Sample records for renal afferent arterioles

  1. Rapid inhibition of vasoconstriction in renal afferent arterioles by aldosterone.

    Uhrenholt, T R; Schjerning, J; Hansen, P B; Nørregaard, R; Jensen, B L; Sorensen, G L; Skøtt, O


    Aldosterone has been suggested to elicit vessel contraction via a nongenomic mechanism. We tested this proposal in microdissected, perfused rabbit renal afferent arterioles. Aldosterone had no effect on internal diameter in concentrations from 10(-10) to 10(-5) mol/L, but aldosterone abolished the ability of 100 mmol/L KCl to induce vascular contraction. The inhibitory effect of aldosterone was observed from 1 pmol/L. The inhibitory effect was significant after 5 minutes and maximal after 20 minutes and was fully reversible. Actinomycin D (10(-6) mol/L) prolonged the effect of aldosterone. The effect was abolished by the mineralocorticoid receptor antagonist spironolactone (10(-7) mol/L) but not by the glucocorticoid receptor antagonist mifepristone (10(-6) mol/L). The K+-mediated increase of intracellular calcium concentration in afferent arterioles was not affected by aldosterone. Mineralocorticoid receptor was detected by reverse transcription-polymerase chain reaction and immunohistochemistry in rat renal vasculature and rabbit endothelial cells. Inhibition of phosphatidylinositol (PI)-3 kinase with LY 294002 (3x10(-6) mol/L) restored sensitivity to K+ in the presence of aldosterone, and afferent arterioles were immunopositive for PI-3 kinase subunit p110alpha. Inhibition of NO formation by L-NAME (10(-4) mol/L) or inhibition of soluble guanylyl cyclase with 1H-(1,2,4)Oxadiazolo[4,3-a]quinoxaline-1-one restored K+-induced vasoreactivity in the presence of aldosterone. Similar to aldosterone, the NO donor sodium nitroprusside inhibited K+-induced vascular contraction. Geldanamycin (10(-6) mol/L), an inhibitor of heat shock protein 90, abolished aldosterone-induced vasorelaxation. We conclude that aldosterone inhibits depolarization-induced vasoconstriction in renal afferent arterioles by a rapid nongenomic mechanism that is initiated by mineralocorticoid receptor activation and involves PI-3 kinase, protein kinase B, and heat shock protein 90-mediated

  2. Constriction velocities of renal afferent and efferent arterioles of mice are not related to SMB expression.

    Patzak, Andreas; Petzhold, Daria; Wronski, Thomas; Martinka, Peter; Babu, Gopal J; Periasamy, Muthu; Haase, Hannelore; Morano, Ingo


    Constriction of renal arterioles contributes significantly to the control of perfusion and glomerular filtration. Afferent but not efferent arterioles express smooth muscle myosin heavy chain B (SMB) (with a 5'-insert of seven amino acids). The aim of the present study was to investigate (1) the constriction characteristics of afferent and efferent arterioles under physiologic load and (2) whether expression of SMB may causally contribute to these constriction characteristics. We compared constriction parameters [constriction amplitude, maximal rate of constriction velocity ("dc/dt(max)"), and time to half-maximal constriction (t(1/2)) of in vitro perfused renal afferent and efferent arterioles of wild-type (smb(+/+)] and homozygous SMB knockout [smb(-/-)] mice upon stimulation with angiotensin II (Ang II) (10(-8) mol/L) and potassium chloride (KCl) (100 mmol/L). SMB expression was investigated by double-labeling immunofluorescence. Contraction amplitude and dc/dt(max) of mouse afferent arterioles upon Ang II stimulation were significantly greater compared to efferent arterioles. However, constriction amplitudes, dc/dt(max), and t(1/2) of afferent as well as efferent arterioles upon Ang II stimulation were similar in smb(+/+) and smb(-/-) mice. Constriction amplitudes upon KCl stimulation of afferent arterioles were similar in both smb(+/+) and smb(-/-) mice. Furthermore, KCl-induced dc/dt(max) and t(1/2) of afferent arterioles were similar in both smb(+/+) and smb(-/-) mice. SMB expression could be detected in afferent but not efferent arterioles in smb(+/+) mice. No SMB expression in either arteriole could be observed in smb(-/-) mice. Our results suggest that the presence of different alternatively 5'-spliced smooth muscle-myosin heavy chain (SM-MHC) isoforms does not dominate the different contractile features of physiologically loaded renal afferent or efferent arterioles.

  3. Vasodilatation of afferent arterioles and paradoxical increase of renal vascular resistance by furosemide in mice

    Oppermann, Mona; Hansen, Pernille B; Castrop, Hayo;


    Loop diuretics like furosemide have been shown to cause renal vasodilatation in dogs and humans, an effect thought to result from both a direct vascular dilator effect and from inhibition of tubuloglomerular feedback. In isolated perfused afferent arterioles preconstricted with angiotensin II or N...... that furosemide, despite its direct vasodilator potential in isolated afferent arterioles, causes a marked increase in flow resistance of the vascular bed of the intact mouse kidney. We suggest that generation of angiotensin II and/or a vasoconstrictor prostaglandin combined with compression of peritubular...

  4. Superoxide enhances Ca2+ entry through L-type channels in the renal afferent arteriole.

    Vogel, Paul A; Yang, Xi; Moss, Nicholas G; Arendshorst, William J


    Reactive oxygen species regulate cardiovascular and renal function in health and disease. Superoxide participates in acute calcium signaling in afferent arterioles and renal vasoconstriction produced by angiotensin II, endothelin, thromboxane, and pressure-induced myogenic tone. Known mechanisms by which superoxide acts include quenching of nitric oxide and increased ADP ribosyl cyclase/ryanodine-mediated calcium mobilization. The effect(s) of superoxide on other calcium signaling pathways in the renal microcirculation is poorly understood. The present experiments examined the acute effect of superoxide generated by paraquat on calcium entry pathways in isolated rat afferent arterioles. The peak increase in cytosolic calcium concentration caused by KCl (40 mmol/L) was 99±14 nmol/L. The response to this membrane depolarization was mediated exclusively by L-type channels because it was abolished by nifedipine but was unaffected by the T-type channel blocker mibefradil. Paraquat increased superoxide production (dihydroethidium fluorescence), tripled the peak response to KCl to 314±68 nmol/L (Psuperoxide and not of hydrogen peroxide. Unaffected by paraquat and superoxide was calcium entry through store-operated calcium channels activated by thapsigargin-induced calcium depletion of sarcoplasmic reticular stores. Also unresponsive to paraquat was ryanodine receptor-mediated calcium-induced calcium release from the sarcoplasmic reticulum. Our results provide new evidence that superoxide enhances calcium entry through L-type channels activated by membrane depolarization in rat cortical afferent arterioles, without affecting calcium entry through store-operated entry or ryanodine receptor-mediated calcium mobilization.

  5. Differential effects of superoxide and hydrogen peroxide on myogenic signaling, membrane potential, and contractions of mouse renal afferent arterioles.

    Li, Lingli; Lai, En Yin; Wellstein, Anton; Welch, William J; Wilcox, Christopher S


    Myogenic contraction is the principal component of renal autoregulation that protects the kidney from hypertensive barotrauma. Contractions are initiated by a rise in perfusion pressure that signals a reduction in membrane potential (Em) of vascular smooth muscle cells to activate voltage-operated Ca(2+) channels. Since ROS have variable effects on myogenic tone, we investigated the hypothesis that superoxide (O2 (·-)) and H2O2 differentially impact myogenic contractions. The myogenic contractions of mouse isolated and perfused single afferent arterioles were assessed from changes in luminal diameter with increasing perfusion pressure (40-80 mmHg). O2 (·-), H2O2, and Em were assessed by fluorescence microscopy during incubation with paraquat to increase O2 (·-) or with H2O2 Paraquat enhanced O2 (·-) generation and myogenic contractions (-42 ± 4% vs. -19 ± 4%, P contractions (-10 ± 1% vs. -19 ± 2%, P contractions with paraquat without preventing the reduction in Em Myogenic contractions were independent of the endothelium and largely independent of nitric oxide. We conclude that O2 (·-) and H2O2 activate different signaling pathways in vascular smooth muscle cells linked to discreet membrane channels with opposite effects on Em and voltage-operated Ca(2+) channels and therefore have opposite effects on myogenic contractions.

  6. Vascular smooth muscle cells express the alpha(1A) subunit of a P-/Q-type voltage-dependent Ca(2+)Channel, and It is functionally important in renal afferent arterioles

    Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D


    in rat aorta, brain, aortic smooth muscle cells (A7r5), VSMCs, and mesangial cells. Immunolabeling with an anti-alpha(1A) antibody was positive in acid-macerated, microdissected preglomerular vessels and in A7r5 cells. Patch-clamp experiments on aortic A7r5 cells showed 22+/-4% (n=6) inhibition of inward...... Ca(2+) current by omega-Agatoxin IVA (10(-8) mol/L), which in this concentration is a specific inhibitor of P-type VDCCs. Measurements of intracellular Ca(2+) in afferent arterioles with fluorescence-imaging microscopy showed 32+/-9% (n=10) inhibition of the K(+)-induced rise in Ca(2...... preglomerular resistance vessels and aorta, as well as mesangial cells, and that P-type VDCCs contribute to Ca(2+) influx in aortic and renal VSMCs and are involved in depolarization-mediated contraction in renal afferent arterioles....

  7. Development of the renal arterioles.

    Sequeira Lopez, Maria Luisa S; Gomez, R Ariel


    The kidney is a highly vascularized organ that normally receives a fifth of the cardiac output. The unique spatial arrangement of the kidney vasculature with each nephron is crucial for the regulation of renal blood flow, GFR, urine concentration, and other specialized kidney functions. Thus, the proper and timely assembly of kidney vessels with their respective nephrons is a crucial morphogenetic event leading to the formation of a functioning kidney necessary for independent extrauterine life. Mechanisms that govern the development of the kidney vasculature are poorly understood. In this review, we discuss the anatomical development, embryological origin, lineage relationships, and key regulators of the kidney arterioles and postglomerular circulation. Because renal disease is associated with deterioration of the kidney microvasculature and/or the reenactment of embryonic pathways, understanding the morphogenetic events and processes that maintain the renal vasculature may open new avenues for the preservation of renal structure and function and prevent the progression of renal disease.

  8. Estimation of the number of angiotensin II AT1 receptors in rat kidney afferent and efferent arterioles

    Razga, Zsolt; Nyengaard, Jens Randel


    of angiotensin II AT1 receptors along the length of the arterioles and per arteriole, we combined immunoelectron microscopy with stereology. RESULTS: The number of AT1 receptor molecules was significantly lower in the renin-positive smooth muscle cells (SMCs) than in the renin-negative SMCs of the afferent......OBJECTIVE: To examine the effects of the renin-angiotensin system (RAS) on renal arterioles to determine the association between the distribution of angiotensin II AT1 receptors and the morphologic and physiologic heterogeneity of renal arterioles. STUDY DESIGN: To estimate the number...... and efferent arterioles. There were no significant differences along and between the afferent and efferent arterioles in relative number of AT1 receptors of endothelial cells or SMCs. CONCLUSION: Our results suggest that the heterogeneous activity of angiotensin II in SMCs and the different permeabilities...

  9. Chloride is essential for contraction of afferent arterioles after agonists and potassium

    Jensen, B L; Ellekvist, Peter; Skøtt, O


    A depolarizing chloride efflux has been suggested to activate voltage-dependent calcium channels in renal afferent arteriolar smooth muscle cells in response to vasoconstrictors. To test this proposal, rabbit afferent arterioles were microperfused, and the contractile dose responses to norepineph......A depolarizing chloride efflux has been suggested to activate voltage-dependent calcium channels in renal afferent arteriolar smooth muscle cells in response to vasoconstrictors. To test this proposal, rabbit afferent arterioles were microperfused, and the contractile dose responses......). Reintroduction of chloride fully restored the sensitivity to norepinephrine. Contractions after ANG II and potassium were totally abolished in the absence of chloride (n = 6). In additional experiments (n = 7), the arteriolar contraction to 100 mM potassium was abolished only 1 min after removal of extracellular...... chloride. We conclude that norepinephrine and ANG II use different mechanisms for contraction and that extracellular chloride is essential for contraction in afferent arterioles after activation of voltage-dependent calcium channels. We suggest that a chloride influx pathway is activated concomitantly...

  10. Intracellular signalling pathways in the vasoconstrictor response of mouse afferent arterioles to adenosine

    Hansen, Pernille B. Lærkegaard; Friis, Ulla Glenert; Uhrenholt, Torben Rene


    AIMS: Adenosine causes vasoconstriction of afferent arterioles of the mouse kidney through activation of adenosine A(1) receptors and Gi-mediated stimulation of phospholipase C. In the present study, we further explored the signalling pathways by which adenosine causes arteriolar vasoconstriction....... METHODS AND RESULTS: Adenosine (10(-7) M) significantly increased the intracellular calcium concentration in mouse isolated afferent arterioles measured by fura-2 fluorescence. Pre-treatment with thapsigargin (2 microM) blocked the vasoconstrictor action of adenosine (10(-7) M) indicating that release...

  11. Blockade of chloride channels by DIDS stimulates renin release and inhibits contraction of afferent arterioles

    Jensen, B L; Skøtt, O


    arterioles with the chloride channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Renin secretion was equally enhanced by omission of extracellular calcium and by addition of 0.5 mM DIDS. The inhibitory effect of calcium was blocked by DIDS. The stimulatory effects of low calcium [with....... Norepinephrine (5 x 10(-7)-1 x 10(-6) M) and angiotensin II (1 x 10(-8)-10(-6) M) evoked reversible and dose-dependent contractions of microperfused rabbit afferent arterioles. DIDS (0.5 mM) did not affect the basal diameter of the arterioles but strongly inhibited the response to angiotensin II and attenuated...... the duration of the contractile response to norepinephrine. The results support the hypothesis that DIDS-sensitive calcium-activated chloride channels are involved in regulation of renin release and in the afferent arteriolar contraction after angiotensin II but do not play a pivotal role in the response...

  12. Identification and function of adenosine A3 receptor in afferent arterioles.

    Lu, Yan; Zhang, Rui; Ge, Ying; Carlstrom, Mattias; Wang, Shaohui; Fu, Yiling; Cheng, Liang; Wei, Jin; Roman, Richard J; Wang, Lei; Gao, Xichun; Liu, Ruisheng


    Adenosine plays an important role in regulation of renal microcirculation. All receptors of adenosine, A1, A2A, A2B, and A3, have been found in the kidney. However, little is known about the location and function of the A3 receptor in the kidney. The present study determined the expression and role of A3 receptors in mediating the afferent arteriole (Af-Art) response and studied the interaction of A3 receptors with angiotensin II (ANG II), A1 and A2 receptors on the Af-Art. We found that the A3 receptor expressed in microdissected isolated Af-Art and the mRNA levels of A3 receptor were 59% of A1. In the isolated microperfused Af-Art, A3 receptor agonist IB-MECA did not have a constrictive effect. Activation of A3 receptor dilated the preconstricted Af-Art by norepinephrine and blunted the vasoconstrictive effect of both adenosine A1 receptor activation and ANG II on the Af-Art, respectively. Selective A2 receptor antagonist (both A2A and A2B) had no effect on A3 receptor agonist-induced vasodilation, indicating that the dilatory effect of A3 receptor activation is not mediated by activation of A2 receptor. We conclude that the A3 receptor is expressed in the Af-Art, and activation of the A3 receptor dilates the Af-Art.

  13. Remodeling of Afferent Arterioles From Mice With Oxidative Stress Does Not Account for Increased Contractility but Does Limit Excessive Wall Stress.

    Li, Lingli; Feng, Di; Luo, Zaiming; Welch, William J; Wilcox, Christopher S; Lai, En Yin


    Because superoxide dismutase (SOD) knockout enhances arteriolar remodeling and contractility, we hypothesized that remodeling enhances contractility. In the isolated and perfused renal afferent arterioles from SOD wild type (+/+) and gene-deleted mice, contractility was assessed from reductions in luminal diameter with perfusion pressure from 40 to 80 mm Hg (myogenic responses) or angiotensin II (10(-6) mol/L), remodeling from media:lumen area ratio, superoxide (O2 (·-)) and hydrogen peroxide (H2O2) from fluorescence microscopy, and wall stress from wall tension/wall thickness. Compared with +/+ strains, arterioles from SOD1-/-, SOD2+/-, and SOD3-/- mice developed significantly (Premodeling. Although remodeling does not enhance contractility, it does prevent the potentially damaging effects of increased wall stress.

  14. Fluorescence histochemistry and autoradiography of adrenergic nerves in the renal juxtaglomerular complex of mammals and man, with special regard to the efferent arteriole.

    Dolezel, S; Edvinsson, L; Owman, C; Owman, T


    The adrenergic innervation of the juxtaglomerular complex was studied in kidneys from mice, rats, guinea-pigs, rabbits, cats, dogs, pigs, monkeys, and humans using fluorescence histochemistry of neuronal noradrenaline and autoradiography of 3H-noradrenaline. The localization of the nerves was established by phase contrast optics or by perfusing the vascular system with India ink. Adrenergic nerve terminals, exhibiting a formaldehyde-induced fluorescence and having the ability to take up and accumulate 3H-noradrenaline, were easily identified when they enclosed the glomerular afferent arteriole. They continued in between and close to the macula densa and lacis cells to supply the glomerular efferent arteriole. The nerves could be seen to accompany this arteriole for a considerable distance until they branched off to the vasa recta in the juxtamedullary region and to adjacent cortical veins. This innervation pattern was found to be a constant feature except in kidneys from guinea-pigs and cats, in which post-glomerular units. The fluorescence in all adrenergic fibres supplying the juxtaglomerular complex disappeared after removal of the aortico-renal ganglion, showing that they belong to a common system of renal sympathetic nerves.

  15. Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension.

    Banek, Christopher T; Knuepfer, Mark M; Foss, Jason D; Fiege, Jessica K; Asirvatham-Jeyaraj, Ninitha; Van Helden, Dusty; Shimizu, Yoji; Osborn, John W


    Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension. © 2016 American Heart Association, Inc.

  16. The role of the renal afferent and efferent nerve fibers in heart failure.

    Booth, Lindsea C; May, Clive N; Yao, Song T


    Renal nerves contain afferent, sensory and efferent, sympathetic nerve fibers. In heart failure (HF) there is an increase in renal sympathetic nerve activity (RSNA), which can lead to renal vasoconstriction, increased renin release and sodium retention. These changes are thought to contribute to renal dysfunction, which is predictive of poor outcome in patients with HF. In contrast, the role of the renal afferent nerves remains largely unexplored in HF. This is somewhat surprising as there are multiple triggers in HF that have the potential to increase afferent nerve activity, including increased venous pressure and reduced kidney perfusion. Some of the few studies investigating renal afferents in HF have suggested that at least the sympatho-inhibitory reno-renal reflex is blunted. In experimentally induced HF, renal denervation, both surgical and catheter-based, has been associated with some improvements in renal and cardiac function. It remains unknown whether the effects are due to removal of the efferent renal nerve fibers or afferent renal nerve fibers, or a combination of both. Here, we review the effects of HF on renal efferent and afferent nerve function and critically assess the latest evidence supporting renal denervation as a potential treatment in HF.

  17. Intercellular calcium signaling and nitric oxide feedback during constriction of rabbit renal afferent arterioles

    Uhrenholt, Torben Rene; Schjerning, J; Vanhoutte, Paul M. G.


    Vasoconstriction and increase in the intracellular calcium concentration ([Ca(2+)](i)) of vascular smooth muscle cells may cause an increase of endothelial cell [Ca(2+)](i), which, in turn, augments nitric oxide (NO) production and inhibits smooth muscle cell contraction. This hypothesis was tested...

  18. Impaired excitability of renal afferent innervation after exposure to the inflammatory chemokine CXCL1.

    Ditting, Tilmann; Freisinger, Wolfgang; Rodionova, Kristina; Schatz, Johannes; Lale, Nena; Heinlein, Sonja; Linz, Peter; Ott, Christian; Schmieder, Roland E; Scrogin, Karie E; Veelken, Roland


    Recently, we showed that renal afferent neurons exhibit a unique firing pattern, i.e., predominantly sustained firing, upon stimulation. Pathological conditions such as renal inflammation likely alter excitability of renal afferent neurons. Here, we tested whether the proinflammatory chemokine CXCL1 alters the firing pattern of renal afferent neurons. Rat dorsal root ganglion neurons (Th11-L2), retrogradely labeled with dicarbocyanine dye, were incubated with CXCL1 (20 h) or vehicle before patch-clamp recording. The firing pattern of neurons was characterized as tonic, i.e., sustained action potential (AP) firing, or phasic, i.e., renal afferents treated with vehicle, 58.9% exhibited a tonic firing pattern vs. 7.8%, in unlabeled, nonrenal neurons (P renal neurons; hence the occurrence of tonic neurons with sustained firing upon electrical stimulation decreased (35.6 vs. 58.9%, P renal afferents from a predominantly tonic to a more phasic firing pattern, suggesting that CXCL1 reduced the sensitivity of renal afferent units upon stimulation.

  19. Chloride regulates afferent arteriolar contraction in response to depolarization

    Hansen, P B; Jensen, B L; Skott, O


    . The results show that K+-induced contraction of smooth muscle cells in the afferent arteriole is highly sensitive to chloride, whereas neurotransmitter release and ensuing contraction is not dependent on chloride. Thus, there are different activation pathways for depolarizing vasoconstrictors......-Renal vascular reactivity is influenced by the level of dietary salt intake. Recent in vitro data suggest that afferent arteriolar contractility is modulated by extracellular chloride. In the present study, we assessed the influence of chloride on K+-induced contraction in isolated perfused rabbit...... afferent arterioles. In 70% of vessels examined, K+-induced contraction was abolished by acute substitution of bath chloride. Consecutive addition of Cl- (30, 60, 80, 100, 110, and 117 mmol/L) restored the sensitivity to K+, and half-maximal response was observed at 82 mmol/L chloride. The calcium channel...

  20. T-type voltage-gated calcium channels regulate the tone of mouse efferent arterioles

    Poulsen, Christian B; Al-Mashhadi, Rozh H; Cribbs, Leanne L;


    Voltage-gated calcium channels are important for the regulation of renal blood flow and the glomerular filtration rate. Excitation-contraction coupling in afferent arterioles is known to require activation of these channels and we studied their role in the regulation of cortical efferent arteriolar...... tone. We used microdissected perfused mouse efferent arterioles and found a transient vasoconstriction in response to depolarization with potassium; an effect abolished by removal of extracellular calcium. The T-type voltage-gated calcium channel antagonists mibefradil and nickel blocked this potassium....... Low concentrations of nickel, an agent that blocks Ca(v)3.2, had a similar effect. Thus, T-type voltage-gated calcium channels are functionally important for depolarization-induced vasoconstriction and subsequent dilatation in mouse cortical efferent arterioles.Kidney International advance online...

  1. Impact of Pregnancy on Underlying Renal Disease

    Baylis, Chris


    Normal pregnancy involves marked renal vasodilation and large increases in glomerular filtration rate (GFR). Studies in rats reveal that the gestational renal vasodilation is achieved by parallel reductions in tone in afferent and efferent arterioles so GFR rises without a change in glomerular blood pressure. There is some evidence from animal studies that increased renal generation of nitric oxide (NO) may be involved. Although chronic renal vasodilation has been implicated in causing progre...

  2. Chaos and non-linear phenomena in renal vascular control

    Yip, K P; Holstein-Rathlou, N H


    Renal autoregulation of blood flow depends on the functions of the tubuloglomerular feedback (TGF) system and the myogenic response of the afferent arteriole. Studies of the dynamic aspects of these control mechanisms at the level of both the single nephron and the whole kidney have revealed a va...

  3. Renal origin of rat urinary epidermal growth factor

    Nexø, Ebba; Poulsen, Steen Seier


    was below the detection limit of the assay. Renal production of EGF was confirmed by immunohistochemistry demonstrating EGF immunoreactivity in the afferent arteriole of the juxtaglomerular apparatus. EGF in the submandibular glands and in urine was found to differ with chromatofocusing and reverse...

  4. Effect of stimulation of afferent renal nerves on plasma levels of vasopressin

    Caverson, M.M.; Ciriello, J.


    Experiments were done in ..cap alpha..-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1/sup 0/) component locked in time with the stimulus and a secondary (2/sup 0/) component that had a long onset latency and that outlasted the stimulation period. The 1/sup 0/ and 2/sup 0/ components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively. Autonomic blockage with hexamethonium bromide and atropine methylbromide abolished the 1/sup 0/ component. Administration of the vasopressin V/sub 1/-vascular receptor antagonist d(CH/sub 2/)/sub 5/ VAVP during autonomic blockade abolished the 2/sup 0/C component. Plasma concentrations of AVP measured by radioimmunoassay increased from control levels of 5.2 +/- 0.9 to 53.6 +/- 18.6 pg/ml during a 5-min period of stimulation of ARN. Plasma AVP levels measured 20-40 min after simulation were not significantly different from control values. These data demonstrate that sensory information originating in the kidney alters the release of vasopressin from the neurohypophysis and suggest that ARN are an important component of the neural circuitry involved in homeostatic mechanisms controlling arterial pressure.

  5. 老年人原发性膜性肾病肾小动脉病变的特点%The pathological changes of renal arterioles in the elderly with idiopathic membranous nephropathy

    王艺萍; 王梅; 王素霞; 鄂洁; 郑欣


    目的 观察老年原发性膜性肾病患者肾小动脉病变的发生情况及其特点.方法 选取2000年1月至2005年12月在我院住院并经肾穿刺活检确诊的原发性膜性肾病患者168例,分为老年组(≥60岁)和非老年组(<60岁),分析两组患者肾小动脉病变的发生情况及其影响因素.结果 老年组收缩压、舒张压、血肌酐水平、血尿发生率显著高于非老年组,而eGFR则显著低于非老年组.肾小球球性或节段硬化的比例以及肾小管萎缩和肾间质纤维化程度老年组重于非老年组.肾脏小动脉病变的发生率以及严重程度均明显重于非老年组.多因素分析显示,高血压、年龄、肾小管间质慢性损伤是肾脏小动脉病变发生的独立影响因素.进一步将血压正常且小管间质病变匹配的老年与非老年组患者比较,老年患者.肾小动脉病变的发生率以及严重程度仍重于非老年患者(P<0.05),肾小动脉病变表现为肌层增厚,合并玻璃样变的比例高.结论 老年原发性膜性肾病患者肾小动脉病变的发生率以及严重程度均明显高于非老年患者,合并玻璃样变的比率高,其可能是影响老年原发性肾脏病患者预后不良的重要因素.%Objective To observe the pathological changes of renal arterioles in the elderly with idiopathic membranous nephropathy. Methods One hundred and sixty-eight patients with clinical and biopsy-proven idiopathic membranous nephropathy from Jan 2000 to Dec 2005 were enrolled.The characteristics and influence factors of the renal arterioles lesions in the elderly group(44 cases)and non-elderly group(124 cases)were analyzed. Results The systolic blood pressure.diastolic blood pressure.the level of serum creatinine and the incidenee of hematuria were higher in the elderly group,but the eGFR was lower.The ratios of global and segmental glomerulosclerosis and degrees of tubular interstitial damage and fibrosis were more severe in the

  6. Analysis of interaction between TGF and the myogenic response in renal blood flow autoregulation

    Feldberg, R; Colding-Jørgensen, M; Holstein-Rathlou, N H


    The present study investigates the interaction between the tubuloglomerular feedback (TGF) response and the myogenic mechanism by use of a mathematical model. The two control mechanisms are implemented in a spatially distributed model of the rat renal juxtamedullary afferent arteriole. The model....... The contribution of TGF to smooth muscle activity is assumed to be a linear function of the glomerular capillary pressure. The results show that the myogenic response plays an important role in renal blood flow autoregulation. Without a myogenic response, mechanisms such as TGF that are localized in the distal...... located in the distal part of the afferent arteriole. An ascending myogenic response could enhance the regulatory efficiency of the TGF mechanism by increasing the open-loop gain of the system. However, such a synergistic interaction will only be observed when the two mechanisms operate on more or less...

  7. Impact of pregnancy on underlying renal disease.

    Baylis, Chris


    Normal pregnancy involves marked renal vasodilation and large increases in glomerular filtration rate (GFR). Studies in rats reveal that the gestational renal vasodilation is achieved by parallel reductions in tone in afferent and efferent arterioles so GFR rises without a change in glomerular blood pressure. There is some evidence from animal studies that increased renal generation of nitric oxide (NO) may be involved. Although chronic renal vasodilation has been implicated in causing progression of renal disease in nonpregnant states by glomerular hypertension, there are no long-term deleterious effects of pregnancies on the kidney when maternal renal function is normal because glomerular blood pressure remains normal. When maternal renal function is compromised before conception, there are no long-term adverse effects on renal function in most types of renal disease, providing that the GFR is well maintained before conception. When serum creatinine exceeds approximately 1.4 mg/dL, pregnancy may accelerate the renal disease increases and when serum creatinine >2 mg/dL, the chances are greater than 1 in 3 that pregnancy will hasten the progression of the renal disease. The available animal studies suggest that glomerular hypertension does not occur despite diverse injuries. Thus, the mechanisms of the adverse interaction between pregnancy and underlying renal disease remain unknown.

  8. Effects of efonidipine hydrochloride on renal arteriolar diameters in spontaneously hypertensive rats.

    Nakamura, Masuhisa; Notoya, Mitsuru; Kohda, Yuka; Yamashita, Junji; Takashita, Yuko; Gemba, Munekazu


    Efonidipine, a calcium antagonist, has been reported to dilate not only afferent but also efferent arterioles, thereby reducing glomerular hydrostatic pressure. We investigated the effect of chronic treatment with efonidipine or lisinopril on the afferent and efferent arteriolar diameters by the vascular cast technique. Four-week-old spontaneously hypertensive rats (SHR) were divided into three groups: untreated, efonidipine (25 mg/kg/day)-treated, and lisinopril (3 mg/kg/day)-treated. At 22 weeks of age, the renal vasculatures were fixed at the maximally dilated condition. The morphometrical measurements showed that the treatments with efonidipine and lisinopril caused structural alteration of the vasculature, resulting in significantly greater efferent arteriolar diameters than in untreated SHR. In addition, lisinopril-treated rats had wider afferent lumina. The renoprotective effect of efonidipine and lisinopril might be partly due to the structurally larger efferent arteriolar lumen.

  9. Heterogeneous Downregulation of Angiotensin II AT1-A and AT1-B Receptors in Arterioles in STZ-Induced Diabetic Rat Kidneys

    Zsolt Razga


    Full Text Available Introduction. The renin granulation of kidney arterioles is enhanced in diabetes despite the fact that the level of angiotensin II in the diabetic kidney is elevated. Therefore, the number of angiotensin II AT1-A and AT1-B receptors in afferent and efferent arteriole’s renin-positive and renin-negative smooth muscle cells (SMC was estimated. Method. Immunohistochemistry at the electron microscopic level was combined with 3D stereological sampling techniques. Results. In diabetes the enhanced downregulation of AT1-B receptors in the renin-positive than in the renin-negative SMCs in both arterioles was resulted: the significant difference in the number of AT1 (AT1-A + AT1-B receptors between the two types of SMCs in the normal rats was further increased in diabetes and in contrast with the significant difference observed between the afferent and efferent arterioles in the normal animals, there was no such difference in diabetes. Conclusions. The enhanced downregulation of the AT1-B receptors in the renin-negative SMCs in the efferent arterioles demonstrates that the regulation of the glomerular filtration rate by the pre- and postglomerular arterioles is changed in diabetes. The enhanced downregulation of the AT1-B receptors in the renin-positive SMCs in the arterioles may result in an enhanced level of renin granulation in the arterioles.

  10. Contribution of renal purinergic receptors to renal vasoconstriction in angiotensin II-induced hypertensive rats.

    Franco, Martha; Bautista, Rocio; Tapia, Edilia; Soto, Virgilia; Santamaría, José; Osorio, Horacio; Pacheco, Ursino; Sánchez-Lozada, L Gabriela; Kobori, Hiroyuki; Navar, L Gabriel


    To investigate the participation of purinergic P2 receptors in the regulation of renal function in ANG II-dependent hypertension, renal and glomerular hemodynamics were evaluated in chronic ANG II-infused (14 days) and Sham rats during acute blockade of P2 receptors with PPADS. In addition, P2X1 and P2Y1 protein and mRNA expression were compared in ANG II-infused and Sham rats. Chronic ANG II-infused rats exhibited increased afferent and efferent arteriolar resistances and reductions in glomerular blood flow, glomerular filtration rate (GFR), single-nephron GFR (SNGFR), and glomerular ultrafiltration coefficient. PPADS restored afferent and efferent resistances as well as glomerular blood flow and SNGFR, but did not ameliorate the elevated arterial blood pressure. In Sham rats, PPADS increased afferent and efferent arteriolar resistances and reduced GFR and SNGFR. Since purinergic blockade may influence nitric oxide (NO) release, we evaluated the role of NO in the response to PPADS. Acute blockade with N(ω)-nitro-l-arginine methyl ester (l-NAME) reversed the vasodilatory effects of PPADS and reduced urinary nitrate excretion (NO(2)(-)/NO(3)(-)) in ANG II-infused rats, indicating a NO-mediated vasodilation during PPADS treatment. In Sham rats, PPADS induced renal vasoconstriction which was not modified by l-NAME, suggesting blockade of a P2X receptor subtype linked to the NO pathway; the response was similar to that obtained with l-NAME alone. P2X1 receptor expression in the renal cortex was increased by chronic ANG II infusion, but there were no changes in P2Y1 receptor abundance. These findings indicate that there is an enhanced P2 receptor-mediated vasoconstriction of afferent and efferent arterioles in chronic ANG II-infused rats, which contributes to the increased renal vascular resistance observed in ANG II-dependent hypertension.

  11. Integrin mobilizes intracellular Ca(2+) in renal vascular smooth muscle cells

    Chan, W L; Holstein-Rathlou, N H; Yip, K P


    Peptides with the Arg-Gly-Asp (RGD) motif induce vasoconstriction in rat afferent arterioles by increasing the intracellular Ca(2+) concentration ([Ca(2+)](i)) in vascular smooth muscle cells (VSMC). This finding suggests that occupancy of integrins on the plasma membrane of VSMC might affect...... vascular tone. The purpose of this study was to determine whether occupancy of integrins by exogenous RGD peptides initiates intracellular Ca(2+) signaling in cultured renal VSMC. When smooth muscle cells were exposed to 0.1 mM hexapeptide GRGDSP, [Ca(2+)](i) rapidly increased from 91 +/- 4 to 287 +/- 37 n...

  12. Reversible anuric acute kidney injury secondary to acute renal autoregulatory dysfunction.

    Imbriano, Louis J; Maesaka, John K; Drakakis, James; Mattana, Joseph


    Autoregulation of glomerular capillary pressure via regulation of the resistances at the afferent and efferent arterioles plays a critical role in maintaining the glomerular filtration rate over a wide range of mean arterial pressure. Angiotensin II and prostaglandins are among the agents which contribute to autoregulation and drugs which interfere with these agents may have a substantial impact on afferent and efferent arteriolar resistance. We describe a patient who suffered an episode of anuric acute kidney injury following exposure to a nonsteroidal anti-inflammatory agent while on two diuretics, an angiotensin-converting enzyme inhibitor, and an angiotensin receptor blocker. The episode completely resolved and we review some of the mechanisms by which these events may have taken place and suggest the term "acute renal autoregulatory dysfunction" to describe this syndrome.

  13. Assessment of Renal Perfusion in a Canine Model Using FS069, A New Transpulmonary Echocontrast Agent.

    Mobarek, Sameh K.; Kates, Marc A.; Murgo, Joseph P.; Moreno, Carlos A.; Revall, Susan; Cheirif, Jorge


    We have previously demonstrated the safety and efficacy of FS069, a new transpulmonary echocontrast agent, for myocardial opacification. To our knowledge, no information exists regarding the use of this agent for transcutaneous assessment of renal perfusion. We studied 14 mongrel dogs using intravenously administered FS069. Renal ultrasound imaging was performed with a Hewlett-Packard Sonos 1500 using a 3.5-MHz transducer. Renal blood flow (ReBF) was altered using renal artery occlusion in four dogs and dipyridamole (0.56 mg/kg IV) in ten dogs. Renal perfusion was quantitatively assessed before and after each intervention using background subtracted peak intensity. ReBF was assessed with radiolabeled microspheres in ten dogs. Renal opacification was observed in all 14 dogs at baseline. The intravenous contrast dose required to produce optimal renal opacification ranged from 0.3-0.7 cc. After renal artery occlusion, peak intensity was reduced from 5.4 +/- 5.8 to 0.93 +/- 1.1 units (r = 0.99, P change from baseline). The inverse relation between ReBF and peak intensity observed suggests vasoconstriction of the afferent arterioles in response to dipyridamole and a reduced clearance of the contrast. These findings are in agreement with previous data demonstrating decreased renal thallium clearance postdipyridamole administration. Our data document the feasibility to assess renal perfusion under various flow states after intravenous injection of FS069.

  14. Diaphragm arterioles are less responsive to alpha1- adrenergic constriction than gastrocnemius arterioles.

    Aaker, Aaron; Laughlin, M H


    The sympathetic nervous system has greater influence on vascular resistance in low-oxidative, fast-twitch skeletal muscle than in high-oxidative skeletal muscle (17). The purpose of this study was to test the hypothesis that arterioles isolated from low-oxidative, fast-twitch skeletal muscle [the white portion of gastrocnemius (WG)] possess greater responsiveness to adrenergic constriction than arterioles isolated from high-oxidative skeletal muscle [red portion of the gastrocnemius muscle (RG) and diaphragm (Dia)]. Second-order arterioles (2As) were isolated from WG, RG, and Dia of rats and reactivity examined in vitro. Results reveal that Dia 2As constrict less to norepinephrine (NE) (10(-9) to 10 (-4) M) than 2As from RG and WG, which exhibited similar NE-induced constrictions. This difference was not endothelium dependent, because responses of denuded 2As were similar to those of intact arterioles. The blunted NE-induced constrictor response of Dia 2As appears to be the result of differences in alpha1-receptor effects because 1) arterioles from Dia also responded less to selective alpha1-receptor stimulation with phenylephrine than RG and WG arterioles; 2) arterioles from Dia, RG, and WG dilated similarly to isoproterenol (10(-9) to 10(-4) M) and did not respond to selective alpha2-receptor stimulation with UK-14304; and 3) endothelin-1 produced similar constriction in 2As from Dia, RG, and WG. We conclude that differences in oxidative capacity and/or fiber type composition of muscle tissue do not explain different NE responsiveness of Dia 2As compared with 2As from gastrocnemius muscle. Differences in alpha1-adrenergic constrictor responsiveness among arterioles in skeletal muscle may contribute to nonuniform muscle blood flow responses observed during exercise and serve to maintain blood flow to Dia during exercise-induced increases in sympathetic nerve activity.

  15. Ischemia-induced glomerular parietal epithelial cells hyperplasia: Commonly misdiagnosed cellular crescent in renal biopsy.

    Zeng, Yeting; Wang, Xinrui; Xie, Feilai; Zheng, Zhiyong


    Ischemic pseudo-cellular crescent (IPCC) that is induced by ischemia and composed of hyperplastic glomerular parietal epithelial cells resembles cellular crescent. In this study, we aimed to assess the clinical and pathological features of IPCC in renal biopsy to avoid over-diagnosis and to determine the diagnostic basis. 4 IPCC cases diagnosed over a 4-year period (2012-2015) were evaluated for the study. Meanwhile, 5 cases of ANCA-associated glomerulonephritis and 5 cases of lupus nephritis (LN) were selected as control. Appropriate clinical data, morphology, and immunohistochemical features of all cases were retrieved. Results showed that the basement membrane of glomerulus with IPCC appeared as a concentric twisted ball, and glomerular cells of the lesion were reduced even entirely absent, and the adjacent afferent arterioles showed sclerosis or luminal stenosis. Furthermore, immune globulin deposition, vasculitis, and fibrinous exudate have not been observed in IPCC. While the cellular crescents showed diverse characteristics in both morphology and immunostaining in the control group. Therefore, these results indicated that IPCC is a sort of ischemic reactive hyperplasia and associated with sclerosis, stenosis, or obstruction of adjacent afferent arterioles, which is clearly different from cellular crescents result from glomerulonephritis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  16. Intrarenal artery injection of capsaicin activates spontaneous activity of renal afferent nerve fibers%肾动脉内注射辣椒素兴奋肾神经传入纤维的自发活动

    马慧娟; 武宇明; 马会杰; 张丽华; 何瑞荣


    The effects of intrarenal artery injection of capsaicin on multi- and single-unit spontaneous discharges of renal afferent nerve fibers were investigated in anesthetized rabbits. The results obtained are as follows: ( 1 ) intrarenal artery injection of capsaicin (20, 40, and 60 nmol/kg) increased the renal afferent nerve activity (ARNA) in a dose-dependent manner with unchanged arterial pressure; (2) pretreatment with ruthenium red (40 mmol/kg), a capsaicin receptor antagonist, completely abolished the effect of capsaicin; and (3) pretreatment with a nitric oxide synthase inhibitor L-NAME ( N6-nitro-L-arginine methylester, 0. 1 mmol/kg), significantly enhanced the ARNA response to capsaicin. The results suggest that intrarenal artery injection of capsaicin can activate ARNA via capsaicin receptors in anesthetized rabbits and that nitric oxide may be involved in regulating the activity of renal sensory nerve fibers as an inhibitory neurotransmitter.%应用记录肾传入神经多单位和单位放电的方法,观察肾动脉内注射辣椒素对麻醉家兔肾神经传入纤维自发放电活动的影响.结果表明:(1)肾动脉内注射辣椒素20、40和60nmol/kg可呈剂量依赖性地兴奋肾传入纤维的活动,而动脉血压不变;(2)静脉内预先应用辣椒素受体阻断剂钌红(40 mmok/kg),可完全阻断辣椒素对肾传入纤维的兴奋作用.(3)静脉内预先注射一氧化氮合酶抑制剂L-NAME(0.1 mmo/kg),能延长并增强肾传入神经对辣椒素的反应.以上结果提示:肾动脉内应用辣椒素可兴奋肾传入纤维的自发放电活动.一氧化氮作为抑制因素参与辣椒素诱导的肾传入神经兴奋.

  17. Angiotensin II and renal prostaglandin release in the dog. Interactions in controlling renal blood flow and glomerular filtration rate.

    Bugge, J F; Stokke, E S


    of prostaglandin synthesis is located to the glomerulus. We therefore postulate that renal prostaglandins attenuate the effects of angiotensin II on glomerular surface area and the filtration barrier, and not on the afferent arterioles as previously suggested.

  18. Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of PTH.

    Amann, K; Törnig, J; Flechtenmacher, C; Nabokov, A; Mall, G; Ritz, E


    Abnormalities in cardiovascular structures, e.g. LV hypertrophy and thickening of vessels (arteries, arterioles, veins) are hallmarks of renal failure. They are in part independent of elevated blood pressure. Parathyroid hormone (PTH) has been shown to affect cardiac function and has also been identified as a permissive factor in the genesis of cardiac fibrosis. The present study in rats with experimental renal failure was designed to examine whether PTH was permissive for wall thickening of intramyocardial arterioles as well. Male SD rats were sham operated or subtotally nephrectomized and maintained for 2 weeks. Subgroups of subtotally nephrectomized (SNX) rats were parathyroidectomized (PTX). Saline or rat 1, 34 PTH was administered by osmotic minipump. Eucalcaemia was maintained in PTX animals by a high-calcium diet (3%). Serum calcium was not statistically different between the groups. After perfusion fixation, intramyocardial arterioles were assessed using stereological techniques (wall thickness; wall/lumen ratio; minimal lumen diameter; length density). In random samples of the left ventricle, wall thickness of arterioles was 2.2 +/- 0.25 microns in sham-op controls and 2.76 +/- 0.41 in SNX (n = at least 8 animals per group). SNX-PTX animals+solvent did not differ significantly from sham-op controls (2.08 +/- 0.42 microns), while SNX-PTX animals+PTH had values not significantly different from SNX (2.59 +/- 0.54 microns). Differences in wall thickness were not paralleled by differences in systolic blood pressure (sham-op 110 +/- 13.3 mmHg; SNX 138 +/- 8.4 mmHg, SNX-PTX+solvent 142 +/- 5.2 mmHg; SNX-PTX+PTH 148 +/- 5.7 mmHg). PTH treated animals showed signs of marked vascular smooth-muscle cell and endothelial-cell activation. The data suggest that wall thickening of intramyocardial arterioles in short-term experimental uraemia is dependent upon the presence of PTH (permissive effect).

  19. Multiphoton imaging of renal tissues in vitro.

    Peti-Peterdi, János


    The highly inhomogeneous and light-scattering structure of living renal tissue makes the application of conventional imaging techniques more difficult compared with other parenchymal organs. On the other hand, key physiological processes of the kidney, such as regulation of glomerular filtration, hemodynamics, concentration, and dilution, involve complex interactions between multiple cell types and otherwise inaccessible structures that necessitate visual approaches. An ideal solution is multiphoton excitation fluorescence microscopy, a state-of-the-art imaging technique superior for deep optical sectioning of living tissue samples. Here, we review the basics and advantages of multiphoton microscopy and provide examples for its application in renal physiology using dissected cortical and medullary tissues in vitro. In combination with microperfusion techniques, the major functions of the juxtaglomerular apparatus, tubuloglomerular feedback and renin release, can be studied with high spatial and temporal resolution. Salt-dependent changes in macula densa cell volume, vasoconstriction of the afferent arteriole, and activity of an intraglomerular precapillary sphincter composed of renin granular cells are visualized in real time. Release and tissue activity of renin can be studied on the individual granule level. Imaging of the living inner medulla shows how interstitial cells interconnect cells of the vasa recta, loop of Henle, and collecting duct. In summary, multiphoton microscopy is an exciting new optical sectioning technique that has great potential for numerous future developments and is ideal for applications that require deep optical sectioning of living tissue samples.

  20. Arterioles in cerebral amyloid angiopathy and vascular dementia

    ZHU Guang-ming; ZHANG Wei-wei; LIU Ying; LI Juan


    Background Small cerebrovascular lesions are one of the most important factors in cerebral amyloid angiopathy (CM) and vascular dementia (VaD). We analyzed the difference of arteriolar pathology between CM patients (CMs) and vascular dementia patients without CAA (VaDs).Methods Ten deceased CMs and twelve deceased VaDs were available for this study. Five deceased patients without known cerebrovascular diseases served as controls. These patients were all autopsy cases. All transversely cut arterioles in the gray matter and white matter with an external diameter equal to or larger than 30 μm and with a maximum of 300 μm were examined. The internal and external diameters of arterioles were measured. Results The external diameter of gray matter arterioles in the CAAs was significantly greater than in controls. In gray matter arterioles, the diameter of the lumen in VaDs was markedly smaller than in the CAAs, whereas there was no significant difference between CAAs and controls. CMs and VaDs may cause remarkable thickening of the arteriolar walls in either white matter or gray matter. The sclerotic index of arterioles in VaDs was significantly greater than in CAAs and controls. Conclusions Stenosis of arterioles occurred in both CM and VaD, but the tendency was greater in VaD. Arterioles of CM were also expanded in gray matter, which may be related to lobar hemorrhage. The loss and/or degeneration of vascular smooth muscle cells was predominant in CM, while the over-proliferation of vascular smooth muscle cells was greater in VaD.

  1. In vivo visualization of characteristics of renal microcirculation in hypertensive and diabetic rats.

    Yamamoto, T; Tomura, Y; Tanaka, H; Kajiya, F


    We developed a videomicroscope system with a charge-coupled device camera and evaluated it in the investigation of the glomerular microcirculation in normal [Wistar-Kyoto (WKY)], spontaneously hypertensive (SHR), and streptoyotocin-induced diabetic rats (STZ). In WKY, the diameter of the afferent arterioles (Af) was 11.9 +/- 0.7 microm and that of the efferent arterioles (Ef) was 8.9 +/- 0.7 microm. Af and Ef in each glomerulus could be visualized simultaneously with continuous recording of blood pressure and renal blood flow. In SHR, Af diameter was constricted to approximately 60% of that in WKY. A dose-dependent dilation of Af and Ef was observed after administration of barnidipine (1-10 microg/kg iv), a calcium channel antagonist, in all three groups. No change was seen in the Af-to-Ef diameter ratio (Af/Ef ratio) in WKY. In SHR, the Af/Ef ratio increased significantly because of the marked dilation of Af after barnidipine administration. In contrast, barnidipine dilated Ef in STZ, causing a significant reduction in the Af/Ef ratio. This system can analyze in vivo glomerular microcirculation and systemic macrocirculation simultaneously, allowing more direct investigation of the characteristics of and acute changes in glomerular microcirculation in pathological animals.

  2. Connexin abundance in resistance vessels from the renal microcirculation in normo- and hypertensive rats

    Braunstein, Thomas Hartig; Sørensen, Charlotte Mehlin; Holstein-Rathlou, Niels-Henrik


    The expression of connexins in renal arterioles is believed to have a profound impact on conducted responses, regulation of arteriolar tonus and renal blood flow. We have previously shown that in renal preglomerular arterioles, conducted vasomotor responses are 40% greater in spontaneously...... with SD and SHR. This high abundance of Cx37 was not related to blood pressure because normotensive SD demonstrated a level of Cx37 similar to that of SHR. Additionally, we found no evidence for an increased abundance of Cx40 and Cx43 in renal arterioles of SHR when compared with normotensive counterparts....

  3. Renal Arterial Network Structure by Computed Tomography, and Nephron-Arterial Interactions


    Our goal is to predict interactions that develop among nephrons and between nephrons and the arterial network that supports them. We have developed a computationally simple but physiologically-based mathematical model of the kidney vascular tree to study renal autoregulation in ensembles of inter......Our goal is to predict interactions that develop among nephrons and between nephrons and the arterial network that supports them. We have developed a computationally simple but physiologically-based mathematical model of the kidney vascular tree to study renal autoregulation in ensembles...... of interacting nephrons not directly available for experimentation. The study combines computed tomography (CT) of a renal vascular cast at 2 micrometer resolution with simulation. The CT scan showed a bifurcating branching structure with as many as 7 bifurcations between arcuate arteries and the renal surface......, with afferent arterioles originating from all arterial structures, including arcuate arteries. The modeling component has 2 novel features: a probability based vascular tree based on the data from the CT images, and a network of arteries supplying several simple whole nephron models coupled electrotonically...

  4. Rhythmic components in renal autoregulation: Nonlinear modulation phenomena

    Pavlov, A. N.; Sosnovtseva, Olga; Pavlova, O. N.;


    Autoregulation of nephron blood flow involves two oscillatory processes: the tubular-flow sensitive tubuloglomerular feedback (TGF) mechanism and the blood-pressure sensitive myogenic mechanism. Both act to regulate the diameter of the afferent arteriole, which carries blood to the nephron...

  5. Differential adenosine sensitivity of diaphragm and skeletal muscle arterioles.

    Aaker, Aaron; Laughlin, M H


    The hyperemic response in exercising skeletal muscle is dependent on muscle fiber-type composition and fiber recruitment patterns, but the vascular control mechanisms producing exercise hyperemia in skeletal muscle remain poorly understood. The purpose of this study was to test the hypothesis that arterioles from white, low-oxidative skeletal muscle are less responsive to adenosine-induced dilation than are arterioles from diaphragm (Dia) and red, high-oxidative skeletal muscle. Second-order arterioles (2As) were isolated from the white portion of gastrocnemius muscle (WG; low-oxidative, fast-twitch muscle tissue) and two types of high-oxidative skeletal muscle [Dia and red portion of gastrocnemius muscle (RG)] of rats. Results reveal that 2As from all three types of muscle dilated in response to the endothelium-dependent dilator acetylcholine (WG: 48 +/- 3%, Dia: 51 +/- 3%, RG: 74 +/- 3%). In contrast, adenosine dilated only 2As from WG (48 +/- 4%) and Dia (46 +/- 5%) but not those from RG (5 +/- 5%). Thus adenosine-induced dilator responses differed among 2As of these different types of muscle tissue. However, the results do not support our hypothesis because 2As from Dia and WG dilated in response to adenosine, whereas 2As from RG did not. We conclude that the adenosine responsiveness of 2As from rat skeletal muscle cannot be predicted only by the fiber-type composition or oxidative capacity of the skeletal muscle tissue wherein the arteriole lies.

  6. Pentosan polysulfate treatment preserves renal autoregulation in ANG II-infused hypertensive rats via normalization of P2X1 receptor activation.

    Guan, Zhengrong; Fuller, Barry S; Yamamoto, Tatsuo; Cook, Anthony K; Pollock, Jennifer S; Inscho, Edward W


    Inflammatory factors are elevated in animal and human subjects with hypertension and renal injury. We hypothesized that inflammation contributes to hypertension-induced renal injury by impairing autoregulation and microvascular reactivity to P2X(1) receptor activation. Studies were conducted in vitro using the blood-perfused juxtamedullary nephron preparation. Rats receiving ANG II (60 ng/min) infusion were treated with the anti-inflammatory agent pentosan polysulfate (PPS) for 14 days. The magnitude and progression of hypertension were similar in ANG II and ANG II+PPS-treated rats (169 ± 5 vs. 172 ± 2 mmHg). Afferent arterioles from control rats exhibited normal autoregulatory behavior with diameter decreasing from 18.4 ± 1.6 to 11.4 ± 1.7 μm when perfusion pressure was increased from 70 to 160 mmHg. In contrast, pressure-mediated vasoconstriction was markedly attenuated in ANG II-treated rats, and diameter remained essentially unchanged over the range of perfusion pressures. However, ANG II-treated rats receiving PPS exhibited normal autoregulatory behavior compared with ANG II alone rats. Arteriolar reactivity to ATP and β,γ-methylene ATP was significantly reduced in ANG II hypertensive rats compared with controls. Interestingly, PPS treatment preserved normal reactivity to P2 and P2X(1) receptor agonists despite the persistent hypertension. The maximal vasoconstriction was 79 ± 3 and 81 ± 2% of the control diameter for ATP and β,γ-methylene ATP, respectively, similar to responses in control rats. PPS treatment significantly reduced α-smooth muscle actin staining in afferent arterioles and plasma transforming growth factor-β1 concentration in ANG II-treated rats. In conclusion, PPS normalizes autoregulation without altering ANG II-induced hypertension, suggesting that inflammatory processes reduce P2X(1) receptor reactivity and thereby impair autoregulatory behavior in ANG II hypertensive rats.

