strict control of transport capacity by changes in substrate concentrations. This allosteric modulation has been confirmed in several experimental models, the nucleoside transporter in chromaffin and endothelial cells from adrenal medulla and the nucleotide vesicular transporter in the chromaffin cell granules and rat brain synaptic vesicles. Taking into account these considerations, the mnemonic regulation described here could be a widespread mechanism among transporter proteins. Drug Dev. Res. 52:11,21, 2001. © 2001 Wiley-Liss, Inc. [source] Magnetic resonance imaging evaluation of 264 horses with foot pain: The podotrochlear apparatus, deep digital flexor tendon and collateral ligaments of the distal interphalangeal jointEQUINE VETERINARY JOURNAL, Issue 4 2007S. DYSON Summary Reasons for performing study: To improve understanding of the interrelationships between injuries of the podotrochlear apparatus and deep digital flexor tendon (DDFT). Hypotheses: There is a difference in frequency of different types of lesions at different anatomical sites of the DDFT. Lesions of the collateral sesamoidean ligament (CSL), distal sesamoidean impar ligament (DSIL), distal interphalangeal (DIP) joint and navicular bursa are seen in association with lesions of the navicular bone. Methods: The magnetic resonance (MR) images of 264 horses with unilateral or bilateral foot pain were analysed and graded. Descriptive statistics were performed to establish the frequency of occurrence of DDFT lesion types at different anatomical levels, and lesions of the CSL, DSIL, navicular bursa, DIP joint and collateral ligaments (CLs) of the DIP joint. A Chi-square test was used to test for a difference in the proportion of navicular bone grades between limbs with and without DDFT lesions at each level, and to compare navicular bone grades for limbs with and without each of DSIL, CSL, navicular bursa or DIP joint lesions. Results: Lesions of the DDFT occurred in 82.6% of limbs, occurring most commonly at the level of the CSL (59.4%) and the navicular bone (59.0%). Core lesions predominated at the level of the proximal phalanx (90.3%), whereas at the level of the CSL and navicular bone core lesions, sagittal splits and dorsal abrasions were most common. There was a positive association between DDFT lesions and navicular bone pathology involving all aspects of the bone. Lesions of the DSIL (38.2% limbs) were more common than those of the CSL (10.5%), but the presence of either was associated with abnormalities of the navicular bone, especially involving the proximal or distal borders and the medulla. Conclusions and clinical relevance: There are close interactions between injuries of the components of the podotrochlear apparatus, the DDFT, the navicular bursa and the DIP joint. Further knowledge about the biomechanical risk factors for injury may have importance for both disease prevention and management. [source] Analysis of a radiographic technique for measurement of equine metacarpal bone shapeEQUINE VETERINARY JOURNAL, Issue S33 2001L. J. WALTER Summary Accuracy and limitations of a radiographic technique were established for measurement of metacarpal bone shape in horses. A radiographic index (RI) has been used to measure changes in third metacarpal (Mc3) bone shape in response to training in young racehorses. The aim of these experiments was to determine the effects of positioning of the radiographic equipment on RI measurements from lateromedial radiographs of a left ex vivo metacarpus. Repeatability of the RI measurement in left lateromedial and right mediolateral view Mc3s were evaluated. The width of the dorsal cortex (DC), palmar cortex (PC) and medulla (M) were measured at a position 25 mm distal to the nutrient foramen and the RI calculated where RI = [(DC+PC)/M] x [DC/PC]. The reference RI values were obtained from 12 standard lateromedial radiographs. Factors analysed included the optimum focus-object distance, the angle at which the x-ray machine was positioned, the distance of the cassette from the limb, and the horizontal angle and vertical tilt of the cassette. The RI values included within the confidence interval (mean ° 1.96 x s.d.) were considered sufficiently accurate. The optimum focus-object distance was 1 m. Accurate measurements were obtained when the cassette was held as close to the limb as possible with the horizontal angle not exceeding 5°. The x-ray machine needed to be orientated within 6° of the lateromedial plane. These findings suggest that the radiographic index can be used to measure Mc3 bone shape, providing there is accurate alignment of the x-ray machine, cassette, and limb, with respect to one another. [source] Endothelin receptor selectivity in chronic kidney disease: rationale and review of recent evidenceEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2009W. Neuhofer Abstract Endothelin (ET) is a potent vasoconstrictory peptide with proinflammatory and profibrotic properties that exerts its biological effects through two