  7. Cerebellar and afferent ataxias.

    Pandolfo, Massimo; Manto, Mario


    Ataxia is the predominant manifestation of many acquired and inherited neurologic disorders affecting the cerebellum, its connections, and the afferent proprioceptive pathways. This article reviews the phenomenology and etiologies of cerebellar and afferent ataxias and provides indications for a rational approach to diagnosis and management. The pathophysiology of ataxia is being progressively understood and linked to the functional organization of the cerebellum. The impact of cerebellar diseases on different neurologic functions has been better defined and shown not to be limited to loss of motor coordination. The role of autoimmunity is increasingly recognized as a cause of sporadic cases of ataxia. Large collaborative studies of long duration are providing crucial information on the clinical spectrum and natural history of both sporadic ataxias (such as the cerebellar form of multiple system atrophy) and inherited ataxias. New dominant and recessive ataxia genes have been identified. On the therapeutic front, progress mostly concerns the development of treatments for Friedreich ataxia. Ataxia is the clinical manifestation of a wide range of disorders. In addition to accurate clinical assessment, MRI plays a major role in the diagnostic workup, allowing us to distinguish degenerative conditions from those due to other types of structural damage to the cerebellar or proprioceptive systems. Diagnostic algorithms based on clinical features, imaging, and neurophysiologic and biochemical parameters can be used to guide genetic testing for hereditary ataxias, the diagnosis of which is likely to be greatly improved by the introduction of new-generation DNA-sequencing approaches. Some rare forms of ataxia can be treated, so their diagnosis should not be missed. Proven symptomatic treatments for ataxia are still lacking, but intensive physical therapy appears to be helpful.

  8. Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles.

    Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi; Hongo, Kazuhiro; Dacey, Ralph G


    We investigated in cerebral penetrating arterioles the signaling mechanisms and dose-dependency of extracellular magnesium-induced vasodilation and also its vasodilatory effects in vessels preconstricted with agonists associated with delayed cerebral vasospasm following SAH. Male rat penetrating arterioles were cannulated. Their internal diameters were monitored. To investigate mechanisms of magnesium-induced vasodilation, inhibitors of endothelial function, potassium channels and endothelial impairment were tested. To simulate cerebral vasospasm we applied several spasmogenic agonists. Increased extracellular magnesium concentration produced concentration-dependent vasodilation, which was partially attenuated by non-specific calcium-sensitive potassium channel inhibitor tetraethylammonium, but not by other potassium channel inhibitors. Neither the nitric oxide synthase inhibitor L-NNA nor endothelial impairment induced by air embolism reduced the dilation. Although the magnesium-induced vasodilation was slightly attenuated by the spasmogen ET-1, neither application of PF2α nor TXA2 analog effect the vasodilation. Magnesium induced a concentration- and smooth muscle cell-dependent dilation in cerebral penetrating arterioles. Calcium-sensitive potassium channels of smooth muscle cells may play a key role in magnesium-induced vasodilation. Magnesium also dilated endothelium-impaired vessels as well as vessels preconstricted with spasmogenic agonists. These results provide a fundamental background for the clinical use of magnesium, especially in treatment against delayed cerebral ischemia or vasospasm following SAH.

  9. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice

    Lee, Craig R.; Imig, John D.; Edin, Matthew L.; Foley, Julie; DeGraff, Laura M.; Bradbury, J. Alyce; Graves, Joan P.; Lih, Fred B.; Clark, James; Myers, Page; Perrow, A. Ligon; Lepp, Adrienne N.; Kannon, M. Alison; Ronnekleiv, Oline K.; Alkayed, Nabil J.; Falck, John R.; Tomer, Kenneth B.; Zeldin, Darryl C.


    Renal cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) regulate sodium transport and blood pressure. Although endothelial CYP-derived EETs are potent vasodilators, their contribution to the regulation of blood pressure remains unclear. Consequently, we developed transgenic mice with endothelial expression of the human CYP2J2 and CYP2C8 epoxygenases to increase endothelial EET biosynthesis. Compared to wild-type littermate controls, an attenuated afferent arteriole constrictor response to endothelin-1 and enhanced dilator response to acetylcholine was observed in CYP2J2 and CYP2C8 transgenic mice. CYP2J2 and CYP2C8 transgenic mice demonstrated modestly, but not significantly, lower mean arterial pressure under basal conditions compared to wild-type controls. However, mean arterial pressure was significantly lower in both CYP2J2 and CYP2C8 transgenic mice during coadministration of N-nitro-l-arginine methyl ester and indomethacin. In a separate experiment, a high-salt diet and subcutaneous angiotensin II was administered over 4 wk. The angiotensin/high-salt-induced increase in systolic blood pressure, proteinuria, and glomerular injury was significantly attenuated in CYP2J2 and CYP2C8 transgenic mice compared to wild-type controls. Collectively, these data demonstrate that increased endothelial CYP epoxygenase expression attenuates afferent arteriolar constrictor reactivity and hypertension-induced increases in blood pressure and renal injury in mice. We conclude that endothelial CYP epoxygenase function contributes to the regulation of blood pressure.—Lee, C. R., Imig, J. D., Edin, M. E., Foley, J., DeGraff, L. M., Bradbury, J. A., Graves, J. P., Lih, F. B., Clark, J., Myers, P., Perrow, A. L., Lepp, A. N., Kannon, M. A., Ronnekleiv, O. K., Alkayed, N. J., Falck, J. R., Tomer, K. B., Zeldin, D. C. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice. PMID:20495177

  10. Electrical coupling between smooth muscle and endothelium in arterioles of the guinea-pig small intestine

    Crane, G. J.; Kotecha, N.; Luff, S. E.; Neild, T. O.


    Equations describing the steady-state passive electrical properties of arterioles have been derived. The arteriole was modelled as having two thin layers of cells (muscle and endothelium) with strong electrical coupling between cells within a layer and variable coupling between the layers. The model indicated that spread of membrane potential changes was highly dependent on the thickness of cells within the layers. The model was also used to identify the optimal experimental strategy for detecting coupling between the two layers, and experiments were carried out on arterioles from the guinea-pig small intestine. Thickness of the endothelial layer was measured using electron microscopy and was found to be around 0.5 μm. Electrical input resistance was measured in intact arterioles and compared to input resistance of arterioles from which the endothelium had been removed. The experiments confirmed that there was a strong electrical coupling between the muscle and endothelium in these vessels.

  11. Differential effects of the adenosine A1 receptor agonist adenosine amine congener on renal, femoral and carotid vascular conductance in preterm fetal sheep.

    Booth, Lindsea C; Tummers, Leonie; Jensen, Ellen C; Barrett, Carolyn J; Malpas, Simon C; Gunn, Alistair J; Bennet, Laura


    1. Adenosine A(1) receptor activation is critical for endogenous neuroprotection from hypoxia-ischaemia, raising the possibility that treatment with A(1) receptor agonists may be an effective physiological protection strategy for vulnerable preterm infants. However, the A(1) receptor can mediate unwanted systemic effects, including vasoconstriction of the afferent glomerular arteriole. There is limited information on whether this occurs at doses that improve cerebral perfusion in the immature brain. 2. Therefore, in the present study, we examined whether infusion of the selective A(1) receptor agonist adenosine amine congener (ADAC) is associated with reduced renal perfusion in chronically instrumented preterm (0.7 gestation) fetal sheep. In the present study, ADAC was given in successive doses of 2.5, 5.0 and 15.0 microg, 45 min apart. 3. Treatment with ADAC was associated with a marked reduction in renal vascular conductance (and blood flow), whereas carotid conductance was increased and there was no significant effect on femoral conductance. In contrast with the stable effects of increasing ADAC dose on vascular conductance, there was a significant dose-related fall in fetal heart rate and blood pressure. 4. In conclusion, these short-term data support the concern that A(1) receptor agonist infusion can selectively impair renal perfusion, even at low doses.

  12. Pharmacology of airway afferent nerve activity

    Carr Michael J


    Full Text Available Abstract Afferent nerves in the airways serve to regulate breathing pattern, cough, and airway autonomic neural tone. Pharmacologic agents that influence afferent nerve activity can be subclassified into compounds that modulate activity by indirect means (e.g. bronchial smooth muscle spasmogens and those that act directly on the nerves. Directly acting agents affect afferent nerve activity by interacting with various ion channels and receptors within the membrane of the afferent terminals. Whether by direct or indirect means, most compounds that enter the airspace will modify afferent nerve activity, and through this action alter airway physiology.

  13. Relationship between Serum Uric Acid Levels and Kidney Arteriole Resistance in Patients with Type 2 Diabetes Associated with Hypertension

    Wu Wodong; Mai Ciguang; Liang Weixiang; Xie Yinong; Liao Zhida; Yang Junqing


    Objectives To investigate the relationship between serum uric acid levels and arteriole resistance detected with the color Doppler energy imaging (CDEI) and to explore the risks of impaired regulation of vascular tone by uric acid in kidneys of hypertension patients. Methods In 12 healthy control cases, 28 non-diabetic hypertension (nNIDDM +H) cases and 25 type 2 diabetic hypertension (NIDDM+H) cases, uric acid (UA)levels were measured with uricase-peroxidase method.Arteriole resistance index (RI) and pulsate index (PI) in separate sections of renal artery included MAR,SRA, IRA were detected using CDEI with 2.1~4.2 Hz Doppler transducer in kidneys. Results In comparison,UA was significantly higher in non-diabetic hypertension group and diabetic hypertension group than in control group (P < 0.01, separately). UA levels was also significantly higher in NIDDM +H group than in nNIDDM +H, P < 0.029. RI in separate sections of renal artery was significantly higher in nNIDDM+H, or NIDDM+H group than in control group ( all P < 0.01 ),and it was significantly higher in NIDDM +H than nNIDDM +H groups (P < 0.05 and P < 0.01). In nNIDDM +H and NIDDM +H groups UA levels and IRA-RI could be elevated significantly following with the impaired heart function being aggravated (X2=13.028, P=0.005, X2=13.29, P=0.004); the dosage of HCT being increased ( X2 =14.216, P=0.001, X2 =14.661, P=0.001); the levels of GHbA1 being excessed unnormally (P=0.000). The correlation between UA and IRA-RI in both hypertension groups were directly related, in nNIDDM+H group r=0.842, P=0.000, in NIDDM+H group, r=0.797, P=0.000. Conclusions Uric acid levels and IRA-RI in hyper-tension patients were directly related. Uric acid levels and IRA-RI could be partly dependent on the severity of heart dysfunction, diuretic dose, and serum glucose status of diabete patients in long-term. Uric acid and the xanthine oxidase metabolic pathway may contribute to impaired regulation of arteriole tone in

  14. Renal infarction due to lupus vasculopathy.

    Varalaxmi, B; Sandeep, P; Sridhar, A V S S N; Raveendra, P; Kishore, C Krishna; Ram, R; Kumar, V Siva


    In the ISN/RPS 2003 classification of lupus nephritis (LN) renal vascular lesions are not mentioned. We present a patient with postpartum lupus vasculopathy. The renal biopsy in our patient showed concentric intimal thickening with narrowed lumen. No inflammatory changes were found. It also revealed immunoglobulin and complement deposition on the wall of the arteriole. These changes indicate lupus vasculopathy. The glomeruli revealed diffuse proliferative glomerulonephritis, with wire loops and cellular crescent in one glomerulus. The patient showed improvement with immunosuppression.

  15. GABA in Paraventricular Nucleus Regulates Adipose Afferent Reflex in Rats.

    Lei Ding

    Full Text Available Chemical stimulation of white adipose tissue (WAT induces adipose afferent reflex (AAR, and thereby causes a general sympathetic activation. Paraventricular nucleus (PVN is important in control of sympathetic outflow. This study was designed to investigate the role of γ-aminobutyric acid (GABA in PVN in regulating the AAR.Experiments were carried out in anesthetized rats. Renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP were continuously recorded. AAR was evaluated by the RSNA and MAP responses to electrical stimulation of the right epididymal WAT (eWAT afferent nerve. Electrical stimulation of eWAT afferent nerve increase RSNA. Bilateral microinjection of the GABAA receptor agonist isoguvacine or the GABAB receptor agonist baclofen attenuated the AAR. The effect of isoguvacine on the AAR was greater than that of baclofen. The GABAA receptor antagonist gabazine enhanced the AAR, while the GABAB receptor antagonist CGP-35348 had no significant effect on the AAR. Bilateral PVN microinjection of vigabatrin, a selective GABA-transaminase inhibitor, to increase endogenous GABA levels in the PVN abolished the AAR. The inhibitory effect of vigabatrin on the AAR was attenuated by the pretreatment with gabazine or CGP-35348. Pretreatment with combined gabazine and CGP-35348 abolished the effects of vigabatrin.Activation of GABAA or GABAB receptors in the PVN inhibits the AAR. Blockade of GABAA receptors in the PVN enhances the AAR. Endogenous GABA in the PVN plays an important role in regulating the AAR.


    夏晓红; 何瑞荣


    目的和方法:采用电生理学技术观察一氧化氮(NO)和心房钠尿肽(A NP)对肾动脉内注射内皮索(ET)所致麻醉大鼠肾神经传入放电(RANA)的影响。结 果:①肾动脉内注射ET-1后平均动脉压(MAP)先有短暂的降低随后为较显著的持 久增高,RANA明显增加;②肾动脉内分别注射NO前体L-Arg和ANP后,ET-1的上述效应 即被阻抑。结论:肾动脉内注射ET-1引起RANA明显增加,而此效应可 被同一途径注射NO和ANP所消除。%By using electrophysiological technique, the effects of nitric oxide (NO) and atrial natriuretic peptide (ANP) on renal afferent nerve activity (RANA) induced by intrarenal arterial injection of endothelin-1(ET-1) were examined in anesthetized rat. Results: (1) In response to intrarenal arterial injection of ET-1 (1μg/kg)MAP was initially decreased and subsequently increased, and RANA was increased to 208.33±16.60%(P<0.001). ( 2)Pretreatment with L-Arg or ANP could effectively inhibit the above biological actions induced by ET-1. Conclusion: Intrarenal arterial in jection of ET-1 can markedly induce the increase in RANA, an effect which is ab olishd by L-arg or ANP administered by the same route.

  17. Effect of red blood cells on platelet activation and thrombus formation in tortuous arterioles

    Jennifer K. W. Chesnutt


    Full Text Available Thrombosis is a major contributor to cardiovascular disease, which can lead to myocardial infarction and stroke. Thrombosis may form in tortuous microvessels, which are often seen throughout the human body, but the microscale mechanisms and processes are not well understood. In straight vessels, the presence of red blood cells (RBCs is known to push platelets toward walls, which may affect platelet aggregation and thrombus formation. However in tortuous vessels, the effects of RBC interactions with platelets in thrombosis are largely unknown. Accordingly, the objective of this work was to determine the physical effects of RBCs, platelet size, and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A discrete element computational model was used to simulate the transport, collision, adhesion, aggregation, and shear-induced platelet activation of hundreds of individual platelets and RBCs in thrombus formation in tortuous arterioles. Results showed that high shear stress near the inner sides of curved arteriole walls activated platelets to initiate thrombosis. RBCs initially promoted platelet activation, but then collisions of RBCs with mural thrombi reduced the amount of mural thrombus and the size of emboli. In the absence of RBCs, mural thrombus mass was smaller in a highly tortuous arteriole compared to a less tortuous arteriole. In the presence of RBCs however, mural thrombus mass was larger in the highly tortuous arteriole compared to the less tortuous arteriole. As well, smaller platelet size yielded less mural thrombus mass and smaller emboli, either with or without RBCs. This study shed light on microscopic interactions of RBCs and platelets in tortuous microvessels, which have implications in various pathologies associated with thrombosis and bleeding.

  18. Effect of Red Blood Cells on Platelet Activation and Thrombus Formation in Tortuous Arterioles.

    Chesnutt, Jennifer K W; Han, Hai-Chao


    Thrombosis is a major contributor to cardiovascular disease, which can lead to myocardial infarction and stroke. Thrombosis may form in tortuous microvessels, which are often seen throughout the human body, but the microscale mechanisms and processes are not well understood. In straight vessels, the presence of red blood cells (RBCs) is known to push platelets toward walls, which may affect platelet aggregation and thrombus formation. However in tortuous vessels, the effects of RBC interactions with platelets in thrombosis are largely unknown. Accordingly, the objective of this work was to determine the physical effects of RBCs, platelet size, and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A discrete element computational model was used to simulate the transport, collision, adhesion, aggregation, and shear-induced platelet activation of hundreds of individual platelets and RBCs in thrombus formation in tortuous arterioles. Results showed that high shear stress near the inner sides of curved arteriole walls activated platelets to initiate thrombosis. RBCs initially promoted platelet activation, but then collisions of RBCs with mural thrombi reduced the amount of mural thrombus and the size of emboli. In the absence of RBCs, mural thrombus mass was smaller in a highly tortuous arteriole compared to a less tortuous arteriole. In the presence of RBCs however, mural thrombus mass was larger in the highly tortuous arteriole compared to the less tortuous arteriole. As well, smaller platelet size yielded less mural thrombus mass and smaller emboli, either with or without RBCs. This study shed light on microscopic interactions of RBCs and platelets in tortuous microvessels, which have implications in various pathologies associated with thrombosis and bleeding.

  19. Juvenile growth reduces the influence of epithelial sodium channels on myogenic tone in skeletal muscle arterioles.

    Kang, Lori S; Masilamani, Shyama; Boegehold, Matthew A


    Previous studies have documented that rapid juvenile growth is accompanied by functional changes in the arteriolar endothelium, but much less is known about functional changes in arteriolar smooth muscle over this period. In this study, we investigate the possible contribution of epithelial sodium channels (ENaC) to the myogenic behaviour of arterioles at two stages of juvenile growth. The effects of the ENaC inhibitor benzamil on different levels of myogenic tone were studied in isolated gracilis muscle arterioles from rats aged 21-28 days ("weanlings") and 42-49 days ("juveniles"). ENaC subunit expression in the arteriolar wall was also determined, and the interaction between ENaC and nitric oxide (NO) in regulating vascular tone was explored by combined use of benzamil and N(G) -monomethyl-l-arginine (l-NMMA). At physiological pressures, both steady-state myogenic tone and the dynamic adjustments in this tone triggered by acute pressure changes were less in juvenile arterioles than in weanling arterioles. α, β and γ ENaC protein was present in arterioles at both ages, but benzamil only had an effect on myogenic tone in weanling arterioles. In these vessels, benzamil increased, rather than decreased, myogenic tone, and this effect was prevented by l-NMMA or endothelial removal. These findings suggest that although ENaC is present in gracilis muscle arterioles of both weanling and juvenile rats, it is not obligatory for the genesis of myogenic activity in these vessels at either age. However, ENaC activity can significantly modulate the level of myogenic tone through stimulation of endothelial NO release at an early stage of growth. © 2016 John Wiley & Sons Australia, Ltd.

  20. Role of calcium-activated potassium channels with small conductance in bradykinin-induced vasodilation of porcine retinal arterioles

    Dalsgaard, Thomas; Kroigaard, Christel; Bek, Toke


    (Ca)) conductance are involved in regulation of endothelium-dependent vasodilation in retinal arterioles was investigated. METHODS: Porcine retinal arterioles (diameter approximately 112 microm, N = 119) were mounted in microvascular myographs for isometric tension recordings. The arterioles were contracted......(Ca) channels contribute to NO-mediated relaxation induced by bradykinin and NS309 and, hence, may play an important role in retinal arterial endothelial function....

  1. Connexin mimetic peptides fail to inhibit vascular conducted calcium responses in renal arterioles

    Sørensen, Charlotte Mehlin; Salomonsson, Max; Braunstein, Thomas Hartig;


    of mimetic peptides directed against one or more connexins. Preglomerular resistance vessels were microdissected from kidneys of Sprague-Dawley rats and loaded with fura 2. The vessels were stimulated locally by applying electrical current through a micropipette, and the conducted calcium response...... was measured 500 mum from the site of stimulation. Application of connexin mimetic peptides directed against Cx40, 37/43, 45, or a cocktail with equimolar amounts of each, did not inhibit the propagated response, whereas the nonselective gap junction uncoupler carbenoxolone completely abolished the propagated...... mimetic peptides directed against Cx40, 37/43, or 45. Further studies are needed to determine whether conducted vasoconstriction is mediated via previously undescribed pathways....

  2. Oxygen sensing and conducted vasomotor responses in mouse cremaster arterioles in situ

    Ngo, Thuc Anh; Jensen, Lars Jørn; Riemann, Mads Achen


    This study examines mechanisms by which changes in tissue oxygen tension elicit vasomotor responses and whether localized changes in oxygen tension initiates conducted vasomotor responses in mouse cremaster arterioles. Intravital microscopy was used to visualize the mouse cremaster microcirculation....... The cremaster was superfused with Krebs' solution with different oxygen tensions, and a gas exchange chamber was used to induce localized changes in oxygen tension. In arterioles where red blood cells were removed by buffer perfusion, arterioles responded with same magnitudes of vasodilatation (DeltaD = 16.......0 +/- 4.9 mum) when changing from high (PO(2) = 242.5 +/- 13.3 mm Hg) to low (PO(2) = 22.5 +/- 4.8 mm Hg) oxygen tension as seen in the intact cremaster circulation (DeltaD = 18.7 +/- 1.0 mum). Blockade of NO synthases by L: -NAME and adenosine receptors by DPCPX had no effects on vasomotor responses...

  3. Presence of Kimmelstiel-Wilson like lesions in canine renal faillure

    Vala, Helena; Mega, A. C.; Mesquita, J.; Nóbrega, C.; Cruz, R.; Esteves, F.; C. Santos; Teixeira de Lemos, E.; Reis, F.


    Background: Nodular increases in mesangial matrix is the definition of Kimmelstiel-Wilson (K-W) lesions. In man, focal mesangiolyses and K-W nodules were positively associated with diabetes, proteinuria and hyalinization of afferent and efferent arterioles. Although, nodular sclerotic lesions may also occur in the absence of diabetic nephropathy and are clinically related to hypertension, smoking, hypercholesterolemia, among others. This study aimed to assess the presence of nodular ...

  4. Streptozotocin-induced diabetes decreases conducted vasoconstrictor response in mouse cremaster arterioles

    Rai, A; Riemann, M; Gustafsson, F


    . The mouse cremasteric arterioles were stimulated locally with KCl and the resulting local response as well as conducted responses at 500 microm and 1000 microm were measured in control and STZ treated mice. Diabetes (n=8) induced by intraperitoneal injection of STZ in a dose of 100 mg/kg (mean blood glucose...... reduces conducted vasoconstriction to KCl in mouse cremasteric arterioles, and combined treatment with both an oxygen radical scavenger and a protein kinase C beta II inhibitor improves the reduced conducted vasoconstriction....

  5. The blood pressure-induced diameter response of retinal arterioles decreases with increasing diabetic maculopathy

    Frederiksen, Christian Alcaraz; Jeppesen, Peter; Knudsen, Søren Tang;


    were measured using the Retinal Vessel Analyzer (RVA, Imedos, Germany) before, during, and after an increase in the blood pressure induced by isometric exercise. Additionally, the retinal thickness was measured using optical coherence tomography scanning. RESULTS: The arterioles contracted during......BACKGROUND: The aim of the study was to compare the diameter response of retinal arterioles and retinal thickness in patients with different stages of diabetic maculopathy during an increase in the arterial blood pressure. METHODS: Four groups each consisting of 19 individuals were studied. Group...

  6. Effects of cadmium on the renal and skeletal muscle microcirculation in rats

    Zhang Chong.


    The effects of cadmium on the arteriolar diameters of the kidney and skeletal muscle were quantified, because of the hypertensive effect of cacmium. The effect of cacmium on the constrictor response of the renal arterioles to angiotensin II (Ang II) were also assessed. In vivo preparations of the rat hydronephrotic kidney and cremaster muscle were used for direct visualization of the microvessels with intravital television microscopy. Hydronephrosis was induced in twenty-seven male Wistar-Kyoto rats (150-180 g) by unilateral ureter ligation. The hydronephrotic kidney, with intact cortical circulation and innervation, was exteriorized in a specially designed bath for microcirculation observation 6-8 weeks following the ureter ligation. The cremaster muscle experiments were conducted in another thirty-seven male WKY rats (120-180 g). Disparate effects of cadmium were observed in these two microcirculation beds. Topical cadmium (1.35 [mu]M-0.45 mM) increased the diameters of the pre- and postglomerular vessels in the hydronephrotic kidney maximally by 15-26%. Cadmium (0.27 mM) inhibited the Ang II response of the arterioles non-competitively. However, intraperitoneally injected cadmium (2 mg/kg), which significantly increased the mean arterial pressure, did not dilate the arterioles nor alter the Ang II response. On the other hand, cadmium (13.5 [mu]M-0.72 mM) constricted the larger arterioles in the cremaster muscle (60-160 [mu]m) concentration-dependently, but not small arterioles (15-30 [mu]m). In summary, topical cadmium dilates renal arterioles and decreases their reactivity to Ang II, but constricts the larger cremaster arterioles. The disparate effects of cadmium suggest different Ca[sup 2+] utilization mechanisms in different vascular beds. The construction of the cremaster arterioles may contribute to cadmium-induced hypertension by increasing peripheral resistance.

  7. Spontaneous high frequency diameter oscillations of larger retinal arterioles are reduced in type 2 diabetes mellitus

    Bek, Toke; Jeppesen, Peter; Kanters, Jørgen K.


    Diabetic retinopathy is characterized by morphological changes in the retina secondary to disturbances in retinal blood flow. Vasomotion is a mechanism for regulating blood flow by spontaneous oscillations in the diameter of retinal resistance arterioles, and has been shown to be disturbed outsid...

  8. Ruptured Retinal Arterial Macroaneurysm Secondary to Toxoplasmic Kyrieleis Arteriolitis: A Case Report

    Natalie Huang


    Full Text Available Purpose: The aim of this report was to describe multimodal ocular imaging findings in a patient who presented with a ruptured retinal arterial macroaneurysm (RAM associated with toxoplasmic Kyrieleis arteriolitis. Methods: We report the case of a 64-year-old man with a history of systemic hypertension and dense amblyopia of the left eye who presented with decreased vision and new floaters in the left eye. Color fundus photography, spectral-domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography were used as diagnostic imaging tools. Results: No signs of hypertensive retinopathy were noted in the right eye. Multiple chorioretinal scars characteristic of previous toxoplasmosis were revealed in the left eye, with one covering most of the macula. Periarterial plaques or Kyrieleis arteriolitis were observed in retinal arteries surrounding the toxoplasmic retinal scars. Multiple RAMs were observed in these vessels, one of which was acutely ruptured. A perivenular plaque associated with a chronic branch retinal vein occlusion (BRVO was noted along the same arcade at the arteriovenous crossing. Conclusion: RAM formation and BRVO can present as possible long-term complications of toxoplasmic Kyrieleis arteriolitis. This is the first reported case demonstrating an association between toxoplasmic Kyrieleis arteriolitis and RAM formation.

  9. Retinal arterioles have impaired reactivity to hyperoxia in type 1 diabetes

    Justesen, Birgitte L; Mistry, Paresh; Chaturvedi, Nish


    24-50 years) 29 with (male : female ratio 2.6 : 1) and 32 without (male : female ratio 0.7 : 1) diabetes, inhaled hypoxic, hyperoxic and normoxic-hypercapnic gas mixtures for 3-5 mins. The diameters of arterioles and venules were measured using digital retinal images taken before and after gas...

  10. Angiotensin II modulates conducted vasoconstriction to norepinephrine and local electrical stimulation in rat mesenteric arterioles

    Gustafsson, F; Holstein-Rathlou, N H


    M) or a local depolarizing current was continuously applied onto mesenteric arterioles using micropipettes. Local and conducted vasoconstriction was measured using videomicroscopy. Conducted responses were measured 200-1000 microns upstream from the application site. RESULTS: Systemic infusion of ANG II (4 ng...

  11. Conducted vasoconstriction in rat mesenteric arterioles: role for dihydropyridine-insensitive Ca(2+) channels

    Gustafsson, F; Andreasen, D; Salomonsson, Max;


    The aim of this study was to evaluate the role of voltage-operated Ca(2+) channels in the initiation and conduction of vasoconstrictor responses to local micropipette electrical stimulation of rat mesenteric arterioles (28 +/- 1 microm, n = 79) in vivo. Local and conducted (600 microm upstream fr...

  12. Contribution of nitric oxide synthase isoforms to cholinergic vasodilation in murine retinal arterioles.

    Gericke, Adrian; Goloborodko, Evgeny; Sniatecki, Jan J; Steege, Andreas; Wojnowski, Leszek; Pfeiffer, Norbert


    Nitric oxide synthases (NOSs) are critically involved in regulation of ocular perfusion. However, the contribution of the individual NOS isoforms to vascular responses is unknown in the retina. Because some previous findings suggested an involvement of inducible nitric oxide synthase (iNOS) in the regulation of retinal vascular tone, a major goal of the present study was to examine the hypothesis that iNOS is involved in mediating cholinergic vasodilation responses of murine retinal arterioles. Another subject of this study was to test the contribution of the other two NOS isoforms, neuronal (nNOS) and endothelial NOS (eNOS), to cholinergic retinal arteriole responses. Expression of individual NOS isoforms was determined in murine retinal arterioles using real-time PCR. All three NOS isoforms were expressed in retinal arterioles. However, eNOS mRNA was found to be most, and iNOS mRNA least abundant. To examine the functional relevance of iNOS for mediating vascular responses, retinal vascular preparations from gene-targeted iNOS-deficient mice (iNOS-/-) and wild-type mice were studied in vitro. Changes in luminal vessel diameter in response to the thromboxane mimetic 9,11-dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U-46619), the endothelium-dependent vasodilator acetylcholine, and the nitric oxide donor nitroprusside were measured by video microscopy. To determine the contribution of individual NOS isoforms to cholinergic vasodilation responses, retinas from iNOS-/- and wild-type mice were incubated with Nω-nitro-l-arginine methyl ester (l-NAME), a non-isoform-selective inhibitor of NOS, 7-nitroindazole, a selective nNOS blocker and aminoguanidine, a selective iNOS inhibitor. U-46619 evoked concentration-dependent vasoconstriction that was similar in retinal arterioles from iNOS-/- and wild-type mice. In retinal arterioles preconstricted with U-46619, acetylcholine and nitroprusside produced dose-dependent dilation that did not differ between iNOS-/- and

  13. A morphometric study of the hepatic arterioles in end-stage primary sclerosing cholangitis.

    Fiel, M Isabel; Sima, Hamid R; Azarian, Amirabbas; Schiano, Thomas D


    Primary sclerosing cholangitis (PSC) is typified by a heterogeneous histology with periductal fibroinflammatory lesions. The hepatic arterioles in PSC have not been well characterized. Using image analysis, we sought to examine the dimensions of hepatic arterioles in PSC. We identified 30 livers from patients transplanted for PSC as well as 10 explants each from cirrhotic patients (serving as controls) having primary biliary cirrhosis, hepatitis C (HCV), and alcoholic liver disease. At least two representative hematoxylin and eosin-stained slides were selected, and ten cross-sectioned hepatic arterioles were photographed for image analysis. The vessels were measured at their longest span and width based on the outer portions of the tunica media. Wall thickness was measured at its thickest portion from the intima to the outer portion of the tunica media; the perimeter of the luminal area was outlined by the endothelial lining, generating the total luminal area. Mean arteriolar length, width, and wall thickness (p = 0.012, p = 0.004, p = 0.001, respectively) were greater in the PSC group; luminal area was similar between the groups. When compared to the individual sub-groups, wall thickness of arterioles in PSC remained significantly greater. End-stage PSC has even larger-sized arterioles and greater wall thickness as compared to that of other cirrhotic livers. This increased wall thickness found in PSC cannot be solely attributed to cirrhosis itself. These vessel changes may potentially be the result of, or contribute to, the pathogenesis of PSC.

  14. Vasodilator effects of adenosine on retinal arterioles in streptozotocin-induced diabetic rats.

    Nakazawa, Taisuke; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio


    Adenosine is a potent vasodilator of retinal blood vessels and is implicated to be a major regulator of retinal blood flow during metabolic stress, but little is known about the impact of diabetes on the role of adenosine in regulation of retinal hemodynamics. Therefore, we examined how diabetes affects adenosine-induced vasodilation of retinal arterioles. Male Wistar rats were treated with streptozotocin (80 mg/kg, intraperitoneally), and experiments were performed 6-8 weeks later. Rats were treated with tetrodotoxin (50 microg/kg, intravenously [i.v.]) to eliminate any nerve activity and prevent movement of the eye and infused with methoxamine continuously to maintain adequate systemic circulation. Fundus images were captured with a digital camera that was equipped with a special objective lens, and diameters of retinal arterioles were measured. Adenosine increased diameters of retinal arterioles and decreased systemic blood pressure. These responses were significantly attenuated by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg, i.v.) and the adenosine triphosphate-dependent K+ (K(ATP)) channel blocker glibenclamide (20 mg/kg, i.v.). The depressor responses to adenosine were reduced in diabetic rats, whereas diabetes did not alter vasodilation of retinal arterioles to adenosine. In contrast, both depressor response and vasodilation of retinal arteriole to acetylcholine were reduced in diabetic rats. The retinal vasodilator responses to adenosine and acetylcholine observed in diabetic rats were diminished by N(G)-nitro-L-arginine methyl ester. There were no differences in the responses to pinacidil, a K(ATP) channel opener, between the diabetic and nondiabetic rats. These results suggest that both the activation of nitric oxide synthase and opening of K(ATP) channels contribute to the vasodilator effects of adenosine in rats in vivo. However, diabetes has no significant impact on the vasodilation mediated by these mechanisms in

  15. II!D I

    occur in primary malignant hypertension (MHT) either as a result of ... proliferation (MIP) in the interlobular artery and afferent arteriole, and .... which there are several causes.l7'>! ... late consequence of attemps at mitigating the loss of renal.

  16. Whisker-related afferents in superior colliculus.

    Castro-Alamancos, Manuel A; Favero, Morgana


    Rodents use their whiskers to explore the environment, and the superior colliculus is part of the neural circuits that process this sensorimotor information. Cells in the intermediate layers of the superior colliculus integrate trigeminotectal afferents from trigeminal complex and corticotectal afferents from barrel cortex. Using histological methods in mice, we found that trigeminotectal and corticotectal synapses overlap somewhat as they innervate the lower and upper portions of the intermediate granular layer, respectively. Using electrophysiological recordings and optogenetics in anesthetized mice in vivo, we showed that, similar to rats, whisker deflections produce two successive responses that are driven by trigeminotectal and corticotectal afferents. We then employed in vivo and slice experiments to characterize the response properties of these afferents. In vivo, corticotectal responses triggered by electrical stimulation of the barrel cortex evoke activity in the superior colliculus that increases with stimulus intensity and depresses with increasing frequency. In slices from adult mice, optogenetic activation of channelrhodopsin-expressing trigeminotectal and corticotectal fibers revealed that cells in the intermediate layers receive more efficacious trigeminotectal, than corticotectal, synaptic inputs. Moreover, the efficacy of trigeminotectal inputs depresses more strongly with increasing frequency than that of corticotectal inputs. The intermediate layers of superior colliculus appear to be tuned to process strong but infrequent trigeminal inputs and weak but more persistent cortical inputs, which explains features of sensory responsiveness, such as the robust rapid sensory adaptation of whisker responses in the superior colliculus. Copyright © 2016 the American Physiological Society.

  17. Reticulospinal actions on primary afferent depolarization of cutaneous and muscle afferents in the isolated frog neuraxis.

    González, H; Jiménez, I; Rudomin, P


    The effects of the brainstem reticular formation on the intraspinal excitability of low threshold cutaneous and muscle afferents were studied in the frog neuraxis isolated together with the right hindlimb nerves. Stimulation of low threshold fibers (less than two times threshold) in cutaneous nerves produced short latency, negative field potentials in the ipsilateral dorsal neuropil (200-400 microns depth) that reversed to positivity at deeper regions (500-700 microns). Stimulation of low threshold fibers (less than two times threshold) in muscle nerves produced, instead, negative response that acquired their maximum amplitude in the ventral neuropil (700-900 microns depth). These electrophysiological findings suggest, in agreement with observations in the cat, that low threshold cutaneous and muscle afferents end at different sites in the spinal cord. Intraspinal microstimulation applied within the dorsal neuropil produced antidromic responses in low threshold cutaneous afferents that were increased in size following stimulation of the dorsal or ventral roots, as well as of the brainstem reticular formation. This increase in excitability is interpreted as being due to primary afferent depolarization (PAD) of the intraspinal terminals of cutaneous fibers. Antidromic responses recorded in muscle nerves following intraspinal stimulation within the ventral neuropil were also increased following conditioning stimulation of adjacent dorsal or ventral roots. However, stimulation of the bulbar reticular formation produced practically no changes in the antidromic responses, but was able to inhibit the PAD of low threshold muscle afferents elicited by stimulation of the dorsal or ventral roots. It is suggested that the PAD of low threshold cutaneous and muscle afferents is mediated by independent sets of interneurons. Reticulospinal fibers would have excitatory connections with the interneurons mediating the PAD of cutaneous fibers and inhibitory connections with the

  18. Perivascular action of the local anaesthetic, lidocaine, on pial terminal arterioles: direct observations on the microcirculation.

    Altura, B. M.; Lassoff, S.


    Considerable controversy currently exists with respect to whether or not local anaesthetics exert direct action on cerebral arteriolar tone. In situ experiments were therefore undertaken on pial terminal arterioles of rats to determine whether or not perivascular application of lidocaine exerts any action on such cerebral vessels. Vessel size was assessed with an image-splitting television microscope recording system. The vessels studied ranged in size from 25 to 30 micron. Lidocaine was appl...

  19. Increased renal renin content in mice lacking the Na+/H+ exchanger NHE2.

    Hanner, Fiona; Chambrey, Régine; Bourgeois, Soline; Meer, Elliott; Mucsi, István; Rosivall, László; Shull, Gary E; Lorenz, John N; Eladari, Dominique; Peti-Peterdi, János


    Macula densa (MD) cells express the Na(+)/H(+) exchanger (NHE) isoform NHE2 at the apical membrane, which may play an important role in tubular salt sensing through the regulation of cell volume and intracellular pH. These studies aimed to determine whether NHE2 participates in the MD control of renin synthesis. Renal renin content and activity and elements of the MD signaling pathway were analyzed using wild-type (NHE2(+/+)) and NHE2 knockout (NHE2(-/-)) mice. Immunofluorescence studies indicated that NHE2(-/-) mice lack NHE3 at the MD apical membrane, so the other apical NHE isoform has not compensated for the lack of NHE2. Importantly, the number of renin-expressing cells in the afferent arteriole in NHE2(-/-) mice was increased approximately 2.5-fold using renin immunohistochemistry. Western blotting confirmed approximately 20% higher renal cortical renin content in NHE2(-/-) mice compared with wild type. No-salt diet for 1 wk significantly increased renin content and activity in NHE2(+/+) mice, but the response was blunted in NHE2(-/-) mice. Renal tissue renin activity and plasma renin concentration were elevated three- and twofold, respectively, in NHE2(-/-) mice compared with wild type. NHE2(-/-) mice also exhibited a significantly increased renal cortical cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase (mPGES) expression, indicating MD-specific mechanisms responsible for the increased renin content. Significant and chronic activation of ERK1/2 was observed in MD cells of NHE2(-/-) kidneys. Removal of salt or addition of NHE inhibitors to cultured mouse MD-derived (MMDD1) cells caused a time-dependent activation of ERK1/2. In conclusion, the NHE2 isoform appears to be important in the MD feedback control of renin secretion, and the signaling pathway likely involves MD cell shrinkage and activation of ERK1/2, COX-2, and mPGES, all well-established elements of the MD-PGE(2)-renin release pathway.

  20. Unmyelinated visceral afferents exhibit frequency dependent action potential broadening while myelinated visceral afferents do not.

    Li, Bai-Yan; Feng, Bin; Tsu, Hwa Y; Schild, John H


    Sensory information arising from visceral organ systems is encoded into action potential trains that propagate along afferent fibers to target nuclei in the central nervous system. These information streams range from tight patterns of action potentials that are well synchronized with the sensory transduction event to irregular, patternless discharge with no clear correlation to the sensory input. In general terms these afferent pathways can be divided into unmyelinated and myelinated fiber types. Our laboratory has a long standing interest in the functional differences between these two types of afferents in terms of the preprocessing of sensory information into action potential trains (synchrony, frequency, duration, etc.), the reflexogenic consequences of this sensory input to the central nervous system and the ionic channels that give rise to the electrophysiological properties of these unique cell types. The aim of this study was to determine whether there were any functional differences in the somatic action potential characteristics of unmyelinated and myelinated vagal afferents in response to different rates of sensory nerve stimulation. Our results showed that activity and frequency-dependent widening of the somatic action potential was quite prominent in unmyelinated but not myelinated vagal afferents. Spike broadening often leads to increased influx of Ca(2+) ions that has been associated with a diverse range of modulatory mechanisms both at the cell body and central synaptic terminations (e.g. increased neurotransmitter release.) We conclude that our observations are indicative of fundamentally different mechanisms for neural integration of sensory information arising from unmyelinated and myelinated vagal afferents.

  1. Reduced angiotensin II levels cause generalized vascular dysfunction via oxidant stress in hamster cheek pouch arterioles.

    Priestley, Jessica R C; Buelow, Matthew W; McEwen, Scott T; Weinberg, Brian D; Delaney, Melanie; Balus, Sarah F; Hoeppner, Carlyn; Dondlinger, Lynn; Lombard, Julian H


    We investigated the effect of suppressing plasma angiotensin II (ANG II) levels on arteriolar relaxation in the hamster cheek pouch. Arteriolar diameters were measured via television microscopy during short-term (3-6days) high salt (HS; 4% NaCl) diet and angiotensin converting enzyme (ACE) inhibition with captopril (100mg/kg/day). ACE inhibition and/or HS diet eliminated endothelium-dependent arteriolar dilation to acetylcholine, endothelium-independent dilation to the NO donor sodium nitroprusside, the prostacyclin analogs carbacyclin and iloprost, and the KATP channel opener cromakalim; and eliminated arteriolar constriction during KATP channel blockade with glibenclamide. Scavenging of superoxide radicals and low dose ANG II infusion (25ng/kg/min, subcutaneous) reduced oxidant stress and restored arteriolar dilation in arterioles of HS-fed hamsters. Vasoconstriction to topically-applied ANG II was unaffected by HS diet while arteriolar responses to elevation of superfusion solution PO2 were unaffected (5% O2, 10% O2) or reduced (21% O2) by HS diet. These findings indicate that sustained exposure to low levels of circulating ANG II leads to widespread dysfunction in endothelium-dependent and independent vascular relaxation mechanisms in cheek pouch arterioles by increasing vascular oxidant stress, but does not potentiate O2- or ANG II-induced constriction of arterioles in the distal microcirculation of normotensive hamsters. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

    Chesnutt, Jennifer K. W.; Han, Hai-Chao


    Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD) and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD and arteriole tortuosity play important roles in platelet activation and thrombus formation.

  3. KV 7.4 channels participate in the control of rodent renal vascular resting tone

    Salomonsson, M.; Brasen, Jens Christian; Braunstein, Thomas Hartig


    ) was measured using an ultrasonic flow probe. The isometric tension of rat interlobar arteries was examined in a wire myograph. Mice afferent arteriolar diameter was assessed utilizing the perfused juxtamedullary nephron technique. Results: Immunofluorescence revealed that KV7.4 channels were expressed in rat...... afferent arterioles. The KV7 blocker XE991 dose-dependently increased the isometric tension of rat interlobar arteries and caused a small (approx. 4.5%) RBF reduction in vivo. Nifedipine abolished these effects. Likewise, XE991 reduced mouse afferent arteriolar diameter by approx. 5%. The KV7.......2–5 stimulator flupirtine dose-dependently relaxed isolated rat interlobar arteries and increased (approx. 5%) RBF in vivo. The RBF responses to NE or Ang II administration were not affected by pre-treatment with XE991 or flupirtine. XE991 pre-treatment caused a minor augmentation of the acetylcholine...

  4. Renal vascular effects of calcium channel blockers in hypertension.

    Benstein, J A; Dworkin, L D


    Recent evidence suggests that calcium channel blockers have specific effects on renal hemodynamics in patients with hypertension and may also slow the progression of chronic renal failure. When these agents are studied in vitro, their predominant effect is to reverse afferent arteriolar vasoconstriction induced by catecholamines or angiotensin II. Because efferent resistance may remain high, glomerular filtration rate rises while renal blood flow remains low. The effects in vivo are less consistent. In human hypertension, calcium channel blockers lower renal resistance and may raise both renal blood flow and glomerular filtration rate. In experimental models of chronic renal disease, calcium channel blockers slow the progression of renal damage; however, variable effects on renal hemodynamics have been found. Other factors implicated in the progression of renal damage, including compensatory renal hypertrophy, platelet aggregation, and calcium deposition, may also be favorably influenced by these agents. Recent studies suggest that calcium channel blockers may have similar protective effects in patients with hypertension and chronic renal disease.

  5. Pain processing by spinal microcircuits: afferent combinatorics.

    Prescott, Steven A; Ratté, Stéphanie


    Pain, itch, heat, cold, and touch represent different percepts arising from somatosensory input. How stimuli give rise to these percepts has been debated for over a century. Recent work supports the view that primary afferents are highly specialized to transduce and encode specific stimulus modalities. However, cross-modal interactions (e.g. inhibition or exacerbation of pain by touch) support convergence rather than specificity in central circuits. We outline how peripheral specialization together with central convergence could enable spinal microcircuits to combine inputs from distinctly specialized, co-activated afferents and to modulate the output signals thus formed through computations like normalization. These issues will be discussed alongside recent advances in our understanding of microcircuitry in the superficial dorsal horn.

  6. Renal histology in polycystic kidney disease with incipient and advanced renal failure.

    Zeier, M; Fehrenbach, P; Geberth, S; Möhring, K; Waldherr, R; Ritz, E


    Renal specimens were obtained at surgery or postmortem from patients with autosomal dominant polycystic kidney disease (ADPKD). Patients had either serum creatinine (SCr) below 350 mumol/liter (N = 12) or terminal renal failure (N = 50). Specimens were examined by two independent observers using a carefully validated score system. Mean glomerular diameters were similar in ADPKD patients with early renal failure (176 +/- 38 microns) and in victims of traffic accidents (177 +/- 23 microns), while they were significantly greater in diabetics with comparable renal function (205 +/- 16 microns). Glomerular diameters in ADPKD patients with terminal renal failure (191 +/- 45 microns) and with early renal failure were not significantly different. On average, 29% of glomeruli (17 to 62) were globally sclerosed in early renal failure, and 49% (19 to 93) in terminal renal failure. The proportion of glomeruli with segmental sclerosis was less than 4% in both groups. Marked vascular sclerosis, interstitial fibrosis, and tubular atrophy were present in early renal failure, and even more so in terminal renal failure. Interstitial infiltrates were scarce and consisted mainly of CD4 positive lymphocytes and CD68 positive macrophages. Immunestaining with monoclonal renin antibodies showed an increased juxtaglomerular index and expression of renin by arterioles adjacent to cysts, as well as by cyst wall epithelia. The data show more severe vascular and interstitial, but not glomerular, changes in ADPKD with advanced as compared to early renal failure.

  7. p66Shc regulates renal vascular tone in hypertension-induced nephropathy.

    Miller, Bradley; Palygin, Oleg; Rufanova, Victoriya A; Chong, Andrew; Lazar, Jozef; Jacob, Howard J; Mattson, David; Roman, Richard J; Williams, Jan M; Cowley, Allen W; Geurts, Aron M; Staruschenko, Alexander; Imig, John D; Sorokin, Andrey


    Renal preglomerular arterioles regulate vascular tone to ensure a large pressure gradient over short distances, a function that is extremely important for maintaining renal microcirculation. Regulation of renal microvascular tone is impaired in salt-sensitive (SS) hypertension-induced nephropathy, but the molecular mechanisms contributing to this impairment remain elusive. Here, we assessed the contribution of the SH2 adaptor protein p66Shc (encoded by Shc1) in regulating renal vascular tone and the development of renal vascular dysfunction associated with hypertension-induced nephropathy. We generated a panel of mutant rat strains in which specific modifications of Shc1 were introduced into the Dahl SS rats. In SS rats, overexpression of p66Shc was linked to increased renal damage. Conversely, deletion of p66Shc from these rats restored the myogenic responsiveness of renal preglomerular arterioles ex vivo and promoted cellular contraction in primary vascular smooth muscle cells (SMCs) that were isolated from renal vessels. In primary SMCs, p66Shc restricted the activation of transient receptor potential cation channels to attenuate cytosolic Ca2+ influx, implicating a mechanism by which overexpression of p66Shc impairs renal vascular reactivity. These results establish the adaptor protein p66Shc as a regulator of renal vascular tone and a driver of impaired renal vascular function in hypertension-induced nephropathy.

  8. Models of utricular bouton afferents: role of afferent-hair cell connectivity in determining spike train regularity.

    Holmes, William R; Huwe, Janice A; Williams, Barbara; Rowe, Michael H; Peterson, Ellengene H


    Vestibular bouton afferent terminals in turtle utricle can be categorized into four types depending on their location and terminal arbor structure: lateral extrastriolar (LES), striolar, juxtastriolar, and medial extrastriolar (MES). The terminal arbors of these afferents differ in surface area, total length, collecting area, number of boutons, number of bouton contacts per hair cell, and axon diameter (Huwe JA, Logan CJ, Williams B, Rowe MH, Peterson EH. J Neurophysiol 113: 2420-2433, 2015). To understand how differences in terminal morphology and the resulting hair cell inputs might affect afferent response properties, we modeled representative afferents from each region, using reconstructed bouton afferents. Collecting area and hair cell density were used to estimate hair cell-to-afferent convergence. Nonmorphological features were held constant to isolate effects of afferent structure and connectivity. The models suggest that all four bouton afferent types are electrotonically compact and that excitatory postsynaptic potentials are two to four times larger in MES afferents than in other afferents, making MES afferents more responsive to low input levels. The models also predict that MES and LES terminal structures permit higher spontaneous firing rates than those in striola and juxtastriola. We found that differences in spike train regularity are not a consequence of differences in peripheral terminal structure, per se, but that a higher proportion of multiple contacts between afferents and individual hair cells increases afferent firing irregularity. The prediction that afferents having primarily one bouton contact per hair cell will fire more regularly than afferents making multiple bouton contacts per hair cell has implications for spike train regularity in dimorphic and calyx afferents.NEW & NOTEWORTHY Bouton afferents in different regions of turtle utricle have very different morphologies and afferent-hair cell connectivities. Highly detailed computational

  9. Modulation of long-latency afferent inhibition by the amplitude of sensory afferent volley.

    Turco, Claudia V; El-Sayes, Jenin; Fassett, Hunter J; Chen, Robert; Nelson, Aimee J


    Long-latency afferent inhibition (LAI) is the inhibition of the transcranial magnetic stimulation (TMS) motor-evoked potentials (MEP) by the sensory afferent volley following electrical stimulation of a peripheral nerve. It is unknown how the activation of sensory afferent fibers relates to the magnitude of LAI. This study investigated the relationship between LAI and the sensory nerve action potentials (SNAP) from the median nerve (MN) and the digital nerves (DN) of the second digit. LAI was obtained by delivering nerve stimulation 200 ms before a TMS pulse delivered over the motor cortex. Experiment 1 assessed the magnitude of LAI following stimulation of the contralateral MN or DN using nerve stimulus intensities relative to the maximum SNAP (SNAPmax) of that nerve and two TMS intensities (0.5- and 1-mV MEP). Results indicate that MN LAI is maximal at ~50% SNAPmax, when presumably all sensory afferents are recruited for TMS of 0.5-mV MEP. For DN, LAI appears at ~50% SNAPmax and does not increase with further recruitment of sensory afferents. Experiment 2 investigated the magnitude of LAI following ipsilateral nerve stimulation at intensities relative to SNAPmax Results show minimal LAI evoked by ipsilateral MN and no LAI following ipsilateral DN stimulation. Implications for future studies investigating LAI include adjusting nerve stimulation to 50% SNAPmax to obtain maximal LAI. Additionally, MN LAI can be used as a marker for neurological disease or injury by using a nerve stimulation intensity that can evoke a depth of LAI capable of increasing or decreasing.NEW & NOTEWORTHY This is the first investigation of the relationship between long-latency afferent inhibition (LAI) and the sensory afferent volley. Differences exist between median and digital nerve LAI. For the median nerve, LAI increases until all sensory fibers are presumably recruited. In contrast, digital nerve LAI does not increase with the recruitment of additional sensory fibers but rather is

  10. Hair-Cell Versus Afferent Adaptation in the Semicircular Canals

    Rabbitt, R. D.; Boyle, R.; Holstein, G. R.; Highstein, S. M.


    The time course and extent of adaptation in semicircular canal hair cells was compared to adaptation in primary afferent neurons for physiological stimuli in vivo to study the origins of the neural code transmitted to the brain. The oyster toadfish, Opsanus tau, was used as the experimental model. Afferent firing-rate adaptation followed a double-exponential time course in response to step cupula displacements. The dominant adaptation time constant varied considerably among afferent fibers an...

  11. K+ Currents in Isolated Vestibular Afferent Calyx Terminals

    Dhawan, Ritu; Mann, Scott E; Meredith, Frances L; Rennie, Katherine J


    Vestibular hair cells transduce mechanical displacements of their hair bundles into an electrical receptor potential which modulates transmitter release and subsequent action potential firing in afferent neurons...

  12. Differentiation of arterioles from venules in mouse histology images using machine learning

    Elkerton, J. S.; Xu, Yiwen; Pickering, J. G.; Ward, Aaron D.


    Analysis and morphological comparison of arteriolar and venular networks are essential to our understanding of multiple diseases affecting every organ system. We have developed and evaluated the first fully automatic software system for differentiation of arterioles from venules on high-resolution digital histology images of the mouse hind limb immunostained for smooth muscle α-actin. Classifiers trained on texture and morphologic features by supervised machine learning provided excellent classification accuracy for differentiation of arterioles and venules, achieving an area under the receiver operating characteristic curve of 0.90 and balanced false-positive and false-negative rates. Feature selection was consistent across cross-validation iterations, and a small set of three features was required to achieve the reported performance, suggesting potential generalizability of the system. This system eliminates the need for laborious manual classification of the hundreds of microvessels occurring in a typical sample, and paves the way for high-throughput analysis the arteriolar and venular networks in the mouse.

  13. Changes in vascular extracellular matrix composition during decidual spiral arteriole remodeling in early human pregnancy.

    Smith, Samantha D; Choudhury, Ruhul H; Matos, Patricia; Horn, James A; Lye, Stephen J; Dunk, Caroline E; Aplin, John D; Jones, Rebecca L; Harris, Lynda K


    Uterine spiral arteriole (SA) remodeling in early pregnancy involves a coordinated series of events including decidual immune cell recruitment, vascular cell disruption and loss, and colonization by placental-derived extravillous trophoblast (EVT). During this process, decidual SA are converted from narrow, muscular vessels into dilated channels lacking vasomotor control. We hypothesized that this extensive alteration in SA architecture must require significant reorganization and/or breakdown of the vascular extracellular matrix (ECM). First trimester decidua basalis (30 specimens) was immunostained to identify spiral arterioles undergoing trophoblast-independent and -dependent phases of remodeling. Serial sections were then immunostained for a panel of ECM markers, to examine changes in vascular ECM during the remodeling process. The initial stages of SA remodeling were characterized by loss of laminin, elastin, fibrillin, collagen types III, IV and VI from the basement membrane, vascular media and/or adventitia, and surrounding decidual stromal cells. Loss of ECM correlated with disruption and disorganization of vascular smooth muscle cells, and the majority of changes occurred prior to extensive colonization of the vessel wall by EVT. The final stages of SA remodeling, characterized by the arrival of EVT, were associated with the increased mural deposition of fibronectin and fibrinoid. This study provides the first detailed analysis of the spatial and temporal loss of ECM from the walls of remodeling decidual SA in early pregnancy.

  14. Acute hyperglycemia-induced endothelial dysfunction in retinal arterioles in cats.

    Sogawa, Kenji; Nagaoka, Taiji; Izumi, Naohiro; Nakabayashi, Seigo; Yoshida, Akitoshi


    To investigate the effects of acute hyperglycemia on retinal microcirculation and endothelial function in cats and removal of superoxide to prevent retinal endothelial dysfunction from hyperglycemia. Hyperglycemia was induced by intravenous injection of 25% glucose to maintain the plasma glucose concentration at 30 mM. Laser Doppler velocimetry was used to measure the vessel diameter (D) and blood velocity (V) simultaneously and calculated retinal blood flow (RBF) in second-order retinal arterioles in cats. Intravitreous, endothelial-dependent vasodilator bradykinin (BK) and endothelium-independent vasodilator sodium nitroprusside (SNP) were administered into the vitreous cavity to evaluate endothelial function in the retinal arterioles. To control osmolality, 25% mannitol was administered the same way. Systemic hyperoxia was induced to noninvasively examine endothelial function during hyperglycemia. To determine the effect of the superoxide on the hyperglycemia-induced changes in the retinal circulation, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) was administered in drinking water for 14 days before the experiment. The D, V, and RBF increased with acute hyperglycemia and mannitol compared with baseline. BK-induced increases in D, V, and RBF significantly declined, whereas SNP-induced increases were unattenuated during acute hyperglycemia. Return of the decreased RBF to baseline after cessation of systemic hyperoxia was significantly (P oxidative stress. Systemic hyperoxia can be used to noninvasively evaluate retinal endothelial function during hyperglycemia.

  15. Permeabilities of single arterioles and venules in the frog skin: a functional and morphological study.

    Olesen, S P; de Saint-Aubain, M L; Bundgaard, M


    The permeability of single subcutaneous microvessels in the frog skin was determined with electrophysiological techniques after only minimal surgical intervention. The organization of blood vessels in the frog skin is described at the microscopic level. Transmission electron microscopy showed that the subcutaneous microvessels belong to the class of "continuous" vessels (H. Bennett, J. Luft, and J. Hampton, 1959, Amer. J. Physiol. 196, 381-390). Capillaries in the true sense of the word are rare in this subcutaneous tissue. The electrical resistance of the endothelium in well defined segments of the subcutaneous microvessels was determined by means of current injection and voltage recording microelectrodes using cable theory for the analysis. The average resistances were 70 and 24 omega.cm2 for arterioles and venules, respectively; the mean values of the two groups were significantly different (P less than 0.001). These figures are close to those obtained on microvessels in skeletal muscle (S.-P. Olesen and C. Crone, 1983, Biophys. J. 42, 31-41), but are about one order of magnitude higher than resistances of mesenteric microvessels. The calculated sodium permeabilities were for arterioles: PNa+ = 1.6 x 10(-5) cm sec(-1) and for venules: 4.6 x 10(-5) cm sec(-1).

  16. Impaired renal function is related to deep and mixed, but not strictly lobar cerebral microbleeds in patients with ischaemic stroke and TIA.

    Banerjee, Gargi; Wahab, Kolawole W; Gregoire, Simone M; Jichi, Fatima; Charidimou, Andreas; Jäger, Hans R; Rantell, Khadija; Werring, David J


    The vasculature of the brain and kidneys are similarly vulnerable to hypertension, so their microvascular damage may be correlated. We investigated the relationship of renal function to the anatomical distribution of cerebral microbleeds (CMBs), a marker of underlying cerebral small vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy), in a Western patient cohort. This was a retrospective study of referrals to a hospital stroke service. All patients with clinical data and a T2*-weighted gradient-recalled echo (T2*-GRE) MRI were included. MRI scans were rated for CMBs using the Microbleed Anatomical Rating Scale. Renal function was assessed by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula. We included 202 patients, 39 with CMBs (19.3 %); 15 had "strictly lobar", 12 had "strictly deep" and 12 had "mixed" CMBs. Patients without CMBs had a higher eGFR than those with CMBs (mean difference 6.50 ml/min/1.73 m(2), 95 % CI -14.73 to 1.72 ml/min/1.73 m(2), p = 0.121). Multivariable analysis found that those with deep and mixed CMBs had a lower eGFR than those without CMBs (mean difference -10.70 ml/min/1.73 m(2), 95 % CI -20.35 to -1.06 ml/min/1.73 m(2), p = 0.030). There was no difference in eGFR found between those with strictly lobar CMBs and those without CMBs (mean difference -1.59 ml/min/1.73 m(2), 95 % CI -13.08 to 9.89 ml/min/1.73 m(2), p = 0.79). In a Western patient cohort, there appears to be an association between eGFR and the presence of deep and mixed CMBs, but not strictly lobar CMBs. This suggests a shared vulnerability of renal afferent and cerebral deep and superficial perforating arterioles to systemic hypertension. The arteriopathy underlying strictly lobar CMBs (i.e. cerebral amyloid angiopathy), appears to be less related to renal impairment.

  17. Relationship of wall-to-lumen ratio of retinal arterioles with clinic and 24-hour blood pressure.

    Salvetti, Massimo; Agabiti Rosei, Claudia; Paini, Anna; Aggiusti, Carlo; Cancarini, Anna; Duse, Sarah; Semeraro, Francesco; Rizzoni, Damiano; Agabiti Rosei, Enrico; Muiesan, Maria Lorenza


    Wall-to-lumen ratio of retinal arterioles might serve as an in vivo parameter of vascular damage. We analyzed the impact of brachial clinic blood pressure (BP), of central BP, and of 24-hour BP on wall-to-lumen ratio (WLR) of retinal arterioles. In 295 subjects (147 men; age range, 22-72 years; mean age, 54±7 years), WLR of retinal arterioles was assessed in vivo using scanning laser Doppler flowmetry. In addition, clinic and 24-hour BP values were measured. Central hemodynamics was assessed by pulse wave analysis. In treated patients with essential hypertension (n=100), a higher WLR (0.29±0.18 versus 0.23±0.13; P=0.009) was observed in comparison with normotensive individuals (n=119); no significant differences were observed between treated and untreated hypertensive patients (0.29±0.18 versus 0.28±0.18; P=0.7). WLR of retinal arterioles was significantly related to clinic systolic (r=0.18; P=0.002) and pulse pressure (r=0.20; P=0.001), to 24-hour systolic (r=0.25; P=0.0001) and pulse pressure (r=0.17; P=0.005), and to central systolic (r=0.16; P=0.006) and pulse pressure (r=0.18; P=0.002). Multiple regression analysis revealed that only mean systolic 24-hour BP was independently associated with an increased WLR of retinal arterioles. In this large group of hypertensive patients and normotensive individuals, 24-hour systolic BP seems to be the strongest determinant of increased WLR of retinal arterioles.

  18. Roles of Caveolin-1 in Angiotensin II-Induced Hypertrophy and Inward Remodeling of Cerebral Pial Arterioles.

    Umesalma, Shaikamjad; Houwen, Frederick Keith; Baumbach, Gary L; Chan, Siu-Lung


    Angiotensin II (Ang II) is a major determinant of inward remodeling and hypertrophy in pial arterioles that may have an important role in stroke during chronic hypertension. Previously, we found that epidermal growth factor receptor is critical in Ang II-mediated hypertrophy that may involve caveolin-1 (Cav-1). In this study, we examined the effects of Cav-1 and matrix metalloproteinase-9 (MMP9) on Ang II-mediated structural changes in pial arterioles. Cav-1-deficient (Cav-1(-/-)), MMP9-deficient (MMP9(-/-)), and wild-type mice were infused with either Ang II (1000 ng/kg per minute) or saline via osmotic minipumps for 28 days (n=6-8 per group). Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of pial arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined histologically in pressurized fixed pial arterioles. Expression of Cav-1, MMP9, phosphorylated epidermal growth factor receptor, and Akt was determined by Western blotting and immunohistochemistry. Deficiency of Cav-1 or MMP9 did not affect Ang II-induced hypertension. Ang II increased the expression of Cav-1, phosphorylated epidermal growth factor receptor, and Akt in wild-type mice, which was attenuated in Cav-1(-/-) mice. Ang II-induced hypertrophy, inward remodeling, and increased MMP9 expression in pial arterioles were prevented in Cav-1(-/-) mice. Ang II-mediated increases in MMP9 expression and inward remodeling, but not hypertrophy, were prevented in MMP9(-/-) mice. In conclusion, Cav-1 is essential in Ang II-mediated inward remodeling and hypertrophy in pial arterioles. Cav-1-induced MMP9 is exclusively involved in inward remodeling, not hypertrophy. Further studies are needed to determine the role of Akt in Ang II-mediated hypertrophy. © 2016 American Heart Association, Inc.

  19. [Sympathetic nerve activity in chronic renal failure - what are the therapeutic options?].

    Hausberg, M; Tokmak, F


    Patients with chronic renal failure are characterized by a tonic elevation of sympathetic tone. This factor largely contributes to their increased cardiovascular risk. The increased sympathetic drive is caused by activiation of renal afferent fibers in the diseased kidneys. Therapeutic options for hypertensive patients with chronic renal failure with respect to their sympathetic overactivity are inhibitors of the renin-angiotensin-system and central sympatholytic drugs. The role of catheter-based renal denervation in these patients is currently under investigation.

  20. Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension.

    Xiong, Xiao-Qing; Chen, Wei-Wei; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing


    We recently found that adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure in normal rats. The study was designed to test the hypothesis that AAR contributes to sympathetic activation in obesity hypertension. Male rats were fed with a control diet (12% kcal as fat) or high-fat diet (42% kcal as fat) for 12 weeks to induce obesity hypertension. Stimulation of WAT with capsaicin increased renal sympathetic nerve activity and mean arterial pressure. Both AAR and WAT afferent activity were enhanced in obesity hypertension (OH) compared with obesity nonhypertension (ON) and in ON compared with obesity-resistant or control diet rats. WAT sensory denervation induced by resiniferatoxin caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in OH than ON and in ON than obesity-resistant or control. The depressor effect of resiniferatoxin lasted ≥ 3 weeks in OH. Leptin antagonist in WAT reduced renal sympathetic nerve activity and mean arterial pressure in OH. WAT injection of capsaicin increased plasma renin, angiotensin II, and norepinephrine levels in OH and caused more c-fos expression in paraventricular nucleus in OH than ON and in ON than obesity-resistant or control rats. Inhibiting paraventricular nucleus neurons with lidocaine attenuated renal sympathetic nerve activity in OH and ON, decreased mean arterial pressure in OH, and abolished the capsaicin-induced AAR in all groups. The results indicate that enhanced AAR contributes to sympathetic activation in OH, and paraventricular nucleus plays an important role in the enhanced AAR and sympathetic activation in OH.

  1. Renal involvement in primary antiphospholipid syndrome.

    Marcantoni, Carmelita; Emmanuele, Carmela; Scolari, Francesco


    Antiphospholipid syndrome is an autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or pregnancy-related problems associated with persistently elevated levels of antiphospholipid antibodies. The kidney is a major target organ in both primary and secondary antiphospholipid syndrome. This review describes several aspects of the renal involvement in the primary form of the syndrome, in particular the histological pattern of the so-called antiphospholipid syndrome nephropathy (APSN). APSN is a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries, recanalizing thrombi in arteries and arterioles, and focal atrophy, a constellation of morphological lesions suggestive of primary antiphospholipid syndrome.

  2. Inhibitory Effects of Dopamine on Noradrenaline-induced Constriction of Arterioles in vivo in the Striated Cremaster Muscle

    Matsubayashi, Hiroaki


    The effect of dopamine on the arterioles (50.8 ~ 95.2 μm) in the cremaster muscle was examined to determine its effect on microcirculation. Anesthetized rats were used under a light microscope connected to a videocamera. Drugs were applied using small round filter paper (370 μm in diameter) containing the drug and placed in the immediate vicinity of the arteriole on the cremaster with a micromanipulator. The dose of the drug applied was represented by concentration of the drug solution in whi...

  3. Extraocular muscle afferent signals modulate visual attention.

    Balslev, Daniela; Newman, William; Knox, Paul C


    Extraocular muscle afferent signals contribute to oculomotor control and visual localization. Prompted by the close links between the oculomotor and attention systems, it was investigated whether these proprioceptive signals also modulated the allocation of attention in space. A suction sclera contact lens was used to impose an eye rotation on the nonviewing, dominant eye. With their viewing, nondominant eye, participants (n = 4) fixated centrally and detected targets presented at 5° in the left or right visual hemifield. The position of the viewing eye was monitored throughout the experiment. As a control, visual localization was tested using finger pointing without visual feedback of the hand, whereas the nonviewing eye remained deviated. The sustained passive rotation of the occluded, dominant eye, while the other eye maintained central fixation, resulted in a lateralized change in the detectability of visual targets. In all participants, the advantage in speed and accuracy for detecting right versus left hemifield targets that occurred during a sustained rightward eye rotation of the dominant eye was reduced or reversed by a leftward eye rotation. The control experiment confirmed that the eye deviation procedure caused pointing errors consistent with an approximately 2° shift in perceived eye position, in the direction of rotation of the nonviewing eye. With the caveat of the small number of participants, these results suggest that extraocular muscle afferent signals modulate the deployment of attention in visual space.

  4. TRPA1 Mediates Amplified Sympathetic Responsiveness to Activation of Metabolically Sensitive Muscle Afferents in Rats with Femoral Artery Occlusion

    Jihong eXing


    Full Text Available Autonomic responses to stimulation of mechanically and metabolically sensitive muscle afferent nerves during static contraction are augmented in rats with femoral artery occlusion. Moreover, metabolically sensitive transient receptor potential cation channel subfamily A, member 1 (TRPA1 has been reported to contribute to sympathetic nerve activity (SNA and arterial blood pressure (BP responses evoked by static muscle contraction. Thus, in the present study, we examined the mechanisms by which afferent nerves’ TRPA1plays a role in regulating amplified sympathetic responsiveness due to a restriction of blood flow directed to the hindlimb muscles. Our data show that 24-72 hrs of femoral artery occlusion 1 upregulates the protein levels of TRPA1 in dorsal root ganglion (DRG tissues; 2 selectively increases expression of TRPA1 in DRG neurons supplying metabolically sensitive afferent nerves of C-fiber (group IV; and 3 enhances renal SNA and BP responses to AITC (a TRPA1 agonist injected into the arterial blood supply of the hindlimb muscles. In addition, our data demonstrate that blocking TRPA1 attenuates SNA and BP responses during muscle contraction to a greater degree in ligated rats than those responses in control rats. In contrast, blocking TRPA1 fails to attenuate SNA and BP responses during passive tendon stretch in both groups. Overall, results of this study indicate that alternations in muscle afferent nerves’TRPA1 likely contribute to enhanced sympathetically mediated autonomic responses via the metabolic component of the muscle reflex under circumstances of chronic muscle ischemia.

  5. Is there a role for T-type Ca2+ channels in regulation of vasomotor tone in mesenteric arterioles?

    Jensen, Lars Jørn; Holstein-Rathlou, Niels-Henrik


    The largest peripheral blood pressure drop occurs in terminal arterioles (<40 microm lumen diameter). L-type voltage-dependent Ca2+ channels (VDCCs) are considered the primary pathway for Ca2+ influx during physiologic activation of vascular smooth muscle cells (VSMC). Recent evidence suggests th...

  6. Chicken (Gallus domesticus) inner ear afferents

    Hara, H.; Chen, X.; Hartsfield, J. F.; Hara, J.; Martin, D.; Fermin, C. D.


    Neurons from the vestibular (VG) and the statoacoustic (SAG) ganglion of the chick (Gallus domesticus) were evaluated histologically and morphometrically. Embryos at stages 34 (E8 days), 39 (E13 days) and 44 (E18 days) were sacrificed and temporal bones microdissected. Specimens were embedded in JB-4 methacrylate plastic, and stained with a mixture of 0.2% toluidine blue (TB) and 0.1% basic Fuschin in 25% ethanol or with a mixture of 2% TB and 1% paraphenylenediamine (PDA) for axon and myelin measurement study. Images of the VIIIth nerve were produced by a V150 (R) color imaging system and the contour of 200-300 neuronal bodies (perikarya) was traced directly on a video screen with a mouse in real time. The cross-sectional area of VG perikarya was 67.29 micrometers2 at stage 34 (E8), 128.46 micrometers2 at stage 39 (E13) and 275.85 micrometers2 at stage 44 (E18). The cross-sectional area of SAG perikarya was 62.44 micrometers2 at stage 34 (E8), 102.05 micrometers2 at stage 39 (E13) and 165.02 micrometers2 at stage 44 (E18). A significant cross-sectional area increase of the VG perikarya between stage 39 (E13) and stage 44 (E18) was determined. We randomly measured the cross-sectional area of myelin and axoplasm of hatchling afferent nerves, and found a correspondence between axoplasmic and myelin cross-sectional area in the utricular, saccular and semicircular canal nerve branches of the nerve. The results suggest that the period between stage 34 (E8) and 39 (E13) is a critical period for afferent neuronal development. Physiological and behavioral vestibular properties of developing and maturing hatchlings may change accordingly. The results compliment previous work by other investigators and provide valuable anatomical measures useful to correlate physiological data obtained from stimulation of the whole nerve or its parts.

  7. Patterns of primary afferent depolarization of segmental and ascending intraspinal collaterals of single joint afferents in the cat.

    Rudomin, P; Lomelí, J


    We have examined in the anesthetized cat the threshold changes produced by sensory and supraspinal stimuli on intraspinal collaterals of single afferents from the posterior articular nerve (PAN). Forty-eight fibers were tested in the L3 segment, in or close to Clarke's column, and 70 fibers in the L6-L7 segments within the intermediate zone. Of these, 15 pairs of L3 and L6-L7 collaterals were from the same afferent. Antidromically activated fibers had conduction velocities between 23 and 74 m/s and peripheral thresholds between 1.1 and 4.7 times the threshold of the most excitable fibers (xT), most of them below 3 xT. PAN afferents were strongly depolarized by stimulation of muscle afferents and by cutaneous afferents, as well as by stimulation of the bulbar reticular formation and the midline raphe nuclei. Stimulation of muscle nerves (posterior biceps and semitendinosus, quadriceps) produced a larger PAD (primary afferent depolarization) in the L6-L7 than in the L3 terminations. Group II were more effective than group I muscle afferents. As with group I muscle afferents, the PAD elicited in PAN afferents by stimulation of muscle nerves could be inhibited by conditioning stimulation of cutaneous afferents. Stimulation of the cutaneous sural and superficial peroneal nerves increased the threshold of few terminations (i.e., produced primary afferent hyperpolarization, PAH) and reduced the threshold of many others, particularly of those tested in the L6-L7 segments. Yet, there was a substantial number of terminals where these conditioning stimuli had minor or no effects. Autogenetic stimulation of the PAN with trains of pulses increased the intraspinal threshold in 46% and reduced the threshold in 26% of fibers tested in the L6-L7 segments (no tests were made with trains of pulses on fibers ending in L3). These observations indicate that PAN afferents have a rather small autogenetic PAD, particularly if this is compared with the effects of heterogenetic stimulation

  8. Trauma renal Renal trauma

    Gerson Alves Pereira Júnior


    Full Text Available Apresentamos uma revisão sobre trauma renal, com ênfase na avaliação radiológica, particularmente com o uso da tomografia computadorizada, que tem se tornado o exame de eleição, ao invés da urografia excretora e arteriografia. O sucesso no tratamento conservador dos pacientes com trauma renal depende de um acurado estadiamento da extensão da lesão, classificado de acordo com a Organ Injury Scaling do Colégio Americano de Cirurgiões. O tratamento conservador não-operatório é seguro e consiste de observação contínua, repouso no leito, hidratação endovenosa adequada e antibioti- coterapia profilática, evitando-se uma exploração cirúrgica desnecessária e possível perda renal. As indicações para exploração cirúrgica imediata são abdome agudo, rápida queda do hematócrito ou lesões associadas determinadas na avaliação radiológica. Quando indicada, a exploração renal após controle vascular prévio é segura, permitindo cuidadosa inspeção do rim e sua reconstrução com sucesso, reduzindo a probabilidade de nefrectomia.We present a revision of the renal trauma with emphasis in the radiographic evaluation, particularly CT scan that it has largely replaced the excretory urogram and arteriogram in the diagnostic worh-up and management of the patient with renal trauma. The successful management of renal injuries depends upon the accurate assessment of their extent in agreement with Organ Injury Scaling classification. The conservative therapy managed by careful continuous observation, bed rest, appropriate fluid ressuscitation and prophylactic antibiotic coverage after radiographic staging for severely injured kidneys can yield favorable results and save patients from unnecessary exploration and possible renal loss. The indications for immediate exploratory laparotomy were acute abdomen, rapidly dropping hematocrit or associated injuries as determinated from radiologic evaluation. When indicated, renal exploration

  9. Primary afferent response to signals in the intestinal lumen.

    Raybould, H


    The first recordings of vagal afferent nerve fibre activity were performed by Paintal in the early 1950s. In these experiments, he showed that phenyldiguanide (later recognized as a 5-HT3 receptor agonist) stimulated the firing of C-fibres innervating the intestine. In the following years, ample physiological and psychological studies have demonstrated the importance of afferent information arising from the gut in the regulation of gastrointestinal function and behaviour. Many stimuli are capable of eliciting these functional effects and of stimulating afferent fibre discharge, including mechanical, chemical, nutrient- and immune-derived stimuli. Studies in the last 10 years have begun to focus on the precise sensory transduction mechanisms by which these visceral primary afferent nerve terminals are activated and, like the contribution by Zhu et al. in this issue of The Journal of Physiology, are revealing some novel and exciting findings.

  10. Renal arteriography

    ... Read More Acute arterial occlusion - kidney Acute kidney failure Aneurysm Atheroembolic renal disease Blood clots Renal cell carcinoma Renal venogram X-ray Review Date 1/5/2016 Updated by: Jason Levy, ...

  11. Presynaptic selection of afferent inflow in the spinal cord.

    Rudomin, P


    The synaptic effectiveness of sensory fibers ending in the spinal cord of vertebrates can be centrally controlled by means of specific sets of GABAergic interneurons that make axo-axonic synapses with the terminal arborizations of the afferent fibers. In the steady state, the intracellular concentration of chloride ions in these terminals is higher than that predicted from a passive distribution, because of an active transport mechanism. Following the release of GABA by spinal interneurons and activation of GABA(A) receptors in the afferent terminals, there is an outwardly directed efflux of chloride ions that produces primary afferent depolarization (PAD) and reduces transmitter release (presynaptic inhibition). Studies made by intrafiber recording of PAD, or by measuring changes in the intraspinal threshold of single afferent terminals (which is reduced during PAD), have further indicated that muscle and cutaneous afferents have distinctive, but modifiable PAD patterns in response to segmental and descending stimuli. This has suggested that PAD and presynaptic inhibition in the various types of afferents is mediated by separate sets of last-order GABAergic interneurons. Direct activation, by means of intraspinal microstimulation, of single or small groups of last-order PAD-mediating interneurons shows that the monosynaptic PAD elicited in Ia and Ib afferents can remain confined to some sets of the intraspinal collaterals and not spread to nearby collaterals. The local character of PAD allows cutaneous and descending inputs to selectively inhibit the PAD of segmental and ascending intraspinal collaterals of individual muscle spindle afferents. It thus seems that the intraspinal branches of the sensory fibers are not hard wired routes that diverge excitation to spinal neurons, but are instead dynamic pathways that can be centrally controlled to address information to selected neuronal targets. This feature appears to play an important role in the selection of

  12. Visceral perception: sensory transduction in visceral afferents and nutrients.

    Raybould, H E


    The possible mechanisms that may be involved in nutrient detection in the wall of the gastrointestinal tract are reviewed. There is strong functional and electrophysiological evidence that both intrinsic and extrinsic primary afferent neurones mediate mechano- and chemosensitive responses in the gastrointestinal tract. This review focuses on the extrinsic afferent pathways as these are the ones that convey information to the central nervous system which is clearly necessary for perception to occur.

  13. Biliary stone causing afferent loop syndrome and pancreatitis

    André Roncon Dias; Roberto Iglesias Lopes


    We report the case of an 84-year-old female who had a partial gastrectomy with Billroth-Ⅱ anastomosis 24years ago for a benign peptic ulcer who now presented an acute pancreatitis secondary to an afferent loop syndrome. The syndrome was caused by a gallstone that migrated through a cholecystoenteric fistula. This is the first description in the literature of a biliary stone causing afferent loop syndrome.

  14. Is there a role for T-type Ca2+ channels in regulation of vasomotor tone in mesenteric arterioles?

    Jensen, Lars Jørn; Holstein-Rathlou, Niels-Henrik


    was predominantly expressed in endothelial cells. Voltage-dependent Ca2+ entry was inhibited by the new specific T-type blockers R(-)-efonidipine and NNC 55-0396. The effect of NNC 55-0396 persisted in depolarized arterioles, suggesting an unusually high activation threshold of mesenteric T-type channels. T......-type channels were not necessary for conduction of vasoconstriction, but appear to be important for local electromechanical coupling in VSMC. The first direct demonstration of endothelial T-type channels warrants new investigations of their role in vascular biology.......The largest peripheral blood pressure drop occurs in terminal arterioles (channels (VDCCs) are considered the primary pathway for Ca2+ influx during physiologic activation of vascular smooth muscle cells (VSMC). Recent evidence suggests...

  15. The Effect of Ovariectomy and Estrogen on Penetrating Brain Arterioles and Blood-brain Barrier Permeability

    Cipolla, Marilyn J.; Godfrey, Julie A.; Wiegman, Marchien J.


    Objective We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood-brain barrier (BBB) permeability. Methods Female ovariectomized Sprague Dawley rats were replaced with estradiol (E2) and estriol (E3) (OVX+E; N=13) and compared to ovariectomized animals without replacement (OVX; N=14) and intact controls (CTL, proestrous; N=13). Passive and active diameters, percent tone and passive distensibility of pressurized PA were compared. In addition, BBB permeability to Lucifer Yellow, a marker of transcellular transport, was compared in cerebral arteries. Results Ovariectomy increased myogenic tone in PA compared to CTL that was not ameliorated by estrogen treatment. Percent tone at 75 mmHg for CTL vs. OVX and OVX+E was 44 ± 3% vs. 51 ± 1% and 54 ± 3% (p<0.01 vs. CTL for both). No differences were found in passive diameters or distensibility between the groups. BBB permeability increased 500% in OVX vs. CTL animals, however, estrogen replacement restored barrier properties: flux of Lucifer Yellow for CTL, OVX and OVX+E was (ng/mL): 3.4 ± 1.2, 20.2 ± 5.3 (p<0.01 vs. CTL) and 6.15 ± 1.2 (n.s.). Conclusions These results suggest that estrogen replacement may not be beneficial for small vessel disease in the brain, but may limit BBB disruption and edema under conditions that cause it. PMID:19905968

  16. NADPH Oxidase Activity in Cerebral Arterioles Is a Key Mediator of Cerebral Small Vessel Disease—Implications for Prevention

    Mark F. McCarty


    Full Text Available Cerebral small vessel disease (SVD, a common feature of brain aging, is characterized by lacunar infarcts, microbleeds, leukoaraiosis, and a leaky blood-brain barrier. Functionally, it is associated with cognitive decline, dementia, depression, gait abnormalities, and increased risk for stroke. Cerebral arterioles in this syndrome tend to hypertrophy and lose their capacity for adaptive vasodilation. Rodent studies strongly suggest that activation of Nox2-dependent NADPH oxidase activity is a crucial driver of these structural and functional derangements of cerebral arterioles, in part owing to impairment of endothelial nitric oxide synthase (eNOS activity. This oxidative stress may also contribute to the breakdown of the blood-brain barrier seen in SVD. Hypertension, aging, metabolic syndrome, smoking, hyperglycemia, and elevated homocysteine may promote activation of NADPH oxidase in cerebral arterioles. Inhibition of NADPH oxidase with phycocyanobilin from spirulina, as well as high-dose statin therapy, may have potential for prevention and control of SVD, and high-potassium diets merit study in this regard. Measures which support effective eNOS activity in other ways—exercise training, supplemental citrulline, certain dietary flavonoids (as in cocoa and green tea, and capsaicin, may also improve the function of cerebral arterioles. Asian epidemiology suggests that increased protein intakes may decrease risk for SVD; conceivably, arginine and/or cysteine—which boosts tissue glutathione synthesis, and can be administered as N-acetylcysteine—mediate this benefit. Ameliorating the risk factors for SVD—including hypertension, metabolic syndrome, hyperglycemia, smoking, and elevated homocysteine—also may help to prevent and control this syndrome, although few clinical trials have addressed this issue to date.

  17. Afferent innervation of the utricular macula in pigeons

    Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David


    Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were

  18. Significance of KATP channels, L-type Ca2+ channels and CYP450-4A enzymes in oxygen sensing in mouse cremaster muscle arterioles In vivo

    Ngo, Anh Thuc; Riemann, Mads; Holstein-Rathlou, Niels-Henrik; Torp-Pedersen, Christian; Jensen, Lars J?rn


    Background ATP-sensitive K+ channels (KATP channels), NO, prostaglandins, 20-HETE and L-type Ca2+ channels have all been suggested to be involved in oxygen sensing in skeletal muscle arterioles, but the role of the individual mechanisms remain controversial. We aimed to establish the importance of these mechanisms for oxygen sensing in arterioles in an in vivo model of metabolically active skeletal muscle. For this purpose we utilized the exteriorized cremaster muscle of anesthetized mice, in...

  19. Patterns of connectivity of spinal interneurons with single muscle afferents.

    Quevedo, J; Eguibar, J R; Lomeli, J; Rudomin, P


    A technique was developed to measure, in the anesthetized and paralyzed cat under artificial ventilation, changes of excitability to intraspinal stimulation simultaneously in two different afferent fibers or in two collaterals of the same afferent fiber. Intraspinal stimulation reduced the threshold of single muscle afferent fibers ending in the intermediate nucleus. This effect was seen with strengths below those required to activate the afferent fiber tested (1.5-12 microA), occurred at a short latency (1.5-2.0 ms), reached a maximum between 15 and 30 ms, and lasted up to 100 ms. The effects produced by graded stimulation applied at the shortest conditioning-testing stimulus time intervals increased by fixed steps, suggesting recruitment of discrete elements, most likely of last-order interneurons mediating primary afferent depolarization (PAD). The short-latency increases in excitability produced by the weakest effective intraspinal stimuli were usually detected only in the collateral closest to the stimulating micropipette, indicating that the stimulated interneurons mediating PAD have spatially restricted actions. The short-latency PAD produced by intraspinal stimuli, as well as the PAD produced by stimulation of the posterior biceps and semitendinosus (PBSt) nerve or by stimulation of the bulbar reticular formation (RF), was depressed 19-30 min after the i.v. injection of 0.5 mg/kg of picrotoxin, suggesting that all these effects were mediated by GABAergic mechanisms. The PAD elicited by stimulation of muscle and/or cutaneous nerves was depressed following the i.v. injection of (-)-baclofen, whereas the PAD elicited in the same collateral by stimulation of the RF was baclofen-resistant. The short-latency PAD produced by intraspinal stimulation was not always depressed by i.v. injections of (-)-baclofen. Baclofen-sensitive and baclofen-resistant monosynaptic PADs could be produced in different collaterals of the same afferent fiber. The results suggest that

  20. Behcet's syndrome and renal involvement: a histological and immunofluorescent study of eleven renal biopsies.

    Herreman, G; Beaufils, H; Godeau, P; Cassou, B; Wechsler, B; Boujeau, J; Chomette, G


    The finding of focal glomerulonephritis in a patient with Behcet's syndrome led us to perform systematic renal biopsies in ten other patients with the disease. None of the patients had symptoms of renal disease. Proteinuria was found in five, two of whom had associated leukocyturia. By light microscopy mesangial and extramembranous glomerular deposits were observed in eight patients. Arterioles in ten patients showed subendothelial and medial hyaline deposits. A granular pattern of fluorescent staining identified the presence of the third component of complement in these deposits. Circulating immune deposits were sought and found in six out of seven patients. The finding of circulating immune complexes and deposition of complement in glomerular and arteriolar tissues supports an immune complex mediated nephropathy and is consistent with the hypothesis of an immunological pathogenesis in Behcet's syndrome.

  1. Genioglossus muscle responses to upper airway pressure changes: afferent pathways.

    Mathew, O P; Abu-Osba, Y K; Thach, B T


    The afferent pathway of an upper airway reflex in which genioglossus muscle electromyographic (GG EMG) activity is influenced by pharyngeal pressure changes was investigated in 20 anesthetized rabbits. We took advantage of the fact that the upper airway was separated into two compartments by pharyngeal closure occurring when the animals breathe through a tracheostomy. This allowed pressure to be delivered selectively either to the nose and nasopharynx or to the larynx and hypopharynx. Midcervical vagotomy did not eliminate the GG EMG response to pressure stimuli. On the other hand high cervical vagotomy or superior laryngeal nerve section eliminated the response in the laryngeal compartment, but not in the nasopharyngeal compartment. Topical anesthesia of the mucosa of the nose, pharynx, and larynx abolished the response in both compartments. Therefore we conclude that more than one afferent pathway exists for this upper airway pressure reflex; the primary afferent pathway from the laryngeal compartment is the superior laryngeal branch of the vagus nerve, whereas the primary afferent pathway for the nasopharynx is nonvagal. Trigeminal nerve, glossopharyngeal nerve, and/or nervus intermedius carry nonvagal afferents from the nasopharynx and nose. The topical anesthetic and nerve section studies suggest that superficial receptors mediate this response. The occurrence of swallowing in response to upper airway pressure changes and its elimination by topical anesthesia or superior mechanoreceptors may mediate both genioglossus respiratory responses and swallowing responses.

  2. Gut vagal afferents differentially modulate innate anxiety and learned fear.

    Klarer, Melanie; Arnold, Myrtha; Günther, Lydia; Winter, Christine; Langhans, Wolfgang; Meyer, Urs


    Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior.

  3. Relationships between retinal arteriole anatomy and aortic geometry and function and peripheral resistance in hypertensives.

    Rosenbaum, David; Kachenoura, Nadjia; Koch, Edouard; Paques, Michel; Cluzel, Philippe; Redheuil, Alban; Girerd, Xavier


    Microvascular remodeling and large artery stiffness are key determinants of cardiovascular hemodynamics and can now be studied with new non-invasive methods. Our objective was to study the relationships between retinal arteriole anatomy and aortic geometry and function and peripheral resistance (total peripheral resistance (TPR)) in hypertensives. In 80 subjects (age 52±13 years; 53% males; including 23 normotensives and 57 hypertensives, among which 29 were uncontrolled hypertensives), we used: (1) the new non-invasive RTX1 adaptive optics (AO) camera (Imagine Eyes, Orsay, France) to measure the wall-to-lumen ratio (WLR) on retinal microvasculature; (2) cardiovascular magnetic resonance (CMR) imaging to assess aortic stiffness, geometry and cardiac output; and (3) the validated SphymoCor Xcel device to measure central blood pressure (BP) and carotido-femoral pulse wave velocity (Cf-PWV). TPR was calculated as the central mean BP/cardiac output ratio. WLR and TPR were significantly higher and aortic distensibility was significantly lower in hypertensives. Aortic dilation and arch elongation were found in uncontrolled hypertensives. In the univariate analysis, WLR was positively correlated with central BP (PTPR (PTPR (P=0.002) independent of age, BMI, gender, antihypertensive treatments, aortic diameter and central SBP. As expected, age was the major correlate of ascending aorta distensibility and Cf-PWV. New non-invasive vascular imaging methods are complementary for the detection of the deleterious effects of aging or high BP on large and small arteries. AO examination could represent a useful tool for the study and follow-up of microvasculature anatomical changes.

  4. Intraluminal pressure stimulates MAPK phosphorylation in arterioles: temporal dissociation from myogenic contractile response.

    Spurrell, Brian E; Murphy, Timothy V; Hill, Michael A


    Members of the MAPK family of enzymes, p42/44 and p38, have been implicated in both the regulation of contractile function and growth responses in vascular smooth muscle. We determined whether such kinases are activated during the arteriolar myogenic response after increases in intraluminal pressure. Particular emphasis was placed on temporal aspects of activation to determine whether such phosphorylation events parallel the known time course for myogenic contraction. Experiments used single cannulated arterioles isolated from the cremaster muscle of rats with some vessels loaded with the fluorescent Ca2+-sensitive dye fura 2 (2 microM). The p42/44 inhibitor PD-98059 (50 microM) caused vasodilation but did not prevent pressure-induced myogenic constriction. The vasodilator response was accompanied by decreased smooth muscle intracellular Ca2+. Western blotting revealed a significant increase in the level of phosphorylation of p42/44 15 min after the application of a 30- to 100-mmHg pressure step. Phosphorylation of p42/44 was a late event that appeared to be temporally dissociated from contraction, which was complete within 1-5 min. EGF (80 nM) caused marked phosphorylation of p42/44 but only acted as a weak vasoconstrictor. The p38 inhibitor SB-203580 (10 microM) did not alter baseline diameter, nor did it prevent myogenic vasoconstriction. Consistent with these observations, SB-203580 did not cause a measurable change in intracellular Ca2+. The results demonstrate activation of the p42/44 class of MAPK resulting from increased transmural pressure. Such activation is, however, dissociated from the acute pressure-induced vasoconstrictor response in terms of time course and may represent the activation of compensatory, but parallel, pathways, including those related to growth and remodeling.

  5. Flow structures and red blood cell dynamics in arteriole of dilated or constricted cross section.

    Gambaruto, Alberto M


    Vessel with 'circular' or 'star-shaped' cross sections are studied, representing respectively dilated or constricted cases where endothelial cells smoothly line or bulge into the lumen. Computational haemodynamics simulations are carried out on idealised periodic arteriole-sized vessels, with red blood cell 'tube' hematocrit value=24%. A further simulation of a single red blood cell serves for comparison purposes. The bulk motion of the red blood cells reproduces well-known effects, including the presence of a cell-free layer and the apparent shear-thinning non-Newtonian rheology. The velocity flow field is analysed in a Lagrangian reference frame, relative to any given red blood cell, hence removing the bulk coaxial motion and highlighting instead the complex secondary flow patterns. An aggregate formation becomes apparent, continuously rearranging and dynamic, brought about by the inter-cellular fluid mechanics interactions and the deformability properties of the cells. The secondary flow field induces a vacillating radial migration of the red blood cells. At different radial locations, the red blood cells express different residence times, orientation and shape. The shear stresses exerted by the flow on the vessel wall are influenced by the motion of red blood cells, despite the presence of the cell-free layer. Spatial (and temporal) variations of wall shear stress patters are observed, especially for the 'circular' vessel. The 'star-shaped' vessel bears considerable stress at the protruding endothelial cell crests, where the stress vectors are coaxially aligned. The bulging endothelial cells hence regularise the transmission of stresses on the vessel wall.

  6. Adipose afferent reflex: sympathetic activation and obesity hypertension.

    Xiong, X-Q; Chen, W-W; Zhu, G-Q


    Excessive sympathetic activity contributes to the pathogenesis of hypertension and the progression of the related organ damage. Adipose afferent reflex (AAR) is a sympatho-excitatory reflex that the afferent activity from white adipose tissue (WAT) increases sympathetic outflow and blood pressure. Hypothalamic paraventricular nucleus (PVN or PVH) is one of the central sites in the control of the AAR, and ionotropic glutamate receptors in the nucleus mediate the AAR. The AAR is enhanced in obesity and obesity hypertension. Enhanced WAT afferent activity and AAR contribute to the excessive sympathetic activation and hypertension in obesity. Blockage of the AAR attenuates the excessive sympathetic activity and hypertension. Leptin may be one of sensors in the WAT for the AAR, and is involved in the enhanced AAR in obesity and hypertension. This review focuses on the neuroanatomical basis and physiological functions of the AAR, and the important role of the enhanced AAR in the pathogenesis of obesity hypertension.

  7. Renal Osteodystrophy

    Aynur Metin Terzibaşoğlu


    Full Text Available Chronic renal insufficiency is a functional definition which is characterized by irreversible and progressive decreasing in renal functions. This impairment is in collaboration with glomeruler filtration rate and serum creatinine levels. Besides this, different grades of bone metabolism disorders develop in chronic renal insufficiency. Pathologic changes in bone tissue due to loss of renal paranchyme is interrelated with calcium, phosphorus vitamine-D and parathyroid hormone. Clinically we can see high turnover bone disease, low turnover bone disease, osteomalacia, osteosclerosis and osteoporosis in renal osteodystropy. In this article we aimed to review pathology of bone metabolism disorders due to chronic renal insufficiency, clinic aspects and treatment approaches briefly.

  8. An experimental study of VEGF induced changes in vasoactivity in pig retinal arterioles and the influence of an anti-VEGF agent

    Su Er-Ning


    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF plays an important role in ocular physiology. Anti-VEGF agents are now used for treatment of common retinal diseases. This study characterises the vasoactive properties of VEGF in isolated perfused pig retinal arterioles under normal tone or endothelin-1 (ET-1 pre-contracted conditions and determines the influence of an anti VEGF agent on VEGF induced vasoactivity. Methods An isolated perfused retinal arteriole preparation was used. The outer diameter of retinal vessels was monitored at 2 second intervals in response to VEGF and the anti VEGF agent, bevacizumab. The effect of intraluminal delivery of VEGF was determined over a wide concentration range (10-16 to 10-7 M both with and without pre-contraction with ET-1 (3 x 10-9 M. Bevacizumab (0.35 mg mL-1 was applied extraluminally to determine the influence of bevacizumab on VEGF induced vasoactive changes on ET-1 pre-contracted vessels. Results In retinal arterioles with normal tone, VEGF induced a concentration dependent contraction at low concentrations, reaching 93.5% at 10-11 M and then contraction was reduced at higher concentrations, recovering to 98.1% at 10-7 M. VEGF produced a potent concentration dependent vasodilatation in arterioles pre-contracted with ET-1. VEGF induced vasodilatation in arterioles pre-contracted with ET-1 was significantly inhibited by bevacizumab. Conclusions VEGF induced vasoactive changes in pig retinal arterioles are dependent on concentration and vascular tone. Bevacizumab inhibits VEGF-induced vasodilatation in pre-contracted arterioles.

  9. Differential Progressive Remodeling of Coronary and Cerebral Arteries and Arterioles in an Aortic Coarctation Model of Hypertension

    Heather N. Hayenga


    Full Text Available OBJECTIVES: Effects of hypertension on arteries and arterioles often manifest first as a thickened wall, with associated changes in passive material properties (e.g., stiffness or function (e.g., cellular phenotype, synthesis and removal rates, and vasomotor responsiveness. Less is known, however, regarding the relative evolution of such changes in vessels from different vascular beds.METHODS: We used an aortic coarctation model of hypertension in the mini-pig to elucidate spatiotemporal changes in geometry and wall composition (including layer-specific thicknesses as well as presence of collagen, elastin, smooth muscle, endothelial, macrophage, and hematopoietic cells in three different arterial beds, specifically aortic, cerebral, and coronary, and vasodilator function in two different arteriolar beds, the cerebral and coronary.RESULTS: Marked geometric and structural changes occurred in the thoracic aorta and left anterior descending coronary artery within 2 weeks of the establishment of hypertension and continued to increase over the 8-week study period. In contrast, no significant changes were observed in the middle cerebral arteries from the same animals. Consistent with these differential findings at the arterial level, we also found a diminished nitric oxide-mediated dilation to adenosine at 8 weeks of hypertension in coronary arterioles, but not cerebral arterioles.CONCLUSION: These findings, coupled with the observation that temporal changes in wall constituents and the presence of macrophages differed significantly between the thoracic aorta and coronary arteries, confirm a strong differential progressive remodeling within different vascular beds. Taken together, these results suggest a spatiotemporal progression of vascular remodeling, beginning first in large elastic arteries and delayed in distal vessels.

  10. Automated detection and measurement of isolated retinal arterioles by a combination of edge enhancement and cost analysis.

    José A Fernández

    Full Text Available Pressure myography studies have played a crucial role in our understanding of vascular physiology and pathophysiology. Such studies depend upon the reliable measurement of changes in the diameter of isolated vessel segments over time. Although several software packages are available to carry out such measurements on small arteries and veins, no such software exists to study smaller vessels (<50 µm in diameter. We provide here a new, freely available open-source algorithm, MyoTracker, to measure and track changes in the diameter of small isolated retinal arterioles. The program has been developed as an ImageJ plug-in and uses a combination of cost analysis and edge enhancement to detect the vessel walls. In tests performed on a dataset of 102 images, automatic measurements were found to be comparable to those of manual ones. The program was also able to track both fast and slow constrictions and dilations during intraluminal pressure changes and following application of several drugs. Variability in automated measurements during analysis of videos and processing times were also investigated and are reported. MyoTracker is a new software to assist during pressure myography experiments on small isolated retinal arterioles. It provides fast and accurate measurements with low levels of noise and works with both individual images and videos. Although the program was developed to work with small arterioles, it is also capable of tracking the walls of other types of microvessels, including venules and capillaries. It also works well with larger arteries, and therefore may provide an alternative to other packages developed for larger vessels when its features are considered advantageous.

  11. Reactive oxygen species facilitate the EDH response in arterioles by potentiating intracellular endothelial Ca(2+) release.

    Chidgey, James; Fraser, Paul A; Aaronson, Philip I


    There is abundant evidence that H2O2 can act as an endothelium-derived hyperpolarizing factor in the resistance vasculature. However, whilst scavenging H2O2 can abolish endothelial dependent hyperpolarization (EDH) and the associated vascular relaxation in some arteries, EDH-dependent vasorelaxation can often be mimicked only by using relatively high concentrations of H2O2. We have examined the role of H2O2 in EDH-dependent vasodilatation by simultaneously measuring vascular diameter and changes in endothelial cell (EC) [Ca(2+)]i during the application of H2O2 or carbachol, which triggers EDH. Carbachol (10µM) induced dilatation of phenylephrine-preconstricted rat cremaster arterioles was largely (73%) preserved in the presence of indomethacin (3µM) and l-NAME (300µM). This residual NO- and prostacyclin-independent dilatation was reduced by 89% upon addition of apamin (0.5µM) and TRAM-34 (10µM), and by 74% when an extracellular ROS scavenging mixture of SOD and catalase (S&C; 100Uml(-1) each) was present. S&C also reduced the carbachol-induced EC [Ca(2+)]i increase by 74%. When applied in Ca(2+)-free external medium, carbachol caused a transient increase in EC [Ca(2+)]i. This was reduced by catalase, and was enhanced when 1µM H2O2 was present in the bath. H2O2 -induced dilatation, which occurred only at concentrations ≥100µM, was reduced by a blocking antibody to TRPM2, which had no effect on carbachol-induced responses. Similarly, iberotoxin and Rp-8bromo cGMP reduced the vasodilatation induced by H2O2, but not by carbachol. Inhibiting PLC, PLA2 or CYP450 2C9 each greatly reduced the carbachol-induced increase in EC [Ca(2+)]i and vasodilatation, but adding 10µM H2O2 during PLA2 or CYP450 2C9 inhibition completely restored both responses. The nature of the effective ROS species was investigated by using Fe(2+) chelators to block the formation of ∙OH. A cell permeant chelator was able to inhibit EC Ca(2+) store release, but cell impermeant chelators

  12. Neurons in the preBötzinger complex and VRG are located in proximity to arterioles in newborn mice

    Falk, Sarah; Rekling, Jens C


    The constant cyclic respiratory activity in the brainstem requires an un-interrupted blood flow providing glucose and O(2) to neurons generating respiratory rhythm. Here we used a combination of classical vascular visualization techniques, and calcium imaging, to compare the microvascular structure....... Presumed arterioles then pass dorso-medially with a high density immediately lateral to the midline, and mid-laterally at approximately 60% of the midline-to-lateral edge distance. Calcium imaging, using Fluo-8, AM, showed that active PBC/VRG neurons are located in the same region where a high density...

  13. "Sausage-string" appearance of arteries and arterioles can be caused by an instability of the blood vessel wall

    Jacobsen, Jens Christian Brings; Beierholm, Ulrik; Mikkelsen, Rene


    in vascular wall tension. Despite much research, the mechanisms underlying the sausage pattern have remained unknown. Here we present an anisotropic model of the vessel wall and show that the sausage pattern can arise because of an instability of the vessel wall. The model reproduces many of the key features...... phenomenon. Experimental data suggest that the structural changes induced by the instability may cause secondary damage to the wall of small arteries and arterioles in the form of endothelial hyperpermeability followed by local fibrinoid necrosis of the vascular wall....

  14. Modeling columnar spatiotemporal dynamics of nitric oxide as a primary controlling element of arteriole dilation during neurovascular coupling


    Although the mechanism of neurovascular coupling remains inadequately understood,physiological research has indicated that the dilation of arterioles located within the cerebral cortex column might represent the primary mechanism of hemodynamic response during neurovascular coupling.This study examined the spatiotemporal pattern of NO diffusion induced by functional stimuli at column spatial resolution.Our modeling makes it possible to explore the responses of mediating factors to functional stimuli from a four-dimensional view,which may lead the way to decoding the mechanism of neurovascular coupling.

  15. Sensations evoked by microstimulation of single mechanoreceptive afferents innervating the human face and mouth.

    Trulsson, M; Essick, G K


    Intraneural microneurography and microstimulation were performed on single afferent axons in the inferior alveolar and lingual nerves innervating the face, teeth, labial, or oral mucosa. Using natural mechanical stimuli, 35 single mechanoreceptive afferents were characterized with respect to unit type [fast adapting type I (FA I), FA hair, slowly adapting type I and II (SA I and SA II), periodontal, and deep tongue units] as well as size and shape of the receptive field. All afferents were subsequently microstimulated with pulse trains at 30 Hz lasting 1.0 s. Afferents recordings whose were stable thereafter were also tested with single pulses and pulse trains at 5 and 60 Hz. The results revealed that electrical stimulation of single FA I, FA hair, and SA I afferents from the orofacial region can evoke a percept that is spatially matched to the afferent's receptive field and consistent with the afferent's response properties as observed on natural mechanical stimulation. Stimulation of FA afferents typically evoked sensations that were vibratory in nature; whereas those of SA I afferents were felt as constant pressure. These afferents terminate superficially in the orofacial tissues and seem to have a particularly powerful access to perceptual levels. In contrast, microstimulation of single periodontal, SA II, and deep tongue afferents failed to evoke a sensation that matched the receptive field of the afferent. These afferents terminate more deeply in the tissues, are often active in the absence of external stimulation, and probably access perceptual levels only when multiple afferents are stimulated. It is suggested that the spontaneously active afferents that monitor tension in collagen fibers (SA II and periodontal afferents) may have the role to register the mechanical state of the soft tissues, which has been hypothesized to help maintain the body's representation in the central somatosensory system.

  16. Gut chemosensing: interactions between gut endocrine cells and visceral afferents.

    Raybould, Helen E


    Chemosensing in the gastrointestinal tract is less well understood than many aspects of gut mechanosensitivity; however, it is important in the overall function of the GI tract and indeed the organism as a whole. Chemosensing in the gut represents a complex interplay between the function of enteroendocrine (EEC) cells and visceral (primarily vagal) afferent neurons. In this brief review, I will concentrate on a new data on endocrine cells in chemosensing in the GI tract, in particular on new findings on glucose-sensing by gut EEC cells and the importance of incretin peptides and vagal afferents in glucose homeostasis, on the role of G protein coupled receptors in gut chemosensing, and on the possibility that gut endocrine cells may be involved in the detection of a luminal constituent other than nutrients, the microbiota. The role of vagal afferent pathways as a downstream target of EEC cell products will be considered and, in particular, exciting new data on the plasticity of the vagal afferent pathway with respect to expression of receptors for GI hormones and how this may play a role in energy homeostasis will also be discussed.

  17. Temperature-dependent variation in afferent nerve discharge in rat jejunum

    Gregersen, Hans; Yang, Jian; Zhao, Jingbo


    baseline discharge and on distension-induced afferent fibers innervating the rat jejunum. Methods: Multi-unit afferent activity was recorded in vitro from jejunum afferents from 9 Wistar rats. The segments were immersed in oxygenated Krebs solution varied between 21–43 °C. The mesenteric nerve bundle...

  18. Regenerating sprouts of axotomized cat muscle afferents express characteristic firing patterns to mechanical stimulation.