pharmacologically distinct receptor subtypes, namely ETA and ETB. In addition to its substantial contribution to normal renal function, a large body of evidence suggests that derangement of the renal ET system is involved in the initiation and progression of chronic kidney disease (CKD) in diabetes, hypertension and glomerulonephritis. Thus, the use of ET receptor antagonists (ERAs) may offer potential novel treatment strategies in CKD. Recent literature on the role of the renal ET system in the healthy kidney was reviewed. In addition, an unbiased PubMed search was performed for studies published during the last 5 years that addressed the effects of ERAs in CKD. A particular objective was to extract information regarding whether selective or nonselective ERAs may have therapeutic potential in humans. ET-1 acts primarily as an autocrine or paracrine factor in the kidney. In normal physiology, ET-1 promotes diuresis and natriuresis by local production and action through ETB receptors in the renal medulla. In pathology, ET-1 mediates vasoconstriction, mesangial-cell proliferation, extracellular matrix production and inflammation, effects that are primarily conveyed by ETA receptors. Results obtained in animal models and in humans with the use of ERAs in CKD are encouraging; nevertheless, it is still under debate which receptor subtype should be targeted. According to most studies, selective inhibition of ETA receptors appears superior compared with nonselective ERAs because this approach does not interfere with the natriuretic, antihypertensive and ET clearance effects of ETB receptors. Although preliminary data in humans are promising, the potential role of ERAs in patients with CKD and the question of which receptor subtype should be targeted can only be clarified in randomized clinical trials. [source] Intercellular MHC transfer between thymic epithelial and dendritic cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2008Virginie Millet Abstract Thymic dendritic cells (DC) and epithelial cells play a major role in central tolerance but their respective roles are still controversial. Epithelial cells have the unique ability to ectopically express peripheral tissue-restricted antigens conferring self-tolerance to tissues. Paradoxically, while negative selection seems to occur for some of these antigens, epithelial cells, contrary to DC, are poor negative selectors. Using a thymic epithelial cell line, we show the functional intercellular transfer of membrane material, including MHC molecules, occurring between epithelial cells. Using somatic and bone marrow chimeras, we show that this transfer occurs efficiently in vivo between epithelial cells and, in a polarized fashion, from epithelial to DC. This novel mode of transfer of MHC-associated, epithelial cell-derived self-antigens onto DC might participate to the process of negative selection in the thymic medulla. [source] Tolerance to non-opioid analgesics in PAG involves unresponsiveness of medullary pain-modulating neurons in male ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2009Victor Tortorici Abstract Opiate analgesia can be hampered by a reduction in pharmacological effectiveness (tolerance), and this crucially depends on the periaqueductal gray matter (PAG). Non-opioids like metamizol (dipyrone) or aspirin also induce PAG-dependent analgesia and tolerance, but the neuronal bases of this tolerance are unknown. Metamizol is a pyrazolon derivative and cyclooxygenase inhibitor with widespread use as an analgesic in Europe and Latin America. Metamizol was microinjected into the PAG of awake male rats, and antinociception was assessed by the tail flick (TF) and hot plate (HP) tests. Microinjection twice daily for 2.5 days caused tolerance to metamizol. The rats were then anesthetized and recordings from pain-facilitating on-cells and pain-inhibiting off-cells of the rostral ventromedial medulla (RVM) were performed. PAG microinjection of morphine or metamizol depresses on-cells, activates off-cells and thus inhibits nociception, including TF and HP. In metamizol-tolerant rats, however, PAG microinjection of metamizol failed to affect on- or off-cells, and this is interpreted as the reason for tolerance. In metamizol-tolerant rats morphine microinjection into PAG also failed to affect RVM neurons or nociception (cross-tolerance). In naïve, non-tolerant rats the antinociceptive effect of PAG-microinjected metamizol or morphine was blocked when CTOP, a ,-opioid antagonist, was previously microinjected into the same PAG site. These results emphasize a close relationship between opioid and non-opioid analgesic mechanisms in the PAG and show that, like morphine, tolerance to metamizol involves a failure of on- and off-cells to, respectively, disfacilitate and inhibit nociception. Cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting. [source] Origin of the earliest correlated neuronal activity in the chick embryo revealed by optical imaging with voltage-sensitive dyesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009Yoko Momose-Sato Abstract Spontaneous correlated neuronal activity during early development spreads like a wave by recruiting a large number of neurons, and is considered to play a fundamental role in neural development. One important and as yet unresolved question is where the activity originates, especially at the earliest stage of wave expression. In other words, which part of the brain differentiates first as a source of the correlated activity, and how does it change as development proceeds? We assessed this issue by examining the spatiotemporal patterns of the depolarization wave, the optically identified primordial correlated activity, using the optical imaging technique with voltage-sensitive dyes. We surveyed the region responsible for the induction of the evoked and spontaneous depolarization waves in chick embryos, and traced its developmental changes. The results showed that the wave initially originated in a restricted area near the obex and was generated by multiple regions at later stages. We suggest that the upper cervical cord/lower medulla near the obex is the kernel that differentiates first as the source of the correlated activity, and that regional and temporal differences in neuronal excitability might underlie the developmental profile of wave generation in early chick embryos. [source] C1 neurons in the rat rostral ventrolateral medulla differentially express vesicular monoamine transporter 2 in soma and axonal compartmentsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2008C. P. Sevigny Abstract Vesicular monoamine transporter 2 (VMAT2) packages biogenic amines into large dense core and synaptic vesicles for either somatodendritic or synaptic release from neurons of the CNS. Whilst the distribution of VMAT2 has been well characterized in many catecholaminergic cell groups, its localization amongst C1 adrenergic neurons in the medulla has not been examined in detail. Within the rostral ventrolateral medulla (RVLM), C1 neurons are a group of barosensitive, adrenergic neurons. Rostral C1 cells project to the thoracic spinal cord and are considered sympathetic premotor neurons. The majority of caudal C1 cells project rostrally to regions such as the hypothalamus. The present study sought to quantitate the somatodendritic expression of VMAT2 in C1 neurons, and to assess the subcellular distribution of the transporter. Immunoreactivity for VMAT2 occurred in 31% of C1 soma, with a high proportion of these in the caudal part of the RVLM. Retrograde tracing studies revealed that only two of 43 bulbospinal C1 neurons contained faint VMAT2-immunoreactivity, whilst 88 ± 5% of rostrally projecting neurons were VMAT2-positive. A lentivirus, designed to express green fluorescent protein exclusively in noradrenergic and adrenergic neurons, was injected into the RVLM to label C1 neurons. Eighty-three percent of C1 efferents that occurred in close proximity to sympathetic preganglionic neurons within the T3 intermediolateral cell column contained VMAT2-immunoreactivity. These data demonstrate differential distribution of VMAT2 within different subpopulations of C1 neurons and suggest that this might reflect differences in somatodendritic vs. synaptic release of catecholamines. [source] Premotor sympathetic neurons of conditioned fear in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2008Pascal Carrive Abstract Conditioned fear to context, a pure form of psychological stress, is associated with sympathetically mediated changes including a marked hypertension. To identify the possible premotor sympathetic neurons mediating these changes, we conducted double-immunolabelling experiments combining fear-induced Fos with retrograde tracing from the thoracic cord (T2-L1). Presympathetic groups showing the greatest increase in the proportion of spinally projecting cells double-labelled with Fos compared with resting controls were the perifornical area (PeF; 22.7% vs. 0.4%) and paraventricular nucleus (Pa; 10.5% vs. 0.2%) in the hypothalamus, and the A5 noradrenergic group (33.6% vs. 0.2%) in the pons. In contrast, there was only a small increase in the presympathetic groups of the rostral ventral medulla, including the lateral paragigantocellular group (LPGi; 4.3% vs. 0.5%), raphe magnus and pallidus (1.1% vs. 0.6% and 1.8% vs. 0.5%), and the vasopressor group of the rostral ventrolateral medulla (RVLM; 1.9% vs. 0.8%). PeF, Pa, A5 and LPGi accounted for 21, 15, 16 and 6% of all the double-labelled cells, respectively, and RVLM for only 1%. Double-immunolabelling of Fos and tyrosine hydroxylase confirmed that many A5 neurons were activated (19%) and that practically no C1 neurons in RVLM were (1.3%). The results suggest that the main premotor sympathetic drive of the fear response comes from hypothalamic (PeF and Pa) and A5 neurons that project directly to the thoracic cord and bypass medullary presympathetic groups, and that the vasopressor premotor sympathetic neurons of the RVLM are unlikely to mediate the