    Johnson, R D; Munson, J B


    1. In cats, we studied the physiological properties of regenerating sprouts of muscle afferent fibers and compared them with sprouts from cutaneous afferent fibers. 2. Muscle nerves to the triceps surae and cutaneous sural nerves were axotomized in the popliteal fossa, and the proximal ends were inserted into nerve cuffs. Six days later, we recorded action potentials from single Groups I and II muscle and mostly Group II cutaneous afferents driven by mechanostimulation of the cuff. 3. Most muscle afferent sprouts (91%) had a regular slowly adapting discharge in response to sustained mechanical displacement of the cuff, particularly to sustained stretch stimuli, whereas most cutaneous afferents (92%) did not. Muscle afferents were more likely to have a spontaneous discharge and afterdischarge. 4. Group II muscle afferent sprouts had lower stretch thresholds and a higher incidence of spontaneous discharge compared with Group I fiber sprouts, whereas Group I fibers had a higher incidence of high-frequency afterdischarge to mechanical stimuli. 5. We conclude that, 6 days after axotomy, regenerating sprouts of muscle afferents, particularly Group II afferents, have become mechanosensitive in the absence of a receptor target and exhibit physiological properties similar to those found when innervating their native muscle but significantly different from sprouts of cutaneous afferents. Expression of these native muscle afferent firing patterns after the inappropriate reinnervation of hairy skin may be due to inherent properties of the muscle afferent fiber.

  19. DMPD: Afferent pathways of pyrogen signaling. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 9917870 Afferent pathways of pyrogen signaling. Blatteis CM, Sehic E, Li S. Ann N Y... Acad Sci. 1998 Sep 29;856:95-107. (.png) (.svg) (.html) (.csml) Show Afferent pathways of pyrogen signaling.... PubmedID 9917870 Title Afferent pathways of pyrogen signaling. Authors Blatteis CM, Sehic E, Li S. Publica

  20. Calcineurin inhibitor toxicity in renal allografts: Morphologic clues from protocol biopsies

    Sharma Alok


    Full Text Available Background: Calcineurin inhibitors (cyclosporine and tacrolimus are important constituents of post renal transplant immunosuppression. However, renal toxicity limits their utility. Histological features of calcineurin inhibitor toxicity (CNIT have been the subject of few studies using protocol biopsy samples, and consensus on diagnostic criteria is still evolving. Aims: To analyze the spectrum of histological changes in protocol renal allograft biopsies with evidence of CNIT and identify additional features that are likely to help the pathologist in arriving at a diagnosis. Materials and Methods: One hundred and forty protocol allograft biopsies performed at 1, 6 and 12 months post renal transplant were studied. The defining features of CNIT included: isometric vacuolization of proximal tubular cells, arteriolar hyalinosis with medial/peripheral nodules and striped pattern of tubular atrophy/interstitial fibrosis. Other features such as global glomerulosclerosis, vacuolization of smooth muscle cells of arterioles, tubular microcalcinosis, ischemic shrinkage of glomeruli and hyperplasia of juxtaglomerular apparatus (JGA were also analyzed and graded semiquantitatively. Results: CNIT was seen in 17/140 protocol biopsies (12.1%. In addition to the diagnostic criteria, arteriolar hyalinosis, smooth muscle cell vacuolization of arterioles and hyperplasia of JGA were found to be useful indicators of CNIT. Conclusions: There is a relatively high incidence of CNIT in protocol allograft biopsies. A critical analysis of renal biopsy in adequate number of serial step sections to identify these features is mandatory, as many of these features are subtle and are likely to be missed if not specifically sought.

  1. Renal perfusion scintiscan

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  2. Renal sympathetic nervous system and the effects of denervation on renal arteries

    Arun; Kannan; Raul; Ivan; Medina; Nagapradeep; Nagajothi; Saravanan; Balamuthusamy


    Resistant hypertension is associated with chronic activation of the sympathetic nervous system resulting in various comorbidities. The prevalence of resistant hypertension is often under estimated due to various reasons. Activation of sympathetic nervous system at the renal-as well as systemic-level contributes to the increased level of catecholamines and resulting increase in the blood pressure. This increased activity was demonstrated by increased muscle sympathetic nerve activity and renal and total body noradrenaline spillover. Apart from the hypertension, it is hypothesized to be associated with insulin resistance, congestive heart failure and obstructive sleep apnea. Renal denervation is a novel procedure where the sympathetic afferent and efferent activity is reduced by various techniques and has been used successfully to treat drug-resistant hypertension improvement of various metabolic derangements.Renal denervation has the unique advantage of offering the denervation at the renal level, thus mitigating the systemic side effects. Renal denervation can be done by various techniques including radiofrequency ablation, ultrasound guided ablation and chemical ablation. Various trials evaluated the role of renal denervation in the management of resistant hypertension and have found promising results. More studies are underway to evaluate the role of renal denervation in patients presenting with resistant hypertension in different scenarios. Appropriate patient selection might be the key in determining the effectiveness of the procedure.

  3. Senescence Marker Protein-30 (SMP30 Deficiency Impairs Myocardium-Induced Dilation of Coronary Arterioles Associated with Reactive Oxygen Species

    Hiroyuki Mizukami


    Full Text Available Senescence marker protein-30 (SMP30 decreases with aging. Mice with SMP30 deficiency, a model of aging, have a short lifespan with increased oxidant stress. To elucidate SMP30’s effect on coronary circulation derived from myocytes, we measured the changes in the diameter of isolated coronary arterioles in wild-type (WT mice exposed to supernatant collected from isolated paced cardiac myocytes from SMP30 KO or WT mice. Pacing increased hydrogen peroxide in myocytes, and hydrogen peroxide was greater in SMP30 KO myocytes compared to WT myocytes. Antimycin enhanced and FCCP (oxidative phosphorylation uncoupler in mitochondria decreased superoxide production in both groups. Addition of supernatant from stimulated myocytes, either SMP30 KO or WT, caused vasodilation. The degree of the vasodilation response to supernatant was smaller in SMP30 KO mice compared to WT mice. Administration of catalase to arterioles eliminated vasodilation in myocyte supernatant of WT mice and converted vasodilation to vasoconstriction in myocyte supernatant of SMP30 KO mice. This vasoconstriction was eliminated by olmesartan, an angiotensin II receptor antagonist. Thus, SMP30 deficiency combined with oxidant stress increases angiotensin and hydrogen peroxide release from cardiac myocytes. SMP30 plays an important role in the regulation of coronary vascular tone by myocardium.

  4. Targeting vascular amyloid in arterioles of Alzheimer disease transgenic mice with amyloid β protein antibody-coated nanoparticles.

    Poduslo, Joseph F; Hultman, Kristi L; Curran, Geoffry L; Preboske, Gregory M; Chamberlain, Ryan; Marjańska, Małgorzata; Garwood, Michael; Jack, Clifford R; Wengenack, Thomas M


    The relevance of cerebral amyloid angiopathy (CAA) to the pathogenesis of Alzheimer disease (AD) and dementia in general emphasizes the importance of developing novel targeting approaches for detecting and treating cerebrovascular amyloid (CVA) deposits. We developed a nanoparticle-based technology that uses a monoclonal antibody against fibrillar human amyloid-β42 that is surface coated onto a functionalized phospholipid monolayer. We demonstrate that this conjugated nanoparticle binds to CVA deposits in arterioles of AD transgenic mice (Tg2576) after infusion into the external carotid artery using 3 different approaches. The first 2 approaches use a blood vessel enrichment of homogenized brain and a leptomeningeal vessel preparation from thin tangential brain slices from the surface of the cerebral cortex. Targeting of CVA by the antibody-coated nanoparticle was visualized using fluorescent lissamine rhodamine-labeled phospholipids in the nanoparticles, which were compared with fluorescent staining of the endothelial cells and amyloid deposits using confocal laser scanning microscopy. The third approach used high-field strength magnetic resonance imaging of antibody-coated iron oxide nanoparticles after infusion into the external carotid artery. Dark foci of contrast enhancement in cortical arterioles were observed in T2*-weighted images of ex vivo AD mouse brains that correlated histologically with CVA deposits. The targeting ability of these nanoparticles to CVA provides opportunities for the prevention and treatment of CAA.

  5. Androgen action via testicular arteriole smooth muscle cells is important for Leydig cell function, vasomotion and testicular fluid dynamics.

    Michelle Welsh

    Full Text Available Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO. Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.

  6. BKCa and KV channels limit conducted vasomotor responses in rat mesenteric terminal arterioles

    Hald, Bjørn Olav; Jacobsen, Jens Christian Brings; Braunstein, Thomas Hartig


    smooth muscle cells (VSMC) simulations of both membrane potential and intracellular [Ca(2+)] were performed. The "characteristic" length constant, ¿, was approximated using a modified cable equation in both experiments and simulations. We hypothesized that K(+) conductance in the arteriolar wall limit......Intracellular Ca(2+) signals underlying conducted vasoconstriction to local application of a brief depolarizing KCl stimulus was investigated in rat mesenteric terminal arterioles (cells (EC) and vascular...... the electrotonic spread of a local depolarization along arterioles by current dissipation across the VSMC plasma membrane. Thus, we anticipated an increased ¿ by inhibition of voltage-activated K(+) channels. Application of the BK(Ca) channel blocker iberiotoxin (100 nM) onto mesenteric arterioles in vitro...

  7. Coronary Arterioles in Type 2 Diabetic (db/db) Mice Undergo a Distinct Pattern of Remodeling Associated with Decreased Vessel Stiffness

    Katz, Paige S.; Trask, Aaron J.; Souza-Smith, Flavia M.; Hutchinson, Kirk R.; Galantowicz, Maarten L.; Lord, Kevin C.; Stewart, James A.; Cismowski, Mary J.; Varner, Kurt J.; Lucchesi, Pamela A.


    Background Little is known about the impact of type 2 diabetes mellitus (DM) on coronary arteriole remodeling. The aim of this study was to determine the mechanisms that underlie coronary arteriole structural remodeling in type 2 diabetic (db/db) mice. Methods and Results Passive structural properties of septal coronary arterioles isolated from 12- and 16-wk-old diabetic db/db and control mice were assessed by pressure myography. Coronary arterioles from 12-wk-old db/db mice were structurally similar to age-matched controls. By 16-wks of age, coronary wall thickness was increased in db/db arterioles (p < 0.01), while luminal diameter was reduced (Control: 118±5μm; db/db: 102±4μm, p < 0.05), augmenting the wall-to-lumen ratio by 58% (Control: 5.9±0.6; db/db: 9.5±0.4, p < 0.001). Inward hypertrophic remodeling was accompanied by a 56% decrease in elastic modulus (p < 0.05, indicating decreased vessel coronary wall stiffness) and a ~30% reduction in coronary flow reserve in diabetic mice. Interestingly, aortic pulse wave velocity and femoral artery incremental modulus were increased (p < 0.05) in db/db mice, indicating macrovascular stiffness. Molecular tissue analysis revealed increased elastin-to-collagen ratio in diabetic coronaries when compared to control and a decrease in the same ratio in the diabetic aortas. Conclusions These data show that coronary arterioles isolated from type 2 diabetic mice undergo inward hypertrophic remodeling associated with decreased stiffness and increased elastin-to-collagen ratio which results in a decreased coronary flow reserve. This study suggests that coronary microvessels undergo a different pattern of remodeling from macrovessels in type 2 DM. PMID:21744279

  8. Distinct recurrent versus afferent dynamics in cortical visual processing.

    Reinhold, Kimberly; Lien, Anthony D; Scanziani, Massimo


    How intracortical recurrent circuits in mammalian sensory cortex influence dynamics of sensory representation is not understood. Previous methods could not distinguish the relative contributions of recurrent circuits and thalamic afferents to cortical dynamics. We accomplish this by optogenetically manipulating thalamus and cortex. Over the initial 40 ms of visual stimulation, excitation from recurrent circuits in visual cortex progressively increased to exceed direct thalamocortical excitation. Even when recurrent excitation exceeded thalamic excitation, upon silencing thalamus, sensory-evoked activity in cortex decayed rapidly, with a time constant of 10 ms, which is similar to a neuron's integration time window. In awake mice, this cortical decay function predicted the time-locking of cortical activity to thalamic input at frequencies thalamocortical synapses disrupted the fidelity of sensory transmission. Thus, we determine dynamics intrinsic to cortical recurrent circuits that transform afferent input in time.

  9. Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

    Jihong Xing


    Full Text Available Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA and blood pressure (BP responses during static exercise in heart failure (HF. In this study, we examined engagement of bradykinin (BK in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.


    Luo Pifu; Zhang Jingdong; Li Jishuo


    Neural pathways and synaptic connections from the trigeminal mesencephalic nucleus (Vme) neurons to the cranial motor nuclei were studied in the rat using double labelling methodologies of intracellular Neurobiotin staining combined with retrograde horseradish peroxidase (HRP) transport, anterograde biotinylated dextran amine (BDA) tracing combined with retrograde HRP transport, and a dual fluorescent labelling of BDA anterograde combined tracing with Cholera Toxin B (CTB) retrograde transport. Direct projections and synapses were demonstrated from Vme neuronal boutons to motoneurons (MNs) of the trigeminal motor nucleus (Vmo), the hypoglossal nucleus (Ⅻ) and the ambiguus nucleus (Amb). Indirect projections and pathways from Vme neurons to the cranial motor nuclei including Vmo, Ⅻ, the facial nucleus (Ⅶ) and the cervical spinal cord (C1~5) were seen to relay on their premotor neurons. The premotor neurons of above cranial motor nuclei were overlapped in bilateral premotor neuronal pool including the parvocellular reticular formation (PCRt) and its alpha division (PCRtA), the dorsomedial part of the spinal trigeminal nucleus oralis (Vodm), and interpolaris (Vidm), the medullary reticular nucleus dorsal division (MdD), the supratrigeminal region (Vsup) and the dorsomedial part of the principal trigeminal sensory nucleus (Vpdm).Synapses between Vme neuronal boutons and Vmo and Ⅻ MNs and Ⅻ premotor neurons were predominantly asymmetric.There were four types of synaptic organizations, i.e. synaptic convergence; synaptic divergence presynaptic inhibition and afferent feedforward inhibition seen between Vme boutons and Vmno, Ⅻ MNs and between Vme boutons and Ⅻ premotor neurons.The results of present studies have demonstrated direct pathways from the trigeminal proprioceptive afferents to Vmo, Ⅻ and Amb MNs, and indirect pathways from the trigeminal proprioceptive afferents to bilateral Vmno, Ⅻ, Ⅶ and C1~s via their premotor neurons. It provides

  11. Mechanically insensitive afferents (MIAs) in cutaneous nerves of monkey.

    Meyer, R A; Davis, K D; Cohen, R H; Treede, R D; Campbell, J N


    A problem in the study of nociceptors is that intense stimuli are used to locate the receptive field (RF), and thus the receptor may be damaged before the first responses are recorded. In addition, some nociceptors do not respond to the mechanical stimuli often used to search for the RF. To overcome these problems, an electrical search technique was developed to locate the RF of cutaneous nociceptors. In the hairy skin of anesthetized monkey, we used this technique to locate the RF of 63 A delta-fibers and 22 C-fibers that had extremely high thresholds or were unresponsive to mechanical stimuli. We refer to these afferents as mechanically insensitive afferents (MIAs). Ten A delta-fiber MIAs had a short latency response to stepped heat stimuli and could be responsible for first pain sensation. Five A delta-fiber MIAs and one C-fiber MIA did not respond to mechanical or heat stimuli but did respond to injection into the electrical RF of an artificial inflammatory soup containing histamine, bradykinin, prostaglandin E1, and serotonin. These chemoreceptors might be responsible for the pain and itch sensations that result from chemical stimuli. Some MIAs became more responsive to mechanical stimuli after injection into the RF of the inflammatory soup and, thus, may contribute to the hyperalgesia to mechanical stimuli associated with cutaneous injury. A large proportion of the A delta-fiber (48%) and C-fiber (30%) afferents in this study were insensitive to mechanical stimuli. The role of these MIAs in sensation needs to be studied further. The electrical search technique enables a systematic study of these afferents to be performed. This technique may also be of use to identify and characterize dorsal horn neurons that have inputs from MIAs.

  12. Enhanced Muscle Afferent Signals during Motor Learning in Humans.

    Dimitriou, Michael


    Much has been revealed concerning human motor learning at the behavioral level [1, 2], but less is known about changes in the involved neural circuits and signals. By examining muscle spindle responses during a classic visuomotor adaptation task [3-6] performed by fully alert humans, I found substantial modulation of sensory afferent signals as a function of adaptation state. Specifically, spindle control was independent of concurrent muscle activity but was specific to movement direction (representing muscle lengthening versus shortening) and to different stages of learning. Increased spindle afferent responses to muscle stretch occurring early during learning reflected individual error size and were negatively related to subsequent antagonist activity (i.e., 60-80 ms thereafter). Relative increases in tonic afferent output early during learning were predictive of the subjects' adaptation rate. I also found that independent spindle control during sensory realignment (the "washout" stage) induced afferent signal "linearization" with respect to muscle length (i.e., signals were more tuned to hand position). The results demonstrate for the first time that motor learning also involves independent and state-related modulation of sensory mechanoreceptor signals. The current findings suggest that adaptive motor performance also relies on the independent control of sensors, not just of muscles. I propose that the "γ" motor system innervating spindles acts to facilitate the acquisition and extraction of task-relevant information at the early stages of sensorimotor adaptation. This designates a more active and targeted role for the human proprioceptive system during motor learning.

  13. Characterisation of the primary afferent spinal innervation of mouse uterus

    Geraldine eHerweijer


    Full Text Available The primary afferent innervation of the uterus is incompletely understood. The aim of this study was to identify the location and characteristics of primary afferent neurons that innervate the uterine horn of mice and correlate the different morphological types of putative primary afferent nerve endings, immunoreactive to the sensory marker, calcitonin gene related peptide (CGRP. Using retrograde tracing, injection of 5-10µL of 1,1'-didodecyl-3,3,3,3'-tetramethylindocarbocyanine perchlorate (DiI into discrete single sites in each uterine horn revealed a biomodal distribution of sensory neurons in dorsal root ganglia (DRG with peak labelling occurring between T13-L3 and a second smaller peak between L6-S1. The mean cross sectional area of labelled cells was 463 µm2 +/- SEM. A significantly greater proportion of labelled neurons consisted of small cell bodies (<300 µm2 in the sacral spinal cord (S2 compared with peak labelling at the lumbar (L2 region. In both sections and whole mount preparations, immunohistochemical staining for CGRP revealed substantial innervation of the uterus by CGRP-positive nerve fibres located primarily at the border between the circular and longitudinal muscle layers (N=4. The nerve endings were classified into three distinct types: single, branching or complex, that often aligned preferentially in either the circular or longitudinal axis of the smooth muscles. Complex endings were often associated with mesenteric vessels. We have identified that the cell bodies of primary afferent neurons innervating the mouse uterus lie primarily in DRG at L2 and S1 spinal levels. Also, the greatest density of CGRP immunoreactivity lies within the myometrium, with at least three different morphological types of nerve endings identified. These findings will facilitate further investigations into the mechanisms underlying sensory transduction in mouse uterus.

  14. How to test for a relative afferent pupillary defect (RAPD

    David C Broadway


    Full Text Available The 'swinging light test' is used to detect a relative afferent pupil defect (RAPD: a means of detecting differences between the two eyes in how they respond to a light shone in one eye at a time. The test can be very useful for detecting unilateral or asymmetrical disease of the retina or optic nerve (but only optic nerve disease that occurs in front of the optic chiasm.


    A. V. Govorov


    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  16. Renal angiomyolipoma

    Holm-Nielsen, P; Sørensen, Flemming Brandt


    lesion. Three cases of renal angiomyolipoma, 2 of which underwent perfusion-fixation, were studied by electron microscopy to clarify the cellular composition of this lesion. In the smooth muscle cells abundant accumulation of glycogen was found, whereas the lipocytes disclosed normal ultrastructural......-specific vesicular structures. These findings suggest a secondary vascular damage, i.e. the thickened vessels may not be a primary, integral part of renal angiomyolipoma. Evidence of a common precursor cell of renal angiomyolipoma was not disclosed. It is concluded that renal angiomyolipoma is a hamartoma composed...

  17. The Role of L- and T-Type Calcium Channels in Local and Remote Calcium Responses in Rat Mesenteric Terminal Arterioles

    Braunstein, Thomas Hartig; Inoue, Ryuji; Cribbs, Leanne;


    Background/Aims: The roles of intercellular communication and T-type versus L-type voltage-dependent Ca(2+) channels (VDCCs) in conducted vasoconstriction to local KCl-induced depolarization were investigated in mesenteric arterioles. Methods: Ratiometric Ca(2+) imaging (R) using Fura-PE3...

  18. Significance of KATP channels, L-type Ca2+ channels and CYP450-4A enzymes in oxygen sensing in mouse cremaster muscle arterioles In vivo

    Ngo, Thuc Anh; Riemann, Mads; von Holstein-Rathlou, Niels-Henrik


    of these mechanisms for oxygen sensing in arterioles in an in vivo model of metabolically active skeletal muscle. For this purpose we utilized the exteriorized cremaster muscle of anesthetized mice, in which the cremaster muscle was exposed to controlled perturbation of tissue PO₂....

  19. Intracranial pressure elevation reduces flow through collateral vessels and the penetrating arterioles they supply. A possible explanation for 'collateral failure' and infarct expansion after ischemic stroke.

    Beard, Daniel J; McLeod, Damian D; Logan, Caitlin L; Murtha, Lucy A; Imtiaz, Mohammad S; van Helden, Dirk F; Spratt, Neil J


    Recent human imaging studies indicate that reduced blood flow through pial collateral vessels ('collateral failure') is associated with late infarct expansion despite stable arterial occlusion. The cause for 'collateral failure' is unknown. We recently showed that intracranial pressure (ICP) rises dramatically but transiently 24 hours after even minor experimental stroke. We hypothesized that ICP elevation would reduce collateral blood flow. First, we investigated the regulation of flow through collateral vessels and the penetrating arterioles arising from them during stroke reperfusion. Wistar rats were subjected to intraluminal middle cerebral artery (MCA) occlusion (MCAo). Individual pial collateral and associated penetrating arteriole blood flow was quantified using fluorescent microspheres. Baseline bidirectional flow changed to MCA-directed flow and increased by >450% immediately after MCAo. Collateral diameter changed minimally. Second, we determined the effect of ICP elevation on collateral and watershed penetrating arteriole flow. Intracranial pressure was artificially raised in stepwise increments during MCAo. The ICP increase was strongly correlated with collateral and penetrating arteriole flow reductions. Changes in collateral flow post-stroke appear to be primarily driven by the pressure drop across the collateral vessel, not vessel diameter. The ICP elevation reduces cerebral perfusion pressure and collateral flow, and is the possible explanation for 'collateral failure' in stroke-in-progression.

  20. Effect of hypergravity on the development of vestibulocerebellar afferent fibers

    Bruce, L. L.

    Gravity is a critical factor in the normal development of the vestibular system, as prolonged prenatal exposures to either micro- or hypergravity will alter the pattern of projections from specific vestibular organs to specific targets in the vestibular nuclei. This study addresses the effect of gravity on the development of vestibulocerebellar projections. In adult rats the semicircular canal afferents project mainly to the cerebellar nodulus whereas the otolith maculae project mainly to the ventral uvula of the cerebellum. To determine if the distribution pattern of these afferents is altered by exposures to altered gravity, 10 pregnant rats were exposed to hypergravity (1.5g) from embryonic day 12 (before vestibular ganglion neurons contact vestibular nuclei) to embryonic day 21 (near the time when the vestibular system becomes functional). Controls were exposed to Earth's gravity but otherwise received the same treatment. At the end of the exposure the embryos were deeply anesthetized and fixed by transcardiac perfusion with 4% paraformaldehyde in 0.1 M phosphate buffer (pH7.4). Filter strips coated with DiI and PTIR were implanted into the saccule (gravistatic vestibular receptor) or into the posterior vertical canal (angular acceleration receptor), and allowed to diffuse for 2 weeks at 37°C. Then the brains were dissected and sectioned for fluorescent confocal imaging. Examination of the control cerebella revealed that the canal and otolith afferents have reached the nodulus and uvula, and axons extend into the internal granular, Purkinje, and molecular layers. Projections from the saccule and posterior vertical canal were partially segregated into their respective domains, the uvula and nodulus. In contrast, in hypergravity-exposed rat fetuses the saccule and posterior vertical canal projections were poorly segregated, and both organs contributed labeled fibers to all layers of the nodulus and uvula. This contrasts with the increased afferent segregation

  1. Human intersegmental reflexes from intercostal afferents to scalene muscles.

    McBain, Rachel A; Taylor, Janet L; Gorman, Robert B; Gandevia, Simon C; Butler, Jane E


    What is the central question of this study? The aim was to determine whether specific reflex connections operate between intercostal afferents and the scalene muscles in humans, and whether these connections operate after a clinically complete cervical spinal cord injury. What is the main finding and its importance? This is the first description of a short-latency inhibitory reflex connection between intercostal afferents from intercostal spaces to the scalene muscles in able-bodied participants. We suggest that this reflex is mediated by large-diameter afferents. This intercostal-to-scalene inhibitory reflex is absent after cervical spinal cord injury and may provide a way to monitor the progress of the injury. Short-latency intersegmental reflexes have been described for various respiratory muscles in animals. In humans, however, only short-latency reflex responses to phrenic nerve stimulation have been described. Here, we examined the reflex connections between intercostal afferents and scalene muscles in humans. Surface EMG recordings were made from scalene muscles bilaterally, in seven able-bodied participants and seven participants with motor- and sensory-complete cervical spinal cord injury (median 32 years postinjury, range 5 months to 44 years). We recorded the reflex responses produced by stimulation of the eighth or tenth left intercostal nerve. A short-latency (∼38 ms) inhibitory reflex was evident in able-bodied participants, in ipsilateral and contralateral scalene muscles. This bilateral intersegmental inhibitory reflex occurred in 46% of recordings at low stimulus intensities (at three times motor threshold). It was more frequent (in 75-85% of recordings) at higher stimulus intensities (six and nine times motor threshold), but onset latency (38 ± 9 ms, mean ± SD) and the size of inhibition (23 ± 10%) did not change with stimulus intensity. The reflex was absent in all participants with spinal cord injury. As the intercostal

  2. Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats.

    Shi, Ying-Xian; Chen, Ying; Zhu, Yi-Zhun; Huang, Guo-Ying; Moore, Philip Keith; Huang, Shan-Hong; Yao, Tai; Zhu, Yi-Chun


    Hydrogen sulfide (H(2)S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to examine the hypothesis that chronic treatment with sodium hydrosulfide (NaHS, an H(2)S donor) is able to prevent left-ventricular remodeling in spontaneously hypertensive rats (SHR). Four-week-old SHR were treated with NaHS (10, 30, and 90 micromol x kg(-1) x day(-1)), a combination of NaHS (30 micromol x kg(-1) x day(-1)) and glibenclamide (5 mg x kg(-1) x day(-1)), glibenclamide alone (5 mg x kg(-1) x day(-1)), hydralazine alone (10 mg x kg(-1) x day(-1)), and placebo for 3 mo. At the end of the treatment period, variables such as cardiac geometry and function, intramyocardial arterioles ranging in diameter from 25 to 100 microm, perivascular and interstitial collagen content, reactive oxygen species (ROS), thiol groups, conjugated dienes, and DNA base modification were examined. The novel finding of the present study is that chronic NaHS treatment prevented the hypertrophy of intramyocardial arterioles and ventricular fibrosis, as well as decreased myocardial ROS and conjugated diene levels. The cardioprotective effects were blunted by coadministration of glibenclamide, suggesting a role of ATP-sensitive potassium channels in mediating the action of NaHS. Hydralazine caused a comparable reduction of blood pressure compared with NaHS treatment; however, it exerted no effect on the remodeling process or on ROS and conjugated diene levels. Moreover, NaHS treatment caused an increase in myocardial thiol group levels, whereas DNA base modification was not altered by NaHS treatment. In conclusion, the superior cardioprotective effects of NaHS treatment are worthy to be further explored to develop novel therapeutic approaches for the treatment of cardiac remodeling in hypertension.

  3. Renal cancer

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.


    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all acknowle

  4. Renal fallure


    920705 Endothelin and acute renal failure:study on their relationship and possiblemechanisms. LIN Shanyan(林善锬), et al.Renal Res Lab, Huashan Hosp, Shanghai MedUniv, Shanghai, 200040. Natl Med J China 1992;72(4): 201-205. In order to investigate the role of endothelin

  5. Renal cancer.

    Corgna, E.; Betti, M.; Gatta, G.; Roila, F.; Mulder, P.H.M. de


    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  6. Renal cancer

    Corgna, Enrichetta; Betti, Maura; Gatta, Gemma; Roila, Fausto; De Mulder, Pieter H. M.


    In Europe, renal cancer (that is neoplasia of the kidney, renal pelvis or ureter (ICD-9 189 and ICD-10 C64-C66)) ranks as the seventh most common malignancy in men amongst whom there are 29,600 new cases each year (3.5% of all cancers). Tobacco, obesity and a diet poor in vegetables are all

  7. Primary afferent depolarization of muscle afferents elicited by stimulation of joint afferents in cats with intact neuraxis and during reversible spinalization.

    Quevedo, J; Eguibar, J R; Jiménez, I; Schmidt, R F; Rudomin, P


    1. In the anesthetized and artificially ventilated cat, stimulation of the posterior articular nerve (PAN) with low strengths (1.2-1.4 x T) produced a small negative response (N1) in the cord dorsum of the lumbosacral spinal cord with a mean onset latency of 5.2 ms. Stronger stimuli (> 1.4 x T) produced two additional components (N2 and N3) with longer latencies (mean latencies 7.5 and 15.7 ms, respectively), usually followed by a slow positivity lasting 100-150 ms. With stimulus strengths above 10 x T there was in some experiments a delayed response (N4; mean latency 32 ms). 2. Activation of posterior knee joint nerve with single pulses and intensities producing N1 responses only, usually produced no dorsal root potentials (DRPs), or these were rather small. Stimulation with strengths producing N2 and N3 responses produced distinct DRPs. Trains of pulses were clearly more effective than single pulses in producing DRPs, even in the low-intensity range. 3. Cooling the thoracic spinal cord to block impulse conduction, increased the DRPs and the N3 responses produced by PAN stimulation without significantly affecting the N2 responses. Reversible spinalization also increased the DRPs produced by stimulation of cutaneous nerves. In contrast, the DRPs produced by stimulation of group I afferents from flexors were reduced. 4. Conditioning electrical stimulation of intermediate and high-threshold myelinated fibers in the PAN depressed the DRPs produced by stimulation of group I muscle and of cutaneous nerves. 5. Analysis of the intraspinal threshold changes of single Ia and Ib fibers has provided evidence that stimulation of intermediate and high threshold myelinated fibers in the posterior knee joint nerve inhibits the primary afferent depolarization (PAD) of Ia fibers, and may either produce PAD or inhibit the PAD in Ib fibers, in the same manner as stimulation of cutaneous nerves. In 7/16 group I fibers the inhibition of the PAD was increased during reversible

  8. TRPV1 marks synaptic segregation of multiple convergent afferents at the rat medial solitary tract nucleus.

    James H Peters

    Full Text Available TRPV1 receptors are expressed on most but not all central terminals of cranial visceral afferents in the caudal solitary tract nucleus (NTS. TRPV1 is associated with unmyelinated C-fiber afferents. Both TRPV1+ and TRPV1- afferents enter NTS but their precise organization remains poorly understood. In horizontal brainstem slices, we activated solitary tract (ST afferents and recorded ST-evoked glutamatergic excitatory synaptic currents (ST-EPSCs under whole cell voltage clamp conditions from neurons of the medial subnucleus. Electrical shocks to the ST produced fixed latency EPSCs (jitter<200 µs that identified direct ST afferent innervation. Graded increases in shock intensity often recruited more than one ST afferent and ST-EPSCs had consistent threshold intensity, latency to onset, and unique EPSC waveforms that characterized each unitary ST afferent contact. The TRPV1 agonist capsaicin (100 nM blocked the evoked TRPV1+ ST-EPSCs and defined them as either TRPV1+ or TRPV1- inputs. No partial responses to capsaicin were observed so that in NTS neurons that received one or multiple (2-5 direct ST afferent inputs--all were either blocked by capsaicin or were unaltered. Since TRPV1 mediates asynchronous release following TRPV1+ ST-evoked EPSCs, we likewise found that recruiting more than one ST afferent further augmented the asynchronous response and was eliminated by capsaicin. Thus, TRPV1+ and TRPV1- afferents are completely segregated to separate NTS neurons. As a result, the TRPV1 receptor augments glutamate release only within unmyelinated afferent pathways in caudal medial NTS and our work indicates a complete separation of C-type from A-type afferent information at these first central neurons.

  9. Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum.

    Feng, Bin; Brumovsky, Pablo R; Gebhart, Gerald F


    Information about colorectal distension (i.e., colorectal dilation by increased intraluminal pressure) is primarily encoded by stretch-sensitive colorectal afferents in the pelvic nerve (PN). Despite anatomic differences between rectum and distal colon, little is known about the functional roles of colonic vs. rectal afferents in the PN pathway or the quantitative nature of mechanosensory encoding. We utilized an in vitro mouse colorectum-PN preparation to investigate pressure-encoding characteristics of colorectal afferents. The colorectum with PN attached was dissected, opened longitudinally, and pinned flat in a Sylgard-lined chamber. Action potentials of afferent fibers evoked by circumferential stretch (servo-controlled force actuator) were recorded from the PN. Stretch-sensitive fibers were categorized into the following four groups: colonic muscular, colonic muscular/mucosal, rectal muscular, and rectal muscular/mucosal. Seventy-nine stretch-sensitive PN afferents evenly distributed into the above four groups were studied. Rectal muscular afferents had significantly greater stretch-responses than the other three groups. Virtually all rectal afferents (98%) had low thresholds for response and encoded stimulus intensity into the noxious range without obvious saturation. Most colonic afferents (72%) also had low thresholds (18 mmHg) for response. These high-threshold colonic afferents were sensitized to stretch by inflammatory soup; response threshold was significantly reduced (from 23 to 12 mmHg), and response magnitude significantly increased. These results suggest that the encoding of mechanosensory information differs between colonic and rectal stretch-sensitive PN afferents. Rectal afferents have a wide response range to stretch, whereas high-threshold colonic afferents likely contribute to visceral nociception.

  10. The future of GI and liver research: editorial perspectives. IV. Visceral afferents: an update.

    Raybould, Helen E


    The number of articles published in American Journal of Physiology Gastrointestinal and Liver Physiology over the last 15 years on visceral afferents has increased dramatically. This reflects our growing ability to study the characteristics and function of visceral afferents and also the recognition of their importance in the maintenance of homeostasis and also in a number of pathophysiological conditions. However, there are several key unanswered questions concerning the function of visceral afferents that await further investigation.

  11. Degeneration of primary afferent terminals following brachial plexus extensive avulsion injury in rats

    Muñetón-Gómez, Vilma; Taylor, Julian S.; Averill, Sharon; Priestley, John V.; Nieto-Sampedro, Manuel


    Important breakthroughs in the understanding regeneration failure in an injured CNS have been made by studies of primary afferent neurons. Dorsal rhizotomy has provided an experimental model of brachial plexus (BP) avulsion. This is an injury in which the central branches of primary afferents are disrupted at their point of entry into the spinal cord, bringing motor and sensory dysfunction to the upper limbs. In the present work, the central axonal organization of primary afferents was examin...

  12. Renal denervation: a new therapeutic approach for resistant hypertension

    Cao Longxing; Fu Qiang; Wang Binghui; Li Zhiliang


    Objective To review the advances in studies on renal denervation.Data sources References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014.Study selection Articles with keywords "renal denervation" and "resistant hypertension" were selected.Results Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity.Renal denervation is a new,catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries.Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases,Symplicity HTN 3 study,the most rigorous clinical trial of renal denervation to date,failed to meet its primary endpoint.The procedure also has other limitations such as the lack of long term,efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure.An overview of current renal denervation devices holding Conformité Européenne mark is also included in this review.Conclusions Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity.In its early stage of clinical application,the efficacy of the procedure is still controversial.Large scale,blind,randomized,controlled clinical trials are still necessary to address the limitations of the procedure.

  13. Renal teratogens.

    Morgan, Thomas M; Jones, Deborah P; Cooper, William O


    In utero exposure to certain drugs early in pregnancy may adversely affect nephrogenesis. Exposure to drugs later in pregnancy may affect the renin-angiotensin system, which could have an impact on fetal or neonatal renal function. Reduction in nephron number and renal function could have adverse consequences for the child several years later. Data are limited on the information needed to guide decisions for patients and providers regarding the use of certain drugs in pregnancy. The study of drug nephroteratogenicity has not been systematized, a large, standardized, global approach is needed to evaluate the renal risks of in utero drug exposures.

  14. Device-based approaches for renal nerve ablation for hypertension and beyond

    Alicia Ann Thorp


    Full Text Available Animal and human studies have demonstrated that chronic activation of renal sympathetic nerves is critical in the pathogenesis and perpetuation of treatment-resistant hypertension. Bilateral renal denervation has emerged as a safe and effective, non-pharmacological treatment for resistant hypertension that involves the selective ablation of efferent and afferent renal nerves to lower blood pressure. However, the most recent and largest randomized controlled trial failed to confirm the primacy of renal denervation over a sham procedure, prompting widespread re-evaluation of the therapy’s efficacy. Disrupting renal afferent sympathetic signalling to the hypothalamus with renal denervation lowers central sympathetic tone, which has the potential to confer additional clinical benefits beyond blood pressure control. Specifically, there has been substantial interest in the use of renal denervation as either a primary or adjunct therapy in pathological conditions characterized by central sympathetic over-activity such as renal disease, heart failure and metabolic-associated disorders. Recent findings from pre-clinical and proof-of–concept studies appear promising with renal denervation shown to confer cardiovascular and metabolic benefits, largely independent of changes in blood pressure. This review explores the pathological rationale for targeting sympathetic renal nerves for blood pressure control. Latest developments in renal nerve ablation modalities designed to improve procedural success are discussed along with prospective findings on the efficacy of renal denervation to lower blood pressure in treatment-resistant hypertensive patients. Preliminary evidence in support of renal denervation as a possible therapeutic option in disease states characterized by central sympathetic over-activity is also presented.

  15. Meningeal afferent signaling and the pathophysiology of migraine.

    Burgos-Vega, Carolina; Moy, Jamie; Dussor, Gregory


    Migraine is the most common neurological disorder. Attacks are complex and consist of multiple phases but are most commonly characterized by intense, unilateral, throbbing headache. The pathophysiology contributing to migraine is poorly understood and the disorder is not well managed with currently available therapeutics, often rendering patients disabled during attacks. The mechanisms most likely to contribute to the pain phase of migraine require activation of trigeminal afferent signaling from the cranial meninges and subsequent relay of nociceptive information into the central nervous system in a region of the dorsal brainstem known as the trigeminal nucleus caudalis. Events leading to activation of meningeal afferents are unclear, but nerve endings within this tissue are mechanosensitive and also express a variety of ion channels including acid-sensing ion channels and transient receptor-potential channels. These properties may provide clues into the pathophysiology of migraine by suggesting that decreased extracellular pH and environmental irritant exposure in the meninges contributes to headache. Neuroplasticity is also likely to play a role in migraine given that attacks are triggered by routine events that are typically nonnoxious in healthy patients and clear evidence of sensitization occurs during an attack. Where and how plasticity develops is also not clear but may include events directly on the afferents and/or within the TNC. Among the mediators potentially contributing to plasticity, calcitonin gene-related peptide has received the most attention within the migraine field but other mechanisms may also contribute. Ultimately, greater understanding of the molecules and mechanisms contributing to migraine will undoubtedly lead to better therapeutics and relief for the large number of patients across the globe who suffer from this highly disabling neurological disorder.

  16. Kv1 channels and neural processing in vestibular calyx afferents

    Frances L Meredith


    Full Text Available Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia. Future investigations of such potential plasticity require a better understanding of the electrophysiological mechanisms underlying the known heterogeneity of afferent discharge under normal conditions. This study advances this understanding by examining the role of the Kv1 potassium channel family in mediating action potentials in specialized vestibular afferent calyx endings in the gerbil crista and utricle. Pharmacological agents selective for different sub-types of Kv1 channels were tested on membrane responses in whole cell recordings in the crista. Kv1 channels sensitive to α-dendrotoxin and dendrotoxin-K were found to prevail in the central regions, whereas K+ channels sensitive to margatoxin, which blocks Kv1.3 and 1.6 channels, were more prominent in peripheral regions. Margatoxin-sensitive currents showed voltage-dependent inactivation. Dendrotoxin-sensitive currents showed no inactivation and dampened excitability in calyces in central neuroepithelial regions. The differential distribution of Kv1 potassium channels in vestibular afferents supports their importance in accurately relaying gravitational and head movement signals through specialized lines to the central nervous system. Pharmacological modulation of specific groups of K+ channels could help alleviate vestibular dysfunction on earth and in space.

  17. Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis

    Roos, Ewa M.; Herzog, Walter; Block, Joel A


    Lower-extremity muscle strength and afferent sensory dysfunction, such as reduced proprioceptive acuity, are potentially modifiable putative risk factors for knee osteoarthritis (OA). Findings from current studies suggest that muscle weakness is a predictor of knee OA onset, while there is confli...... with previous knee injuries) are easily identified, and may benefit from exercise interventions to prevent or delay OA onset....... a possibility for achieving preventive structure or load modifications. In contrast, large randomized controlled trials of patients with established OA have failed to demonstrate beneficial effects of strengthening exercises. Subgroups of individuals who are at increased risk of knee OA (such as those...

  18. Sarcoidose renal



    Full Text Available Em uma mulher de 62 anos, branca, em avaliação pré-operatória de facectomia, foram detectadas alterações urinárias, tendo sido firmados os diagnósticos de calculose renal esquerda e exclusão renal homolateral. No pré-operatório da nefrectomia foram evidenciados processo pulmonar intersticial bilateral e adenopatia torácica, cuja investigação foi adiada para após a cirurgia. No rim retirado foram detectados granulomas epitelióides não necrotizantes, o mesmo ocorrendo posteriormente em biópsia transbrônquica. A paciente foi tratada com metilprednisolona, com discreta melhora pulmonar, o que não ocorreu com a função renal. O diagnóstico final foi de sarcoidose com envolvimento pulmonar, ganglionar torácico e renal.

  19. Renal failure


    930150 Epidermal growth factor and its recep-tor in the renal tissue of patients with acute re-nal failure and normal persons.LIU Zhihong(刘志红),et al.Jinling Hosp,Nanjing,210002.Natl Med J China 1992;72(10):593-595.Epidermal growth factor(EGF)and its receptor(EGF-R)were identified by immunohis-tochemical method(4 layer PAP)in the renaltissue specimens obtained from 11 normal kid-neys and 17 cases of acute renal failure(ARF).The quantitative EGF and EGF-R in the tissuewere expressed as positive tubules per mm~2.The amount of EGF and EGF-R in renal tissue

  20. Renal failure


    2005234 Association between serum fetuin-A and clinical outcome in end-stage renal disease patients. WANG Kai(王开), Dept Renal Dis, Renji Hosp Shanghai, 2nd Med Univ, Shanghai 200001. Chin J Nephrol, 2005;21(2):72-75. Objective: To investigate the change of serum fetuin-A level before and after dialysis, and the association of serum fetuin-A level with clinical parameters

  1. Renal failure


    950351 Serum erythropoietin levels in chronic renalinsufficiency.ZHAI Depei(翟德佩),et al.DeptNephrol.General Hosp,Tianjin Med Univ,Tianjin,300000.Tianjin Med J 1995;23(1):19-21.Patients with chronic renal insufficiency(CRI) areoften associated with anemia.The deficiency of EPOproduction in the kidney is thought to be a key factorin the pathogenesis of renal anemia.Serum erythropoi-

  2. Renal failure


    2008463 Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats. TANG Xiaopeng(唐晓鹏), et al. Dept Nephrol, 2nd Affili Hosp Chongqing Med Univ, Chongqing 400010.Chin J Nephrol 2008;24(6):417-421. Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction

  3. Renal Hemangiopericytoma

    İbrahim Halil Bozkurt


    Full Text Available Hemangiopericytoma is an uncommon perivascular tumor originating from pericytes in the pelvis, head and tneck, and the meninges; extremely rarely in the urinary system. We report a case of incidentally detected renal mass in which radiologic evaluation was suggestive of renal cell carcinoma. First, we performed partial nephrectomy, and then, radical nephrectomy because of positive surgical margins and the pathological examination of the surgical specimen that revealed a hemangiopericytoma. No additional treatment was administered.

  4. A histopathological score on baseline biopsies from elderly donors predicts outcome 1 year after renal transplantation

    Toft, Birgitte G; Federspiel, Birgitte H; Sørensen, Søren S


    Kidneys from elderly deceased patients and otherwise marginal donors may be considered for transplantation and a pretransplantation histopathological score for prediction of postoperative outcome is warranted. In a retrospective design, 29 baseline renal needle biopsies from elderly deceased donors...... wall thickness of arteries and/or arterioles. Nineteen renal baseline biopsies from 15 donors (age: 64 ± 10 years) were included and following consensus the histopathological score was 4.3 ± 2.1 (intraclass correlation coefficient: 0.81; confidence interval: 0.66-0.92). The donor organs were used...... for single renal transplantation (recipient age: 47 ± 3 years). Two grafts were lost after the transplantation. In the remaining 17 recipients the 1-year creatinine clearance (54 ± 6 mL/min) correlated to the baseline histopathological score (r(2) = 0.59; p

  5. Anatomy and physiology of the afferent visual system.

    Prasad, Sashank; Galetta, Steven L


    The efficient organization of the human afferent visual system meets enormous computational challenges. Once visual information is received by the eye, the signal is relayed by the retina, optic nerve, chiasm, tracts, lateral geniculate nucleus, and optic radiations to the striate cortex and extrastriate association cortices for final visual processing. At each stage, the functional organization of these circuits is derived from their anatomical and structural relationships. In the retina, photoreceptors convert photons of light to an electrochemical signal that is relayed to retinal ganglion cells. Ganglion cell axons course through the optic nerve, and their partial decussation in the chiasm brings together corresponding inputs from each eye. Some inputs follow pathways to mediate pupil light reflexes and circadian rhythms. However, the majority of inputs arrive at the lateral geniculate nucleus, which relays visual information via second-order neurons that course through the optic radiations to arrive in striate cortex. Feedback mechanisms from higher cortical areas shape the neuronal responses in early visual areas, supporting coherent visual perception. Detailed knowledge of the anatomy of the afferent visual system, in combination with skilled examination, allows precise localization of neuropathological processes and guides effective diagnosis and management of neuro-ophthalmic disorders.

  6. Interactions between visceral afferent signaling and stimulus processing

    Hugo D Critchley


    Full Text Available Visceral afferent signals to the brain influence thoughts, feelings and behaviour. Here we highlight the findings of a set of empirical investigations in humans concerning body-mind interaction that focus on how feedback from states of autonomic arousal shapes cognition and emotion. There is a longstanding debate regarding the contribution of the body, to mental processes. Recent theoretical models broadly acknowledge the role of (autonomically-mediated physiological arousal to emotional, social and motivational behaviours, yet the underlying mechanisms are only partially characterized. Neuroimaging is overcoming this shortfall; first, by demonstrating correlations between autonomic change and discrete patterns of evoked, and task-independent, neural activity; second, by mapping the central consequences of clinical perturbations in autonomic response and; third, by probing how dynamic fluctuations in peripheral autonomic state are integrated with perceptual, cognitive and emotional processes. Building on the notion that an important source of the brain’s representation of physiological arousal is derived from afferent information from arterial baroreceptors, we have exploited the phasic nature of these signals to show their differential contribution to the processing of emotionally-salient stimuli. This recent work highlights the facilitation at neural and behavioral levels of fear and threat processing that contrasts with the more established observations of the inhibition of central pain processing during baroreceptors activation. The implications of this body-brain-mind axis are discussed.

  7. Effects of intratympanic gentamicin on vestibular afferents and hair cells in the chinchilla.

    Hirvonen, Timo P; Minor, Lloyd B; Hullar, Timothy E; Carey, John P


    Gentamicin is toxic to vestibular hair cells, but its effects on vestibular afferents have not been defined. We treated anesthetized chinchillas with one injection of gentamicin (26.7 mg/ml) into the middle ear and made extracellular recordings from afferents after 5-25 (early) or 90-115 days (late). The relative proportions of regular, intermediate, and irregular afferents did not change after treatment. The spontaneous firing rate of regular afferents was lower (P galvanic currents was unaffected for all afferents. Intratympanic gentamicin treatment reduced the histological density of all hair cells by 57% (P = 0.04). The density of hair cells with calyx endings was reduced by 99% (P = 0.03), although some remaining hair cells had other features suggestive of type I morphology. Type II hair cell density was not significantly reduced. These findings suggest that a single intratympanic gentamicin injection causes partial damage and loss of vestibular hair cells, particularly type I hair cells or their calyceal afferent endings, does not damage the afferent spike initiation zones, and preserves enough hair cell synaptic activity to drive the spontaneous activity of vestibular afferents.

  8. Primary afferent depolarization and flexion reflexes produced by radiant heat stimulation of the skin.

    Burke, R E; Rudomin, P; Vyklický, L; Zajac, F E


    1. The reflex effects of pulses of intense radiant heat applied to the skin of the central plantar pad have been studied in unanaesthetized (decerebrate) spinal cats.2. Pad heat pulses produced flexion of the ipsilateral hind limb and increased ipsilateral flexor monosynaptic reflexes, due to post-synaptic excitation of flexor alpha motoneurones. These effects were accompanied by reduction of extensor monosynaptic reflexes and post-synaptic inhibition of extensor motoneurones.3. Ipsilateral (and contralateral) pad heat pulses consistently evoked negative dorsal root potentials (DRPs) as well as increased excitability of both cutaneous and group Ib muscle afferent terminals. The excitability of group Ia afferents was sometimes also increased during pad heat pulses, but to a lesser extent.4. Pad heat pulses produced negative DRPs in preparations in which positive DRP components could be demonstrated following electrical stimulation of both skin and muscle nerves.5. The motor and primary afferent effects of heat pulses always accompanied one another, beginning after the pad surface temperature had reached rather high levels (usually 48-55 degrees C).6. Negative DRPs increased excitability of cutaneous and group Ib afferents, and motoneurone activation produced by pad heat pulses was essentially unmodified when conduction in large myelinated afferents from the central plantar pad was blocked by cooling the posterior tibial nerve trunk.7. It is concluded that adequate noxious activation of cutaneous afferents of small diameter produces primary afferent depolarization in a variety of large diameter afferent fibres, as well as post-synaptic effects in alpha motoneurones.

  9. Persistence of PAD and presynaptic inhibition of muscle spindle afferents after peripheral nerve crush.

    Enríquez-Denton, M; Manjarrez, E; Rudomin, P


    Two to twelve weeks after crushing a muscle nerve, still before the damaged afferents reinnervate the muscle receptors, conditioning stimulation of group I fibers from flexor muscles depolarizes the damaged afferents [M. Enriquez, I. Jimenez, P. Rudomin, Changes in PAD patterns of group I muscle afferents after a peripheral nerve crush. Exp. Brain Res., 107 (1996), 405-420]. It is not known, however, if this primary afferent depolarization (PAD) is indeed related to presynaptic inhibition. We now show in the cat that 2-12 weeks after crushing the medial gastrocnemius nerve (MG), conditioning stimulation of group I fibers from flexors increases the excitability of the intraspinal terminals of both the intact lateral gastrocnemius plus soleus (LGS) and of the previously damaged MG fibers ending in the motor pool, because of PAD. The PAD is associated with the depression of the pre- and postsynaptic components of the extracellular field potentials (EFPs) evoked in the motor pool by stimulation of either the intact LGS or of the previously damaged MG nerves. These observations indicate, in contrast to what has been reported for crushed cutaneous afferents [K.W. Horch, J.W. Lisney, Changes in primary afferent depolarization of sensory neurones during peripheral nerve regeneration in the cat, J. Physiol., 313 (1981), 287-299], that shortly after damaging their peripheral axons, the synaptic efficacy of group I spindle afferents remains under central control. Presynaptic inhibitory mechanisms could be utilized to adjust the central actions of muscle afferents not fully recovered from peripheral lesions.

  10. CCK enhances response to gastric distension by acting on capsaicin-insensitive vagal afferents

    van de Wall, EHEM; Duffy, P; Ritter, RC


    Capsaicin treatment destroys vagal afferent C fibers and markedly attenuates reduction of food intake and induction of hindbrain Fos expression by CCK. However, both anatomical and electrophysiological data indicate that some gastric vagal afferents are not destroyed by capsaicin. Because CCK enhanc

  11. Modulation of gastrointestinal afferent sensitivity by a novel substituted benzamide (ecabapide).

    Jiang, W; Grundy, D


    The effects of ecabapide, a novel substituted benzamide compound (3-[2-(3,4-dimethoxyphenyl)ethylcarbamoylmethyl]amino-N-methylb enzamide) that has gastrointestinal prokinetic action, were examined on the discharge of extrinsic afferent nerves supplying the stomach and jejunum in anaesthetized rats. Ecabapide (60 and 180 microg kg(-1), i.v.) had no effect on the baseline discharge of vagal gastric distension-sensitive afferents or the stimulus-response profile to gastric distension. Ecabapide also had no effect on either spontaneous jejunal mesenteric afferent nerve discharge or responses to intestinal distension. Ecabapide (180 microg kg(-1)) significantly inhibited the maximum discharge of jejunal afferents induced by cholecystokinin (CCK8; 50 pmol, i.v.), whereas it failed to inhibit the excitatory action of 2-methyl-5-hydroxytryptamine (2Me-5-HT; 10 microg, i.v.), a selective 5-HT3 receptor agonist. A model of acute focal intestinal ischaemia was used to evaluate the actions of ecabapide on the discharge of activated jejunal afferents. Ischaemia produced a substantial increase in afferent discharge which was reproducible when the duration of ischaemia was limited to less than 10 min and repeated every 15 min. Ecabapide at doses of 60 and 180 microg kg(-1) significantly reduced ischaemia-induced increases in afferent discharge. In addition to its therapeutic efficacy as a gastrointestinal prokinetic agent, these findings show also that ecabapide may also have an inhibitory action on the discharge of intestinal afferents activated by ischaemia.

  12. MMP-2 Is Mainly Expressed in Arterioles and Contributes to Cerebral Vascular Remodeling Associated with TGF-β1 Signaling.