hypertensive pressure response of contextual fear. [source] Optical imaging of medullary ventral respiratory network during eupnea and gasping In situEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2006Jeffrey T. Potts Abstract In severe hypoxia, respiratory rhythm is shifted from an eupneic, ramp-like motor pattern to gasping characterized by a decrementing pattern of phrenic motor activity. However, it is not known whether hypoxia reconfigures the spatiotemporal organization of the central respiratory rhythm generator. Using the in situ arterially perfused juvenile rat preparation, we investigated whether the shift from eupnea to gasping was associated with a reconfiguration of the spatiotemporal pattern of respiratory neuronal activity in the ventral medullary respiratory network. Optical images of medullary respiratory network activity were obtained from male rats (4,6 weeks of age). Part of the medullary network was stained with a voltage-sensitive dye (di-2 ANEPEQ) centred both within, and adjacent to, the pre-Bötzinger complex (Pre-BötC). During eupnea, optical signals initially increased prior to the onset of phrenic activity and progressively intensified during the inspiratory phase peaking at the end of inspiration. During early expiration, fluorescence was also detected and slowly declined throughout this phase. In contrast, hypoxia shifted the respiratory motor pattern from eupnea to gasping and optical signals were restricted to inspiration only. Areas active during gasping showed fluorescence that was more intensive and covered a larger region of the rostral ventrolateral medulla compared to eupnea. Regions exhibiting peak inspiratory fluorescence did not coincide spatially during eupnea and gasping. Moreover, there was a recruitment of additional medullary regions during gasping that were not active during eupnea. These results provide novel evidence that the shift in respiratory motor pattern from eupnea to gasping appears to be associated with a reconfiguration of the central respiratory rhythm generator characterized by changes in its spatiotemporal organization. [source] Ret deficiency in mice impairs the development of A5 and A6 neurons and the functional maturation of the respiratory rhythmEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2005J. C. Viemari Abstract Although a normal respiratory rhythm is vital at birth, little is known about the genetic factors controlling the prenatal maturation of the respiratory network in mammals. In Phox2a mutant mice, which do not express A6 neurons, we previously hypothesized that the release of endogenous norepinephrine by A6 neurons is required for a normal respiratory rhythm to occur at birth. Here we investigated the role of the Ret gene, which encodes a transmembrane tyrosine kinase receptor, in the maturation of norepinephrine and respiratory systems. As Ret -null mutants (Ret,/,) did not survive after birth, our experiments were performed in wild-type (wt) and Ret,/, fetuses exteriorized from pregnant heterozygous mice at gestational day 18. First, in wt fetuses, quantitative in situ hybridization revealed high levels of Ret transcripts in the pontine A5 and A6 areas. Second, in Ret,/, fetuses, high-pressure liquid chromatography showed significantly reduced norepinephrine contents in the pons but not the medulla. Third, tyrosine hydroxylase immunocytochemistry revealed a significantly reduced number of pontine A5 and A6 neurons but not medullary norepinephrine neurons in Ret,/, fetuses. Finally, electrophysiological and pharmacological experiments performed on brainstem ,en bloc' preparations demonstrated impaired resting respiratory activity and abnormal responses to central hypoxia and norepinephrine application in Ret,/, fetuses. To conclude, our results show that Ret gene contributes to the prenatal maturation of A6 and A5 neurons and respiratory system. They support the hypothesis that the normal maturation of the respiratory network requires afferent activity corresponding to the A6 excitatory and A5 inhibitory input balance. [source] Somatic and visceral afferents to the ,vasodepressor region' of the caudal midline medulla in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2003Jason R. Potas Abstract Previous research has found that the integrity of a restricted region of the caudal midline medulla (including caudal portions of nucleus raphé obscurus and nucleus raphé pallidus) was critical for vasodepression (hypotension, bradycardia, decreased cardiac contractility) evoked either by haemorrhage or deep pain. In this anatomical tracing study we found that the vasodepressor part of the caudal midline medulla (CMM) receives inputs arising from spinal cord, spinal trigeminal nucleus (SpV) and nucleus of the solitary tract (NTS). Specifically: (i) a spinal,CMM projection arises from neurons of the deep dorsal horn, medial ventral horn and lamina X at all spinal segmental levels, with approximately 60% of the projection originating from the upper cervical spinal cord (C1,C4); (ii) a SpV,CMM projection arises primarily from neurons at the transition between subnucleus caudalis and subnucleus interpolaris; (iii) a NTS,CMM projection arises primarily from neurons in ventrolateral and medial subnuclei. In combination, the specific spinal, SpV and NTS regions which project to the CMM receive the complete range of somatic and visceral afferents known to trigger vasodepression. The role(s) of each specific projection is discussed. [source] O2 -sensing after carotid chemodenervation: hypoxic ventilatory responsiveness and upregulation of tyrosine hydroxylase mRNA in brainstem catecholaminergic cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2000Jean-Christophe Roux Abstract Ventilatory responses to acute and long-term hypoxia are classically triggered by carotid chemoreceptors. The chemosensory inputs are carried within the carotid sinus nerve to the nucleus tractus solitarius and the brainstem respiratory centres. To investigate whether hypoxia acts directly on brainstem neurons or secondarily via carotid body inputs, we tested the ventilatory responses to acute and long-term hypoxia in rats with bilaterally transected carotid sinus nerves and in sham-operated rats. Because brainstem catecholaminergic neurons are part of the chemoreflex pathway, the ventilatory response to hypoxia was studied in association with the expression of tyrosine hydroxylase (TH). TH mRNA levels were assessed in the brainstem by in situ hybridization and hypoxic ventilatory responses were measured in vivo by plethysmography. After long-term hypoxia, TH mRNA levels in the nucleus tractus solitarius and ventrolateral medulla increased similarly in chemodenervated and sham-operated rats. Ventilatory acclimatization to hypoxia developed in chemodenervated rats, but to a lesser extent than in sham-operated rats. Ventilatory response to acute hypoxia, which was initially low in chemodenervated rats, was fully restored within 21 days in long-term hypoxic rats, as well as in normoxic animals which do not overexpress TH. Therefore, activation of brainstem catecholaminergic neurons and ventilatory adjustments to hypoxia occurred independently of carotid chemosensory inputs. O2 -sensing mechanisms unmasked by carotid chemodenervation triggered two ventilatory adjustments: (i) a partial acclimatization to long-term hypoxia associated with TH upregulation; (ii) a complete restoration of acute hypoxic responsivity independent of TH upregulation. [source] Synaptically released 5-HT modulates the activity of tonically discharging neuronal populations in the rostral ventral medulla (RVM)EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000Pascale Piguet Abstract There is substantial evidence for an important modulating role of monoamines (catecholamines and serotonin, 5-HT) in the rostral ventral medulla (RVM), a region which plays an important role in cardiovascular and nociceptive functions. We investigated in slices the role of endogenous monoamines in the synaptic control of the activity of rat RVM neuronal populations using intracellular recordings in the lateral RVM plus lateral aspect of nucleus paragigantocellularis lateralis. A triple-labelling protocol allowed us to identify the location of impaled neurons and their eventual monoaminergic phenotype within the serotonergic and catecholaminergic populations of the RVM. Focal electrical stimulation revealed the existence of a functional monoaminergic input onto RVM neurons which was mediated by endogenous 5-HT acting at inhibitory 5-HT1A receptors but did not involve noradrenergic neurotransmission. The slow 5-HT-mediated inhibitory postsynaptic potential (IPSP) was only observed in the regularly discharging neurons, which were found to be neither catecholaminergic nor serotonergic. The synaptic release of 5-HT was, itself, under an inhibitory control involving GABAA (,-aminobutyric acid) receptors. Moreover, we characterized the effect of the 5-HT-releasing agent fenfluramine on this functional 5-HT-mediated synaptic transmission. Our results show that the effect of fenfluramine is biphasic consisting of an initial prolongation of the serotonergic IPSP followed by a decrease in amplitude. Our data provide a basis for the previously reported inhibitory effects of exogenously applied serotonin agonists/antagonists on the autonomic functions controlled by the RVM. This 5-HT pathway, which functionally links the serotonergic and catecholaminergic regions, might play an important role in cardiovascular and nociceptive functions. [source] To breathe or not to breathe?EXPERIMENTAL PHYSIOLOGY, Issue 1 2009That is the question Our understanding of the role of the brain in respiratory rhythm generation and regulation began the early nineteenth century. Over the next 150 years the neuronal groups in the medulla oblongata and pons that were involved in eupnoea and in gasping were identified by techniques involving the lesioning of areas of the lower brainstem, several transections across the brainstem