    Hua, Ye; Zhang, Weifeng; Xie, Zhenying; Xu, Nanfei; Lu, Yunnan


    There is increasing evidence to suggest that matrix metalloproteinases (MMPs) play a crucial role in vascular remodeling. It has been reported that hypoxia stimulated MMP-9 expression in brain endothelial cells and MMP-9 plays an important role in cerebral vascular remodeling. However, little is known about MMP-2 in the cerebral vessels remodeling. Herein, the aim of this study is to examine the class of vessel and cell type expressing MMP-2 in cerebral vessels and to investigate its potential role in vascular remodeling. In the present study, dual-immunofluorescence assay showed that MMP-2 was mainly expressed in arterioles. In addition, we found that MMP-2 expression in cerebral vessels was derived from endothelial cells, not astrocyte cells. Notably, in the normoxic central nervous system (CNS), there was no effect on vascular development, integrity, or endothelial proliferation when MMP-2 was knocked out, but lack of MMP-2 led to defective arteriolar remodeling and associated with transforming growth factor β1 (TGF-β1) signaling in CNS. Moreover, blocking TGF-β with SB431542, a specific TGF-β inhibitor, significantly reduced the messenger RNA (mRNA) and protein expression levels of MMP-2 in human umbilical vein endothelial cells (HUVECs). Our findings reveal that the level of MMP-2 is high in arteriolar endothelial cells and demonstrate a novel connection between MMP-2 and TGF-β1 signaling in cerebral vascular remodeling.

  13. Increased pressure-induced tone in rat parenchymal arterioles vs. middle cerebral arteries: role of ion channels and calcium sensitivity.

    Cipolla, Marilyn J; Sweet, Julie; Chan, Siu-Lung; Tavares, Matthew J; Gokina, Natalia; Brayden, Joseph E


    Brain parenchymal arterioles (PAs) are high-resistance vessels that branch off pial arteries and perfuse the brain parenchyma. PAs are the target of cerebral small vessel disease and have been shown to have greater pressure-induced tone at lower pressures than pial arteries. We investigated mechanisms by which brain PAs have increased myogenic tone compared with middle cerebral arteries (MCAs), focusing on differences in vascular smooth muscle (VSM) calcium and ion channel function. The amount of myogenic tone and VSM calcium was measured using Fura 2 in isolated and pressurized PAs and MCAs. Increases in intraluminal pressure caused larger increases in tone and cytosolic calcium in PAs compared with MCAs. At 50 mmHg, myogenic tone was 37 ± 5% for PAs vs. 6.5 ± 4% for MCAs (P channel (VDCC) inhibitor nifedipine than MCAs (EC50 for PAs was 3.5 ± 0.4 vs. 82.1 ± 2.1 nmol/l for MCAs;P channel inhibitor iberiotoxin, whereas MCAs constricted ∼15%. Thus increased myogenic tone in PAs appears related to differences in ion channel activity that promotes VSM membrane depolarization but not to a direct sensitization of the contractile apparatus to calcium.

  14. Simulation of platelet, thrombus and erythrocyte hydrodynamic interactions in a 3D arteriole with in vivo comparison.

    Weiwei Wang

    Full Text Available Cylindrical blood vessels, ellipsoid platelets and biconcave-shaped deformable erythrocytes (RBCs are important participants in hemostasis and thrombosis. However, due to the challenge of combining these components in simulation tools, few simulation studies have included all of them in realistic three-dimensional models. In the present study, we apply a recently developed simulation model to incorporate these components and analyze the flow in a thrombotic tubular arteriole, particularly the detailed hydrodynamic interactions between the thrombus shape, RBCs and platelets. It was found that at certain azimuth positions, the velocity drops in the proximity of both the upstream and downstream edge of the thrombus, which is accompanied by a rapid velocity increase in the narrowed region. The RBCs alter the flow profiles significantly from the typical low Reynolds (Re number flow, and also enhance the deposition of free flowing platelets onto the thrombus. By evaluating the platelet-thrombus interaction and platelet-RBC interaction together, several mechanisms of platelet deposition augmentation are identified. With in vivo data comparison, our model illustrates the potential of future thrombosis studies that incorporate detailed receptor-ligand adhesion modules.

  15. Symmetry recovery of cell-free layer after bifurcations of small arterioles in reduced flow conditions: effect of RBC aggregation.

    Ng, Yan Cheng; Namgung, Bumseok; Tien, Sim Leng; Leo, Hwa Liang; Kim, Sangho


    Heterogeneous distribution of red blood cells (RBCs) in downstream vessels of arteriolar bifurcations can be promoted by an asymmetric formation of cell-free layer (CFL) in upstream vessels. Consequently, the CFL widths in subsequent downstream vessels become an important determinant for tissue oxygenation (O2) and vascular tone change by varying nitric oxide (NO) availability. To extend our previous understanding on the formation of CFL in arteriolar bifurcations, this study investigated the formation of CFL widths from 2 to 6 vessel-diameter (2D-6D) downstream of arteriolar bifurcations in the rat cremaster muscle (D = 51.5 ± 1.3 μm). As the CFL widths are highly influenced by RBC aggregation, the degree of aggregation was adjusted to simulate levels seen during physiological and pathological states. Our in vivo experimental results showed that the asymmetry of CFL widths persists along downstream vessels up to 6D from the bifurcating point. Moreover, elevated levels of RBC aggregation appeared to retard the recovery of CFL width symmetry. The required length of complete symmetry recovery was estimated to be greater than 11D under reduced flow conditions, which is relatively longer than interbifurcation distances of arterioles for vessel diameter of ∼50 μm. In addition, our numerical prediction showed that the persistent asymmetry of CFL widths could potentially result in a heterogeneous vasoactivity over the entire arteriolar network in such abnormal flow conditions.

  16. Relationship between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles evaluated noninvasively by scanning laser Doppler flowmetry.

    Rizzoni, Damiano; Porteri, Enzo; Duse, Sarah; De Ciuceis, Carolina; Rosei, Claudia Agabiti; La Boria, Elisa; Semeraro, Francesco; Costagliola, Ciro; Sebastiani, Adolfo; Danzi, Paola; Tiberio, Guido A M; Giulini, Stefano M; Docchio, Franco; Sansoni, Giovanna; Sarkar, Annamaria; Rosei, Enrico Agabiti


    Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media-to-lumen ratio, are frequently present in hypertensive and/or diabetic patients, and may represent the earliest alteration observed. Furthermore, media-to-lumen ratio of small arteries evaluated by micromyography has a strong prognostic significance; however, its extensive evaluation is limited by the invasivity of the assessment, since a biopsy of subcutaneous fat is needed. Noninvasive measurement of wall-to-lumen of retinal arterioles using scanning laser Doppler flowmetry (SLDF) has recently been introduced. However, this new technique has not yet been compared to micromyographic measurement, generally considered the gold standard approach. We investigated 40 individuals and patients, 24 of them were hypertensive patients and 16 normotensive individuals. All patients underwent a biopsy of subcutaneous fat during an elective surgical intervention. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and media-to-lumen ratio was measured. In addition, an evaluation of wall-to-lumen ratio of retinal arterioles by SLDF was performed (Heidelberg Retina Flowmeter, Heidelberg Engineering). A close correlation was observed between media-to-lumen ratio of subcutaneous small arteries and wall-to-lumen ratio of retinal arterioles (r = 0.76, P < 0.001; P < 0.001, r(2) = 0.57). A noninvasive and easily repeatable procedure (intraobserver and interobserver variation coefficient <13%) such as an evaluation of the arterioles in the fundus oculi by SLDF may provide similar information regarding microvascular morphology compared with an invasive, accurate and prognostically relevant micromyographic measurement of media-to-lumen ratio of subcutaneous small arteries.

  17. Total Reconstruction of the Afferent Loop for Treatment of Radiation-Induced Afferent Loop Obstruction with Segmental Involvement after Pancreaticoduodenectomy with Roux-en-Y Reconstruction

    Konstantinos Blouhos


    Full Text Available As the literature on afferent loop obstruction (ALO after pancreaticoduodenectomy (PD is very limited, standardized rules for its management do not exist. Herein, we report the case of a 65-year-old male patient with chronic ALO who had undergone PD with single Roux-en-Y limb reconstruction and adjuvant chemoradiation therapy for pancreatic head adenocarcinoma 2 years earlier. The patient was brought to the operating room with the diagnosis of radiation enteritis of the afferent loop with segmental involvement and concurrent hepaticojejunostomy (HJ and pancreaticojejunostomy (PJ stricture. Complete mobilization of the afferent loop, removal of the affected segment and reconstruction were performed. Reconstruction of the afferent loop was a one-way option for the surgeons because the Roux-en-Y reconstruction limited endoscopic access to the afferent loop, and the segmental radiation injury of the afferent loop ruled out bypass surgery. However, mobilization of the affected segment through a field of dense adhesions and revision of the HJ and PJ were technically demanding.

  18. Comparison between the effect of static contraction and tendon stretch on the discharge of group III and IV muscle afferents

    Shawn G. Hayes; Angela E. Kindig; Marc P. Kaufman


    ... afferents as does static contraction. We have tested the veracity of this assumption in decerebrated cats by comparing the responses of group III and IV muscle afferents to tendon stretch with those to static contraction...

  19. Presynaptic inhibition of muscle spindle and tendon organ afferents in the mammalian spinal cord.

    Rudomin, P


    More than 30 years ago, Frank and Fuortes proposed that the synaptic effectiveness of muscle spindle afferents associated with spinal motoneurones could be diminished by the activation of nerves from flexor muscles. Since that time, research has focused on disclosing the mode of operation and the spinal pathways involved in this presynaptic inhibitory control. Initially, it was assumed that the same last-order interneurones mediated presynaptic inhibition of both muscle spindle and tendon organ afferent fibres. More recent evidence indicates that the synaptic effectiveness of these two groups of afferents is controlled by separate sets of GABAergic interneurones synapsing directly with the intraspinal terminals of the afferent fibres. This unique arrangement allows for selective control of the information on muscle length or muscle tension, despite the convergence of muscle spindle and tendon organ afferents on second-order interneurones.

  20. Renal haemodynamics and plasma renin in patients with essential hypertension.

    Pedersen, E B; Kornerup, H J


    1. Blood pressure, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in twenty-three patients with essential hypertension and in twenty-one control subjects. Plasma renin concentration was measured in all the hypertensive patients and in fifteen control subjects. 2. GFR and RPF were similar in the hypertensive group and in the control group, whereas the renal vascular resistance was significantly higher in the hypertensive patients. GFR and RPF decreased with increasing blood pressure in both groups. Increasing age induced a further reduction in GFR and RPF in the control subjects but not in the hypertensive patients. 3. Plasma renin concentration in the hypertensive group did not differ from that in the control subjects. The concentration was not correlated to age in either the hypertensive or normal group. 4. Plasma renin index was positively correlated to GFR and RPF and inversely correlated to filtration fraction and renal vascular resistance. 5. It is concluded that GFR and RPF depend on blood pressure in both hypertensive patients and normotensive control subjects. In contrast to the control group, the age effect was negligible in the hypertensive group. It is suggested that renin release depends on changes in renal vascular resistance in the arterioles at the glomerulus and the results support the baroreceptor theory of renin release.

  1. The spectrum of renal involvement in patients with inflammatory myopathies.

    Couvrat-Desvergnes, Grégoire; Masseau, Agathe; Benveniste, Olivier; Bruel, Alexandra; Hervier, Baptiste; Mussini, Jean-Marie; Buob, David; Hachulla, Eric; Rémy, Philippe; Azar, Raymond; Mac Namara, Evelyne; MacGregor, Brigitte; Daniel, Laurent; Lacraz, Adeline; De Broucker, Thomas; Rouvier, Philippe; Carli, Philippe; Laville, Maurice; Dantan, Etienne; Hamidou, Mohamed; Moreau, Anne; Fakhouri, Fadi


    Data regarding the incidence and outcome of renal involvement in patients with inflammatory myopathies (IM) remain scarce. We assessed the incidence and causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in 150 patients with dermatomyositis, polymyositis, and antisynthetase syndrome followed in 3 French referral centers. Renal involvement occurred in 35 (23.3%) patients: AKI in 16 (10.7%), and CKD in 31 (20.7%) patients. The main cause of AKI was drug or myoglobinuria-induced acute tubular necrosis. Male sex, cardiovascular risk factors, cardiac involvement, and initial proteinuria >0.3 g/d were associated with the occurrence of AKI. The outcome of patients with AKI was poor: 13 (81%) progressed to CKD and 2 (12.5%) reached end-stage renal disease. In multivariate survival analysis, age at IM onset, male sex, a history of cardiovascular events, and a previous episode of AKI were associated with the risk of CKD. We also identified 14 IM patients who underwent a kidney biopsy in 10 nephrology centers. Renal pathology disclosed a wide range of renal disorders, mainly immune-complex glomerulonephritis. We identified in 5 patients a peculiar pattern of severe acute renal vascular damage consisting mainly of edematous thickening of the intima of arterioles. We found that AKI and CKD are frequent in patients with IM. Prevention of AKI is crucial in these patients, as AKI is a major contributor to their relatively high risk of CKD. A peculiar pattern of acute vascular damage is part of the spectrum of renal diseases associated with IM.

  2. Doença renal ateroembólica: uma causa de insuficiência renal aguda pouco explorada Atheroembolic renal disease: a cause of acute renal failure not much explored

    Claus Dieter Dummer


    Full Text Available O ateroembolismo é uma doença multisistêmica que afeta vários órgãos, entre os quais o rim, através da liberação de êmbolos de colesterol de uma placa aterosclerótica erosada, ocasionando obstrução vascular em diversos tecidos. A doença renal ateroembólica (DRAE, histologicamente representada por cristais de colesterol nas arteríolas do rim acompanhados de um infiltrado inflamatório perivascular, é causa de insuficiência renal aguda muitas vezes grave e prolongada, que ocorre semanas ou mesmo meses após o episódio embólico. A DRAE apresesenta prognóstico ruim com elevada mortalidade. Apresentamos neste relato o caso de um paciente com DRAE que se manifestou clinicamente dois meses após a realização de um cateterismo cardíaco seguido de uma angioplastia coronária. A prevalência, manifestações clínicas, histologia renal, tratamento e o prognóstico da DRAE são discutidos.Atheroembolism is a multisytemic disease which affects many organs, including the kidneys, by the release of cholesterol emboli to tissues from an erosed atherosclerotic plaque, causing vascular obstruction in many tissues. The atheroembolic renal disease (AERD is histologically represented by cholesterol crystals in renal arterioles with an inflammatory infiltrate around the vessels, and causes acute renal failure that may be severe and prolonged, weeks or even months after the embolic episode. The AERD carries a bad prognosis, with a high mortality. We herein report a case of a patient presenting AERD which was manifested two months after he was submitted to a cardiac catheterism and coronary angioplasty. The prevalence, clinical findings, renal histology, treatment and prognosis of AERD are discussed.

  3. Hydrogen sulfide determines HNO-induced stimulation of trigeminal afferents.

    Wild, Vanessa; Messlinger, Karl; Fischer, Michael J M


    Endogenous NO and hydrogen sulfide form HNO, which causes CGRP release via TRPA1 channel activation in sensory nerves. In the present study, stimulation of intact trigeminal afferent neuron preparations with NO donors, Na2S or both was analyzed by measuring CGRP release as an index of mass activation. Combined stimulation was able to activate all parts of the trigeminal system and acted synergistic compared to stimulation with both substances alone. To investigate the contribution of both substances, we varied their ratio and tracked intracellular calcium in isolated neurons. Our results demonstrate that hydrogen sulfide is the rate-limiting factor for HNO formation. CGRP has a key role in migraine pathophysiology and HNO formation at all sites of the trigeminal system should be considered for this novel means of activation.

  4. Selective cortical and segmental control of primary afferent depolarization of single muscle afferents in the cat spinal cord.

    Eguibar, J R; Quevedo, J; Rudomin, P


    This study was primarily aimed at investigating the selectivity of the cortico-spinal actions exerted on the pathways mediating primary afferent depolarization (PAD) of muscle spindle and tendon organ afferents ending within the intermediate nucleus at the L6-L7 segmental level. To this end we analyzed, in the anesthetized cat, the effects produced by electrical stimulation of sensory nerves and of the cerebral cortex on (a) the intraspinal threshold of pairs of single group I afferent fibers belonging to the same or to different hindlimb muscles and (b) the intraspinal threshold of two collaterals of the same muscle afferent fiber. Afferent fibers were classified in three categories, according to the effects produced by stimulation of segmental nerves and of the cerebral cortex. Twenty-five of 40 fibers (62.5%) were depolarized by stimulation of group I posterior biceps and semitendinosus (PBSt) or tibialis (Tib) fibers, but not by stimulation of the cerebral cortex or of cutaneous and joint nerves, which instead inhibited the PBSt- or Tib-induced PAD (type A PAD pattern, usually seen in Ia fibers). The remaining 15 fibers (37.5%) were all depolarized by stimulation of the PBSt or Tib nerves and the cerebral cortex. Stimulation of cutaneous and joint nerves produced PAD in 10 of those 15 fibers (type B PAD pattern) and inhibited the PBSt- or Tib-induced PAD in the 5 remaining fibers (type C PAD pattern). Fibers with a type B or C PAD pattern are likely to be Ib. Not all sites in the cerebral cortex inhibited with the same effectiveness the segmentally induced PAD of group I fibers with a type A PAD pattern. With the weakest stimulation of the cortical surface, the most effective sites that inhibited the PAD of individual fibers were surrounded by less effective sites, scattered all along the motor cortex (area 4gamma and 6) and sensory cortex (areas 3, 2 and 1), far beyond the area of projection of group I fibers from the hindlimb. With higher strengths of

  5. Intermedin in the paraventricular nucleus attenuates cardiac sympathetic afferent reflex in chronic heart failure rats.

    Xian-Bing Gan

    Full Text Available BACKGROUND AND AIM: Intermedin (IMD is a member of calcitonin/calcitonin gene-related peptide (CGRP family together with adrenomedullin (AM and amylin. It has a wide distribution in the central nervous system (CNS especially in hypothalamic paraventricular nucleus (PVN. Cardiac sympathetic afferent reflex (CSAR is enhanced in chronic heart failure (CHF rats. The aim of this study is to determine the effect of IMD in the PVN on CSAR and its related mechanisms in CHF rats. METHODOLOGY/PRINCIPAL FINDINGS: Rats were subjected to left descending coronary artery ligation to induce CHF or sham-operation (Sham. Renal sympathetic nerve activity (RSNA, mean arterial pressure (MAP and heart rate (HR were recorded. CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin. Acute experiments were carried out 8 weeks after coronary ligation or sham surgery under anesthesia. IMD and angiotensin II (Ang II levels in the PVN were up-regulated in CHF rats. Bilateral PVN microinjection of IMD caused greater decreases in CSAR and the baseline RSNA and MAP in CHF rats than those in Sham rats. The decrease of CSAR caused by IMD was prevented by pretreatment with AM receptor antagonist AM22-52, but not CGRP receptor antagonist CGRP8-37. Ang II in the PVN significantly enhanced CSAR and superoxide anions level, which was inhibited by PVN pretreatment with IMD or tempol (a superoxide anions scavenger in Sham and CHF rats. CONCLUSION: IMD in the PVN inhibits CSAR via AM receptor, and attenuates the effects of Ang II on CSAR and superoxide anions level in CHF rats. PVN superoxide anions involve in the effect of IMD on attenuating Ang II-induced CSAR response.

  6. Renal Cysts

    ... as “simple” cysts, meaning they have a thin wall and contain water-like fluid. Renal cysts are fairly common in ... simple kidney cysts, meaning they have a thin wall and only water-like fluid inside. They are fairly common in ...

  7. Renal failure


    970363 Effect on serum PTH and 1, 25(OH)2 D3levels of rapid correction of metabolic acidosis in CRFpatients with secondary hyperparathyroidism. YUANQunsheng(袁群生), et al. Renal Div, PUMC Hosp,Beijing, 100730. Chin J Nephrol 1996; 12(6): 328-331.

  8. Drug-induced renal injury

    Drugs can cause acute renal failure by causing pre-renal, intrinsic or post-renal toxicity. Pre-renal ... incidence of drug dose adjustment in renal impairment in the SAMJ. ... Fever, haemolytic anaemia, thrombocytopenia, renal impairment and.

  9. The Effects of Diuretics on Intracellular Ca2+ Dynamics of Arteriole Smooth Muscles as Revealed by Laser Confocal Microscopy

    Tamagawa, Yasunori; Saino, Tomoyuki; Matsuura, Makoto; Satoh, Yoh-ichi


    The regulation of cytosolic Ca2+ homeostasis is essential for cells, including vascular smooth muscle cells. Arterial tone, which underlies the maintenance of peripheral resistance in the circulation, is a major contributor to the control of blood pressure. Diuretics may regulate intracellular Ca2+ concentration ([Ca2+]i) and have an effect on vascular tone. In order to investigate the influence of diuretics on peripheral resistance in circulation, we investigated the alteration of [Ca2+]i in testicular arterioles with respect to several categories of diuretics using real-time confocal laser scanning microscopy. In this study, hydrochlorothiazide (100 µM) and furosemide (100 µM) had no effect on the [Ca2+]i dynamics. However, when spironolactone (300 µM) was applied, the [Ca2+]i of smooth muscles increased. The response was considerably inhibited under either extracellular Ca2+-free conditions, the presence of Gd3+, or with a treatment of diltiazem. After the thapsigargin-induced depletion of internal Ca2+ store, the spironolactone-induced [Ca2+]i dynamics was slightly inhibited. Therefore, the spironolactone-induced dynamics of [Ca2+]i can be caused by either a Ca2+ influx from extracellular fluid or Ca2+ mobilization from internal Ca2+ store, with the former being dominant. As tetraethylammonium, an inhibitor of the K+ channel, slightly inhibited the spironolactone-induced [Ca2+]i dynamics, the K+ channel might play a minor role in those dynamics. Tetrodotoxin, a neurotoxic Na+ channel blocker, had no effect, therefore the spironolactone-induced dynamics is a direct effect to smooth muscles, rather than an indirect effect via vessel nerves. PMID:19759873

  10. Local control of information flow in segmental and ascending collaterals of single afferents.

    Lomelí, J; Quevedo, J; Linares, P; Rudomin, P


    In the vertebrate spinal cord, the activation of GABA(gamma-amino-butyric acid)-releasing interneurons that synapse with intraspinal terminals of sensory fibres leading into the central nervous system (afferent fibres) produces primary afferent depolarization and presynaptic inhibition. It is not known to what extent these presynaptic mechanisms allow a selective control of information transmitted through specific sets of intraspinal branches of individual afferents. Here we study the local nature of the presynaptic control by measuring primary afferent depolarization simultaneously in two intraspinal collaterals of the same muscle spindle afferent. One of these collaterals ends at the L6-L7 segmental level in the intermediate nucleus, and the other ascends to segment L3 within Clarke's column, the site of origin of spinocerebellar neurons. Our results indicate that there are central mechanisms that are able to affect independently the synaptic effectiveness of segmental and ascending collaterals of individual muscle spindle afferents. Focal control of presynaptic inhibition thus allows the intraspinal branches of afferent fibres to function as a dynamic assembly that can be fractionated to convey information to selected neuronal targets. This may be a mechanism by which different spinal postsynaptic targets that are coupled by sensory input from a common source could be uncoupled.

  11. Distribution of presumptive chemosensory afferents with FMRFamide- or substance P-like immunoreactivity in decapod crustaceans.

    Schmidt, M


    In five species of decapod crustaceans--Cherax destructor (crayfish), Carcinus maenas (crab), Homarus americanus (clawed lobster), Eriocheir sinensis (crab), Macrobrachium rosenbergii (shrimp)--immunocytochemical stainings revealed the presence of sensory afferents with FMRFamide-like immunoreactivity in the central nervous system. These afferents were extremely thin, very numerous, and innervated all sensory neuropils except the optic and olfactory lobes. In their target neuropils they gave rise to condensed net- or ball-like terminal structures. Only in Homarus americanus but not in any other studied species immunocytochemistry revealed a separate, non-overlapping class of sensory afferents with substance P-like immunoreactivity. Also the afferents with substance P-like immunoreactivity were very thin and numerous, innervated all sensory neuropils except optic and olfactory lobes, and gave rise to condensed terminal structures. From their morphological characteristics it can be concluded that likely both classes of afferents are chemosensory. The substance P-like immunoreactivity suggests a link with the nociceptor afferents of vertebrates, with which both classes of afferents share several other morphological features.

  12. Vagal afferents sense meal-associated gastrointestinal and pancreatic hormones: mechanism and physiological role.

    Iwasaki, Yusaku; Yada, Toshihiko


    Some gastrointestinal and pancreatic hormones are potently secreted by meal intake and reduce food intake, therefore these hormones play a role in the meal-evoked satiety peptides. Previous reports have demonstrated that peripheral administration of these gastrointestinal or pancreatic hormones decrease feeding and the anorectic effects are abolished by lesions of vagal afferent nerves using surgical or chemical protocols, indicative of the involvement of the vagal afferents. Vagal afferent nerves link between several peripheral organs and the nucleus tractus solitarius of the brainstem. The present review focuses on cholecystokinin, peptide YY(3-36), pancreatic polypeptide, and nesfatin-1 released from endocrine cells of the gut and pancreas. These hormonal peptides directly act on and increase cytosolic Ca(2+) in vagal afferent nodose ganglion neurons and finally suppress food intake via vagal afferents. Therefore, peripheral terminals of vagal afferents could sense gastrointestinal and pancreatic hormones and regulate food intake. Here, we review how the vagal afferent neurons sense a variety of gastrointestinal and pancreatic hormones and discuss its physiological significance in regulation of feeding. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Lipolysis sensation by white fat afferent nerves triggers brown fat thermogenesis.

    Garretson, John T; Szymanski, Laura A; Schwartz, Gary J; Xue, Bingzhong; Ryu, Vitaly; Bartness, Timothy J


    Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose tissue (BAT) thermogenesis. WAT is also innervated by sensory nerve fibers that network to metabolic brain areas; moreover, activation of these afferents is reported to increase sympathetic nervous system outflow. However, the endogenous stimuli sufficient to drive WAT afferents during metabolic challenges as well as their functional relation to BAT thermogenesis remain unknown. We tested if local WAT lipolysis directly activates WAT afferent nerves, and then assessed whether this WAT sensory signal affected BAT thermogenesis in Siberian hamsters (Phodopus sungorus). 2-deoxyglucose, a sympathetic nervous system stimulant, caused β-adrenergic receptor dependent increases in inguinal WAT (IWAT) afferent neurophysiological activity. In addition, direct IWAT injections of the β3-AR agonist CL316,243 dose-dependently increased: 1) phosphorylation of IWAT hormone sensitive lipase, an indicator of SNS-stimulated lipolysis, 2) expression of the neuronal activation marker c-Fos in dorsal root ganglion neurons receiving sensory input from IWAT, and 3) IWAT afferent neurophysiological activity, an increase blocked by antilipolytic agent 3,5-dimethylpyrazole. Finally, we demonstrated that IWAT afferent activation by lipolysis triggers interscapular BAT thermogenesis through a neural link between these two tissues. These data suggest IWAT lipolysis activates local IWAT afferents triggering a neural circuit from WAT to BAT that acutely induces BAT thermogenesis.

  14. Renal failure (chronic)

    Clase, Catherine


    Chronic renal failure is characterised by a gradual and sustained decline in renal clearance or glomerular filtration rate (GFR). Continued progression of renal failure will lead to renal function too low to sustain healthy life. In developed countries, such people will be offered renal replacement therapy in the form of dialysis or renal transplantation. Requirement for dialysis or transplantation is termed end-stage renal disease (ESRD).Diabetes, glomerulonephritis, hypertension, pyelone...

  15. Selective cortical control of information flow through different intraspinal collaterals of the same muscle afferent fiber.

    Eguibar, J R; Quevedo, J; Jiménez, I; Rudomin, P


    We have analyzed in the anesthetized cat the effects of electrical stimulation of the cerebral cortex on the intraspinal threshold of two collaterals belonging to the same muscle spindle or tendon organ afferent fiber. The results obtained provide, for the first time, direct evidence showing that the motor cortex is able to modify, in a highly selective manner, the synaptic effectiveness of individual collaterals of the same primary afferent fiber. This presynaptic control could function as a mechanism that allows funneling of information to specific groups of spinal neurons in the presence of extensive intraspinal branching of the afferent fibers.

  16. Opioid Actions in Primary-Afferent Fibers—Involvement in Analgesia and Anesthesia

    Tsugumi Fujita


    Full Text Available Opioids inhibit glutamatergic excitatory transmission from the periphery by activating G-protein coupled opioid receptors in the central terminals of primary-afferent neurons in the spinal substantia gelatinosa, resulting in antinociception. Opioid receptor activation in the peripheral terminals of primary-afferent neurons inhibits the production of action potentials in response to nociceptive stimuli given to the periphery, leading to antinociception. Opioids also exhibit a local anesthetic effect without opioid receptor activation in peripheral nerve fibers. This review article will focus on analgesia and anesthesia produced by the actions of opioids on primary-afferent fibers.

  17. Thin-fiber mechanoreceptors reflexly increase renal sympathetic nerve activity during static contraction.

    Kim, Jong Kyung; Hayes, Shawn G; Kindig, Angela E; Kaufman, Marc P


    The renal vasoconstriction induced by the sympathetic outflow during exercise serves to direct blood flow from the kidney toward the exercising muscles. The renal circulation seems to be particularly important in this regard, because it receives a substantial part of the cardiac output, which in resting humans has been estimated to be 20%. The role of group III mechanoreceptors in causing the reflex renal sympathetic response to static contraction remains an open question. To shed some light on this question, we recorded the renal sympathetic nerve responses to static contraction before and after injection of gadolinium into the arterial supply of the statically contracting triceps surae muscles of decerebrate unanesthetized and chloralose-anesthetized cats. Gadolinium has been shown to be a selective blocker of mechanogated channels in thin-fiber muscle afferents, which comprise the afferent arm of the exercise pressor reflex arc. In decerebrate (n = 15) and chloralose-anesthetized (n = 12) cats, we found that gadolinium (10 mM; 1 ml) significantly attenuated the renal sympathetic nerve and pressor responses to static contraction (60 s) after a latent period of 60 min; both responses recovered after a latent period of 120 min. We conclude that thin-fiber mechanoreceptors supplying contracting muscle are involved in some of the renal vasoconstriction evoked by the exercise pressor reflex.

  18. Renale Osteopathie

    Horn S


    Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Thera...

  19. Renale Knochenerkrankungen

    Mayer G


    Full Text Available Störungen des Mineral- und Knochenstoffwechsels sind bei fast allen Patienten mit chronischen Nierenerkrankungen anzutreffen. Pathogenetisch spielt eine Neigung zur Phosphatretention bei einer Reduktion der glomerulären Filtrationsrate die zentrale Rolle. Neben typischen, aber sehr variablen Veränderungen der Knochenstruktur (renale Osteopathie besteht auch eine sehr enge Assoziation zwischen diesen Störungen und dem massiv erhöhten kardiovaskulären Risiko der Patienten.

  20. Gemcitabine-induced hemolytic uremic syndrome mimicking scleroderma renal crisis presenting with Raynaud's phenomenon, positive antinuclear antibodies and hypertensive emergency.

    Yamada, Yuichiro; Suzuki, Keisuke; Nobata, Hironobu; Kawai, Hirohisa; Wakamatsu, Ryo; Miura, Naoto; Banno, Shogo; Imai, Hirokazu


    A 58-year-old woman who received gemcitabine for advanced gallbladder cancer developed an impaired renal function, thrombocytopenia, Raynaud's phenomenon, digital ischemic changes, a high antinuclear antibody titer and hypertensive emergency that mimicked a scleroderma renal crisis. A kidney biopsy specimen demonstrated onion-skin lesions in the arterioles and small arteries along with ischemic changes in the glomeruli, compatible with a diagnosis of hypertensive emergency (malignant hypertension). The intravenous administration of a calcium channel blocker, the oral administration of an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker and the transfusion of fresh frozen plasma were effective for treating the thrombocytopenia and progressive kidney dysfunction. Gemcitabine induces hemolytic uremic syndrome with accelerated hypertension and Raynaud's phenomenon, mimicking scleroderma renal crisis.

  1. Obesity and renal hemodynamics

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.


    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile

  2. Obesity and renal hemodynamics

    Bosma, R. J.; Krikken, J. A.; van der Heide, J. J. Homan; de Jong, P. E.; Navis, G. J.


    Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile inde

  3. Differential effect of T-type voltage-gated calcium channel disruption on renal plasma flow and glomerular filtration rate in vivo

    Thuesen, Anne D; Andersen, Henrik; Cardel, Majken


    of two T-type Cav knock-out mice strains. Continuous recordings of blood pressure and heart rate, and para-aminohippurate clearance (renal plasma flow) and inulin clearance (GFR) were performed in conscious, chronically catheterized, wild type and Cav 3.1-/- and Cav 3.2-/- mice. Contractility of afferent...

  4. Sympathetic nervous system and chronic renal failure.

    Boero, R; Pignataro, A; Ferro, M; Quarello, F


    The aim of this work was to review evidence on the role of the sympathetic nervous system (SNS) in chronic renal failure (CRF). Three main points are discussed: 1) SNS and pathogenesis of arterial hypertension; 2) SNS and cardiovascular risk; 3) implication of SNS in arterial hypotension during hemodialysis. Several lines of evidence indicate the presence of a sympathetic hyperactivity in CRF, and its relationship with arterial hypertension. It is suggested that diseased kidneys send afferent nervous signals to central integrative sympathetic nuclei, thus contributing to the development and maintenance of arterial hypertension. The elimination of these impulses with nephrectomy could explain the concomitant reduction of blood pressure. Several experiments confirmed this hypothesis. Regarding SNS and cardiovascular risk, some data suggest that reduced heart rate variability identifies an increased risk for both all causes and sudden death, independently from other recognized risk factors. Symptomatic hypotension is a common problem during hemodialysis treatment, occurring in approximately 20-30% of all hemodialysis sessions and is accompanied by acute withdrawal of sympathetic activity, vasodilation and relative bradicardia. This reflex is thought to be evoked by vigorous contraction of a progressively empty left ventricle, activating cardiac mechanoceptors. This inhibits cardiovascular centers through vagal afferents, and overrides the stimulation by baroreceptor deactivation. Alternative explanations include cerebral ischemia and increased production of nitric oxide, which inhibit central sympathetic activity. It is hoped that therapies aimed at modulating sympathetic nerve activity in patients with CRF will ameliorate their prognosis and quality of life.

  5. Changes in PAD patterns of group I muscle afferents after a peripheral nerve crush.

    Enríquez, M; Jiménez, I; Rudomin, P


    In the anesthetized cat we have analyzed the changes in primary afferent depolarization (PAD) evoked in single muscle spindle and tendon organ afferents at different times after their axons were crushed in the periphery and allowed to regenerate. Medial gastrocnemius (MG) afferents were depolarized by stimulation of group I fibers in the posterior biceps and semitendinosus nerve (PBSt), as soon as 2 weeks after crushing their axons in the periphery, in some cases before they could be activated by physiological stimulation of muscle receptors. Two to twelve weeks after crushing the MG nerve, stimulation of the PBSt produced PAD in all MG fibers reconnected with presumed muscle spindles and tendon organs. The mean amplitude of the PAD elicited in afferent fibers reconnected with muscle spindles was increased relative to values obtained from Ia fibers in intact (control) preparations, but remained essentially the same in fibers reconnected with tendon organs. Quite unexpectedly, we found that, between 2 and 12 weeks after crushing the MG nerve, stimulation of the bulbar reticular formation (RF) produced PAD in most afferent fibers reconnected with muscle spindle afferents. The mean amplitude of the PAD elicited in these fibers was significantly increased relative to the PAD elicited in muscle spindle afferents from intact preparations (from 0.08 +/- 0.4 to 0.47 +/- 0.34 mV). A substantial recovery was observed between 6 months and 2.5 years after the peripheral nerve injury. Stimulation of the sural (SU) nerve produced practically no PAD in muscle spindles from intact preparations, and this remained so in those afferents reconnected with muscle spindles impaled 2-12 weeks after the nerve crush. The mean amplitude of the PAD produced in afferent fibers reconnected with tendon organs by stimulation of the PBSt nerve and of the bulbar RF remained essentially the same as the PAD elicited in intact afferents. However, SU nerve stimulation produced a larger PAD in afferents

  6. Lipopolysaccharide-induced hyperalgesia of intracranial capsaicin sensitive afferents in conscious rats

    Kemper, RHA; Spoelstra, MB; Meijler, WJ; Ter Horst, GJ


    Migraineous and non-migraineous headache is reported to be at highest intensity after an infection. This study investigated whether activation of the immune system can induce hyperalgesia in intracranial capsaicin sensitive afferents. The effects of intraperitoneal injected lipopolysaccharides (LPS)

  7. Multiple clusters of release sites formed by individual thalamic afferents onto cortical interneurons ensure reliable transmission.

    Bagnall, Martha W; Hull, Court; Bushong, Eric A; Ellisman, Mark H; Scanziani, Massimo


    Thalamic afferents supply the cortex with sensory information by contacting both excitatory neurons and inhibitory interneurons. Interestingly, thalamic contacts with interneurons constitute such a powerful synapse that even one afferent can fire interneurons, thereby driving feedforward inhibition. However, the spatial representation of this potent synapse on interneuron dendrites is poorly understood. Using Ca imaging and electron microscopy we show that an individual thalamic afferent forms multiple contacts with the interneuronal proximal dendritic arbor, preferentially near branch points. More contacts are correlated with larger amplitude synaptic responses. Each contact, consisting of a single bouton, can release up to seven vesicles simultaneously, resulting in graded and reliable Ca transients. Computational modeling indicates that the release of multiple vesicles at each contact minimally reduces the efficiency of the thalamic afferent in exciting the interneuron. This strategy preserves the spatial representation of thalamocortical inputs across the dendritic arbor over a wide range of release conditions.


    高云芳; 樊小力


    Objective In drugs for invigorating blood circulation, to find a herb that can stimulate afferent discharge of muscle spindle. Methods A single muscle spindle was isolated from sartorial muscle of toad. Using air-gap technique, afferent discharge of the muscle spindle was recorded. Effects of Angelica Sinensis, Salvia Miltiorrhiza, and Safflower on afferent discharge of the muscle spindle were observed. Results Angelica Sinensis could distinctly increase afferent discharge frequency of the muscle spindle, and this increase was dose-dependent. But Salvia Miltiorrhiza and Safflower had no this excitatory effect. Conclusion It is known that Angelica Sinensis can invigorate blood circulation, and we have found its excitatory effect on muscle spindle which makes it possible to serve people with muscle atrophy if more evidences from clinical experiments are available.

  9. Vagal afferent neurons in high fat diet-induced obesity; intestinal microflora, gut inflammation and cholecystokinin.

    de Lartigue, Guillaume; de La Serre, Claire Barbier; Raybould, Helen E


    The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the CNS and influences both GI function and feeding behavior. Vagal afferent neurons (VAN) express receptors for many of the regulatory peptides and molecules released from the intestinal wall, pancreas, and adipocytes that influence GI function, glucose homeostasis, and regulate food intake and body weight. As such, they play a critical role in both physiology and pathophysiology, such as obesity, where there is evidence that vagal afferent function is altered. This review will summarize recent findings on changes in vagal afferent function in response to ingestion of high fat diets and explore the hypothesis that changes in gut microbiota and integrity of the epithelium may not only be important in inducing these changes but may be the initial events that lead to dysregulation of food intake and body weight in response to high fat, high energy diets.

  10. Mechanistic relationship between the vagal afferent pathway, central nervous system and peripheral organs in appetite regulation

    Ueno, Hiroaki; Nakazato, Masamitsu


    .... Of such peptides, gut peptides are known to bind to receptors at the vagal afferent pathway terminal that extend into the mucosal layer of the digestive tract, modulate the electrical activity...

  11. Interneurones in pathways from group II muscle afferents in sacral segments of the feline spinal cord.

    Jankowska, E; Riddell, J S


    1. Properties of dorsal horn interneurones that process information from group II muscle afferents in the sacral segments of the spinal cord have been investigated in the cat using both intracellular and extracellular recording. 2. The interneurones were excited by group II muscle afferents and cutaneous afferents but not by group I muscle afferents. They were most effectively excited by group II afferents of the posterior biceps, semitendinosus, triceps surae and quadriceps muscle nerves and by cutaneous afferents running in the cutaneous femoris, pudendal and sural nerves. The earliest synaptic actions were evoked monosynaptically and were very tightly locked to the stimuli. 3. EPSPs evoked monosynaptically by group II muscle afferents and cutaneous afferents of the most effective nerves were often cut short by disynaptic IPSPs. As a consequence of this negative feedback the EPSPs gave rise to single or double spike potentials and only a minority of interneurones responded with repetitive discharges. However, the neurones that did respond repetitively did so at a very high frequency of discharges (0.8-1.2 ms intervals between the first 2-3 spikes). 4. Sacral dorsal horn group II interneurones do not appear to act directly upon motoneurones because: (i) these interneurones are located outside the area within which last order interneurones have previously been found and (ii) the latencies of PSPs evoked in motoneurones by stimulation of the posterior biceps and semitendinosus, cutaneous femoris and pudendal nerves (i.e. the main nerves providing input to sacral interneurones) are compatible with a tri- but not with a disynaptic coupling. Spatial facilitation of EPSPs and IPSPs following synchronous stimulation of group II and cutaneous afferents of these nerves shows, however, that sacral interneurones may induce excitation or inhibition of motoneurones via other interneurones. 5. Comparison of the properties of group II interneurones in the sacral segments with

  12. Computed tomographic features of afferent loop syndrome: pictorial essay

    Zissin, R. [Tel-Aviv Univ., Dept. of Diagnostic Imaging, Sapir Medical Center, Kfar Saba, Sackler Faculty of Medicine, Tel Aviv (Israel); Hertz, M. [Tel-Aviv Univ., Dept. of Diagnostic Imaging, Chaim Sheba Medical Center, Tel Hashomer, Tel Aviv (Israel); Paran, H. [Tel-Aviv Univ., Dept. of Diagnostic Imaging, Surgery ' A' , Sapir Medical Center, Kfar Saba, Sackler Faculty of Medicine, Tel Aviv (Israel); Osadchy, A. [Tel-Aviv Univ., Dept. of Diagnostic Imaging, Sapir Medical Center, Kfar Saba, Sackler Faculty of Medicine, Tel Aviv (Israel); Gayer, G. [Tel-Aviv Univ., Dept. of Diagnostic Imaging, Assaf Harofe Medical Center, Zrifin, Sackler Faculty of Medicine, Tel Aviv (Israel)


    This pictorial essay reviews the computed tomography (CT) findings of afferent loop syndrome (ALS) in various pathological conditions to demonstrate the contribution of a common imaging modality-that is, abdominal CT, used nowadays for various abdominal complaints-to the diagnosis of ALS. ALS is caused by obstruction of the duodenum and jejunum proximal to a gastrojejunostomy anastomosis. It is a rare complication after Billroth II subtotal gastrectomy and even more rare after total or subtotal gastrectomy with Roux-en-Y reconstruction. Although currently advanced medical treatment and endoscopic interventions have dramatically decreased the necessity of surgery for peptic ulcer disease, ALS may appear years after previously common operations. Alternatively, the use of surgical resection for early gastric cancer nowadays leads to an increasing rate of malignancy-related ALS. Clinically, ALS may be difficult to diagnose as its presentation may be vague and nonspecific, but it has a characteristic appearance on CT. Clinicians and radiologists should therefore be familiar with this rare complication. Prompt recognition and correct diagnosis of this syndrome and its probable etiology are important as a guide for treatment. This review illustrates the CT features of ALS in various conditions. (author)

  13. Dynamic GABAergic afferent modulation of AgRP neurons

    Garfield, Alastair S; Shah, Bhavik P; Burgess, Christian R; Li, Monica M; Li, Chia; Steger, Jennifer S; Madara, Joseph C; Campbell, John N; Kroeger, Daniel; Scammell, Thomas E; Tannous, Bakhos A; Myers, Martin G; Andermann, Mark L; Krashes, Michael J; Lowell, Bradford B


    Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues prior to ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the pre-consummatory modulation of ARCAgRP neurons. In a manner reciprocal to ARCAgRP neurons, ARC-projecting leptin receptor (LepR)-expressing GABAergic DMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, DMHLepR neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARCAgRP neuron activity and feeding behavior. PMID:27643429

  14. Hemispheric asymmetry and somatotopy of afferent inhibition in healthy humans.

    Helmich, R C G; Bäumer, T; Siebner, H R; Bloem, B R; Münchau, A


    A conditioning electrical stimulus to a digital nerve can inhibit the motor-evoked potentials (MEPs) in adjacent hand muscles elicited by transcranial magnetic stimulation (TMS) to the contralateral primary motor cortex (M1) when given 25-50 ms before the TMS pulse. This is referred to as short-latency afferent inhibition (SAI). We studied inter-hemispheric differences (Experiment 1) and within-limb somatotopy (Experiment 2) of SAI in healthy right-handers. In Experiment 1, conditioning electrical pulses were applied to the right or left index finger (D2) and MEPs were recorded from relaxed first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscles ipsilateral to the conditioning stimulus. We found that SAI was more pronounced in right hand muscles. In Experiment 2, electrical stimulation was applied to the right D2 and MEPs were recorded from ipsilateral FDI, extensor digitorum communis (EDC) and biceps brachii (BB) muscles. The amount of SAI did not differ between FDI, EDC and BB muscles. These data demonstrate inter-hemispheric differences in the processing of cutaneous input from the hand, with stronger SAI in the dominant left hemisphere. We also found that SAI occurred not only in hand muscles adjacent to electrical digital stimulation, but also in distant hand and forearm and also proximal arm muscles. This suggests that SAI induced by electrical D2 stimulation is not focal and somatotopically specific, but a more widespread inhibitory phenomenon.

  15. Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.

    Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Qu, Meihua; Xia, Yun; Needleman, Bradley J; Mikami, Dean J; Wood, Jackie D


    Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²⁺ by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals.

  16. Decreased contribution from afferent feedback to the soleus muscle during walking in patients with spastic stroke

    Mazzaro, Nazarena; Nielsen, Jørgen Feldbæk; Grey, Michael James


    We investigated the contribution of afferent feedback to the soleus (SOL) muscle activity during the stance phase of walking in patients with spastic stroke. A total of 24 patients with hemiparetic spastic stroke and age-matched healthy volunteers participated in the study. A robotic actuator...... by the Ashworth score. These results indicate that although the stretch reflex response is facilitated during spastic gait, the contribution of afferent feedback to the ongoing locomotor SOL activity is depressed in patients with spastic stroke....

  17. External QX-314 inhibits evoked cranial primary afferent synaptic transmission independent of TRPV1.

    Hofmann, Mackenzie E; Largent-Milnes, Tally M; Fawley, Jessica A; Andresen, Michael C


    The cell-impermeant lidocaine derivative QX-314 blocks sodium channels via intracellular mechanisms. In somatosensory nociceptive neurons, open transient receptor potential vanilloid type 1 (TRPV1) receptors provide a transmembrane passageway for QX-314 to produce long-lasting analgesia. Many cranial primary afferents express TRPV1 at synapses on neurons in the nucleus of the solitary tract and caudal trigeminal nucleus (Vc). Here, we investigated whether QX-314 interrupts neurotransmission from primary afferents in rat brain-stem slices. Shocks to the solitary tract (ST) activated highly synchronous evoked excitatory postsynaptic currents (ST-EPSCs). Application of 300 μM QX-314 increased the ST-EPSC latency from TRPV1+ ST afferents, but, surprisingly, it had similar actions at TRPV1- ST afferents. Continued exposure to QX-314 blocked evoked ST-EPSCs at both afferent types. Neither the time to onset of latency changes nor the time to ST-EPSC failure differed between responses for TRPV1+ and TRPV1- inputs. Likewise, the TRPV1 antagonist capsazepine failed to prevent the actions of QX-314. Whereas QX-314 blocked ST-evoked release, the frequency and amplitude of spontaneous EPSCs remained unaltered. In neurons exposed to QX-314, intracellular current injection evoked action potentials suggesting a presynaptic site of action. QX-314 acted similarly at Vc neurons to increase latency and block EPSCs evoked from trigeminal tract afferents. Our results demonstrate that QX-314 blocked nerve conduction in cranial primary afferents without interrupting the glutamate release mechanism or generation of postsynaptic action potentials. The TRPV1 independence suggests that QX-314 either acted extracellularly or more likely entered these axons through an undetermined pathway common to all cranial primary afferents.

  18. Termination of electroreceptor and mechanical lateral line afferents in the mormyrid acousticolateral area.

    Bell, C C; Russell, C J


    The projection regions of electroreceptor and mechanical lateral line afferents in electric fish of the mormyridae family are described. Electroreceptor afferents from the posterior dorsal skin run in the dorsal branch of the posterior lateral line nerve. Electroreceptor afferents from ventral skin and mechanical lateral line afferents and efferents run in the ventral branch of the nerve. Horseradish peroxidase (HRP) injections into each branch resulted in filling of its central terminals with the marker enzyme. The method yields a Golgi-like staining of afferent terminals, allowing some aspects of their morphology to be described. Comparison of results from dorsal and ventral branch injections shows the separate medullary regions to which electroreceptor and mechanical afferents project, and also demonstrates four separate somatotopic maps within the electroreceptor region. Mechanical afferents end predominantly ipsilaterally in nucleus anterior and eminentia granularis as has been suggested by others. Ipsilateral endings in nucleus octavius are also seen. Electroreceptor afferents end exclusively in the cortex and nucleus of posterior lateral line lobe (PLLL). Within the cortex there are three distinct maps of the skin surface which are separated from each other by discontinuities in the cellular layers. Somatotopic mapping is also present in the nucleus of PLLL though it is less precise than in the cortical zones. Large club endings of the cells of this nucleus are filled with HRP. Labeled cells are seen within a small midline nucleus located at the level of the eighth nerve just above the medial longitudinal fasciculus. These are probably the cell bodies of lateral line efferents.

  19. Can loss of muscle spindle afferents explain the ataxic gait in Riley–Day syndrome?

    Macefield, Vaughan G.; Norcliffe-Kaufmann, Lucy; Gutiérrez, Joel; Axelrod, Felicia B.; Kaufmann, Horacio


    The Riley–Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10...

  20. Input-output functions of vestibular afferent responses to air-conducted clicks in rats.

    Zhu, Hong; Tang, Xuehui; Wei, Wei; Maklad, Adel; Mustain, William; Rabbitt, Richard; Highstein, Steve; Allison, Jerome; Zhou, Wu


    Sound-evoked vestibular myogenic potentials recorded from the sternocleidomastoid muscles (the cervical vestibular-evoked myogenic potential or cVEMP) and the extraocular muscles (the ocular VEMP or oVEMP) have proven useful in clinical assessment of vestibular function. VEMPs are commonly interpreted as a test of saccular function, based on neurophysiological evidence showing activation of saccular afferents by intense acoustic click stimuli. However, recent neurophysiological studies suggest that the clicks used in clinical VEMP tests activate vestibular end organs other than the saccule. To provide the neural basis for interpreting clinical VEMP testing results, the present study examined the extent to which air-conducted clicks differentially activate the various vestibular end organs at several intensities and durations in Sprague-Dawley rats. Single unit recordings were made from 562 vestibular afferents that innervated the otoliths [inferior branch otolith (IO) and superior branch otolith (SO)], the anterior canal (AC), the horizontal canal (HC), and the posterior canal (PC). Clicks higher than 60 dB SL (re-auditory brainstem response threshold) activated both semicircular canal and otolith organ afferents. Clicks at or below 60 dB SL, however, activated only otolith organ afferents. Longer duration clicks evoked larger responses in AC, HC, and SO afferents, but not in IO afferents. Intra-axonal recording and labeling confirmed that sound sensitive vestibular afferents innervated the horizontal and anterior canal cristae as well as the saccular and utricular maculae. Interestingly, all sound sensitive afferents are calyx-bearing fibers. These results demonstrate stimulus-dependent acoustic activation of both semicircular canals and otolith organs, and suggest that sound activation of vestibular end organs other than the saccule should not be ruled out when designing and interpreting clinical VEMP tests.

  1. Effect of endopeptidase-24.11 inhibitors and C-ANP receptor ligand on responses evoked in arterioles of rat cremaster muscle by atrial natriuretic peptide.

    Peyroux, J.; Beslot, F.; Claperon, N; Fournie-Zaluski, M C; Roques, B P


    1. The present study examined the effect of exogenous atrial natriuretric peptide (ANP), alone or in presence of inhibitors of the two major mechanisms for clearing ANP, metabolism by neutral endopeptidase-24.11 (NEP) and internalization by C-ANP receptors, on arteriolar responses using intravital microscopy on the rat cremaster muscle after intravenous or topical administration of the peptide. 2. Topical application of ANP (3 x 10(-10) to 3 x 10(-8) M) produced a gradual increase in arteriol...

  2. 指侧方静脉动脉化再植末节断指%Veno-arteriolization of finger lateral vein for repairing severed finger tips

    江起庭; 杨丽娜; 冯明生; 江志伟


    Objective To investigate the effect of veno-arteriolization of finger lateral vein for repairing severed finger tips. Methods From March 2007 to April 2013, 42 patients with severed finger tips were admitted to our center, with veno-arteriolization after failure in anastomosing artery of finger over times. 22 patients underwent veno-arteriolization of finger lateral vein. During operation, the digital artery proximal end and the finger lateral vein distal end was anastomosed as the route of blood supply. 20 patients underwent veno-arteriolization of finger pulp vein, the digital artery proximal end and the finger pulp vein distal end was anastomosed as the route of blood supply. Results All patients survived completely and achieved primary healing of wound after operation in veno-arteriolization of finger lateral vein group; 4 fingers necrosis in veno-arteriolization of finger pulp vein group. 27 patients were successfully followed up for 6 to 15 months. In veno-arteriolization of finger lateral vein group, 18 patients were successfully followed up, the fingers had satisfactory appearance, finger pulp was plump with good flexibility, no obvious deformed growth of nail were found, and a sound recovery was obtained in the patients; according to TAM scales, the results were excellent in 12 cases, good in 5 cases and fair in 1 cases, with an excellent and good rate of 94.4%. In veno-arteriolization of finger pulp vein group, 9 patients were successfully followed up, mild atrophy of the fingers;according to TAM scales, the results were excellent in 5 cases, good in 2 cases and fair in 2 cases, with an excellent and good rate of 77.8%. Conclusion The veno-arteriolization of finger lateral vein is a valuable method for repairing severed finger tips.%目的:探讨指侧方静脉动脉化再植末节断指的疗效。方法2007年3月-2013年4月收治末节断指患者42例,均在正常指动脉多次吻合失败后行静脉动脉化再植。22例采用指侧方

  3. Bilateral Renal Mass-Renal Disorder: Tuberculosis

    Ozlem Tiryaki


    Full Text Available A 30-year-old woman has presented complaining of weakness and fatigue to her primary care physician. The renal sonography is a routine step in the evaluation of new onset renal failure. When the renal masses have been discovered by sonography in this setting, the functional imaging may be critical. We reported a case about bilateral renal masses in a young female patient with tuberculosis and renal insufficiency. Magnetic resonance (MR has revealed the bilateral renal masses in patient, and this patient has been referred to our hospital for further management. The patient’s past medical and surgical history was unremarkable.

  4. Distal renal tubular acidosis

    Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA ... excreting it into the urine. Distal renal tubular acidosis (Type I RTA) is caused by a defect ...

  5. Proximal renal tubular acidosis

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  6. Renal tuberculosis

    Džamić Zoran


    Full Text Available Tuberculosis is still a significant health problem in the world, mostly in developing countries. The special significance lies in immunocompromised patients, particularly those suffering from the HIV. Urogenital tuberculosis is one of the most common forms of extrapulmonary tuberculosis, while the most commonly involved organ is the kidney. Renal tuberculosis occurs by hematogenous dissemination of mycobacterium tuberculosis from a primary tuberculosis foci in the body. Tuberculosis is characterized by the formation of pathognomonic lesions in the tissues - granulomata. These granulomata may heal spontaneously or remain stable for years. In certain circumstances in the body associated with immunosuppression, the disease may be activated. Central caseous necrosis occurs within tuberculoma, leading to formation of cavities that destroy renal parenchyma. The process may gain access to the collecting system, forming the caverns. In this way, infection can be spread distally to renal pelvis, ureter and bladder. Scaring of tissue by tuberculosis process may lead to development of strictures of the urinary tract. The clinical manifestations are presented by nonspecific symptoms and signs, so tuberculosis can often be overlooked. Sterile pyuria is characteristic for urinary tuberculosis. Dysuric complaints, flank pain or hematuria may be presented in patients. Constitutional symptoms of fever, weight loss and night sweats are presented in some severe cases. Diagnosis is made by isolation of mycobacterium tuberculosis in urine samples, by cultures carried out on standard solid media optimized for mycobacterial growth. Different imaging studies are used in diagnostics - IVU, CT and NMR are the most important. Medical therapy is the main modality of tuberculosis treatment. The first line anti-tuberculosis drugs include isoniazid, rifampicin, pyrazinamide and ethambutol. Surgical treatment is required in some cases, to remove severely damaged kidney, if

  7. Contribution of renal innervation to hypertension in rat autosomal dominant polycystic kidney disease.

    Gattone, Vincent H; Siqueira, Tibério M; Powell, Charles R; Trambaugh, Chad M; Lingeman, James E; Shalhav, Arieh L


    The kidney has both afferent (sensory) and efferent (sympathetic) nerves that can influence renal function. Renal innervation has been shown to play a role in the pathogenesis of many forms of hypertension. Hypertension and flank pain are common clinical manifestations of autosomal dominant (AD) polycystic kidney disease (PKD). We hypothesize that renal innervation contributes to the hypertension and progression of cystic change in rodent PKD. In the present study, the contribution of renal innervation to hypertension and progression of renal histopathology and dysfunction was assessed in male Han:SPRD-Cy/+ rats with ADPKD. At 4 weeks of age, male offspring from crosses of heterozygotes (Cy/+) were randomized into either 1) bilateral surgical renal denervation, 2) surgical sham denervation control, or 3) nonoperated control groups. A midline laparotomy was performed to allow the renal denervation (i.e., physical stripping of the nerves and painting the artery with phenol/alcohol). Blood pressure (tail cuff method), renal function (BUN) and histology were assessed at 8 weeks of age. Bilateral renal denervation reduced the cystic kidney size, cyst volume density, systolic blood pressure, and improved renal function (BUN) as compared with nonoperated controls. Operated control cystic rats had kidney weights, cyst volume densities, systolic blood pressures, and plasma BUN levels that were intermediate between those in the denervated animals and the nonoperated controls. The denervated group had a reduced systolic blood pressure compared with the operated control animals, indicating that the renal innervations was a major contributor to the hypertension in this model of ADPKD. Renal denervation was efficacious in reducing some pathology, including hypertension, renal enlargement, and cystic pathology. However, sham operation also affected the cystic disease but to a lesser extent. We hypothesize that the amelioration of hypertension in Cy/+ rats was due to the effects

  8. Renale Osteopathie

    Horn S


    Full Text Available Die renale Osteopathie umfaßt Erkrankungen des Knochens, die bei Patienten mit chronischen Nierenerkrankungen auftreten, wie den sekundären bzw. tertiären Hyperparathyreoidismus, die adynamische Knochenerkrankung und die Osteopathie nach Nierentransplantation. Durch die Identifikation des Kalzium-Sensing-Rezeptors bzw. des Vitamin D-Rezeptors hat sich unser Verständnis der Zusammenhänge in den letzten Jahren erheblich verbessert. Neue Medikamente versprechen effizientere Prophylaxe- und Therapiemöglichkeiten. Wir beeinflussen dadurch nicht nur die Morbidität und Lebensqualität, sondern auch die Mortalität unserer Patienten.

  9. Renal disease in pregnancy.

    Thorsen, Martha S; Poole, Judith H


    Anatomic and physiologic adaptations within the renal system during pregnancy are significant. Alterations are seen in renal blood flow and glomerular filtration, resulting in changes in normal renal laboratory values. When these normal renal adaptations are coupled with pregnancy-induced complications or preexisting renal dysfunction, the woman may demonstrate a reduction of renal function leading to an increased risk of perinatal morbidity and mortality. This article will review normal pregnancy adaptations of the renal system and discuss common pregnancy-related renal complications.

  10. Raphe magnus and reticulospinal actions on primary afferent depolarization of group I muscle afferents in the cat.

    Quevedo, J; Eguibar, J R; Jiménez, I; Rudomin, P


    1. In the anaesthetized cat, electrical stimulation of the bulbar reticular formation produced a short latency (2.1 +/- 0.3 ms) positive potential in the cord dorsum. In contrast, stimulation of the nucleus raphe magnus with strengths below 50 microA evoked a slow negative potential with a mean latency of 5.5 +/- 0.6 ms that persisted after sectioning the contralateral pyramid and was abolished by sectioning the ipsilateral dorsolateral funiculus. 2. The field potentials evoked by stimulation of the bulbar reticular formation and of the nucleus raphe magnus had a different intraspinal distribution, suggesting activation of different sets of segmental interneurones. 3. Stimulation of these two supraspinal nuclei produced primary afferent depolarization (PAD) in single Ib fibres and inhibited the PAD elicited by group I volleys in single Ia fibres. The inhibition of the PAD of Ia fibres produced by reticulospinal and raphespinal inputs appears to be exerted on different interneurones along the PAD pathway. 4. It is concluded that, although reticulospinal and raphespinal pathways have similar inhibitory effects on PAD of Ia fibres, and similar excitatory effects on the PAD of Ib fibres, their actions are conveyed by partly independent pathways. This would allow their separate involvement in the control of posture and movement.

  11. A Pilot Study to Evaluate Renal Hemodynamics in Cirrhosis by Simultaneous Glomerular Filtration Rate, Renal Plasma Flow, Renal Resistive Indices and Biomarkers Measurements

    Mindikoglu, Ayse L.; Dowling, Thomas C.; Wong-You-Cheong, Jade J.; Christenson, Robert H.; Magder, Laurence S.; Hutson, William R.; Seliger, Stephen L.; Weir, Matthew R.


    Background Renal hemodynamic measurements are complicated to perform in patients with cirrhosis; yet they provide the best measure of risk to predict hepatorenal syndrome (HRS). Currently, there are no established biomarkers of altered renal hemodynamics in cirrhosis validated by measured renal hemodynamics. Methods In this pilot study, simultaneous measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), renal resistive indices and biomarkers were performed to evaluate renal hemodynamic alterations in 10 patients with cirrhosis (3 patients without ascites, 5 with diuretic sensitive and 2 diuretic refractory ascites). Results Patients with diuretic refractory ascites had the lowest mean GFR (36.5 ml/min/1.73m2) and RPF (133.6 ml/min/1.73m2) when compared to those without ascites (GFR=82.9 ml/min/1.73m2, RPF=229.9 ml/min/1.73m2) and with diuretic-sensitive ascites (GFR=82.3 ml/min/1.73m2, RPF=344.1 ml/min/1.73m2). A higher mean filtration fraction (FF= GFR/RPF=0.36) was noted among those without ascites compared to those with ascites. Higher FF in patients without ascites is most likely secondary to the vasoconstriction in the efferent glomerular arterioles (normal FF≃0.20). In general, renal resistive indices were inversely related to FF. While patients with ascites had lower FF and higher right kidney main and arcuate artery resistive indices, those without ascites had higher FF and lower right kidney main and arcuate artery resistive indices. While cystatin C and beta-2 microglobulin performed better compared to Cr in estimating RPF; beta-trace protein, beta-2 microglobulin, SDMA, and (SDMA+ADMA) performed better in estimating right kidney arcuate artery resistive index. Conclusion The results of this pilot study showed that identification of non-invasive biomarkers of reduced RPF and increased renal resistive indices can identify cirrhotics at risk for HRS at a stage more amenable to therapeutic intervention, and reduce mortality from kidney

  12. Segmental and supraspinal control of synaptic effectiveness of functionally identified muscle afferents in the cat.

    Enríquez, M; Jiménez, I; Rudomin, P


    The present investigation documents the patterns of primary afferent depolarization (PAD) of single, functionally identified muscle afferents from the medial gastrocnemius nerve in the intact, anesthetized cat. Classification of the impaled muscle afferents as from muscle spindles or from tendon organs was made according to several criteria, which comprised measurement of conduction velocity and electrical threshold of the peripheral axons, and the maximal frequency followed by the afferent fibers during vibration, as well as the changes in discharge frequency during longitudinal stretch, the projection of the afferent fiber to the motor pool, and, in unparalyzed preparations, the changes in afferent activity during a muscle twitch. In confirmation of a previous study, we found that most muscle spindle afferents (46.1-66.6%, depending on the combination of criteria utilized for receptor classification) had a type A PAD pattern. That is, they were depolarized by stimulation of group I fibers of the posterior biceps and semitendinosus (PBSt) nerve, but not by stimulation of cutaneous nerves (sural and superficial peroneus) or the bulbar reticular formation (RF), which in many cases inhibited the PBSt-induced PAD. In addition, we found a significant fraction of muscle spindle primaries that were depolarized by stimulation of group I PBSt fibers and also by stimulation of the bulbar RF. Stimulation of cutaneous nerves produced PAD in 9.1-31.2% of these fibers (type B PAD pattern) and no PAD in 8.2-15.4% (type C PAD pattern). In contrast to muscle spindle afferents, only the 7.7-15.4% of fibers from tendon organs had a type A PAD pattern, 23-46.1% had a type B and 50-61.5% a type C PAD pattern. These observations suggest that the neuronal circuitry involved in the control of the synaptic effectiveness of muscle spindles and tendon organs is subjected to excitatory as well as to inhibitory influences from cutaneous and reticulospinal fibers. As shown in the accompanying

  13. Identified proprioceptive afferents and motor rhythm entrainment in the crayfish walking system.

    Elson, R C; Sillar, K T; Bush, B M


    1. In crayfish, Pacifastacus leniusculus, remotion of a walking leg stretches the thoraco-coxal (TC) muscle receptor organ (TCMRO), located at the leg's articulation with the thorax. In vitro, alternate stretch and release of the fourth leg's TCMRO entrained the centrally generated rhythmic motor output to that leg, with the remotor phase of the rhythm entraining to TCMRO stretch, the promoter phase to release. This coordination of motor bursts to afferent input corresponds to that of active, rhythmic movements in vivo. 2. Entrainment was rapid in onset (stable coordination resulting within the first or second stimulus cycle) and was relatively phase-constant (whatever the stimulus frequency, during 1:1 entrainment, remotor bursts began near the onset of stretch and promotor bursts began near the onset of release). Outside the range of 1:1 entrainment, 2:1, 1:2, and 1:3 coordination ratios (rhythm:stimulus) were encountered. Resetting by phasic stimulation of the TCMRO was complete and probabilistic: effective stimuli triggered rapid transitions between the two burst phases. 3. The TCMRO is innervated by two afferents, the nonspiking S and T fibers, which generate graded depolarizing receptor potentials in response to stretch. During proprioceptive entrainment, the more phasic T fiber depolarized and hyperpolarized more rapidly or in advance of the more tonic S fiber. These receptor potentials were modified differently in the two afferents by interaction with central synaptic inputs that were phase-locked to the entrained motor rhythm. 4. Injecting slow sinusoidal current into either afferent alone could entrain motor rhythms: promoter phase bursts were entrained to depolarization of the S fiber or hyperpolarization of the T fiber, whereas the converse response was obtained for remotor phase bursts. 5. During proprioceptive entrainment, tonic hyperpolarization of the S fiber weakened entrained promotor bursts and allowed remotor burst durations to increase

  14. Renal calculus

    Pyrah, Leslie N


    Stone in the urinary tract has fascinated the medical profession from the earliest times and has played an important part in the development of surgery. The earliest major planned operations were for the removal of vesical calculus; renal and ureteric calculi provided the first stimulus for the radiological investigation of the viscera, and the biochemical investigation of the causes of calculus formation has been the training ground for surgeons interested in metabolic disorders. It is therefore no surprise that stone has been the subject of a number of monographs by eminent urologists, but the rapid development of knowledge has made it possible for each one of these authors to produce something new. There is still a technical challenge to the surgeon in the removal of renal calculi, and on this topic we are always glad to have the advice of a master craftsman; but inevitably much of the interest centres on the elucidation of the causes of stone formation and its prevention. Professor Pyrah has had a long an...

  15. [Expert consensus statement on interventional renal sympathetic denervation for hypertension treatment].

    Mahfoud, F; Vonend, O; Bruck, H; Clasen, W; Eckert, S; Frye, B; Haller, H; Hausberg, M; Hoppe, U C; Hoyer, J; Hahn, K; Keller, T; Krämer, B K; Kreutz, R; Potthoff, S A; Reinecke, H; Schmieder, R; Schwenger, V; Kintscher, U; Böhm, M; Rump, L C


    This commentary summarizes the expert consensus and recommendations of the working group 'Herz und Niere' of the German Society of Cardiology (DGK), the German Society of Nephrology (DGfN) and the German Hypertension League (DHL) on renal denervation for antihypertensive treatment. Renal denervation is a new, interventional approach to selectively denervate renal afferent and efferent sympathetic fibers. Renal denervation has been demonstrated to reduce office systolic and diastolic blood pressure in patients with resistant hypertension, defined as systolic office blood pressure ≥ 160 mm Hg and ≥ 150 mm Hg in patients with diabetes type 2, which should currently be used as blood pressure thresholds for undergoing the procedure. Exclusion of secondary hypertension causes and optimized antihypertensive drug treatment is mandatory in every patient with resistant hypertension. In order to exclude pseudoresistance, 24-hour blood pressure measurements should be performed. Preserved renal function was an inclusion criterion in the Symplicity studies, therefore, renal denervation should be only considered in patients with a glomerular filtration rate > 45 ml/min. Adequate centre qualification in both, treatment of hypertension and interventional expertise are essential to ensure correct patient selection and procedural safety. Long-term follow-up after renal denervation and participation in the German Renal Denervation (GREAT) Registry are recommended to assess safety and efficacy after renal denervation over time.

  16. The action of knee joint afferents and the concomitant influence of cutaneous (sural) afferents on the discharge of triceps surae gamma-motoneurones in the cat.

    Ellaway, P H; Davey, N J; Ferrell, W R; Baxendale, R H


    Electrical stimulation of group II joint afferents of the posterior articular nerve (PAN) to the knee evoked short-latency facilitation and/or inhibition of the background discharge of gastrocnemius-soleus (GS) gamma-motoneurones in decerebrated spinal cats. The latencies of these responses were consistent with mediation via segmental oligosynaptic spinal pathways. In addition, a longer-latency facilitation was frequently observed. Mechanical non-noxious stimulation of the skin within the field of innervation of the sural nerve, on the lateral aspect of the heel, suppressed the short-latency facilitation, but not the inhibition or long-latency facilitation. Brief mechanical indentation of the posterior aspect of the knee joint capsule could elicit facilitation or inhibition of gamma-motoneurones. Facilitation, but not inhibition, was blocked by anaesthesia or section of the PAN. Both actions could be suppressed by mechanical stimulation of the heel. We conclude that GS gamma-motoneurones receive both facilitatory and inhibitory segmental inputs from group II articular afferents arising in the knee joint. Cutaneous afferents from the sural field exert a selective inhibitory influence over the facilitation of fusimotor discharge by articular afferents.

  17. Low thyroid function leads to cardiac atrophy with chamber dilatation, impaired myocardial blood flow, loss of arterioles, and severe systolic dysfunction.

    Tang, Yi-Da; Kuzman, James A; Said, Suleman; Anderson, Brent E; Wang, Xuejun; Gerdes, A Martin


    Although thyroid dysfunction has been linked to heart failure, it is not clear whether hypothyroidism alone can cause heart failure. Hypothyroidism was induced in adult rats by treatment with 0.025% propylthiouracil (PTU) for 6 weeks (PTU-S) and 1 year (PTU-L). Echocardiographic measurements, left ventricular (LV) hemodynamics, isolated myocyte length (KOH method), myocardial blood flow (fluorescent microspheres), arteriolar morphometry, and gene expression (Western blot) were determined. Heart weight, heart rate, LV systolic blood pressure, LV ejection fraction, LV fractional shortening, and systolic wall thickness were reduced in PTU-S and PTU-L rats. LV internal diameter in systole increased by 40% in PTU-S and 86% in PTU-L. LV internal dimension in diastole was increased in PTU-S and PTU-L rats, but only PTU-L rats showed a significant increase in myocyte length due to series sarcomere addition. Resting and maximum (adenosine) myocardial blood flow were reduced in both PTU-S and PTU-L rats. Impaired blood flow was due to a large reduction in arteriolar length density and small arterioles in PTU-S and PTU-L (Pcardiac mass. Chamber dilatation in PTU-L rats was due to series sarcomere addition, typical of heart failure. Hypothyroidism resulted in impaired myocardial blood flow due to a dramatic loss of arterioles. Thus, we have identified 2 important new mechanisms by which low thyroid function may lead to heart failure.

  18. Differential modulation of primary afferent depolarization of segmental and ascending intraspinal collaterals of single muscle afferents in the cat spinal cord.

    Rudomin, P; Lomelí, J; Quevedo, J


    We examined primary afferent depolarization (PAD) in the anesthetized cat elicited in 109 pairs of intraspinal collaterals of single group I afferents from the gastrocnemius nerve, one of the pair ending in the L3 segment, around the Clarke's column nuclei, and the other in the L6 segment within the intermediate zone. Tests for refractoriness were made to assess whether the responses produced by intraspinal stimulation in the L3 and L6 segments were due to activation of collaterals of the same afferent fiber. PAD in each collateral was estimated by independent computer-controlled measurement of the intraspinal current required to maintain a constant probability of antidromic firing. In most fibers, stimulation of the ipsilateral posterior biceps and semitendinosus (PBSt) nerve with trains of pulses maximal for group I afferents had a qualitatively similar effect but produced a larger PAD in the L6 than in the L3 collaterals. Stimulation of cutaneous nerves (sural and superficial peroneus) with single pulses and of the posterior articular nerve, the ipsilateral reticular formation, nucleus raphe magnus and contralateral motor cortex with trains of pulses often had qualitatively different effects. They could produce PAD and/or facilitate the PBSt-induced PAD in one collateral, and produce PAH and/or inhibit the PAD in the other collateral. These patterns could be changed in a differential manner by sensory or supraspinal conditioning stimulation. In summary, the present investigation suggests that the segmental and ascending collaterals of individual afferents are not fixed routes for information transmission, but parts of dynamic systems in which information transmitted to segmental reflex pathways and to Clarke's column neurons by common sources can be decoupled by sensory and descending inputs and funneled to specific targets according to the motor tasks to be performed.

  19. Functional analysis of ultra high information rates conveyed by rat vibrissal primary afferents

    André eMaia Chagas


    Full Text Available Sensory receptors determine the type and the quantity of information available for perception. Here, we quantified and characterized the information transferred by primary afferents in the rat whisker system using neural system identification. Quantification of ‘how much’ information is conveyed by primary afferents, using the direct method, a classical information theoretic tool, revealed that primary afferents transfer huge amounts of information (up to 529 bits/s. Information theoretic analysis of instantaneous spike-triggered kinematic stimulus features was used to gain functional insight on ‘what’ is coded by primary afferents. Amongst the kinematic variables tested - position, velocity, and acceleration - primary afferent spikes encoded velocity best. The other two variables contribute to information transfer, but only if combined with velocity. We further revealed three additional characteristics that play a role in information transfer by primary afferents. Firstly, primary afferent spikes show preference for well separated multiple stimuli (i.e. well separated sets of combinations of the three instantaneous kinematic variables. Secondly, spikes are sensitive to short strips of the stimulus trajectory (up to 10 ms pre-spike time, and thirdly, they show spike patterns (precise doublet and triplet spiking. In order to deal with these complexities, we used a flexible probabilistic neuron model fitting mixtures of Gaussians to the spike triggered stimulus distributions, which quantitatively captured the contribution of the mentioned features and allowed us to achieve a full functional analysis of the total information rate indicated by the direct method. We found that instantaneous position, velocity, and acceleration explained about 50% of the total information rate. Adding a 10 ms pre-spike interval of stimulus trajectory achieved 80-90%. The final 10-20% were found to be due to non-linear coding by spike bursts.

  20. Modulation of jaw muscle spindle afferent activity following intramuscular injections with hypertonic saline.

    Ro, J Y; Capra, N F


    Transient noxious chemical stimulation of small diameter muscle afferents modulates jaw movement-related responses of caudal brainstem neurons. While it is likely that the effect is mediated from the spindle afferents in the mesencephalic nucleus (Vmes) via the caudally projecting Probst's tract, the mechanisms of pain induced modulations of jaw muscle spindle afferents is not known. In the present study, we tested the hypothesis that jaw muscle nociceptors gain access to muscle spindle afferents in the same muscle via central mechanisms and alter their sensitivity. Thirty-five neurons recorded from the Vmes were characterized as muscle spindle afferents based on their responses to passive jaw movements, muscle palpation, and electrical stimulation of the masseter nerve. Each cell was tested by injecting a small volume (250 microl) of either 5% hypertonic and/or isotonic saline into the receptor-bearing muscle. Twenty-nine units were tested with 5% hypertonic saline, of which 79% (23/29) showed significant modulation of mean firing rates (MFRs) during one or more phases of ramp-and-hold movements. Among the muscle spindle primary-like units (n = 12), MFRs of 4 units were facilitated, five reduced, two showed mixed responses and one unchanged. In secondary-like units (n = 17), MFRs of 9 were facilitated, three reduced and five unchanged. Thirteen units were tested with isotonic saline, of which 77% showed no significant changes of MFRs. Further analysis revealed that the hypertonic saline not only affected the overall output of muscle spindle afferents, but also increased the variability of firing and altered the relationship between afferent signal and muscle length. These results demonstrated that activation of muscle nociceptors significantly affects proprioceptive properties of jaw muscle spindles via central neural mechanisms. The changes can have deleterious effects on oral motor function as well as kinesthetic sensibility.

  1. The unsilent majority-TRPV1 drives "spontaneous" transmission of unmyelinated primary afferents within cardiorespiratory NTS.

    Andresen, Michael C; Hofmann, Mackenzie E; Fawley, Jessica A


    Cranial primary afferent sensory neurons figure importantly in homeostatic control of visceral organ systems. Of the two broad classes of visceral afferents, the role of unmyelinated or C-type class remains poorly understood. This review contrasts key aspects of peripheral discharge properties of C-fiber afferents and their glutamate transmission mechanisms within the solitary tract nucleus (NTS). During normal prevailing conditions, most information arrives at the NTS through myelinated A-type nerves. However, most of visceral afferent axons (75-90%) in NTS are unmyelinated, C-type axons. Centrally, C-type solitary tract (ST) afferent terminals have presynaptic transient receptor potential vanilloid type 1 (TRPV1) receptors. Capsaicin activation of TRPV1 blocks phasic or synchronous release of glutamate but facilitates release of glutamate from a separate pool of vesicles. This TRPV1-operated pool of vesicles is active at normal temperatures and is responsible for actively driving a 10-fold higher release of glutamate at TRPV1 compared with TRPV1- terminals even in the absence of afferent action potentials. This novel TRPV1 mechanism is responsible for an additional asynchronous release of glutamate that is not present in myelinated terminals. The NTS is rich with presynaptic G protein-coupled receptors, and the implications of TRPV1-operated glutamate offer unique targets for signaling in C-type sensory afferent terminals from neuropeptides, inflammatory mediators, lipid metabolites, cytokines, and cannabinoids. From a homeostatic view, this combination could have broad implications for integration in chronic pathological disturbances in which the numeric dominance of C-type endings and TRPV1 would broadly disturb multisystem control mechanisms.

  2. Serotonin, Dopamine and Noradrenaline Adjust Actions of Myelinated Afferents via Modulation of Presynaptic Inhibition in the Mouse Spinal Cord

    García-Ramírez, David L.; Calvo, Jorge R.; Shawn Hochman; Jorge N Quevedo


    Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD). PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT), dopamine (DA) and noradrenaline...

  3. Renal actinomycosis with concomitant renal vein thrombosis.

    Chang, Dong-Suk; Jang, Won Ik; Jung, Ji Yoon; Chung, Sarah; Choi, Dae Eun; Na, Ki-Ryang; Lee, Kang Wook; Shin, Yong-Tai


    Renal actinomycosis is a rare infection caused by fungi of the genus Actinomyces. A 74-year-old male was admitted to our hospital because of gross hematuria with urinary symptoms and intermittent chills. Computed tomography of the abdomen showed thrombosis in the left renal vein and diffuse, heterogeneous enlargement of the left kidney. After nephrectomy, sulfur granules with chronic suppurative inflammation were seen microscopically, and the histopathological diagnosis was renal actinomycosis. Our case is the first report of renal actinomycosis with renal vein thrombosis.


    Soraia Geraldo Rozza Lopes


    Full Text Available El objetivo del estudio fue comprender el significado de espera del trasplante renal para las mujeres en hemodiálisis. Se trata de un estudio cualitativo-interpretativo, realizado con 12 mujeres en hemodiálisis en Florianópolis. Los datos fueron recolectados a través de entrevistas en profundidad en el domicilio. Fue utilizado el software Etnografh 6.0 para la pre-codificación y posterior al análisis interpretativo emergieron dos categorías: “las sombras del momento actual”, que mostró que las dificultades iniciales de la enfermedad están presentes, pero las mujeres pueden hacer frente mejor a la enfermedad y el tratamiento. La segunda categoría, “la luz del trasplante renal”, muestra la esperanza impulsada por la entrada en la lista de espera para un trasplante.

  5. Renal failure


    930564 Dwell times affect the local host de-fence mechanism of peritoneal dialysis patients.WANG Tao(汪涛),et al.Renal Instit,SunYatsen Med Univ,Guangzhou,510080.Chin JNephrol 1993;9(2):75—77.The effect of different intraperitoneal awelltimes on the local host defence in 6 peritonealdialysis patients was studied.A significant de-crease in the number of peritoneal cells,IgG con-centration and the phagoeytosis and bactericidalactivity of macrophages was determined when thedwell time decreased from 12 to 4 hs or form 4 to0.5hs,but the peroxidase activity in macrophagesincreased significantly.All variables,except theperoxidase activity in macrophages,showed nosignificant difference between patients of high or

  6. Traumatismo renal

    Rocha, Sofia Rosa Moura Gomes da


    Introdução: A realização deste trabalho visa a elaboração de uma revisão sistematizada subordinada à temática da traumatologia renal. Objectivos: Os principais objectivos deste trabalho são: apurar a etiologia, definir a classificação, analisar o diagnóstico e expôr o tratamento e as complicações. Desenvolvimento: Os traumatismos são a principal causa de morte antes dos 40 anos. O rim é o órgão do aparelho génito-urinário mais frequentemente atingido. Os traumatismos renais são mais fre...

  7. Regulation of the renal sympathetic nerves in heart failure

    Rohit eRamchandra


    Full Text Available Heart failure (HF is a serious debilitating condition with poor survival rates and an increasing level of prevalence. Heart failure is associated with an increase in renal norepinephrine spillover, which is an independent predictor of mortality in HF patients. The excessive sympatho-excitation that is a hallmark of heart failure has long-term effects that contribute to disease progression. An increase in directly recorded renal sympathetic nerve activity has also been recorded in animal models of heart failure. This review will focus on the mechanisms controlling sympathetic nerve activity to the kidney during normal conditions and alterations in these mechanisms during heart failure. In particular the roles of afferent reflexes and central mechanisms will be discussed.

  8. Capsaicin-sensitive vagal afferent neurons contribute to the detection of pathogenic bacterial colonization in the gut.

    Riley, T P; Neal-McKinney, J M; Buelow, D R; Konkel, M E; Simasko, S M


    Vagal activation can reduce inflammation and disease activity in various animal models of intestinal inflammation via the cholinergic anti-inflammatory pathway. In the current model of this pathway, activation of descending vagal efferents is dependent on a signal initiated by stimulation of vagal afferents. However, little is known about how vagal afferents are activated, especially in the context of subclinical or clinical pathogenic bacterial infection. To address this question, we first determined if selective lesions of capsaicin-sensitive vagal afferents altered c-Fos expression in the nucleus of the solitary tract (nTS) after mice were inoculated with either Campylobacter jejuni or Salmonella typhimurium. Our results demonstrate that the activation of nTS neurons by intraluminal pathogenic bacteria is dependent on intact, capsaicin sensitive vagal afferents. We next determined if inflammatory mediators could cause the observed increase in c-Fos expression in the nTS by a direct action on vagal afferents. This was tested by the use of single-cell calcium measurements in cultured vagal afferent neurons. We found that tumor necrosis factor alpha (TNFα) and lipopolysaccharide (LPS) directly activate cultured vagal afferent neurons and that almost all TNFα and LPS responsive neurons were sensitive to capsaicin. We conclude that activation of the afferent arm of the parasympathetic neuroimmune reflex by pathogenic bacteria in the gut is dependent on capsaicin sensitive vagal afferent neurons and that the release of inflammatory mediators into intestinal tissue can be directly sensed by these neurons.

  9. Origin and chemical coding of primary afferent neurones supplying the prostate of the dog.

    Arciszewski, M B; Zacharko, A


    Retrograde tracing technique combined with the double-fluorescent immunohistochemistry were used to investigate the distribution and chemical coding of primary afferent neurones supplying the canine prostate. After the injection of Fast Blue (FB) into the prostatic tissue retrogradely-labelled (FB(+)) primary afferent neurones were localized in bilateral L(1)-Ca(1) dorsal root ganglia (DRG). Statistical analysis using anova test showed that there are two major sources of afferent prostate innervation. The vast majority of prostate-supplying primary afferent neurones were located in bilateral L(2)-L(4) DRG (56.9 +/- 0.6%). The second source of the afferent innervation of canine prostate were bilateral S(1)-Ca(1) DRG (40.6 +/- 1.0%). No statistically significant differences were found between average number of FB(+) neurones localized in the left and right DRG (49.5 +/- 1.7 and 50.5 +/- 1.7%, respectively). Immunohistochemistry revealed that FB(+) primary afferent neurones contain several neuropeptides in various combinations. In the prostate-supplying neurones of lumbar and sacro-caudal DRG the immunoreactivity to substance P (SP) and calcitonin gene-related peptide (CGRP) was found most frequently (50 +/- 3.7 and 37.3 +/- 1.9%, respectively). Both in the lumbar and sacro-caudal DRG, considerable population of FB(+) neurones immunoreactive neither to SP nor CGRP were also found (23 +/- 2.6 and 32.8 +/- 2.3%, respectively). In the lumbar DRG 10.7 +/- 1.1% of SP-immunoreactive FB(+) neurones also contained galanin (GAL). In 9.2 +/- 2.2% of the prostate-supplying primary afferent neurones located in the sacro-caudal DRG the co-localization of SP and GAL was also reported. Results of the retrograde tracing experiment demonstrated for the first time sources of afferent innervation of the canine prostate. Double immunohistochemistry revealed that many of the prostate-supplying primary afferent neurones express some of sensory neuropeptides which presumably may be involved

  10. Tonic and phasic differential GABAergic inhibition of synaptic actions of joint afferents in the cat.

    Rudomin, P; Hernández, E; Lomelí, J


    The aim of this study was to examine the functional organization of the spinal neuronal networks activated by myelinated afferent fibers in the posterior articular nerve (PAN) of the anesthetized cat. Particular attention was given to the tonic and phasic GABAa inhibitory modulation of these networks. Changes in the synaptic effectiveness of the joint afferents were inferred from changes in the intraspinal focal potentials produced by electrical stimulation of the PAN. We found that conditioning stimulation of cutaneous nerves (sural, superficial peroneus and saphenous) and of the nucleus raphe magnus often inhibited, in a differential manner, the early and late components of the intraspinal focal potentials produced by stimulation of low and high threshold myelinated PAN afferents, respectively. The degree of the inhibition depended on the strength of both the conditioning and test stimuli and on the segmental level of recording. Conditioning stimulation of group I muscle afferents was less effective, but marked depression of the early and late focal potentials was produced by stimuli exceeding 5 xT. The i.v. injection of 1-2.5 mg/kg of picrotoxin, a GABAa blocker, had relatively minor effects on the early components of the PAN focal potentials, but was able to induce a significant increase of the late components. It also reduced the inhibitory effects of cutaneous and joint nerve conditioning on PAN focal responses. Conditioning autogenetic stimulation with high-frequency trains depressed the PAN focal potentials. The late components of the PAN responses remained depressed several minutes after discontinuing the conditioning train, even after picrotoxin administration. The present observations indicate that the neuronal networks activated by the low threshold PAN afferents show a relatively small post-activation depression and appear to be subjected to a minor tonic inhibitory GABAa control. In contrast, the pathways activated by stimulation of high threshold

  11. Is human muscle spindle afference dependent on perceived size of error in visual tracking?

    Kakuda, N; Wessberg, J; Vallbo, A B


    Impulses of 16 muscle spindle afferents from finger extensor muscles were recorded from the radial nerve along with electromyographic (EMG) activity and kinematics of joint movement. Twelve units were classified as Ia and 4 as II spindle afferents. Subjects were requested to perform precision movements at a single metacarpophalangeal joint in an indirect visual tracking task. Similar movements were executed under two different conditions, i.e. with high and low error gain. The purpose was to explore whether different precision demands were associated with different spindle firing rates. With high error gain, a small but significantly higher impulse rate was found in pooled data from Ia afferents during lengthening movements but not during shortening movements, nor with II afferents. EMG was also significantly higher with high error gain in recordings with Ia afferents. When the effect of EMG was factored out, using partial correlation analysis, the significant difference in Ia firing rate vanished. The findings suggest that fusimotor drive as well as skeletomotor activity were both marginally higher when the precision demand was higher, whereas no indication of independent fusimotor adjustments was found. These results are discussed with respect to data from behaving animals and the role of fusimotor independence in various limb muscles proposed.

  12. cAMP-independent dilation of coronary arterioles to adenosine : role of nitric oxide, G proteins, and K(ATP) channels.

    Hein, T W; Kuo, L


    Adenosine is known to play an important role in the regulation of coronary blood flow during metabolic stress. However, there is sparse information on the mechanism of adenosine-induced dilation at the microcirculatory levels. In the present study, we examined the role of endothelial nitric oxide (NO), G proteins, cyclic nucleotides, and potassium channels in coronary arteriolar dilation to adenosine. Pig subepicardial coronary arterioles (50 to 100 microm in diameter) were isolated, cannulated, and pressurized to 60 cm H(2)O without flow for in vitro study. The arterioles developed basal tone and dilated dose dependently to adenosine. Disruption of endothelium, blocking of endothelial ATP-sensitive potassium (K(ATP)) channels by glibenclamide, and inhibition of NO synthase by N(G)-nitro-L-arginine methyl ester and of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one produced identical attenuation of vasodilation to adenosine. Combined administration of these inhibitors did not further attenuate the vasodilatory response. Production of NO from coronary arterioles was significantly increased by adenosine. Pertussis toxin, but not cholera toxin, significantly inhibited vasodilation to adenosine, and this inhibitory effect was only evident in vessels with an intact endothelium. Tetraethylammonium, glibenclamide, and a high concentration of extraluminal KCl abolished vasodilation of denuded vessels to adenosine; however, inhibition of calcium-activated potassium channels by iberiotoxin had no effect on this dilation. Rp-8-Br-cAMPS, a cAMP antagonist, inhibited vasodilation to cAMP analog 8-Br-cAMP but failed to block adenosine-induced dilation. Furthermore, vasodilations to 8-Br-cAMP and sodium nitroprusside were not inhibited by glibenclamide, indicating that cAMP- and cGMP-induced dilations are not mediated by the activation of K(ATP) channels. These results suggest that adenosine activates both endothelial and smooth muscle pathways to exert

  13. Management of afferent loop obstruction from recurrent metastatic pancreatic cancer using a venting gastrojejunostomy.

    Bakes, Debbie; Cain, Christian; King, Michael; Dong, Xiang Da Eric


    Pancreatic cancer is an aggressive malignancy potentially curable with surgical intervention. Following pancreaticoduodenectomy for suspected pancreatic head malignancy, patients have a high risk for both immediate and delayed problems due to surgical complications and recurrent disease. We report here a patient with pancreatic cancer treated with pancreaticoduodenectomy who developed recurrent disease resulting in obstruction of the afferent limb. The patient developed biliary obstruction and cholangitis at presentation. Her biliary tree failed to dilate which precluded safe percutaneous biliary decompression. During surgical exploration, she was found to have a dilated afferent limb at the level of the transverse mesocolon. The patient underwent decompression of the afferent limb as well as the biliary tree using a venting gastrojejunostomy to the blind loop. This represents a novel surgical approach for management of this complicated and difficult problem.

  14. Monosynaptic connections between primary afferents and giant neurons in the turtle spinal dorsal horn

    Fernández, A; Radmilovich, M; Russo, R E


    This paper reports the occurrence of monosynaptic connections between dorsal root afferents and a distinct cell type-the giant neuron-deep in the dorsal horn of the turtle spinal cord. Light microscope studies combining Nissl stain and transganglionic HRP-labeling of the primary afferents have...... revealed the occurrence of axosomatic and axodendritic contacts between labeled boutons and giant neurons. The synaptic nature of these contacts has been confirmed by use of electron microscope procedures involving the partial three-dimensional reconstruction of identified giant neurons. Intracellular...... recording in spinal cord slices provided functional evidence indicating the monosynaptic connections between dorsal root afferents and giant neurons. The recorded neurons were morphologically identified by means of biocytin injection and with avidin conjugates. Electrical stimulation of the ipsilateral...

  15. Group Ia afferents contribute to short-latency interlimb reflexes in the human biceps femoris muscle

    Stevenson, Andrew James Thomas; Kamavuako, Ernest Nlandu; Geertsen, Svend Sparre


    and velocity of the iKnee rotations. Methods 11 seated participants (mean age: 25 ± 5 years) performed a voluntary isometric knee extension with the ipsilateral leg and contralateral knee flexion to 10% of maximum voluntary contraction (MVC). A mechanical actuator (MTS-Systems Corporation) imposed i...... amplitudes (4 vs. 8°) at the same 150°/s velocity (p’s > 0.08). Conclusion Because fast conducting group Ia muscle spindle afferents are sensitive to changes in muscle stretch velocity, while group II spindle afferents are sensitive to changes in amplitude (Grey et al., JPhysiol., 2001; Matthews, Trends...... Neurosci., 1991), group Ia velocity sensitive muscle spindle afferents likely contribute to the short-latency crossed spinal reflexes in the cBF muscle following iKnee joint rotations. This supports the findings for the short-latency crossed responses in the human soleus muscle (Stubbs & Mrachacz...

  16. Structure of the afferent terminals in terminal ganglion of a cricket and persistent homology.

    Jacob Brown

    Full Text Available We use topological data analysis to investigate the three dimensional spatial structure of the locus of afferent neuron terminals in crickets Acheta domesticus. Each afferent neuron innervates a filiform hair positioned on a cercus: a protruding appendage at the rear of the animal. The hairs transduce air motion to the neuron signal that is used by a cricket to respond to the environment. We stratify the hairs (and the corresponding afferent terminals into classes depending on hair length, along with position. Our analysis uncovers significant structure in the relative position of these terminal classes and suggests the functional relevance of this structure. Our method is very robust to the presence of significant experimental and developmental noise. It can be used to analyze a wide range of other point cloud data sets.

  17. The Potential Role of Catheter-Based Renal Sympathetic Denervation in Chronic and End-Stage Kidney Disease.

    Sata, Yusuke; Schlaich, Markus P


    Sympathetic activation is a hallmark of chronic and end-stage renal disease and adversely affects cardiovascular prognosis. Hypertension is present in the vast majority of these patients and plays a key role in the progressive deterioration of renal function and the high rate of cardiovascular events in this patient cohort. Augmentation of renin release, tubular sodium reabsorption, and renal vascular resistance are direct consequences of efferent renal sympathetic nerve stimulation and the major components of neural regulation of renal function. Renal afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control via hypothalamic integration. Renal denervation of the kidney has been shown to reduce blood pressure in many experimental models of hypertension. Targeting the renal nerves directly may therefore be specifically useful in patients with chronic and end-stage renal disease. In this review, we will discuss the potential role of catheter-based renal denervation in patients with impaired kidney function and also reflect on the potential impact on other cardiovascular conditions commonly associated with chronic kidney disease such as heart failure and arrhythmias.

  18. Contributions of Camillo Golgi to renal histology and embryology.

    Dal Canton, I; Calligaro, A L; Dal Canton, F; Frosio-Roncalli, M; Calligaro, A


    Camillo Golgi was awarded the Nobel prize in 1906 for his studies on the fine anatomy of the central nervous system. His wide present popularity depends on his discovery of the cell apparatus, the tendon mechanoreceptor and the tactile corpuscles of the fingertips that are named after him. However, Golgi also made important contributions to nephrology. In 1882, he published novel observations on the mechanism of renal hypertrophy, which he understood to be due to renal cell proliferation. Two years later, he described tubular cell mitoses in the kidney of a patient with tubulointerstitial nephritis, which he interpreted as an essential part of the repair process. His most important findings, published in 1889, were obtained by studying the microscopic anatomy of the kidney with an original technique that allowed the isolation of whole intact nephrons. He discovered that the ascending limb of Henle's loop always returned to the glomerulus from which the tubule originated, and he realized that the early distal tubule passed between the glomerular arterioles. In addition, applying the same method to dissect nephrons in progressive phases of development, he identified exactly what tubular segments originated from the various parts of the metanephric early S-shaped structure.

  19. Peptide and lipid modulation of glutamatergic afferent synaptic transmission in the solitary tract nucleus

    Michael C. Andresen


    Full Text Available The brainstem nucleus of the solitary tract (NTS holds the first central neurons in major homeostatic reflex pathways. These homeostatic reflexes regulate and coordinate multiple organ systems from gastrointestinal to cardiopulmonary functions. The core of many of these pathways arise from cranial visceral afferent neurons that enter the brain as the solitary tract (ST with more than two-thirds arising from the gastrointestinal system. About one quarter of ST afferents have myelinated axons but the majority are classed as unmyelinated C-fibers. All ST afferents release the fast neurotransmitter glutamate with remarkably similar, high-probability release characteristics. Second order NTS neurons receive surprisingly limited primary afferent information with one or two individual inputs converging on single second order NTS neurons. A- and C-fiber afferents never mix at NTS second order neurons. Many transmitters modify the basic glutamatergic excitatory postsynaptic current (EPSC often by reducing glutamate release or interrupting terminal depolarization. Thus, a distinguishing feature of ST transmission is presynaptic expression of G-protein coupled receptors for peptides common to peripheral or forebrain (e.g. hypothalamus neuron sources. Presynaptic receptors for angiotensin (AT1, vasopressin (V1a, oxytocin (OT, opioid (MOR, ghrelin (GHSR1 and cholecystokinin (CCK differentially control glutamate release on particular subsets of neurons with most other ST afferents unaffected. Lastly, lipid-like signals are transduced by two key ST presynaptic receptors, the transient receptor potential vanilloid type 1 (TRPV1 and the cannabinoid receptor (CB1 that oppositely control glutamate release. Increasing evidence suggests that peripheral nervous signaling mechanisms are repurposed at central terminals to control excitation and are major sites of signal integration of peripheral and central inputs particularly from the hypothalamus.

  20. Differential action of (-)-baclofen on the primary afferent depolarization produced by segmental and descending inputs.

    Quevedo, J; Eguibar, J R; Jiménez, I; Rudomin, P


    The purpose of the present series of experiments was to analyze, in anesthetized and paralyzed cats, the effects of (-)-baclofen and picrotoxin on the primary afferent depolarization (PAD) generated in single Ib afferent fibers by either intraspinal microstimulation or stimulation of the segmental and descending pathways. PAD was estimated by recording dorsal root potentials and by measuring the changes in the intraspinal activation threshold of single Ib muscle afferent fibers. The PAD elicited by stimulation of group I muscle or cutaneous afferents was readily depressed and often abolished 20-40 min after the intravenous injection of 1-2 mg/kg (-)-baclofen. In contrast, the same amounts of (-)-baclofen produced a relatively small depression of the PAD elicited by stimulation of the brainstem reticular formation (RF). The monosynaptic PAD produced in single Ib fibers by intraspinal microstimulation within the intermediate nucleus was depressed and sometimes abolished following the i.v. injections of 1-2 mg/kg (-)-baclofen. Twenty to forty minutes after the i.v. injection of picrotoxin (0.5-1 mg/kg), there was a strong depression of the PAD elicited by stimulation of muscle and cutaneous afferents as well as of the PAD produced by stimulation of the RF and the PAD produced by intraspinal microstimulation. The results obtained suggest that, in addition to its action on primary afferents, (-)-baclofen may depress impulse activity and/or transmitter release in a population of last-order GABAergic interneurons that mediate the PAD of Ib fibers. The existence of GABAb autoreceptors in last-order interneurons mediating the PAD may function as a self-limiting mechanism controlling the synaptic efficacy of these interneurons.

  1. Direct and indirect regulation of spinal cord Ia afferent terminal formation by the γ-Protocadherins

    Tuhina ePrasad


    Full Text Available The Pcdh-γ gene cluster encodes 22 protocadherin adhesion molecules that interact as homophilic multimers and critically regulate synaptogenesis and apoptosis of interneurons in the developing spinal cord. Unlike interneurons, the two primary components of the monosynaptic stretch reflex circuit, dorsal root ganglion sensory neurons and ventral motor neurons, do not undergo excessive apoptosis in Pcdh-γdel/del null mutants, which die shortly after birth. However, as we show here, mutants exhibit severely disorganized Ia proprioceptive afferent terminals in the ventral horn. In contrast to the fine net-like pattern observed in wild-type mice, central Ia terminals in Pcdh-γ mutants are expanded, clumped, and fill the space between individual motor neurons; quantitative analysis shows a ~2.5 fold increase in the area of terminals. Concomitant with this, there is a 70% loss of the collaterals that Ia afferents extend to ventral interneurons, many of which undergo apoptosis in the mutants. The Ia afferent phenotype is ameliorated, though not entirely rescued, when apoptosis is blocked in Pcdh-γ null mice by introduction of a Bax null allele. This indicates that loss of ventral interneurons, which act as intermediate Ia afferent targets, contributes to the disorganization of terminals on motor pools. Restricted mutation of the Pcdh-γ cluster using conditional mutants and multiple Cre transgenic lines (Wnt1-Cre for sensory neurons; Pax2-Cre for ventral interneurons; Hb9-Cre for motor neurons also revealed a direct requirement for the γ-Pcdhs in Ia neurons and ventral interneurons, but not in motor neurons themselves. Together, these genetic manipulations indicate that the γ-Pcdhs are required for the formation of the Ia afferent circuit in two ways: First, they control the survival of ventral interneurons that act as intermediate Ia targets; and second, they provide a homophilic molecular cue between Ia afferents and target ventral interneurons.

  2. Botulinum toxin in migraine: Role of transport in trigemino-somatic and trigemino-vascular afferents.

    Ramachandran, Roshni; Lam, Carmen; Yaksh, Tony L


    Migraine secondary to meningeal input is referred to extracranial regions innervated by somatic afferents that project to homologous regions in the trigeminal nucleus caudalis (TNC). Reported efficacy of extracranial botulinum toxin (BoNT) in treating migraine is surprising since a local extracranial effect of BoNT cannot account for its effect upon meningeal input. We hypothesize that intradermal BoNT acts through central transport in somatic afferents. Anesthetized C57Bl/6 mice (male) received unilateral supraorbital (SO) injections of BoNT-B (1.5 U/40 μl) or saline. 3 days later, mice received ipsilateral (ipsi)-SO capsaicin (20 μl of 0.5mM solution) or meningeal capsaicin (4 μl of 0.35 μM). Pre-treatment with ipsi-SO BoNT-B i) decreased nocicsponsive ipsilateral wiping behavior following ipsi-SO capsaicin; ii) produced cleavage of VAMP in the V1 region of ipsi-TG and in TG neurons showing WGA after SO injection; iii) reduced expression of c-fos in ipsi-TNC following ipsi-SO capsaicin; iv) reduced c-fos activation and NK-1 internalization in ipsi-TNC secondary to ipsi-meningeal capsaicin; and vi) SO WGA did not label dural afferents. We conclude that BoNT-B is taken up by peripheral afferents and transported to central terminals where it inhibits transmitter release resulting in decreased activation of second order neurons. Further, this study supports the hypothesis that SO BoNT exerts a trans-synaptic action on either the second order neuron (which receives convergent input from the meningeal afferent) or the terminal/TG of the converging meningeal afferent.

  3. The organization of primary afferent depolarization in the isolated spinal cord of the frog

    Carpenter, D. O.; Rudomin, P.


    1. The organization of primary afferent depolarization (PAD) produced by excitation of peripheral sensory and motor nerves was studied in the frog cord isolated with hind limb nerves. 2. Dorsal root potentials from sensory fibres (DR-DRPs) were evoked on stimulation of most sensory nerves, but were largest from cutaneous, joint and flexor muscle afferents. With single shock stimulation the largest cutaneous and joint afferent fibres gave DR-DRPs, but potentials from muscle nerves resulted from activation of sensory fibres with thresholds to electrical stimulation higher than 1·2-1·5 times the threshold of the most excitable fibres in the nerve. This suggests that PAD from muscle afferents is probably due to excitation of extrafusal receptors. 3. Dorsal root potentials produced by antidromic activation of motor fibres (VR-DRPs) were larger from extensor muscles and smaller or absent from flexor muscles. The VR-DRPs were produced by activation of the lowest threshold motor fibres. 4. Three types of interactions were found between test and conditioning DRPs from the same or different nerves. With maximal responses occlusion was usually pronounced. At submaximal levels linear summation occurred. Near threshold the conditioning stimulus frequently resulted in a large facilitation of the test DRP. All three types of interactions were found with two DR-DRPs, two VR-DRPs or one DR-DRP and one VR-DRP. 5. The excitability of sensory nerve terminals from most peripheral nerves was increased during the DR-DRP. The magnitude of the excitability increase varied roughly with the magnitude of the DR-DRP evoked by the conditioning stimulus. 6. There was a marked excitability increase of cutaneous and extensor muscle afferent terminals during the VR-DRP. Flexor muscle afferent terminals often showed no excitability changes to ventral root stimulation. In those experiments where afferent terminals from flexor muscles did show an excitability increase, the effects were smaller than

  4. The relaxing effect of perivascular tissue on porcine retinal arterioles in vitro is mimicked by N-methyl-D-aspartate and is blocked by prostaglandin synthesis inhibition

    Holmgaard, Kim; Aalkjaer, Christian; Lambert, John D C


    analogue U46619 was studied on vessels with preserved perivascular retinal tissue and after this tissue had been removed. The influence of the perivascular tissue was studied after addition of NMDA (a specific agonist for a subtype of the glutamate receptor), DL-amino-5-phosphonovaleric acid (DL......PURPOSE: Retinal hyperperfusion resulting from disturbances in the regulation of arteriolar tone is involved in the pathophysiology of a variety of retinal diseases. The mechanisms underlying this regulation of tone involve cellular components in both the vascular wall and the perivascular tissue....... However, previous in vitro studies of the influence of perivascular retinal tissue on retinal tone regulation have been hampered by the release of an endogenous relaxing factor that renders the arteriole insensitive to vasoconstrictors. The purpose of the present study was to test whether N...

  5. Significance of KATP channels, L-type Ca2+ channels and CYP450-4A enzymes in oxygen sensing in mouse cremaster muscle arterioles In vivo

    Ngo, Thuc Anh; Riemann, Mads; von Holstein-Rathlou, Niels-Henrik;


    of these mechanisms for oxygen sensing in arterioles in an in vivo model of metabolically active skeletal muscle. For this purpose we utilized the exteriorized cremaster muscle of anesthetized mice, in which the cremaster muscle was exposed to controlled perturbation of tissue PO₂....

  6. C4d immunoreactivity of intraoperative zero-hour biopsy in renal allograft.

    Lee, C; Park, J H; Suh, J H; Kim, H W; Moon, K C


    C4d deposition in the peritubular capillaries is known to be correlated with antibody-mediated rejection (AMR) in renal allografts. An intraoperative zero-hour biopsy during transplantation is considered an indicator to indirectly determine the status of the donor kidney. In this study, we investigated the relationship between C4d immunoreactivity of intraoperative zero-hour biopsy in renal allograft, thought to be due to donor condition, and acute rejection episodes during follow-up. We collected 147 renal transplantation cases examining intraoperative zero-hour biopsy with C4d immunohistochemical staining. All cases were from the Seoul National University Hospital between 2010 and 2011. Of the 147 cases, 24 (16.3%) showed strong C4d staining in the glomeruli, 38 (25.9%) showed weak staining, and the remainder (57.8%) showed negative staining. Nine cases (6.1%) showed positive C4d staining in the arterioles, and the remainder (93.9%) were negative. There were no significant differences between acute T-cell-mediated rejection and acute AMR episodes in the renal allograft specimens during follow-up according to the glomerular or arteriolar C4d immunoreactivity of the intraoperative zero-hour biopsy specimens.