and focal electrical stimulation. An incomplete picture emerged that stressed the importance of the ventral medulla. Subsequent electrophysiological studies in in vivo, in situ and in vitro preparations have revealed the importance of restricted groups of neurones in this area, within the Bötzinger and pre-Bötzinger nuclei, that are the essential kernel for rhythm generation. The outputs to the spinal motoneurones responsible for the patterning of inspiratory and expiratory discharge are shaped by inputs from these neurones and others within the respiratory complex that determine the activity of respiratory bulbospinal neurones. It is clear that the developmental stage of the preparation is often critical for the pattern of respiratory activity that is generated and that these patterns have important physiological consequences. The models that are currently considered to explain rhythmogenesis are critically evaluated. The respiratory network is subject to regulation from peripheral and central chemoreceptors, amongst other afferent inputs, which act to ensure respiratory homeostasis. The roles of peripheral chemoreceptors as primarily O2 sensors are considered, and the evolution of ideas surrounding their roles is described. New insights into the transduction mechanisms of chemoreception in the carotid body and chemosensitive areas of the ventral medullary surface, specifically in monitoring CO2 levels, are reviewed. As new experimental tools, both genetic and cellular, are emerging, it can be expected that the detailed network architecture and synaptic interactions that pattern respiratory activity in relation to behavioural activity will be revealed over the next years. [source] Central control of thermogenesis in mammalsEXPERIMENTAL PHYSIOLOGY, Issue 7 2008Shaun F. Morrison Thermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature in mammals and birds during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. The primary sources of neurally regulated metabolic heat production are mitochondrial oxidation in brown adipose tissue, increases in heart rate and shivering in skeletal muscle. Thermogenesis is regulated in each of these tissues by parallel networks in the central nervous system, which respond to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate the appropriate sympathetic and somatic efferents. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates thermogenesis and discusses the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E2, to increase body temperature. The cold thermal afferent circuit from cutaneous thermal receptors ascends via second-order thermosensory neurons in the dorsal horn of the spinal cord to activate neurons in the lateral parabrachial nucleus, which drive GABAergic interneurons in the preoptic area to inhibit warm-sensitive, inhibitory output neurons of the preoptic area. The resulting disinhibition of thermogenesis-promoting neurons in the dorsomedial hypothalamus and possibly of sympathetic and somatic premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, activates excitatory inputs to spinal sympathetic and somatic motor circuits to drive thermogenesis. [source] Exposure to a hot environment can activate rostral ventrolateral medulla-projecting neurones in the hypothalamic paraventricular nucleus in conscious ratsEXPERIMENTAL PHYSIOLOGY, Issue 1 2008Joo Lee Cham A major integrative site within the brain for autonomic function is the hypothalamic paraventricular nucleus (PVN). Several studies have suggested that the PVN may be involved in the responses regulating body temperature. Hyperthermia elicits redirection of blood flow from the viscera to the periphery and involves changes in sympathetic nerve activity mediated by the central nervous system. The hypothalamic PVN includes neurones that project to the rostral ventrolateral medulla (RVLM), an important autonomic region involved in the tonic regulation of sympathetic nerve activity. This pathway could contribute to the cardiovascular changes induced by hyperthermia. The PVN has a high concentration of nitrergic neurones and it is known that nitric oxide within the brain mediates heat dissipation. Thus the aims of this study were to determine whether RVLM-projecting neurones in the PVN are activated by heat and whether those neurones are also nitrergic. The results show that, compared with control conditions, exposure of conscious rats to a hot environment of 39°C significantly increased the number of neurones containing a Fos-positive nucleus (a marker of activation) and significantly increased the number of activated RVLM-projecting neurones in the PVN. Also, although heating significantly increased the number of activated nitrergic PVN neurones, triple-labelled neurones (i.e. activated, nitrergic and RVLM projecting) in the PVN were rarely observed. The results suggest that RVLM-projecting neurones in the PVN may play a role in responses to heat exposure but these are not nitrergic. [source] | ||||||||||||||||||||||||||||||||||