  7. Determination of optimal blood pressure for patients with IgA nephropathy based on renal histology.

    Osawa, Y; Narita, I; Imai, N; Iino, N; Iguchi, S; Ueno, M; Shimada, H; Nishi, S; Arakawa, M; Gejyo, F


    To evaluate the optimal BP control for patients with IgA nephropathy (IgAN) based on the histologic severity of the nephropathy and the degree of renal dysfunction. We analyzed 332 consecutive renal biopsy specimens and clinical data from patients with IgAN. Patients were divided into three groups based on their BP at the time of biopsy: an optimal BP (SBP or = 140 mmHg and/or DBP > or = 90 mmHg), and an intermediate BP group. Each biopsy specimen was evaluated for mesangial proliferation, degree of sclerosis and/or hyalinosis of the arterioles and the interlobular artery using a semiquantitative method. Creatinine clearance and the percentage of sclerosed glomeruli were also determined. Both the degree of renal dysfunction and the histologic changes correlated significantly with BP, even in patients with a BP <140/90 mmHg. The patients with an optimal BP at the time of biopsy had significantly less histologic damage with respect to mesangial proliferation and vessel changes than those with an intermediate or hypertensive BP. In the patients with a hypertensive BP, the percentage of sclerotic glomeruli was significantly higher and the creatinine clearance was significantly lower. The optimal BP proposed by the WHO in 1999 prevents histologic evidence of renal damage for patients with IgAN.

  8. Kidney (Renal) Failure

    ... How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain proper fluid ... marrow and strengthen the bones. The term kidney (renal) failure describes a situation in which the kidneys have ...

  9. Renal arteries (image)

    A renal angiogram is a test used to examine the blood vessels of the kidneys. The test is performed ... main vessel of the pelvis, up to the renal artery that leads into the kidney. Contrast medium ...

  10. Functional analysis of ultra high information rates conveyed by rat vibrissal primary afferents

    A.M. Chagas (André); L. Theis (Lucas); B. Sengupta (Biswa); M.C. Stüttgen (Maik); M. Bethge (Matthias); C. Schwarz (Cornelius)


    textabstractSensory receptors determine the type and the quantity of information available for perception. Here, we quantified and characterized the information transferred by primary afferents in the rat whisker system using neural system identification. Quantification of "how much" information is

  11. Nesfatin-1 modulates murine gastric vagal afferent mechanosensitivity in a nutritional state dependent manner.

    Kentish, Stephen J; Li, Hui; Frisby, Claudine L; Page, Amanda J


    Food intake is regulated by vagal afferent signals from the stomach. Nesfatin-1 is an anorexigenic peptide produced within the gastrointestinal tract and has well defined central effects. We aimed to determine if nesfatin-1 can modulate gastric vagal afferent signals in the periphery and further whether this is altered in different nutritional states. Female C57BL/6J mice were fed either a standard laboratory diet (SLD) or a high fat diet (HFD) for 12 weeks or fasted overnight. Plasma nucleobindin-2 (NUCB2; nesfatin-1 precursor)/nesfatin-1 levels were assayed, the expression of NUCB2 in the gastric mucosa and adipose tissue was assessed using real-time quantitative reverse-transcription polymerase chain reaction. An in vitro preparation was used to determine the effect of nesfatin-1 on gastric vagal afferent mechanosensitivity. HFD mice exhibited an increased body weight and adiposity. Plasma NUCB2/nesfatin-1 levels were unchanged between any of the groups of mice. NUCB2 mRNA was detected in the gastric mucosa and gonadal fat of SLD, HFD and fasted mice with no difference in mRNA abundance between groups in either tissue. In SLD and fasted mice nesfatin-1 potentiated mucosal receptor mechanosensitivity, an effect not observed in HFD mice. Tension receptor mechanosensitivity was unaffected by nesfatin-1 in SLD and fasted mice, but was inhibited in HFD mice. In conclusion, Nesfatin-1 modulates gastric vagal afferent mechanosensitivity in a nutritional state dependent manner.

  12. Afferent loop syndrome - a case report; Sindrome da alca aferente - relato de um caso

    Borges, Ana Karina Nascimento; Pinheiro, Marco Antonio Lopes; Galvao, Cristine Norwig [Fundacao Pio XII - Hospital do Cancer de Barretos, SP (Brazil)


    The afferent loop syndrome occurs in patients with previous gastric surgery for tumor, when there is anastomotic edema, use of inappropriate reconstruction technique for gastro jejunostomy or recurrent gastric cancer. Complaints such jaundice, intermittent abdominal distension associated with pain, and vomiting should be investigated in order to rule out this syndrome. (author)

  13. Ghrelin counteracts insulin-induced activation of vagal afferent neurons via growth hormone secretagogue receptor.

    Iwasaki, Yusaku; Dezaki, Katsuya; Kumari, Parmila; Kakei, Masafumi; Yada, Toshihiko


    Vagal afferent nerves sense meal-related gastrointestinal and pancreatic hormones and convey their information to the brain, thereby regulating brain functions including feeding. We have recently demonstrated that postprandial insulin directly acts on the vagal afferent neurons. Plasma concentrations of orexigenic ghrelin and anorexigenic insulin show reciprocal dynamics before and after meals. The present study examined interactive effects of ghrelin and insulin on vagal afferent nerves. Cytosolic Ca(2+) concentration ([Ca(2+)]i) in isolated nodose ganglion (NG) neurons was measured to monitor their activity. Insulin at 10(-7)M increased [Ca(2+)]i in NG neurons, and the insulin-induced [Ca(2+)]i increase was inhibited by treatment with ghrelin at 10(-8)M. This inhibitory effect of ghrelin was attenuated by [D-Lys(3)]-GHRP-6, an antagonist of growth hormone-secretagogue receptor (GHSR). Des-acyl ghrelin had little effect on insulin-induced [Ca(2+)]i increases in NG neurons. Ghrelin did not affect [Ca(2+)]i increases in response to cholecystokinin (CCK), a hormone that inhibits feeding via vagal afferent neurons, indicating that ghrelin selectively counteracts the insulin action. These results demonstrate that ghrelin via GHSR suppresses insulin-induced activation of NG neurons. The action of ghrelin to counteract insulin effects on NG might serve to efficiently inform the brain of the systemic change between fasting-associated ghrelin-dominant and fed-associated insulin-dominant states for the homeostatic central regulation of feeding and metabolism.

  14. Role of primary afferents in the developmental regulation of motor axon synapse numbers on Renshaw cells.

    Siembab, Valerie C; Gomez-Perez, Laura; Rotterman, Travis M; Shneider, Neil A; Alvarez, Francisco J


    Motor function in mammalian species depends on the maturation of spinal circuits formed by a large variety of interneurons that regulate motoneuron firing and motor output. Interneuron activity is in turn modulated by the organization of their synaptic inputs, but the principles governing the development of specific synaptic architectures unique to each premotor interneuron are unknown. For example, Renshaw cells receive, at least in the neonate, convergent inputs from sensory afferents (likely Ia) and motor axons, raising the question of whether they interact during Renshaw cell development. In other well-studied neurons, such as Purkinje cells, heterosynaptic competition between inputs from different sources shapes synaptic organization. To examine the possibility that sensory afferents modulate synaptic maturation on developing Renshaw cells, we used three animal models in which afferent inputs in the ventral horn are dramatically reduced (ER81(-/-) knockout), weakened (Egr3(-/-) knockout), or strengthened (mlcNT3(+/-) transgenic). We demonstrate that increasing the strength of sensory inputs on Renshaw cells prevents their deselection and reduces motor axon synaptic density, and, in contrast, absent or diminished sensory afferent inputs correlate with increased densities of motor axons synapses. No effects were observed on other glutamatergic inputs. We conclude that the early strength of Ia synapses influences their maintenance or weakening during later development and that heterosynaptic influences from sensory synapses during early development regulates the density and organization of motor inputs on mature Renshaw cells.

  15. Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats

    Nelson, David W; Liu, Xiaowen; Holst, Jens Juul


    Small bowel resection stimulates intestinal adaptive growth by a neuroendocrine process thought to involve both sympathetic and parasympathetic innervation and enterotrophic hormones such as glucagon-like peptide-2 (GLP-2). We investigated whether capsaicin-sensitive vagal afferent neurons are es...

  16. Inhibitory mechanisms following electrical stimulation of tendon and cutaneous afferents in the lower limb.

    Khan, Serajul I; Burne, John A


    Electrical stimulation of the Achilles tendon (TES) produced strong reflex depression (duration>250 ms) of a small background contraction in both heads of gastrocnemius (GA) via large diameter electrodes localized to the tendon. The inhibitory responses were produced without electrical (M wave) or mechanical (muscle twitch) signs of direct muscle stimulation. In this study, the contribution of presynaptic and postsynaptic mechanisms to the depression was investigated by studying conditioning effects of tendon afferent stimulation on the mechanical tendon reflex (TR) and magnetic motor evoked potential (MEP). TES completely inhibited the TR over an ISI of 300 ms that commenced before and continued during and after the period of voluntary EMG depression. Tendon afferent conditioning stimuli also partially inhibited the MEP, but over a short time course confined to the period of voluntary EMG depression. The strength and extended time course of tendon afferent conditioning of the TR and its failure to produce a similar depression of the MEP are consistent with a mechanism involving presynaptic inhibition of Ia terminals. Cutaneous (sural nerve) afferent conditioning partially inhibited the TR and MEP over a short time course (ISI voluntary EMG. This was consistent with the postsynaptic origin of cutaneous inhibition of the motoneurons.

  17. Chronic exposure to low dose bacterial lipopolysaccharide inhibits leptin signaling in vagal afferent neurons.

    de La Serre, Claire B; de Lartigue, Guillaume; Raybould, Helen E


    Bacterially derived factors are implicated in the causation and persistence of obesity. Ingestion of a high fat diet in rodents and obesity in human subjects is associated with chronic elevation of low plasma levels of lipopolysaccharide (LPS), a breakdown product of Gram-negative bacteria. The terminals of vagal afferent neurons are positioned within the gut mucosa to convey information from the gut to the brain to regulate food intake and are responsive to LPS. We hypothesized that chronic elevation of LPS could alter vagal afferent signaling. We surgically implanted osmotic mini-pumps that delivered a constant, low-dose of LPS into the intraperitoneal cavity of rats (12.5 μg/kg/hr for 6 weeks). LPS-treated rats developed hyperphagia and showed marked changes in vagal afferent neuron function. Chronic LPS treatment reduced vagal afferent leptin signaling, characterized by a decrease in leptin-induced STAT3 phosphorylation. In addition, LPS treatment decreased cholecystokinin-induced satiety. There was no alteration in leptin signaling in the hypothalamus. These findings offer a mechanism by which a change in gut microflora can promote hyperphagia, possibly leading to obesity.

  18. Immobilization induces changes in presynaptic control of group Ia afferents in healthy humans

    Jensen, Jesper Lundbye; Nielsen, Jens Bo


    maximal voluntary plantar- and dorsiflexion torque (MVC) was significantly reduced and the maximal SOL H-reflex amplitude increased with no changes in Mmax. Decreased presynaptic inhibition of the Ia afferents likely contributed to the increase of the H-reflex size, since we observed a significant...

  19. Synaptic transmission of baro- and chemoreceptors afferents in the NTS second order neurons.

    Accorsi-Mendonça, Daniela; Machado, Benedito H


    Second order neurons in the nucleus tractus solitarius (NTS) process and integrate the afferent information from arterial baroreceptors with high fidelity and precise timing synaptic transmission. Since 2nd-order NTS neurons receiving baroreceptors inputs are relatively well characterized, their electrophysiological profile has been accepted as a general characteristic for all 2nd-order NTS neurons involved with the processing of different sensorial inputs. On the other hand, the synaptic properties of other afferent systems in NTS, such as the peripheral chemoreceptors, are not yet well understood. In this context, in previous studies we demonstrated that in response to repetitive afferents stimulation, the chemoreceptors 2nd-order NTS neurons also presented high fidelity of synaptic transmission, but with a large variability in the latency of evoked responses. This finding is different in relation to the precise timing transmission for baroreceptor 2nd-order NTS neurons, which was accepted as a general characteristic profile for all 2nd order neurons in the NTS. In this brief review we discuss this new concept as an index of complexity of the sensorial inputs to NTS with focus on the synaptic processing of baro- and chemoreceptor afferents.

  20. Afferent and Efferent Connections of the Optic Tectum in the Carp (Cyprinus carpio L.)

    Luiten, P.G.M.


    The afferent and efferent connections of the tectum opticum in the carp (Cyprinus carpio L.) were studied with the HRP method. Following iontophoretic peroxidase injections in several parts of the rectum anterograde transport of the enzyme revealed tectal projections to the lateral geniculate nucleu

  1. Tactile stimulation with kinesiology tape alleviates muscle weakness attributable to attenuation of Ia afferents.

    Konishi, Yu


    Prolonged vibration stimulation to normal individuals could lead to muscle weakness attributable to attenuation of afferent feedback. This weakness is neurophysiologically similar to that seen in patients with knee injury. Theoretically, increasing input to gamma motor neurons could reverse this weakness. Sensory input to these neurons from skin could indirectly increase Ia afferent feedback. The present study examined the effect of this tactile stimulation in the form of Kinesiology tape on muscle weakness attributable to attenuation of afferent feedback. Randomized, crossover design. All participants were measured their eccentric maximal voluntary contractions under the 2 conditions (taping and non-taping). First, maximal voluntary contraction during eccentric contraction was measured as baseline. For the taping condition, Kinesiology tape was applied around each subject's knee joint during maximal voluntary contraction measurement after vibration. For the non-taping condition, tape was not applied during maximal voluntary contraction measurement after vibration. Mean percentage changes between pre- and post-vibration stimulation were compared between two conditions. Maximal voluntary contraction and average electromyography of taping condition was significantly larger than that of non-taping condition. Our results suggest that tactile stimulation in the form of Kinesiology tape inhibits the decline of both strength and electromyography. Alpha motor neuron activity attenuated by prolonged vibration would thus be partially rescued by tactile stimulation. These results indirectly suggest that stimulation of skin around the knee could counter quadriceps femoris weakness due to attenuated Ia afferent activity. Copyright © 2012 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  2. Afferent Innervation, Muscle Spindles, and Contractures Following Neonatal Brachial Plexus Injury in a Mouse Model.

    Nikolaou, Sia; Hu, Liangjun; Cornwall, Roger


    We used an established mouse model of elbow flexion contracture after neonatal brachial plexus injury (NBPI) to test the hypothesis that preservation of afferent innervation protects against contractures and is associated with preservation of muscle spindles and ErbB signaling. A model of preganglionic C5 through C7 NBPI was first tested in mice with fluorescent axons using confocal imaging to confirm preserved afferent innervation of spindles despite motor end plate denervation. Preganglionic and postganglionic injuries were then created in wild-type mice. Four weeks later, we assessed total and afferent denervation of the elbow flexors by musculocutaneous nerve immunohistochemistry. Biceps muscle volume and cross-sectional area were measured by micro computed tomography. An observer who was blinded to the study protocol measured elbow flexion contractures. Biceps spindle and muscle fiber morphology and ErbB signaling pathway activity were assessed histologically and immunohistochemically. Preganglionic and postganglionic injuries caused similar total denervation and biceps muscle atrophy. However, after preganglionic injuries, afferent innervation was partially preserved and elbow flexion contractures were significantly less severe. Spindles degenerated after postganglionic injury but were preserved after preganglionic injury. ErbB signaling was inactivated in denervated spindles after postganglionic injury but ErbB signaling activity was preserved in spindles after preganglionic injury with retained afferent innervation. Preganglionic and postganglionic injuries were associated with upregulation of ErbB signaling in extrafusal muscle fibers. Contractures after NBPI are associated with muscle spindle degeneration and loss of spindle ErbB signaling activity. Preservation of afferent innervation maintained spindle development and ErbB signaling activity, and protected against contractures. Pharmacologic modulation of ErbB signaling, which is being investigated as a

  3. [Renal leiomyoma. Case report].

    Joual, A; Guessous, H; Rabii, R; Benjelloun, M; Benlemlih, A; Skali, K; el Mrini, M; Benjelloun, S


    The authors report a case of renal leiomyoma observed in a 56-year-old man. This cyst presented in the from of loin pain. Computed tomography revealed a homogeneous renal tumor. Treatment consisted of radical nephrectomy. Histological examination of the specimen showed benign renal leiomyoma.

  4. Renal inflammatory myofibroblastic tumor

    Heerwagen, S T; Jensen, C; Bagi, P


    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  5. Renal denervation in the treatment of resistant hypertension: Dead, alive or surviving?

    Al-Fakhouri, Ahmad; Efeovbokhan, Nephertiti; Nakhla, Rami; Khouzam, Rami N


    Hypertension is one of the most common chronic clinical problems encountered by physicians. The prevalence of resistant hypertension is estimated at 9% in the US. Patients with resistant hypertension have been shown to be at higher risk for adverse cardiovascular events, hence the need for greater efforts in improving the treatment of hypertension. The renal sympathetic nerves play an important role in the development of hypertension, mediated via sodium and water retention, increased renin release and alterations in renal blood flow. The proximity of the afferent and efferent renal sympathetic nerves to the adventitia of the renal arteries suggested the feasibility of an endovascular, selective, minimally invasive approach to renal denervation; a potential treatment option for resistant hypertension. While the RAPID, Reduce-HTN, EnligHTN, DENERHTN and Symplicity HTN-1 and -2 studies showed significant benefit of renal denervation in the treatment of resistant hypertension, the results of Oslo RDN, Prague-15 and Symplicity HTN-3 were not so favorable. Future well-designed clinical trials are needed to ascertain the benefits or otherwise of renal denervation in treatment-resistant hypertension.

  6. Spinal afferent neurons projecting to the rat lung and pleura express acid sensitive channels

    Kummer Wolfgang


    Full Text Available Abstract Background The acid sensitive ion channels TRPV1 (transient receptor potential vanilloid receptor-1 and ASIC3 (acid sensing ion channel-3 respond to tissue acidification in the range that occurs during painful conditions such as inflammation and ischemia. Here, we investigated to which extent they are expressed by rat dorsal root ganglion neurons projecting to lung and pleura, respectively. Methods The tracer DiI was either injected into the left lung or applied to the costal pleura. Retrogradely labelled dorsal root ganglion neurons were subjected to triple-labelling immunohistochemistry using antisera against TRPV1, ASIC3 and neurofilament 68 (marker for myelinated neurons, and their soma diameter was measured. Results Whereas 22% of pulmonary spinal afferents contained neither channel-immunoreactivity, at least one is expressed by 97% of pleural afferents. TRPV1+/ASIC3- neurons with probably slow conduction velocity (small soma, neurofilament 68-negative were significantly more frequent among pleural (35% than pulmonary afferents (20%. TRPV1+/ASIC3+ neurons amounted to 14 and 10% respectively. TRPV1-/ASIC3+ neurons made up between 44% (lung and 48% (pleura of neurons, and half of them presumably conducted in the A-fibre range (larger soma, neurofilament 68-positive. Conclusion Rat pleural and pulmonary spinal afferents express at least two different acid-sensitive channels that make them suitable to monitor tissue acidification. Patterns of co-expression and structural markers define neuronal subgroups that can be inferred to subserve different functions and may initiate specific reflex responses. The higher prevalence of TRPV1+/ASIC3- neurons among pleural afferents probably reflects the high sensitivity of the parietal pleura to painful stimuli.

  7. Central distribution of octavolateral afferents and efferents in a teleost (Mormyridae).

    Bell, C C


    The central distribution of afferents from individual eight nerve branches (N VIII) and mechanical lateral line end organs in mormyrid fish are described. Afferents were labeled with horseradish peroxidase (HRP) placed on the cut ends of the different N VIII branches and the anterior and posterior lateral line nerves. Descending, tangential, and magnocellular nuclei receive input almost exclusively from the utriculus and canals. Nucleus octavius receives afferents from the lateral line nerves and all N VIII branches, with one part receiving exclusive and bilateral input from the sacculus. Afferents from both lateral line nerves and all N VII branches, except the sacculus, end in eminentia granularis. Afferents from each of the two lateral line nerves and from each of three otolith branches of N VIII end in different regions of the anterior lateral line lobe, with some areas of overlap. Behavioral studies in other families of fish indicate that the utriculus and canals are critical for postural control, whereas the sacculus and possibly the lagena are concerned with hearing. Such findings, together with the results of this study, suggest that mormyrids and perhaps other fish possess separate auditory and vestibular centers within the octavolateral area. The HRP method also shows the cell bodies and axons of octavolateral efferents. N VIII and lateral line efferents arise from a common nucleus, and the central course of their axons parallels that of facial motoneurons. Axons of efferent cells divide to supply two or more branches of N VIII and some axons supply both lateral line and N VIII end organs.

  8. Identification of multisegmental nociceptive afferents that modulate locomotor circuits in the neonatal mouse spinal cord.

    Mandadi, Sravan; Hong, Peter; Tran, Michelle A; Bráz, Joao M; Colarusso, Pina; Basbaum, Allan I; Whelan, Patrick J


    Compared to proprioceptive afferent collateral projections, less is known about the anatomical, neurochemical, and functional basis of nociceptive collateral projections modulating lumbar central pattern generators (CPG). Quick response times are critical to ensure rapid escape from aversive stimuli. Furthermore, sensitization of nociceptive afferent pathways can contribute to a pathological activation of motor circuits. We investigated the extent and role of collaterals of capsaicin-sensitive nociceptive sacrocaudal afferent (nSCA) nerves that directly ascend several spinal segments in Lissauer's tract and the dorsal column and regulate motor activity. Anterograde tracing demonstrated direct multisegmental projections of the sacral dorsal root 4 (S4) afferent collaterals in Lissauer's tract and in the dorsal column. Subsets of the traced S4 afferent collaterals expressed transient receptor potential vanilloid 1 (TRPV1), which transduces a nociceptive response to capsaicin. Electrophysiological data revealed that S4 dorsal root stimulation could evoke regular rhythmic bursting activity, and our data suggested that capsaicin-sensitive collaterals contribute to CPG activation across multiple segments. Capsaicin's effect on S4-evoked locomotor activity was potent until the lumbar 5 (L5) segments, and diminished in rostral segments. Using calcium imaging we found elevated calcium transients within Lissauer's tract and dorsal column at L5 segments when compared to the calcium transients only within the dorsal column at the lumbar 2 (L2) segments, which were desensitized by capsaicin. We conclude that lumbar locomotor networks in the neonatal mouse spinal cord are targets for modulation by direct multisegmental nSCA, subsets of which express TRPV1 in Lissauer's tract and the dorsal column. J. Comp. Neurol. 521:2870-2887, 2013. © 2013 Wiley Periodicals, Inc.

  9. Postpartum renal vein thrombosis.

    Rubens, D; Sterns, R H; Segal, A J


    Renal vein thrombosis in adults is usually a complication of the nephrotic syndrome. Rarely, it has been reported in nonnephrotic women postpartum. The thrombosis may be a complication of the hypercoagulable state associated with both the nephrotic syndrome and pregnancy. Two postpartum patients with renal vein thrombosis and no prior history of renal disease are reported here. Neither patient had heavy proteinuria. In both cases, pyelonephritis was suspected clinically and the diagnosis of renal vein thrombosis was first suggested and confirmed by radiologic examination. Renal vein thrombosis should be considered in women presenting postpartum with flank pain.

  10. Renal infarction resulting from traumatic renal artery dissection.

    Kang, Kyung Pyo; Lee, Sik; Kim, Won; Jin, Gong Yong; Na, Ki Ryang; Yun, Il Yong; Park, Sung Kwang


    Renal artery dissection may be caused by iatrogenic injury, trauma, underlying arterial diseases such as fibromuscular disease, atherosclerotic disease, or connective tissue disease. Radiological imaging may be helpful in detecting renal artery pathology, such as renal artery dissection. For patients with acute, isolated renal artery dissection, surgical treatment, endovascular management, or medical treatment have been considered effective measures to preserve renal function. We report a case of renal infarction that came about as a consequence of renal artery dissection.



    Objective To investigate the role of NRM in the antinociceptive effect of muscle spindle afferents, the influence of NRM lesion on the inhibitory effect of muscle spindle afferents on the nociceptive responses of wide dynamic range (WDR) neurons and the effects of the muscle spindle afferents on the NRM neuronal activities were observed. Methods The single units of WDR neurons in the spinal dorsal horn were recorded extracellularly, and the inhibitory effects of activating muscle spindle afferents by intravenous administration of succinyicholine (SCH) on the C-fibers evoked responses (C-responses) of WDR neurons were tested before and after lesion of NRM. The ef- fects of the muscle spindle afferents activated by administrating SCH on the single NRM neurons were also examined. Results ①lt was found that the C-responses of WDR neurons were significantly inhibited by intravenously adminis- tration of SCH, and the inhibitory effect was reduced after lesion of NRM ;②The activities of most of the NRM neu- rons could be changed significantly by administrating SCH. According to their responses, NRM neurons could be classified into three types:excitatory, inhibitory and non-responsive neurons, and the responses were dose-depen- dent. Conclusion These results suggest that the muscle spindle afferents evoked by SCH may activate the NRM neu- rons, which plays an important role in the antinociception of muscle spindle afferents.

  12. Cerebral, subcortical, and cerebellar activation evoked by selective stimulation of muscle and cutaneous afferents: an fMRI study.

    Wardman, Daniel L; Gandevia, Simon C; Colebatch, James G


    Abstract We compared the brain areas that showed significant flow changes induced by selective stimulation of muscle and cutaneous afferents using fMRI BOLD imaging. Afferents arising from the right hand were studied in eight volunteers with electrical stimulation of the digital nerve of the index finger and over the motor point of the FDI muscle. Both methods evoked areas of significant activation cortically, subcortically, and in the cerebellum. Selective muscle afferent stimulation caused significant activation in motor-related areas. It also caused significantly greater activation within the contralateral precentral gyrus, insula, and within the ipsilateral cerebellum as well as greater areas of reduced blood flow when compared to the cutaneous stimuli. We demonstrated separate precentral and postcentral foci of excitation with muscle afferent stimulation. We conclude, contrary to the findings with evoked potentials, that muscle afferents evoke more widespread cortical, subcortical, and cerebellar activation than do cutaneous afferents. This emphasizes the importance, for studies of movement, of matching the kinematic aspects in order to avoid the results being confounded by alterations in muscle afferent activation. The findings are consistent with clinical observations of the movement consequences of sensory loss and may also be the basis for the contribution of disturbed sensorimotor processing to disorders of movement.

  13. Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying.

    Raybould, Helen E; Glatzle, Jorg; Robin, Carla; Meyer, James H; Phan, Thomas; Wong, Helen; Sternini, Catia


    Intestinal perfusion with carbohydrates inhibits gastric emptying via vagal and spinal capsaicin-sensitive afferent pathways. The aim of the present study was to determine the role of 1) 5-hydroxytryptamine (5-HT)(3) receptors (5-HT(3)R) in mediating glucose-induced inhibition of gastric emptying and 2) 5-HT(3)R expression in vagal and spinal afferents in innervating the duodenum. In awake rats fitted with gastric and duodenal cannulas, perfusion of the duodenum with glucose (50 and 100 mg) inhibited gastric emptying. Intestinal perfusion of mannitol inhibited gastric emptying only at the highest concentration (990 mosm/kgH(2)O). Pretreatment with the 5-HT(3)R antagonist tropisetron abolished both glucose- and mannitol-induced inhibition of gastric emptying. Retrograde labeling of visceral afferents by injection of dextran-conjugated Texas Red into the duodenal wall was used to identify extrinsic primary afferents. Immunoreactivity for 5-HT(3)R, visualized with an antibody directed to the COOH terminus of the rat 5-HT(3)R, was found in >80% of duodenal vagal and spinal afferents. These results show that duodenal extrinsic afferents express 5-HT(3)R and that the receptor mediates specific glucose-induced inhibition of gastric emptying. These findings support the hypothesis that enterochromaffin cells in the intestinal mucosa release 5-HT in response to glucose, which activates 5-HT(3)R on afferent nerve terminals to evoke reflex changes in gastric motility. The primary glucose sensors of the intestine may be mucosal enterochromaffin cells.

  14. Isolation of TRPV1 independent mechanisms of spontaneous and asynchronous glutamate release at primary afferent to NTS synapses.

    Fenwick, Axel J; Wu, Shaw-Wen; Peters, James H


    Cranial visceral afferents contained within the solitary tract (ST) contact second-order neurons in the nucleus of the solitary tract (NTS) and release the excitatory amino acid glutamate via three distinct exocytosis pathways; synchronous, asynchronous, and spontaneous release. The presence of TRPV1 in the central terminals of a majority of ST afferents conveys activity-dependent asynchronous glutamate release and provides a temperature sensitive calcium conductance which largely determines the rate of spontaneous vesicle fusion. TRPV1 is present in unmyelinated C-fiber afferents and these facilitated forms of glutamate release may underlie the relative strength of C-fibers in activating autonomic reflex pathways. However, pharmacological blockade of TRPV1 signaling eliminates only ~50% of the asynchronous profile and attenuates the temperature sensitivity of spontaneous release indicating additional thermosensitive calcium influx pathways may exist which mediate these forms of vesicle release. In the present study we isolate the contribution of TRPV1 independent forms of glutamate release at ST-NTS synapses. We found ST afferent innervation at NTS neurons and synchronous vesicle release from TRPV1 KO mice was not different to control animals; however, only half of TRPV1 KO ST afferents completely lacked asynchronous glutamate release. Further, temperature driven spontaneous rates of vesicle release were not different from 33 to 37°C between control and TRPV1 KO afferents. These findings suggest additional temperature dependent mechanisms controlling asynchronous and thermosensitive spontaneous release at physiological temperatures, possibly mediated by additional thermosensitive TRP channels in primary afferent terminals.

  15. Different types of spinal afferent nerve endings in stomach and esophagus identified by anterograde tracing from dorsal root ganglia.

    Spencer, Nick J; Kyloh, Melinda; Beckett, Elizabeth A; Brookes, Simon; Hibberd, Tim


    In visceral organs of mammals, most noxious (painful) stimuli as well as innocuous stimuli are detected by spinal afferent neurons, whose cell bodies lie in dorsal root ganglia (DRGs). One of the major unresolved questions is the location, morphology, and neurochemistry of the nerve endings of spinal afferents that actually detect these stimuli in the viscera. In the upper gastrointestinal (GI) tract, there have been many anterograde tracing studies of vagal afferent endings, but none on spinal afferent endings. Recently, we developed a technique that now provides selective labeling of only spinal afferents. We used this approach to identify spinal afferent nerve endings in the upper GI tract of mice. Animals were anesthetized, and injections of dextran-amine were made into thoracic DRGs (T8-T12). Seven days post surgery, mice were euthanized, and the stomach and esophagus were removed, fixed, and stained for calcitonin gene-related peptide (CGRP). Spinal afferent axons were identified that ramified extensively through many rows of myenteric ganglia and formed nerve endings in discrete anatomical layers. Most commonly, intraganglionic varicose endings (IGVEs) were identified in myenteric ganglia of the stomach and varicose simple-type endings in the circular muscle and mucosa. Less commonly, nerve endings were identified in internodal strands, blood vessels, submucosal ganglia, and longitudinal muscle. In the esophagus, only IGVEs were identified in myenteric ganglia. No intraganglionic lamellar endings (IGLEs) were identified in the stomach or esophagus. We present the first identification of spinal afferent endings in the upper GI tract. Eight distinct types of spinal afferent endings were identified in the stomach, and most of them were CGRP immunoreactive. J. Comp. Neurol. 524:3064-3083, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Serotonin, Dopamine and Noradrenaline Adjust Actions of Myelinated Afferents via Modulation of Presynaptic Inhibition in the Mouse Spinal Cord

    García-Ramírez, David L.; Calvo, Jorge R.; Hochman, Shawn; Quevedo, Jorge N.


    Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD). PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT), dopamine (DA) and noradrenaline (NA) on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs) or intracellular excitatory postsynaptic currents (EPSCs). The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs) recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75%) but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic transmission in the

  17. Serotonin, dopamine and noradrenaline adjust actions of myelinated afferents via modulation of presynaptic inhibition in the mouse spinal cord.

    David L García-Ramírez

    Full Text Available Gain control of primary afferent neurotransmission at their intraspinal terminals occurs by several mechanisms including primary afferent depolarization (PAD. PAD produces presynaptic inhibition via a reduction in transmitter release. While it is known that descending monoaminergic pathways complexly regulate sensory processing, the extent these actions include modulation of afferent-evoked PAD remains uncertain. We investigated the effects of serotonin (5HT, dopamine (DA and noradrenaline (NA on afferent transmission and PAD. Responses were evoked by stimulation of myelinated hindlimb cutaneous and muscle afferents in the isolated neonatal mouse spinal cord. Monosynaptic responses were examined in the deep dorsal horn either as population excitatory synaptic responses (recorded as extracellular field potentials; EFPs or intracellular excitatory postsynaptic currents (EPSCs. The magnitude of PAD generated intraspinally was estimated from electrotonically back-propagating dorsal root potentials (DRPs recorded on lumbar dorsal roots. 5HT depressed the DRP by 76%. Monosynaptic actions were similarly depressed by 5HT (EFPs 54%; EPSCs 75% but with a slower time course. This suggests that depression of monosynaptic EFPs and DRPs occurs by independent mechanisms. DA and NA had similar depressant actions on DRPs but weaker effects on EFPs. IC50 values for DRP depression were 0.6, 0.8 and 1.0 µM for 5HT, DA and NA, respectively. Depression of DRPs by monoamines was nearly-identical in both muscle and cutaneous afferent-evoked responses, supporting a global modulation of the multimodal afferents stimulated. 5HT, DA and NA produced no change in the compound antidromic potentials evoked by intraspinal microstimulation indicating that depression of the DRP is unrelated to direct changes in the excitability of intraspinal afferent fibers, but due to metabotropic receptor activation. In summary, both myelinated afferent-evoked DRPs and monosynaptic

  18. Specific and potassium components in the depolarization of the la afferents in the spinal cord of the cat.

    Jiménez, I; Rudomin, P; Solodkin, M; Vyklicky, L


    In the cat spinal cord, primary afferent depolarization (PAD) of group Ia fibers of extensor muscles is produced by high-frequency stimulation (100 Hz) of group I muscle flexor afferents without significant increases in extracellular potassium. On the other hand, the PAD produced by stimulation of mixed and pure cutaneous nerves correlates well with increases in potassium ions. We conclude that the PAD produced by group I muscle afferents results from the activation of specific pathways making axo-axonic synapses with the Ia fiber terminals. The PAD of Ia fibers resulting from activation of cutaneous nerves involves instead unspecific accumulation of potassium ions.

  19. Functional properties of heteromeric P2X(1/5) receptors expressed in HEK cells and excitatory junction potentials in guinea-pig submucosal arterioles.

    Surprenant, A; Schneider, D A; Wilson, H L; Galligan, J J; North, R A


    P2X receptors are ATP-gated cation channels; they form as homomers or heteromers from a family of seven related subunits. In particular, heteromeric channels comprising P2X(2) and P2X(3) subunits, or P2X(1) and P2X(5) subunits, show distinctive physiological and pharmacological properties in heterologous expression systems. There is substantial evidence that one of the native P2X receptors in sensory neurones corresponds to the P2X(2/3) heteromer, but there is no evidence for P2X(1/5) heteromers in native tissue. We recorded currents in response to activation of heteromeric P2X(1/5) receptors expressed in HEK293 cells to characterize further their functional properties. The ATP concentration-response curve had a threshold concentration of 1 nM, and a Hill slope of one. TNP-ATP was a weak partial agonist, and a non-competitive antagonist which inhibited maximal ATP currents by 60%. Increasing or decreasing pH from 7.3 shifted the ATP concentration-response curves to the right by fivefold and decreased the maximum current by 40%. Calcium permeability was lower than that observed for other P2X receptors (P(Ca)/P(Na) ratio=1.1). The nanomolar sensitivity of this receptor revealed a steady release of ATP from HEK293 cells, providing an extracellular concentration which ranged from 3 to 300 nM. Noradrenaline (0.3-30 microM) increased ATP-evoked currents by 35%; this facilitation occurred within 20 ms. We also recorded excitatory junction potentials (EJPs) from guinea-pig submucosal arterioles. EJPs were inhibited by suramin and PPADS (IC(50)s of 0.2 microM and 20 microM) but TNP-ATP (0.1-10 microM) inhibited EJPs by <30%. Noradrenaline (0.3-30 microM in the presence of phentolamine and propranolol) decreased EJPs in control preparations but facilitated EJPs by 5-20% in submucosal arterioles from reserpinized guinea-pigs. These properties are discussed in relation to P2X receptors underlying EJPs at autonomic neuroeffector junctions.

  20. Rescue of neuronal function by cross-regeneration of cutaneous afferents into muscle in cats.

    Nishimura, H; Johnson, R D; Munson, J B


    1. This study investigates the relation between the peripheral innervation of low-threshold cutaneous afferents and the postsynaptic potentials elicited by electrical stimulation of those afferents. 2. In cats deeply anesthetized with pentobarbital sodium, cord dorsum potentials (CDPs) and postsynaptic potentials (PSPs) in spinal motoneurons were elicited by stimulation of the caudal cutaneous sural nerve (CCS), the lateral cutaneous sural nerve (LCS), and the medial gastrocnemius (MG) muscle nerve. We tested 1) unoperated cats, and cats in which CCS has been 2) chronically axotomized and ligated, 3) cut and self-reunited, 4) cut and cross-united with LCS, or 5) cut and cross-united with the MG. Terminal experiments were performed 3-36 mo after initial surgery. 3. In cats in which the CCS had been self-reunited or cross-united distally with LCS, tactile stimulation of the hairy skin normally innervated by the distal nerve activated afferents in the CCS central to the coaptation, indicating that former CCS afferents had regenerated into native or foreign skin, respectively. 4. In cats in which the CCS had been cross-united distally with the MG, both stretch and contraction of the MG muscle activated the former CCS afferents. 5. In unoperated cats, CDPs elicited by stimulation of CCS and of LCS exhibited a low-threshold N1 wave and a higher-threshold N2 wave. These waves were greatly delayed and appeared to merge after chronic axotomy of CCS. Regeneration of CCS into itself, into LCS, or into MG restored the normal latencies and configurations of these potentials. 6. In unoperated cats, stimulation of CCS, of LCS, and of MG each produced PSPs of characteristic configurations in the various subpopulations of motoneurons of the triceps surae. CDPs and PSPs elicited by the CCS cross-regenerated into LCS or MG were typical of those generated by the normal CCS, i.e., there was no evidence of respecification of central synaptic connections to bring accord between center

  1. Cholecystokinin enhances visceral pain-related affective memory via vagal afferent pathway in rats

    Cao Bing


    Full Text Available Abstract Background Pain contains both sensory and affective dimensions. Using a rodent visceral pain assay that combines the colorectal distension (CRD model with the conditioned place avoidance (CPA paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Progress has been made and suggested that activation of vagal afferents plays a role in the behavioral control nociception and memory storage processes. In human patients, electrical vagus nerve stimulation enhanced retention of verbal learning performance. Cholecystokinin-octapeptide (CCK, which is a gastrointestinal hormone released during feeding, has been shown to enhance memory retention. Mice access to food immediately after training session enhanced memory retention. It has been well demonstrated that CCK acting on vagal afferent fibers mediates various physiological functions. We hypothesize that CCK activation of vagal afferent enhances visceral pain-related affective memory. Results In the presented study, infusion of CCK-8 at physiological concentration combining with conditional training significantly increased the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, CCK had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593. The physiological implications were further strengthened by the similar effects observed in the rats with duodenal infusion of 5% peptone, which has been shown to induce increases in plasma CCK levels. CCK-8 receptor antagonist CR-1409 or perivagal application of capsaicin abolished the effect of CCK on aversive visceral pain memory, which was consistent with the notion that vagal afferent modulates affective aspects of visceral pain. CCK does not change

  2. In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization.

    Ford, Anthony P


    Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Aδ-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort. In addition, P2X3 is expressed pre-synaptically at central terminals of C-fiber afferent neurons, where ATP further sensitizes transmission of painful signals. As a result of the selectivity of the expression of P2X3, there is a lower likelihood of adverse effects in the brain, gastrointestinal, or cardiovascular tissues, effects which remain limiting factors for many existing pain therapeutics. In the periphery, ATP (the factor that triggers P2X3 receptor activation) can be released from various cells as a result of tissue inflammation, injury or stress, as well as visceral organ distension, and stimulate these local nociceptors. The P2X3 receptor rationale has aroused a formidable level of investigation producing many reports that clarify the potential role of ATP as a pain mediator, in chronic sensitized states in particular, and has piqued the interest of pharmaceutical companies. P2X receptor-mediated afferent activation has been implicated in inflammatory, visceral, and neuropathic pain states, as well as in airways hyperreactivity, migraine, itch, and cancer pain. It is well appreciated that oftentimes new mechanisms translate poorly from models into clinical efficacy and effectiveness; however, the breadth of activity seen from P2X3 inhibition in models offers

  3. High fat diet induced changes in gastric vagal afferent response to adiponectin.

    Kentish, Stephen J; Ratcliff, Kyle; Li, Hui; Wittert, Gary A; Page, Amanda J


    Food intake is regulated by vagal afferent signals from the stomach. Adiponectin, secreted primarily from adipocytes, also has a role in regulating food intake. However, the involvement of vagal afferents in this effect remains to be established. We aimed to determine if adiponectin can modulate gastric vagal afferent (GVA) satiety signals and further whether this is altered in high fat diet (HFD)-induced obesity. Female C57BL/6J mice were fed either a standard laboratory diet (SLD) or a HFD for 12weeks. Plasma adiponectin levels were assayed, and the expression of adiponectin in the gastric mucosa was assessed using real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The location of adiponectin protein within the gastric mucosa was determined by immunohistochemistry. To evaluate the direct effect of adiponectin on vagal afferent endings we determined adiponectin receptor expression in whole nodose ganglia (NDG) and also specifically in GVA neurons using retrograde tracing and qRT-PCR. An in vitro preparation was used to determine the effect of adiponectin on GVA response to mechanical stimulation. HFD mice exhibited an increased body weight and adiposity and showed delayed gastric emptying relative to SLD mice. Plasma adiponectin levels were not significantly different in HFD compared to SLD mice. Adiponectin mRNA was detected in the gastric mucosa of both SLD and HFD mice and presence of protein was confirmed immunohistochemically by the detection of adiponectin immunoreactive cells in the mucosal layer of the stomach. Adiponectin receptor 1 (ADIPOR1) and 2 (ADIPOR2) mRNA was present in both the SLD and HFD whole NDG and also specifically traced gastric mucosal and muscular neurons. There was a reduction in ADIPOR1 mRNA in the mucosal afferents of the HFD mice relative to the SLD mice. In HFD mice adiponectin potentiated gastric mucosal afferent responses to mucosal stroking, an effect not observed in SLD mice. Adiponectin reduced

  4. Refractory anemia leading to renal hemosiderosis and renal failure

    Sujatha Siddappa; K M Mythri; Kowsalya, R.; Ashish Parekh


    Renal hemosiderosis is a rare cause of renal failure and, as a result, may not be diagnosed unless a detailed history, careful interpretation of blood parameters and renal biopsy with special staining is done. Here, we present a rare case of renal hemosiderosis presenting with renal failure.

  5. Refractory anemia leading to renal hemosiderosis and renal failure

    Sujatha Siddappa


    Full Text Available Renal hemosiderosis is a rare cause of renal failure and, as a result, may not be diagnosed unless a detailed history, careful interpretation of blood parameters and renal biopsy with special staining is done. Here, we present a rare case of renal hemosiderosis presenting with renal failure.

  6. Renal replacement therapy for acute renal failure.

    Macedo, E; Bouchard, J; Mehta, R L


    Renal replacement therapy became a common clinical tool to treat patients with severe acute kidney injury (AKI) since the 1960s. During this time dialytic options have expanded considerably; biocompatible membranes, bicarbonate dialysate and dialysis machines with volumetric ultrafiltration control have improved the treatment for acute kidney injury. Along with advances in methods of intermittent hemodialysis, continuous renal replacement therapies have gained widespread acceptance in the treatment of dialysis-requiring AKI. However, many of the fundamental aspects of the renal replacement treatment such as indication, timing of dialytic intervention, and choice of dialysis modality are still controversial and may influence AKI patient's outcomes. This review outlines current concepts in the use of dialysis techniques for AKI and suggests an approach for selecting the optimal method of renal replacement therapy.

  7. Renal function after renal artery stenting

    George S. Hanzel; Mark Downes; Peter A. McCullough


    @@ Atherosclerotic renal artery stenosis (ARAS), a common clinical finding, is increasing in prevalence as the population ages. ARAS is seen in ~ 7% of persons over 65 years of age1 and in ~ 20% of patients at the time of coronary angiography.2 It is an important cause of chronic kidney disease and may result in 11-14% of cases of end stage renal disease.3

  8. Rimonabant induced anorexia in rodents is not mediated by vagal or sympathetic gut afferents

    Madsen, Andreas Nygaard; Jelsing, Jacob; van de Wall, Esther H E M


    The selective CB1 receptor antagonist rimonabant is a novel weight control agent. Although CB1 receptors and binding sites are present in both the rodent central and peripheral nervous systems, including the afferent vagus nerve, the role of gut afferents in mediating anorexia following CB1R...... blockade is still debated. In the present study we examined rimonabant-induced anorexia in male C57BL/6J mice with subdiaphragmatic vagotomy (VGX) as well as in male Sprague-Dawley rats subjected to either subdiaphragmatic vagal deafferentation (SDA) alone or in combination with a complete celiac...... system, are required for rimonabant to inhibit food intake leading to the hypothesis that centrally located CB1 receptors are the prime mediators of rimonabant-induced anorexia....

  9. Blocking of periodontal afferents with anesthesia and its influence on elevator EMG activity.

    Manns, A E; Garcia, C; Miralles, R; Bull, R; Rocabado, M


    The effect of anesthetic blocking of the periodontal afferents of the canine teeth was studied in order to determine its influence on any changes in the jaw elevation activity. Unilateral integrated EMG recordings were made of the masseter and anterior temporal muscles during maximal voluntary clenching in centric occlusion and laterotrusive position with canine contact. After anesthetic blocking of the periodontal afferents of one or both ipsilateral canines, a significant increase was observed of the EMG activity of both jaw elevator muscles studied, in centric occlusion as well as with canine contact. The elevator activity increase was of a greater magnitude when antagonistic canines were anesthetized. These findings thus support the hypothesis that high threshold periodontal receptors exert an inhibitory effect on jaw elevator muscular activity.

  10. Interaction and regulatory functions of μ- and δ-opioid receptors in nociceptive afferent neurons

    Xu Zhang; Lan Bao


    μ-opioid receptor (MOR) agonists such as morphine are powerful analgesics used for pain therapy.However,the use of these drugs is limited by their side-effects,which include antinociceptive tolerance and dependence.Earlier studies reported that MOR analgesic tolerance is reduced by blockade of δ-opioid receptors (DORs) that interact with MORs.Recent studies show that the MOR/DOR interaction in nociceptive afferent neurons in the dorsal root ganglion may contribute to morphine analgesic tolerance.Further analysis of the mechanisms for regulating the trafficking of receptors,ion channels and signaling molecules in nociceptive afferent neurons would help to understand the nociceptive mechanisms and improve pain therapy.

  11. Activation of kinetically distinct synaptic conductances on inhibitory interneurons by electrotonically overlapping afferents.

    Walker, Harrison C; Lawrence, J Josh; McBain, Chris J


    Mossy fiber (MF) and CA3 collateral (CL) axons activate common interneurons via synapses comprised of different AMPA receptors to provide feedforward and feedback inhibitory control of the CA3 hippocampal network. Because synapses potentially occur over variable electrotonic distances that distort somatically recorded synaptic currents, it is not known whether the underlying afferent-specific synaptic conductances are associated with different time courses. Using a somatic voltage jump technique to alter the driving force at the site of the synapse, we demonstrate that MF and CL synapses overlap in electrotonic location yet differ in conductance time course. Thus, afferent-specific conductance time courses allow single interneurons to differentially integrate feedforward and feedback information without the need to segregate distinct AMPA receptor subunits to different electrotonic domains.

  12. Somatic modulation of spinal reflex bladder activity mediated by nociceptive bladder afferent nerve fibers in cats.

    Xiao, Zhiying; Rogers, Marc J; Shen, Bing; Wang, Jicheng; Schwen, Zeyad; Roppolo, James R; de Groat, William C; Tai, Changfeng


    The goal of the present study was to determine if supraspinal pathways are necessary for inhibition of bladder reflex activity induced by activation of somatic afferents in the pudendal or tibial nerve. Cats anesthetized with α-chloralose were studied after acute spinal cord transection at the thoracic T9/T10 level. Dilute (0.25%) acetic acid was used to irritate the bladder, activate nociceptive afferent C-fibers, and trigger spinal reflex bladder contractions (amplitude: 19.3 ± 2.9 cmH2O). Hexamethonium (a ganglionic blocker, intravenously) significantly (P irritation. Understanding the sites of action for PNS or TNS inhibition is important for the clinical application of pudendal or tibial neuromodulation to treat bladder dysfunctions. Copyright © 2014 the American Physiological Society.

  13. Imaging of renal osteodystrophy

    Jevtic, V. E-mail:


    Chronic renal insufficiency, hemodialysis, peritoneal dialysis, renal transplantation and administration of different medications provoke complex biochemical disturbances of the calcium-phosphate metabolism with wide spectrum of bone and soft tissue abnormalities termed renal osteodystrophy. Clinically most important manifestation of renal bone disease includes secondary hyperparathyroidism, osteomalacia/rickets, osteoporosis, adynamic bone disease and soft tissue calcification. As a complication of long-term hemodialysis and renal transplantation amyloid deposition, destructive spondyloarthropathy, osteonecrosis, and musculoskeletal infections may occur. Due to more sophisticated diagnostic methods and more efficient treatment classical radiographic features of secondary hyperparathyroidism and osteomalacia/rickets are now less frequently seen. Radiological investigations play an important role in early diagnosis and follow-up of the renal bone disease. Although numerous new imaging modalities have been introduced in clinical practice (scintigraphy, CT, MRI, quantitative imaging), plain film radiography, especially fine quality hand radiograph, still represents most widely used examination.

  14. Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat

    Bucinskaite, V; Tolessa, T; Pedersen, J


    The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal...... tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague-Dawley rats. Intravenous administration of GLP-1 (30-1000 pmol kg(-1)), reaching high physiological plasma...... afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents....

  15. Captopril attenuates hypertension and renal injury induced by the vascular endothelial growth factor inhibitor sorafenib

    Nagasawa, Tasuku; Khan, Abdul Hye; Imig, John D


    SUMMARY Vascular endothelial growth factor inhibitors (VEGFi) are known to cause hypertension and renal injury that severely limits their use as an anticancer therapy. We hypothesized that the angiotensin-converting enzyme inhibitor captopril not only prevents hypertension, but also decreases renal injury caused by the VEGFi sorafenib.Rats were administered sorafenib (20 mg/kg per day) alone or in combination with captopril (40 mg/kg per day) for 4 weeks. Sorafenib administration increased blood pressure, which plateaued by day 10.Concurrent treatment with captopril for 4 weeks resulted in a 30 mmHg decrease in blood pressure compared with sorafenib alone (155 ± 5 vs 182 ± 6 mmHg, respectively; P captopril treatment reduced albuminuria by 50% compared with sorafenib alone (20 ± 8 vs 42 ± 9 mg/day, respectively; P captopril-treated rats administered sorafenib. Renal autoregulatory efficiency was determined by evaluating the afferent arteriolar constrictor response to ATP. Sorafenib administration attenuated the vasoconstriction to ATP, whereas concurrent captopril treatment improved ATP reactivity.In conclusion, captopril attenuated hypertension and renal injury and improved renal autoregulatory capacity in rats administered sorafenib. These findings indicate that captopril treatment, in addition to alleviating the detrimental side-effect of hypertension, decreases the renal injury associated with anticancer VEGFi therapies such as sorafenib. PMID:22443474

  16. Effect of elevated interstitial pressure on the renal cortical hemodynamics.

    Källskog, O; Wolgast, M


    The influence of renal interstitial pressure on the resistance pattern within the superficial cortical vasculature has been investigated from determinations of 1) the glomerular blood flow eith a modified microsphere technique and 2) the intravascular hydrostatic pressures. Interstitial pressure was monitored via a 50 mum PVC-catheter placed into the subcapsular interstitial space. Two conditions were analyzed viz. a) elevation of uretheral pressure to 20 mm Hg and b) venous stasis to 10-15 mm Hg. Both conditions produced an increase in the interstitial pressure from 1-2 mm Hg to about 5 mm Hg as well as an increased hilar lymph flow and protein flow of about the same size. The vascular reactions were different, however. Uretheral stasis (but not the stasis of a single nephron) produced a decreased resistance in the afferent arteriolae with a concomitant increae in the pressures in the glomerular capillaries, and the peritobular capillary network. In contrast, venous stasis produced only small changes in the parameters studied but for the obvious rise in the peritubular capillary pressure. The results suggest that factors other than the interstitial pressure are governing the afferent vascular tone; the tubular wall tension might be one of these factors.

  17. Presynaptic α2-GABAA Receptors in Primary Afferent Depolarization and Spinal Pain Control


    Spinal dorsal horn GABAA receptors are found both postsynaptically on central neurons and presynaptically on axons and/or terminals of primary sensory neurons, where they mediate primary afferent depolarization (PAD) and presynaptic inhibition. Both phenomena have been studied extensively on a cellular level, but their role in sensory processing in vivo has remained elusive, due to inherent difficulties to selectively interfere with presynaptic receptors. Here, we address the contribution of ...

  18. Presynaptic {alpha}2-GABAA receptors in primary afferent depolarization and spinal pain control


    Spinal dorsal horn GABA(A) receptors are found both postsynaptically on central neurons and presynaptically on axons and/or terminals of primary sensory neurons, where they mediate primary afferent depolarization (PAD) and presynaptic inhibition. Both phenomena have been studied extensively on a cellular level, but their role in sensory processing in vivo has remained elusive, due to inherent difficulties to selectively interfere with presynaptic receptors. Here, we address the contribution o...

  19. Population coding of forelimb joint kinematics by peripheral afferents in monkeys.

    Tatsuya Umeda

    Full Text Available Various peripheral receptors provide information concerning position and movement to the central nervous system to achieve complex and dexterous movements of forelimbs in primates. The response properties of single afferent receptors to movements at a single joint have been examined in detail, but the population coding of peripheral afferents remains poorly defined. In this study, we obtained multichannel recordings from dorsal root ganglion (DRG neurons in cervical segments of monkeys. We applied the sparse linear regression (SLiR algorithm to the recordings, which selects useful input signals to reconstruct movement kinematics. Multichannel recordings of peripheral afferents were performed by inserting multi-electrode arrays into the DRGs of lower cervical segments in two anesthetized monkeys. A total of 112 and 92 units were responsive to the passive joint movements or the skin stimulation with a painting brush in Monkey 1 and Monkey 2, respectively. Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons. By automatically selecting a subset of recorded units, the SLiR achieved superior generalization performance compared with a regularized linear regression algorithm. The SLiR selected not only putative muscle units that were responsive to only the passive movements, but also a number of putative cutaneous units responsive to the skin stimulation. These results suggested that an ensemble of peripheral primary afferents that contains both putative muscle and cutaneous units encode forelimb joint kinematics of non-human primates.

  20. Lack of central sprouting of primary afferent fibers after ricin deafferentation.

    Pubols, L M; Bowen, D C


    A new deafferentation technique, the application of ricin to peripheral nerves, was used to test for collateral sprouting of undamaged primary afferent fibers within the adult mammalian spinal cord dorsal horn. The right sciatic nerves in rats were injected with ricin 14 to 57 days prior to bilateral labelling of dorsal rootlets with horseradish peroxidase. To equate the number of surviving dorsal root fibers on the two sides, the left sciatic nerves were injected 5 days prior to labelling. In each animal, horseradish peroxidase was applied to a bilateral pair of lumbar or low thoracic dorsal rootlets 18 hours prior to sacrifice to test for sprouting by labelling primary afferent fibers and terminals in the right (experimental) and left (control) dorsal horns. Although there is overlap of degenerated and intact primary afferent fields in this preparation, a postulated precondition for sprouting (Murray and Goldberger: J. Neurosci. 6:3205-3217, '86), we found no evidence for sprouting of undamaged, myelinated afferent fibers in the experimental dorsal horns. The pattern of labelling was symmetrical in all animals, and the density of labelling was not consistently greater on the experimental side. These results support the conclusions of Rodin et al. (J. Comp. Neurol. 215:187-198, '83) and Rodin and Kruger (Somatosens. Res. 2:171-192, '84), who also found no sprouting in the rat's dorsal horn after surgical deafferentation, and do not support the assertion that the difference between the results of those studies and earlier studies in cats was due to a lack of overlap of degenerated and intact dorsal roots in the rat.

  1. Selective activation of primary afferent fibers evaluated by sine-wave electrical stimulation

    Katafuchi Toshihiko; Takaki Atsushi; Rashid Md Harunor; Furue Hidemasa; Koga Kohei; Yoshimura Megumu


    Abstract Transcutaneous sine-wave stimuli at frequencies of 2000, 250 and 5 Hz (Neurometer) are thought to selectively activate Aβ, Aδ and C afferent fibers, respectively. However, there are few reports to test the selectivity of these stimuli at the cellular level. In the present study, we analyzed action potentials (APs) generated by sine-wave stimuli applied to the dorsal root in acutely isolated rat dorsal root ganglion (DRG) preparations using intracellular recordings. We also measured e...

  2. Intercostal muscles and purring in the cat: the influence of afferent inputs.

    Kirkwood, P A; Sears, T A; Stagg, D; Westgaard, R H


    Feline purring has previously been reported as originating in a central oscillator, independent of afferent inputs, and also as not involving expiratory muscles. Here we show, via electromyographic recordings from intercostal muscles, quantified by cross-correlation, that expiratory muscles can be involved and that even if the oscillator is central, reflex components nevertheless play a considerable part in the production of the periodic pattern of muscle activation seen during purring.

  3. Cholinergic modulation of primary afferent glutamatergic transmission in rat medullary dorsal horn neurons.

    Jeong, Seok-Gwon; Choi, In-Sun; Cho, Jin-Hwa; Jang, Il-Sung


    Although muscarinic acetylcholine (mACh) receptors are expressed in trigeminal ganglia, it is still unknown whether mACh receptors modulate glutamatergic transmission from primary afferents onto medullary dorsal horn neurons. In this study, we have addressed the cholinergic modulation of primary afferent glutamatergic transmission using a conventional whole cell patch clamp technique. Glutamatergic excitatory postsynaptic currents (EPSCs) were evoked from primary afferents by electrical stimulation of trigeminal tract and monosynaptic EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices. Muscarine and ACh reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, muscarine reduced the frequency of miniature EPSCs without affecting the current amplitude, suggesting that muscarine acts presynaptically to decrease the probability of glutamate release onto medullary dorsal horn neurons. The muscarine-induced decrease of glutamatergic EPSCs was significantly occluded by methoctramine or AF-DX116, M2 receptor antagonists, but not pirenzepine, J104129 and MT-3, selective M1, M3 and M4 receptor antagonists. The muscarine-induced decrease of glutamatergic EPSCs was highly dependent on the extracellular Ca2+ concentration. Physostigmine and clinically available acetylcholinesterase inhibitors, such as rivastigmine and donepezil, significantly shifted the concentration-inhibition relationship of ACh for glutamatergic EPSCs. These results suggest that muscarine acts on presynaptic M2 receptors to inhibit glutamatergic transmission by reducing the Ca2+ influx into primary afferent terminals, and that M2 receptor agonists and acetylcholinesterase inhibitors could be, at least, potential targets to reduce nociceptive transmission from orofacial tissues.

  4. Fine motor control of the jaw following alteration of orofacial afferent inputs.

    Kumar, Abhishek; Castrillon, Eduardo; Trulsson, Mats; Svensson, Krister G; Svensson, Peter


    The study was designed to investigate if alteration of different orofacial afferent inputs would have different effects on oral fine motor control and to test the hypothesis that reduced afferent inputs will increase the variability of bite force values and jaw muscle activity, and repeated training with splitting of food morsel in conditions with reduced afferent inputs would decrease the variability and lead to optimization of bite force values and jaw muscle activity. Forty-five healthy volunteers participated in a single experimental session and were equally divided into incisal, mucosal, and block anesthesia groups. The participants performed six series (with ten trials) of a standardized hold and split task after the intervention with local anesthesia was made in the respective groups. The hold and split forces along with the corresponding jaw muscle activity were recorded and compared to a reference group. The hold force and the electromyographic (EMG) activity of the masseter muscles during the hold phase were significantly higher in the incisal and block anesthesia group, as compared to the reference group (P motor control. Further, inhibition of afferent inputs from the orofacial or periodontal mechanoreceptors did not increase the variability of bite force values and jaw muscle activity; indicating that the relative precision of the oral fine motor task was not compromised inspite of the anesthesia. The results also suggest the propensity of optimization of bite force values and jaw muscle activity due to repeated splitting of the food morsels, inspite of alteration of sensory inputs. Skill acquisition following a change in oral sensory environment is crucial for understanding how humans learn and re-learn oral motor behaviors and the kind of adaptation that takes place after successful oral rehabilitation procedures.

  5. Influence of locomotor muscle afferent inhibition on the ventilatory response to exercise in heart failure.

    Olson, Thomas P; Joyner, Michael J; Eisenach, John H; Curry, Timothy B; Johnson, Bruce D


    What is the central question of this study? Patients with heart failure often develop ventilatory abnormalities at rest and during exercise, but the mechanisms underlying these abnormalities remain unclear. This study investigated the influence of inhibiting afferent neural feedback from locomotor muscles on the ventilatory response during exercise in heart failure patients. What is the main finding and its importance? Our results suggest that inhibiting afferent feedback from locomotor muscle via intrathecal opioid administration significantly reduces the ventilatory response to exercise in heart failure patients. Patients with heart failure (HF) develop ventilatory abnormalities at rest and during exercise, but the mechanism(s) underlying these abnormalities remain unclear. We examined whether the inhibition of afferent neural feedback from locomotor muscles during exercise reduces exercise ventilation in HF patients. In a randomized, placebo-controlled design, nine HF patients (age, 60 ± 2 years; ejection fraction, 27 ± 2%; New York Heart Association class 2 ± 1) and nine control subjects (age, 63 ± 2 years) underwent constant-work submaximal cycling (65% peak power) with intrathecal fentanyl (impairing the cephalad projection of opioid receptor-sensitive afferents) or sham injection. The hypercapnic ventilatory response was measured to determine whether cephalad migration of fentanyl occurred. There were no differences in hypercapnic ventilatory response within or between groups in either condition. Despite a lack of change in ventilation, tidal volume or respiratory rate, HF patients had a mild increase in arterial carbon dioxide (P(aCO(2)) and a decrease in oxygen (P(aO(2)); P rate at rest. In response to fentanyl during exercise, HF patients had a reduction in ventilation (63 ± 6 versus 44 ± 3 l min(-1), P rate (30 ± 1 versus 26 ± 2 breaths min(-1), P increased P(aCO(2)) (37.3 ± 0.9 versus 43.5 ± 1.1 mmHg, P exercise in HF patients.

  6. Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice

    Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique


    The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors

  7. Unmyelinated afferents constitute a second system coding tactile stimuli of the human hairy skin.

    Vallbo, A B; Olausson, H; Wessberg, J


    Impulses were recorded from unmyelinated afferents innervating the forearm skin of human subjects using the technique of microneurography. Units responding to innocuous skin deformation were selected. The sample (n = 38) was split into low-threshold units (n = 27) and high-threshold units (n = 11) on the basis of three distinctive features, i.e., thresholds to skin deformation, size of response to innocuous skin deformation, and differential response to sharp and blunt stimuli. The low-threshold units provisionally were denoted tactile afferents on the basis of their response properties, which strongly suggest that they are coding some feature of tactile stimuli. They exhibited, in many respects, similar functional properties as described for low-threshold C-mechanoreceptive units in other mammals. However, a delayed acceleration, not previously demonstrated, was observed in response to long-lasting innocuous indentations. It was concluded that human hairy skin is innervated by a system of highly sensitive mechanoreceptive units with unmyelinated afferents akin to the system previously described in other mammals. The confirmation that the system is present in the forearm skin and not only in the face area where it first was identified suggests a largely general distribution although there are indications that the tactile C afferents may be lacking in the very distal parts of the limbs. The functional role of the system remains to be assessed although physiological properties of the sense organs invite to speculations that the slow tactile system might have closer relations to limbic functions than to cognitive and motor functions.

  8. Is ATP a central synaptic mediator for certain primary afferent fibers from mammalian skin?

    Fyffe, R E; Perl, E R


    The possibility that ATP acts as a synaptic mediator at the central terminals of primary afferent fibers was examined by applying it iontophoretically to neurons of the outer layers of the cat spinal cord in vivo. ATP proved to be selectively excitatory for a limited subset of spinal neurons. Those units consistently excited by ATP iontophoresis with very small currents (2-15 nA) responded to gentle mechanical stimulation of the skin and usually evidenced excitatory input from unmyelinated pr...

  9. Electron microscopic observations of terminals of functionally identified afferent fibers in cat spinal cord.

    Egger, M D; Freeman, N C; Malamed, S; Masarachia, P; Proshansky, E


    Using the method of intra-axonal injection of horseradish peroxidase, functionally identified afferent fibers from three slowly adapting (Type I) receptors and one Pacinian corpuscle in the glabrous skin of the hind paw of the cat were stained. Electron microscopic observation of the terminals of these fibers revealed predominantly axodendritic asymmetric synapses containing round, clear vesicles. Multiple synapses on a single dendrite were observed, separated by as little as 900 mm from one another.

  10. Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients.

    Hughes, Patrick A; Moretta, Melissa; Lim, Amanda; Grasby, Dallas J; Bird, Daniel; Brierley, Stuart M; Liebregts, Tobias; Adam, Birgit; Blackshaw, L Ashley; Holtmann, Gerald; Bampton, Peter; Hoffmann, Peter; Andrews, Jane M; Zola, Heddy; Krumbiegel, Doreen


    Alterations in the neuro-immune axis contribute toward viscerosensory nerve sensitivity and symptoms in Irritable Bowel Syndrome (IBS). Inhibitory factors secreted from immune cells inhibit colo-rectal afferents in health, and loss of this inhibition may lead to hypersensitivity and symptoms. We aimed to determine the immune cell type(s) responsible for opioid secretion in humans and whether this is altered in patients with IBS. The β-endorphin content of specific immune cell lineages in peripheral blood and colonic mucosal biopsies were compared between healthy subjects (HS) and IBS patients. Peripheral blood mononuclear cell (PBMC) supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-Endorphin was identified predominantly in monocyte/macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in μ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte/macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS.

  11. Stochastic resonance in the synaptic transmission between hair cells and vestibular primary afferents in development.

    Flores, A; Manilla, S; Huidobro, N; De la Torre-Valdovinos, B; Kristeva, R; Mendez-Balbuena, I; Galindo, F; Treviño, M; Manjarrez, E


    The stochastic resonance (SR) is a phenomenon of nonlinear systems in which the addition of an intermediate level of noise improves the response of such system. Although SR has been studied in isolated hair cells and in the bullfrog sacculus, the occurrence of this phenomenon in the vestibular system in development is unknown. The purpose of the present study was to explore for the existence of SR via natural mechanical-stimulation in the hair cell-vestibular primary afferent transmission. In vitro experiments were performed on the posterior semicircular canal of the chicken inner ear during development. Our experiments showed that the signal-to-noise ratio of the afferent multiunit activity from E15 to P5 stages of development exhibited the SR phenomenon, which was characterized by an inverted U-like response as a function of the input noise level. The inverted U-like graphs of SR acquired their higher amplitude after the post-hatching stage of development. Blockage of the synaptic transmission with selective antagonists of the NMDA and AMPA/Kainate receptors abolished the SR of the afferent multiunit activity. Furthermore, computer simulations on a model of the hair cell - primary afferent synapse qualitatively reproduced this SR behavior and provided a possible explanation of how and where the SR could occur. These results demonstrate that a particular level of mechanical noise on the semicircular canals can improve the performance of the vestibular system in their peripheral sensory processing even during embryonic stages of development. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Modulation of synaptic transmission from segmental afferents by spontaneous activity of dorsal horn spinal neurones in the cat.

    Manjarrez, E; Rojas-Piloni, J G; Jimenez, I; Rudomin, P


    We examined, in the anaesthetised cat, the influence of the neuronal ensembles producing spontaneous negative cord dorsum potentials (nCDPs) on segmental pathways mediating primary afferent depolarisation (PAD) of cutaneous and group I muscle afferents and on Ia monosynaptic activation of spinal motoneurones. The intraspinal distribution of the field potentials associated with the spontaneous nCDPs indicated that the neuronal ensembles involved in the generation of these potentials were located in the dorsal horn of lumbar segments, in the same region of termination of low-threshold cutaneous afferents. During the occurrence of spontaneous nCDPs, transmission from low-threshold cutaneous afferents to second order neurones in laminae III-VI, as well as transmission along pathways mediating PAD of cutaneous and Ib afferents, was facilitated. PAD of Ia afferents was instead inhibited. Monosynaptic reflexes of flexors and extensors were facilitated during the spontaneous nCDPs. The magnitude of the facilitation was proportional to the amplitude of the 'conditioning' spontaneous nCDPs. This led to a high positive correlation between amplitude fluctuations of spontaneous nCDPs and fluctuations of monosynaptic reflexes. Stimulation of low-threshold cutaneous afferents transiently reduced the probability of occurrence of spontaneous nCDPs as well as the fluctuations of monosynaptic reflexes. It is concluded that the spontaneous nCDPs were produced by the activation of a population of dorsal horn neurones that shared the same functional pathways and involved the same set of neurones as those responding monosynaptically to stimulation of large cutaneous afferents. The spontaneous activity of these neurones was probably the main cause of the fluctuations of the monosynaptic reflexes observed under anaesthesia and could provide a dynamic linkage between segmental sensory and motor pathways.

  13. Capsaicin-sensitive vagal afferent neurons contribute to the detection of pathogenic bacterial colonization in the gut


    Vagal activation can reduce inflammation and disease activity in various animal models of intestinal inflammation via the cholinergic anti-inflammatory pathway. In the current model of this pathway, activation of descending vagal efferents is dependent on a signal initiated by stimulation of vagal afferents. However, little is known about how vagal afferents are activated, especially in the context of subclinical or clinical pathogenic bacterial infection. To address this question, we first d...

  14. An electron microscopic study of terminals of rapidly adapting mechanoreceptive afferent fibers in the cat spinal cord.

    Semba, K; Masarachia, P; Malamed, S; Jacquin, M; Harris, S; Yang, G; Egger, M D


    The intra-axonal horseradish peroxidase technique was used to examine the central terminals of 7 A beta primary afferent fibers from rapidly adapting (RA) mechanoreceptors in the glabrous skin of the cat's hindpaw. At the light microscopic level, labelled collaterals were seen to bear occasional boutonlike swellings, mostly (75-82%) of the en passant type. These swellings were distributed more or less uniformly from lamina III to a dorsal part of lamina VI in the dorsal horn, over a maximum longitudinal extent of about 4 mm. At the electron microscopic level, we observed that labelled boutons of RA afferent fibers were 1.0 to 3.3 micrometers in longest sectional dimension, and contained clear, round synaptic vesicles. They frequently formed asymmetric axospinous and axodendritic synapses and commonly appeared to receive contacts from unlabelled structures containing flattened or pleomorphic vesicles plus occasional large dense-cored vesicles. The examination of synaptic connectivity over the entire surface of individual boutons indicated that RA afferent boutons each made contacts with an average of one spine and one dendrite and, in addition, appeared to be postsynaptic to an average of two unlabelled vesicle-containing structures. This synaptic organization was, in general, more complex than that we had seen previously in Pacinian corpuscle (PC) and slowly adapting (SA) type I mechanoreceptive afferent fibers. Our findings indicate that RA, SA, and PC afferent terminals, while displaying some differential synaptic organizations, have many morphological and synaptological characteristics in common. These afferent terminals, in turn, seem to be generally distinguishable from the terminals of muscle spindle Ia afferents or unmyelinated primary afferents.

  15. Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents.

    Perez-Burgos, Azucena; Wang, Bingxian; Mao, Yu-Kang; Mistry, Bhavik; McVey Neufeld, Karen-Anne; Bienenstock, John; Kunze, Wolfgang


    Mounting evidence supports the influence of the gut microbiome on the local enteric nervous system and its effects on brain chemistry and relevant behavior. Vagal afferents are involved in some of these effects. We previously showed that ingestion of the probiotic bacterium Lactobacillus rhamnosus (JB-1) caused extensive neurochemical changes in the brain and behavior that were abrogated by prior vagotomy. Because information can be transmitted to the brain via primary afferents encoded as neuronal spike trains, our goal was to record those induced by JB-1 in vagal afferents in the mesenteric nerve bundle and thus determine the nature of the signals sent to the brain. Male Swiss Webster mice jejunal segments were cannulated ex vivo, and serosal and luminal compartments were perfused separately. Bacteria were added intraluminally. We found no evidence for translocation of labeled bacteria across the epithelium during the experiment. We recorded extracellular multi- and single-unit neuronal activity with glass suction pipettes. Within minutes of application, JB-1 increased the constitutive single- and multiunit firing rate of the mesenteric nerve bundle, but Lactobacillus salivarius (a negative control) or media alone were ineffective. JB-1 significantly augmented multiunit discharge responses to an intraluminal distension pressure of 31 hPa. Prior subdiaphragmatic vagotomy abolished all of the JB-1-evoked effects. This detailed exploration of the neuronal spike firing that encodes behavioral signaling to the brain may be useful to identify effective psychoactive bacteria and thereby offer an alternative new perspective in the field of psychiatry and comorbid conditions.

  16. A DSP for sensing the bladder volume through afferent neural pathways.

    Mendez, Arnaldo; Belghith, Abrar; Sawan, Mohamad


    In this paper, we present a digital signal processor (DSP) capable of monitoring the urinary bladder volume through afferent neural pathways. The DSP carries out real-time detection and can discriminate extracellular action potentials, also known as on-the-fly spike sorting. Next, the DSP performs a decoding method to estimate either three qualitative levels of fullness or the bladder volume value, depending on the selected output mode. The proposed DSP was tested using both realistic synthetic signals with a known ground-truth, and real signals from bladder afferent nerves recorded during acute experiments with animal models. The spike sorting processing circuit yielded an average accuracy of 92% using signals with highly correlated spike waveforms and low signal-to-noise ratios. The volume estimation circuits, tested with real signals, reproduced accuracies achieved by offline simulations in Matlab, i.e., 94% and 97% for quantitative and qualitative estimations, respectively. To assess feasibility, the DSP was deployed in the Actel FPGA Igloo AGL1000V2, which showed a power consumption of 0.5 mW and a latency of 2.1 ms at a 333 kHz core frequency. These performance results demonstrate that an implantable bladder sensor that perform the detection, discrimination and decoding of afferent neural activity is feasible.

  17. Reflex control of locomotion as revealed by stimulation of cutaneous afferents in spontaneously walking premammillary cats.

    Duysens, J


    1. Stimulation of different hindlimb nerves in spontaneously walking premammillary cats was used in order to examine the effects of sensory input on the rhythmic motor output. 2. Stimulation of the tibial or sural nerve at low intensities caused the burst of activity in the triceps surae or semimembranosus to be prolonged if stimuli were given during the extension phase. When applied during the flexion phase, the same stimuli shortened the burst of activity in the pretibial flexors and induced an early onset of the extensor activity, except if stimuli were given at the very beginning of the flexion phase, when flexor burst prolongations or rebounds were observed instead. 3. These effects were related to activation of large cutaneous afferents in these nerves since the results could be duplicated by low-intensity stimulation of the tibial nerve at the ankle or by direct stimulation of the pad. 4. In contrast, activation of smaller afferents by high-intensity stimulation resulted prolongations of the flexor burst and/or shortenings of the extensor burst for stimuli applied before or during these bursts, respectively. 5. It was concluded that the large and small cutaneous afferents make, respectively, inhibitory and excitatory connections with the central structure involved in the generation of flexion during walking.

  18. Comparison of the inhibitory response to tendon and cutaneous afferent stimulation in the human lower limb.

    Rogasch, Nigel C; Burne, John A; Türker, Kemal S


    A powerful early inhibition is seen in triceps surae after transcutaneous electrical stimulation of the Achilles tendon [tendon electrical stimulation (TES)]. The aim of the present study was to confirm results from surface electromyogram (SEMG) recordings that the inhibition is not wholly or partly due to stimulation of cutaneous afferents that may lie within range of the tendon electrodes. Because of methodological limitations, SEMG does not reliably identify the time course of inhibitory and excitatory reflex components. This issue was revisited here with an analysis of changes in single motor unit (SMU) firing rate [peristimulus frequencygram (PSF)] and probability [peristimulus time histogram (PSTH)] to reexamine the time course of inhibitory SMU events that follow purely cutaneous (superficial sural) nerve stimulation. Results were then compared with similar data from TES. When compared with the reflex response to TES, sural nerve stimulation resulted in a longer onset latency of the primary inhibition and a weaker effect on SMU firing probability and rate. PSF also revealed that decreased SMU firing rates persisted during the excitation phase in SEMG, suggesting that the initial inhibition was more prolonged than previously reported. In a further study, the transcutaneous SEMG Achilles tendon response was compared with that from direct intratendon stimulation with insulated needle electrodes. This method should attenuate the SEMG response if it is wholly or partly dependent on cutaneous afferents. However, subcutaneous stimulation of the tendon produced similar components in the SEMG, confirming that cutaneous afferents made little or no contribution to the initial inhibition following TES.

  19. Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

    Gosselink, K. L.; Grindeland, R. E.; Roy, R. R.; Zhong, H.; Bigbee, A. J.; Grossman, E. J.; Edgerton, V. R.


    There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

  20. The Organization of Submodality-Specific Touch Afferent Inputs in the Vibrissa Column

    Katsuyasu Sakurai


    Full Text Available The rodent tactile vibrissae are innervated by several different types of touch sensory neurons. The central afferents of all touch neurons from one vibrissa collectively project to a columnar structure called a barrelette in the brainstem. Delineating how distinct types of sensors connect to second-order neurons within each barrelette is critical for understanding tactile information coding and processing. Using genetic and viral techniques, we labeled slowly adapting (SA mechanosensory neurons, rapidly adapting (RA mechanosensory neurons, afferent synapses, and second-order projection neurons with four different fluorescent markers to examine their connectivity. We discovered that within each vibrissa column, individual sensory neurons project collaterals to multiply distributed locations, inputs from SA and RA afferents are spatially intermixed without any discernible stereotypy or topography, and second-order projection neurons receive convergent SA and RA inputs. Our findings reveal a “one-to-many and many-to-one” connectivity scheme and the circuit architecture for tactile information processing at the first-order synapses.

  1. Peripheral relays in stress-induced activation of visceral afferents in the gut.

    van den Wijngaard, René M; Klooker, Tamira K; de Jonge, Wouter J; Boeckxstaens, Guy E


    Multiple organs are targeted by the stress response, but the focus of this article is on stress-induced activation of visceral afferents in the gut. During recent years it became apparent that mast cells are pivotal in this response. Peripheral corticotrophin releasing factor (CRF) induces their degranulation whereupon mast cell mediators activate visceral afferents. In addition, these mediators are responsible for gut barrier dysfunction and subsequent influx of luminal antigens and bacteria. Some research groups have begun to investigate the possible importance of barrier dysfunction for enhanced visceral sensitivity. After reviewing the current knowledge on CRF-induced mast cell degranulation we will discuss these groundbreaking papers in a more elaborate way. They form the basis for a hypothesis in which not only CRF-induced but also antigen-mediated mast cell degranulation is relevant to stress-related afferent activation. Part of this hypothesis is certainly speculative and needs further investigation. At the end of this article we sum up some of the unanswered questions raised by others and during this review.

  2. Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

    Gosselink, K. L.; Grindeland, R. E.; Roy, R. R.; Zhong, H.; Bigbee, A. J.; Grossman, E. J.; Edgerton, V. R.


    There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

  3. Incidental renal neoplasms

    Rabjerg, Maj; Mikkelsen, Minne Nedergaard; Walter, Steen;


    On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive...... series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients...

  4. Insuficiencia renal aguda.

    Carlos Hernán Mejía


    Acute renal failure (ARF) is a clinic syndrome characterized by decline in renal function occurring over a short time period. Is a relatively common complication in hospitalized critically ill patients and is associated with high morbidity and mortality. ARF has often a multi-factorial etiology syndrome usually approached diagnostically as pre-renal, post-renal, or intrinsic ARF. Most intrinsic ARF is caused by ischemia or nephrotoxins and is classically associated with acute tubular necrosis...


    唐斌; 樊小力; 吴苏娣


    Objective To analyse the antinociceptive effect of red nucleus (RN) and its role in the antinociceptive effect of muscle spindle afferents. Methods The single units of RN or wide dynamic range (WDR) neuron in the spinal cord dorsal horn were extracelluarly recorded. The effects of RN stimulation on nociceptive responses (C-fibers-evoked responses, C-responses) of WDR neurons were observed. The influence of muscle spindle afferents elicited by intravenous administration of succinylcholine (Sch) on the spontaneous discharge of RN neurons and on C-responses of WDR neurons were observed. The effect of muscle spindle afferents on C-responses of WDR neurons after unilateral lesions of RN was also observed. Results Electrical stimulation of the RN produced a significantly inhibitory effect on the nociceptive responses of WDR neurons. RN neurons were excited by muscle spindle afferents. Muscle spindle afferents significantly inhibited C-response of WDR neurons and this inhibitory effect was reduced by lesions of RN. Conclusion RN neurons have a significant antinociceptive effect and might be involved in the antinociceptive effects elicited by muscle spindle afferents.



    Objective To analyse the antinociceptive effect of muscle spindle afferents and the involved mechanism.Methods The single unit of wide dynamic range(WDR) neurons in the spinal cord dorsal horn were recorded extracelluarly.The effects of muscle spindle afferents elicited by intravenous administration of succinylcholine (Sch) on nociceptive responses (C-fibres-evoked responses,C-responses) of WDR neurons were observed before and after bilateral lesions of ventrolateral periaqueduct gray (PAG).And the effects of muscle spindle afferents on the spontaneous discharge of the tail-flick related cell in the rostral ventro medial medulla (RVM) and on the spontaneous discharge of the PAG neurons were observed.Results The C-responses of WDR neurons were significantly inhibited by muscle spindle afferents,and the inhibitory effects were reduced by bilateral lesions of ventrolateral PAG.The spontaneous discharge of the off-cell in the RVM was excited while the on-cell was inhibited by intravenous administration of Sch.The spontaneous discharge of the PAG neurons were excited by muscle spindle afferents.Conclusion Muscle spindle afferents show a distinct effect of antinociception.PAG-RVM descending inhibitory system may play an important role in this nociceptive modulative mechanism.

  7. Isolated Renal Hydatidosis Presenting as Renal Mass: A Diagnostic Dilemma

    Datteswar Hota


    Full Text Available Hydatid disease is a parasitic infestation by larval form of Echinococcus granulosus. Isolated renal involvement is extremely rare. There are no specific signs and symptoms of renal hydatidosis. However it may present as palpable mass, flank pain, hematuria, malaise, fever, and hydatiduria or as a complication of it such as infection, abscess, hemorrhage, necrosis and pelviureteric junction obstruction, renal failure etc. Except hydatiduria, none are pathognomonic for renal hydatidosis. There is no literature on renal hydatidosis presenting as renal mass we report 2 cases of isolated renal hydatidosis, which mimicked a renal mass on imaging study.

  8. Distal renal tubular acidosis in recurrent renal stone formers

    Osther, P J; Hansen, A B; Røhl, H F


    (1.1%) had complete distal renal tubular acidosis and 14 (15.5%) incomplete distal renal tubular acidosis. Our results confirm that distal renal tubular acidification defects are associated with a more severe form of stone disease and make distal renal tubular acidosis one of the most frequent...... metabolic disturbances in renal stone formers. Distal renal tubular acidosis (dRTA) was relatively more common in female stone formers and most often found in patients with bilateral stone disease (36%). Since prophylactic treatment in renal stone formers with renal acidification defects is available...

  9. Renal pelvis or ureter cancer

    Transitional cell cancer of the renal pelvis or ureter; Kidney cancer - renal pelvis; Ureter cancer ... Cancer can grow in the urine collection system, but it is uncommon. Renal pelvis and ureter cancers ...

  10. No apparent role for T-type Ca²⁺ channels in renal autoregulation.

    Frandsen, Rasmus Hassing; Salomonsson, Max; Hansen, Pernille B L; Jensen, Lars J; Braunstein, Thomas Hartig; Holstein-Rathlou, Niels-Henrik; Sorensen, Charlotte Mehlin


    Renal autoregulation protects glomerular capillaries against increases in renal perfusion pressure (RPP). In the mesentery, both L- and T-type calcium channels are involved in autoregulation. L-type calcium channels participate in renal autoregulation, but the role of T-type channels is not fully elucidated due to lack of selective pharmacological inhibitors. The role of T- and L-type calcium channels in the response to acute increases in RPP in T-type channel knockout mice (CaV3.1) and normo- and hypertensive rats was examined. Changes in afferent arteriolar diameter in the kidneys from wild-type and CaV3.1 knockout mice were assessed. Autoregulation of renal blood flow was examined during acute increases in RPP in normo- and hypertensive rats under pharmacological blockade of T- and L-type calcium channels using mibefradil (0.1 μM) and nifedipine (1 μM). In contrast to the results from previous pharmacological studies, genetic deletion of T-type channels CaV3.1 did not affect renal autoregulation. Pharmacological blockade of T-type channels using concentrations of mibefradil which specifically blocks T-type channels also had no effect in wild-type or knockout mice. Blockade of L-type channels significantly attenuated renal autoregulation in both strains. These findings are supported by in vivo studies where blockade of T-type channels had no effect on changes in the renal vascular resistance after acute increases in RPP in normo- and hypertensive rats. These findings show that genetic deletion of T-type channels CaV3.1 or treatment with low concentrations of mibefradil does not affect renal autoregulation. Thus, T-type calcium channels are not involved in renal autoregulation in response to acute increases in RPP.

  11. A Case of Severe Hydroxychloroquine-Induced Retinal Toxicity in a Patient with Recent Onset of Renal Impairment: A Review of the Literature on the Use of Hydroxychloroquine in Renal Impairment

    Rajen Tailor


    Full Text Available We present a case of a 67-year-old female who presented with a twelve-month history of progressive blurred vision in both eyes. The patient was on hydroxychloroquine 200 mg twice a day for eight years for the treatment of scarring alopecia. Two years prior to presenting, the patient was found to have chronic kidney disease stage 3 secondary to hypertension. Examination revealed bilateral reduced visual acuities with attenuated arterioles and pigmentary changes on retinal assessment. Goldmann visual fields showed grossly constricted fields in both eyes. The patient was diagnosed with retinal toxicity secondary to hydroxychloroquine probably potentiated by renal impairment. Risk factors for retinal toxicity secondary to hydroxychloroquine can be broadly divided into dose-related and patient-related factors. Our patient developed severe retinal toxicity despite being on the recommended daily dose (400 mg per day. Although retinal toxicity at this dose has been documented, the development of renal impairment without dose adjustment or close monitoring of visual function is likely to have potentiated retinal toxicity. This case highlights the need to monitor renal function in patients on hydroxychloroquine. Should renal impairment develop, either the drug should be stopped or the dose reduced with close monitoring of visual function by an ophthalmologist.

  12. Intra-Parenchymal Renal Resistive Index Variation (IRRIV) Describes Renal Functional Reserve (RFR): Pilot Study in Healthy Volunteers.

    Samoni, Sara; Nalesso, Federico; Meola, Mario; Villa, Gianluca; De Cal, Massimo; De Rosa, Silvia; Petrucci, Ilaria; Brendolan, Alessandra; Rosner, Mitchell H; Ronco, Claudio


    An increase of glomerular filtration rate after protein load represents renal functional reserve (RFR) and is due to afferent arteriolar vasodilation. Lack of RFR may be a risk factor for acute kidney injury (AKI), but is cumbersome to measure. We sought to develop a non-invasive, bedside method that would indirectly measure RFR. Mechanical abdominal pressure, through compression of renal vessels, decreases blood flow and activates the auto-regulatory mechanism which can be measured by a fall in renal resistive index (RRI). The study aims at elucidating the relationship between intra-parenchymal renal resistive index variation (IRRIV) during abdominal pressure and RFR. In healthy volunteers, pressure was applied by a weight on the abdomen (fluid-bag 10% of subject's body weight) while RFR was measured through a protein loading test. We recorded RRI in an interlobular artery after application of pressure using ultrasound. The maximum percentage reduction of RRI from baseline was compared in the same subject to RFR. We enrolled 14 male and 16 female subjects (mean age 38 ± 14 years). Mean creatinine clearance was 106.2 ± 16.4 ml/min/1.73 m(2). RFR ranged between -1.9 and 59.7 with a mean value of 28.9 ± 13.1 ml/min/1.73 m(2). Mean baseline RRI was 0.61 ± 0.05, compared to 0.49 ± 0.06 during abdominal pressure; IRRIV was 19.6 ± 6.7%, ranging between 3.1% and 29.2%. Pearson's coefficient between RFR and IRRIV was 74.16% (p renal susceptibility to different exposures and the consequent risk for AKI.

  13. Autonomic control of the heart during exercise in humans: role of skeletal muscle afferents.

    Fisher, James P


    What is the topic of this review? The autonomic nervous system plays a key role in bringing about the cardiovascular responses to exercise necessitated by the increased metabolic requirements of the active skeletal muscle. The complex interaction of central and peripheral neural control mechanisms evokes a decrease in parasympathetic activity and an increase sympathetic activity to the heart during exercise. What advances does it highlight? This review presents some of the recent insights provided by human studies into the role of mechanically and metabolically sensitive skeletal muscle afferents in the regulation of cardiac autonomic control during exercise. The autonomic responses to exercise are orchestrated by the interactions of several central and peripheral neural mechanisms. This report focuses on the role of peripheral feedback from skeletal muscle afferents in the autonomic control of the heart during exercise in humans. Heart rate responses to passive calf stretch are abolished with cardiac parasympathetic blockade, indicating that the activation of mechanically sensitive skeletal muscle afferents (muscle mechanoreceptors) can inhibit cardiac parasympathetic activity and is likely to contribute to the increase in heart rate at the onset of exercise. Recent experiments show that the partial restriction of blood flow to the exercising skeletal muscles, to augment the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreceptors) in humans, evokes an increase in heart rate that is attenuated with β1-adrenergic blockade, thus suggesting that this response is principally mediated via an increase in cardiac sympathetic activity. Heart rate remains at resting levels during isolated activation of muscle metaboreceptors with postexercise ischaemia following hand grip, unless cardiac parasympathetic activity is inhibited, whereupon a sympathetically mediated increase in heart rate is unmasked. During postexercise ischaemia following leg

  14. [Hemorrhagic bilateral renal angiomyolipoma].

    Benjelloun, Mohamed; Rabii, Redouane; Mezzour, Mohamed Hicham; Joual, Abdenbi; Bennani, Saâd; el Mrini, Mohamed


    Renal angiomyolipoma is a rare benign tumour, often associated with congenital diseases especially de Bourneville's tuberous sclerosis. Bilateral angiomyolipoma is exceptional. The authors report a case of bilateral renal angiomyolipoma in a 33-year-old patient presenting with haemorrhagic shock. In the light of this case and a review of the literature, the authors discuss the diagnostic and therapeutic aspects of this disease.


    Musso CG


    Full Text Available Renal physiology plays a key role in the pharmacokinetics of many drugs. Knowledge of the particularities of each nephron function (filtration, secretion, reabsorption and excretion and each of renal tubular transport mechanisms (simple diffusion, facilitated diffusion, facilitated transport, active transport, endocytosis and pinocytosis is fundamental to achieve better management of drug prescriptions.

  16. Primary renal hydatidosis

    Johnsy Merla Joel


    Full Text Available Echinococcosis or hydatidosis caused by the tapeworm, Echinococcus granulosus, has the highest prevalence in endemic regions and sheep farming areas. The most common organ involved is the liver (50–75% followed by the lungs (15–20% and other organs (10–20%. Primary involvement of the kidney without the involvement of the liver and lungs, i.e., isolated renal hydatid disease is extremely rare even in endemic areas. The incidence of renal echinococcosis is 2–4%. Renal hydatid cysts usually remain asymptomatic for many years and are multiloculated. A 63-year-old male presented with left loin pain. Computed tomography scan abdomen revealed a presumptive diagnosis of renal hydatid disease. The nephrectomy specimen received in histopathology confirmed the diagnosis. We describe a rare case of primary renal hydatidosis.

  17. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura

    Huang Dongyue


    Full Text Available Abstract Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir and isolectin B4 (IB4 binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent

  18. Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura


    Background Migraine and other headache disorders affect a large percentage of the population and cause debilitating pain. Activation and sensitization of the trigeminal primary afferent neurons innervating the dura and cerebral vessels is a crucial step in the “headache circuit”. Many dural afferent neurons respond to algesic and inflammatory agents. Given the clear role of the transient receptor potential (TRP) family of channels in both sensing chemical stimulants and mediating inflammatory pain, we investigated the expression of TRP channels in dural afferent neurons. Methods We used two fluorescent tracers to retrogradely label dural afferent neurons in adult mice and quantified the abundance of peptidergic and non-peptidergic neuron populations using calcitonin gene-related peptide immunoreactivity (CGRP-ir) and isolectin B4 (IB4) binding as markers, respectively. Using immunohistochemistry, we compared the expression of TRPV1 and TRPA1 channels in dural afferent neurons with the expression in total trigeminal ganglion (TG) neurons. To examine the distribution of TRPM8 channels, we labeled dural afferent neurons in mice expressing farnesylated enhanced green fluorescent protein (EGFPf) from a TRPM8 locus. We used nearest-neighbor measurement to predict the spatial association between dural afferent neurons and neurons expressing TRPA1 or TRPM8 channels in the TG. Results and conclusions We report that the size of dural afferent neurons is significantly larger than that of total TG neurons and facial skin afferents. Approximately 40% of dural afferent neurons exhibit IB4 binding. Surprisingly, the percentage of dural afferent neurons containing CGRP-ir is significantly lower than those of total TG neurons and facial skin afferents. Both TRPV1 and TRPA1 channels are expressed in dural afferent neurons. Furthermore, nearest-neighbor measurement indicates that TRPA1-expressing neurons are clustered around a subset of dural afferent neurons. Interestingly, TRPM

  19. Diameters and wall-to-lumen ratio of retinal arterioles in patients with retinal vein occlusion before and after treatment with dexamethasone intravitreal implants.

    Semeraro, Francesco; Russo, Andrea; Rizzoni, Damiano; Danzi, Paola; Morescalchi, Francesco; Costagliola, Ciro


    To evaluate the diameters and wall-to-lumen ratio (WLR) of retinal arterioles in patients with retinal vein occlusion (RVO) before and after a 0.7 mg dexamethasone (DEX) intravitreal implant and compare it with a matched control group of normal eyes. This was a single-site, multi-investigator, prospective, open-label, observational study in 15 patients with vision loss due to branch or central RVO treated with a single injection of DEX implant. An age-matched control group of 16 normal eyes was recruited. External and internal arteriolar diameters, WLR, and wall thickness were assessed in vivo using scanning-laser Doppler flowmetry. Visual acuity (VA) and central macular thickness (CMT) were evaluated. Mean internal diameter showed a significant reduction in post-treatment RVO patients compared with pre-treatment RVO patients (56.0±18.0 μm vs. 67.9±16.9 μm, respectively; P=0.02). Mean WLR in pre-treatment RVO patients was 0.47±0.19, showing an increase to 0.63±0.23 3 months after treatment (P=0.037). No significant difference was found in arteriolar external diameter between normotensive, pre-treatment, and post-treatment subjects. Treatment with a DEX implant in RVO patients led to significant improvements in both VA and CMT. These changes were accompanied by reductions in arteriolar lumen diameter, which could contribute to decreased capillary leakage and macular swelling.

  20. Renal replacement therapy after cardiac surgery; renal function recovers

    Steinthorsdottir, Kristin Julia; Kandler, Kristian; Agerlin Windeløv, Nis


    To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy.......To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy....

  1. Firing patterns and functional roles of different classes of spinal afferents in rectal nerves during colonic migrating motor complexes in mouse colon.

    Zagorodnyuk, Vladimir P; Kyloh, Melinda; Brookes, Simon J; Nicholas, Sarah J; Spencer, Nick J


    The functional role of the different classes of visceral afferents that innervate the large intestine is poorly understood. Recent evidence suggests that low-threshold, wide-dynamic-range rectal afferents play an important role in the detection and transmission of visceral pain induced by noxious colorectal distension in mice. However, it is not clear which classes of spinal afferents are activated during naturally occurring colonic motor patterns or during intense contractions of the gut smooth muscle. We developed an in vitro colorectum preparation to test how the major classes of rectal afferents are activated during spontaneous colonic migrating motor complex (CMMC) or pharmacologically induced contraction. During CMMCs, circular muscle contractions increased firing in low-threshold, wide-dynamic-range muscular afferents and muscular-mucosal afferents, which generated a mean firing rate of 1.53 ± 0.23 Hz (n = 8) under isotonic conditions and 2.52 ± 0.36 Hz (n = 17) under isometric conditions. These low-threshold rectal afferents were reliably activated by low levels of circumferential stretch induced by increases in length (1-2 mm) or load (1-3 g). In a small proportion of cases (5 of 34 units), some low-threshold muscular and muscular-mucosal afferents decreased their firing rate during the peak of the CMMC contractions. High-threshold afferents were never activated during spontaneous CMMC contractions or tonic contractions induced by bethanechol (100 μM). High-threshold rectal afferents were only activated by intense levels of circumferential stretch (10-20 g). These results show that, in the rectal nerves of mice, low-threshold, wide-dynamic-range muscular and muscular-mucosal afferents are excited during contraction of the circular muscle that occurs during spontaneous CMMCs. No activation of high-threshold rectal afferents was detected during CMMCs or intense contractile activity in naïve mouse colorectum.

  2. The Gomez' equations and renal hemodynamic function in kidney disease research.

    Bjornstad, Petter; Škrtić, Marko; Lytvyn, Yuliya; Maahs, David M; Johnson, Richard J; Cherney, David Z I


    Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease. A major challenge in preventing DKD is the difficulty in identifying high-risk patients at an early, pre-clinical stage. Albuminuria and eGFR as measures of renal function in DKD research and clinical practice are limited by regression of one-third of patients with microalbuminuria to normoalbuminuria and eGFR is biased and imprecise in the normal-elevated range. Moreover, existing methods that are used to assess renal function do not give detailed insight into the location of the renal hemodynamic effects of pharmacological agents at the segmental level. To gain additional information about the intrarenal circulation in-vivo in humans, mathematical equations were developed by Gomez et al in the 1950s. These equations used measurements of GFR, renal blood flow (RBF), effective renal plasma flow (ERPF), renal vascular resistance (RVR), hematocrit and serum protein to calculate afferent and efferent arteriolar resistances, glomerular hydrostatic pressure and filtration pressure. Although indirect and based on physiological assumptions, these techniques have the potential to improve researchers' ability to identify early pre-clinical changes in renal hemodynamic function in patients with a variety of conditions including DKD, thereby offering tremendous potential in mechanistic human research studies. In this review, we focus on the application of Gomez' equations and summarize the potential and limitations of this technique in DKD research. We also summarize illustrative data derived from Gomez' equations in patients with type 1 (T1D) and type 2 diabetes (T2D) and hypertension.

  3. Renal neuroendocrine tumors

    Brian R Lane


    Full Text Available Objectives: Neuroendocrine tumors (NETs are uncommon tumors that exhibit a wide range of neuroendocrine differentiation and biological behavior. Primary NETs of the kidney, including carcinoid tumor, small cell carcinoma (SCC, and large cell neuroendocrine carcinoma (LCNEC are exceedingly rare. Materials and Methods: The clinicopathologic features of renal NETs diagnosed at a single institution were reviewed along with all reported cases in the worldwide literature. Results: Eighty renal NETs have been described, including nine from our institution. Differentiation between renal NETs and the more common renal neoplasms (renal cell carcinoma, transitional cell carcinoma can be difficult since clinical, radiographic, and histopathologic features overlap. Immunohistochemical staining for neuroendocrine markers, such as synaptophysin and chromogranin, can be particularly helpful in this regard. Renal carcinoids are typically slow-growing, may secrete hormones, and pursue a variable clinical course. In contrast, SCC and LCNEC often present with locally advanced or metastatic disease and carry a poor prognosis. Nephrectomy can be curative for clinically localized NETs, but multimodality treatment is indicated for advanced disease. Conclusions: A spectrum of NETs can rarely occur in the kidney. Renal carcinoids have a variable clinical course; SCC and LCNEC are associated with poor clinical outcomes. Diagnosis of NETs, especially LCNEC, requires awareness of their rare occurrence and prudent use of immunohistochemical neuroendocrine markers.

  4. Pregnancy and renal transplantation.

    Başaran, O; Emiroğlu, R; Seçme, S; Moray, G; Haberal, M


    Ovarian dysfunction, anovulatory vaginal bleeding, amenorrhea, high prolactin levels, and loss of libido are the causes of infertility in women with chronic renal failure. After renal transplantation, endocrine function generally improves after recovery of renal function. In this study we retrospectively evaluated the prepregnancy and postdelivery renal function, outcome of gestation, as well as maternal and fetal complications for eight pregnancies in eight renal transplant recipients between November 1975 and March 2003 of 1095 among 1425. Eight planned pregnancies occurred at a mean of 3.6 years posttransplant. Spontaneous abortion occured in the first trimester in one case. One intrauterine growth retardation was observed with a full-term pregnancy; one intrauterine growth retardation and preterm delivery; one preeclampsia with preterm delivery and urinary tract infection; and one preeclampsia with preterm delivery and oligohydramnios. The mean gestation period was 35.5 +/- 3.0 weeks (31.2 to 38.0). Pregnancy had no negative impact on renal function during a 2-year follow-up. No significant proteinuria or acute rejection episodes were observed. Among the seven deliveries, no congenital anomaly was documented and no postpartum problems for the child and the mother were observed. Our study suggests that successful pregnancy is possible in renal transplant recipients. In cases with good graft function and absence of severe proteinuria or hypertension, pregnancy does not affect graft function or patient survival; however, fetal problems are encountered such as intrauterine growth retardation, low birth weight, and preeclampsia.

  5. Renal autotransplantation: current perspectives.

    Stewart, B H; Banowsky, L H; Hewitt, C B; Straffon, R A


    Autotransplantation, with or without an extracorporeal renal operation, has been done 39 times in 37 patients. Indications for the procedure included severe ureteral injury in 4 patients, failed supravesical diversion in 2, renal carcinoma in a solitary kidney in 1, renovascular hypertension in 1 and donor arterial reconstruction before renal transplantation in 29. Success was obtained in all but 2 procedures, both of which involved previously operated kidneys with severe inflammation and adhesions involving the renal pelvis and pedicle. Based on our experience and a review of currently available literature we believe that renal autotransplantation and extracorporeal reconstruction can provide the best solution for patients with severe renovascular and ureteral disease not correctable by conventional operative techniques. The technique can be of particular value in removing centrally located tumors in solitary kidneys and in preparing donor kidneys with abnormal arteries for renal transplantation. The role of autotransplantation in the management of advanced renal trauma and calculus disease is less clear. A long-term comparison of patients treated by extracorporeal nephrolithotomy versus conventional lithotomy techniques will be necessary before a conclusion is reached in these disease categories.

  6. Perioperative acute renal failure.

    Mahon, Padraig


    PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

  7. Afferent roles in hindlimb wipe-reflex trajectories: free-limb kinematics and motor patterns.

    Kargo, W J; Giszter, S F


    The hindlimb wiping reflex of the frog is an example of a targeted trajectory that is organized at the spinal level. In this paper, we examine this reflex in 45 spinal frogs to test the importance of proprioceptive afferents in trajectory formation at the spinal level. We tested hindlimb to hindlimb wiping, in which the wiping or effector limb and the target limb move together. Loss of afferent feedback from the wiping limb was produced by cutting dorsal roots 7-9. This caused altered initial trajectory direction, increased ankle path curvature, knee-joint velocity reversals, and overshooting misses of the target limb. We established that these kinematic and motor-pattern changes were due mainly to the loss of ipsilateral muscular and joint afferents. Loss of cutaneous afferents alone did not alter the initial trajectory up to target limb contact. However, there were cutaneous effects in later motor-pattern phases after the wiping and target limb had made contact: The knee extension or whisk phase of wiping was often lost. Finally, there was a minor and nonspecific excitatory effect of phasic contralateral feedback in the motor-pattern changes after deafferentation. Specific muscle groups were altered as a result of proprioceptive loss. These muscles also showed configuration-based regulation during wiping. Biceps, semitendinosus, and sartorius (all contributing knee flexor torques) all were regulated in amplitude based on the initial position of the limb. These muscles contributed to an initial electromyographic (EMG) burst in the motor pattern. Rectus internus and semimembranosus (contributing hip extensor torques) were regulated in onset but not in the time of peak EMG or in termination of EMG based on initial position. These two muscles contributed to a second EMG burst in the motor pattern. After deafferentation the initial burst was reduced and more synchronous with the second burst, and the second burst often was broadened in duration. Ankle path curvature

  8. New treatment for old disease: management of resistant hypertension by percutaneous renal sympathetic denervation.

    Kanai, Takashi; Krum, Henry


    Hypertension is a major contributor to cardiovascular events, such as stroke and myocardial infarction, with accelerated sympathetic nerve activity implicated in its pathogenesis. However, hypertension in many patients is not adequately controlled, despite the availability of numerous medication classes. Novel procedure-as well as device-based strategies, such as percutaneous renal sympathetic nerve denervation therapy-have been developed to improve blood pressure in these refractory patients. Renal sympathetic denervation delivers not only a decrease in blood pressure levels but also renal as well as systemic sympathetic nerve activity. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which implies no counterregulatory mechanism or re-innervation of afferent renal sympathetic nerve so far. Renal sympathetic denervation is expected to be a promising treatment for patients with hypertension, congestive heart failure, chronic kidney disease, and metabolic syndrome implicated in the pathogenesis of potentiated sympathetic nerve activity. This review will focus on the current devices and procedures, their outcomes and prospects in the treatment of hypertension.

  9. Midterm renal functions following acute renal infarction

    Sakir Ongun


    Full Text Available The aim of this study was to explore clinical features of renal infarction (RI that may have a role in diagnosis and treatment in our patient cohort and provide data on midterm renal functions. Medical records of patients with diagnosis of acute RI, established by contrast enhanced computed tomography (CT and at least 1 year follow-up data, who were hospitalized in our clinic between 1998 and 2012 were retrospectively reviewed; including descriptive data, clinical signs and symptoms, etiologic factors, laboratory findings, and prescribed treatments. Patients with solitary infarct were treated with acetylsalicylic acid (ASA only, whereas patients with atrial fibrillation (AF or multiple or global infarct were treated with anticoagulants. Estimated Glomerular Filtration Rate (eGFR referring to renal functions was determined by the Modification of Diet in Renal Disease (MDRD formula. Twenty-seven renal units of 23 patients with acute RI were identified. The mean age was 59.7 ± 15.7 years. Fourteen patients (60.8% with RI had atrial fibrillation (AF as an etiologic factor of which four had concomitant mesenteric ischemia at diagnosis. At presentation, 20 patients (86.9% had elevated serum lactate dehydrogenase (LDH, 18 patients (78.2% had leukocytosis, and 16 patients (69.5% had microscopic hematuria. Two patients with concomitant mesenteric ischemia and AF passed away during follow up. Mean eGFR was 70.8 ± 23.2 mL/min/1.73 m2 at admission and increased to 82.3 ± 23.4 mL/min/1.73 m2 at 1 year follow up. RI should be considered in patients with persistent flank or abdominal pain, particularly if they are at high risk of thromboembolism. Antiplatelet and/or anticoagulant drugs are both effective treatment options according to the amplitude of the infarct for preserving kidney functions.

  10. Midterm renal functions following acute renal infarction.

    Ongun, Sakir; Bozkurt, Ozan; Demir, Omer; Cimen, Sertac; Aslan, Guven


    The aim of this study was to explore clinical features of renal infarction (RI) that may have a role in diagnosis and treatment in our patient cohort and provide data on midterm renal functions. Medical records of patients with diagnosis of acute RI, established by contrast enhanced computed tomography (CT) and at least 1 year follow-up data, who were hospitalized in our clinic between 1998 and 2012 were retrospectively reviewed; including descriptive data, clinical signs and symptoms, etiologic factors, laboratory findings, and prescribed treatments. Patients with solitary infarct were treated with acetylsalicylic acid (ASA) only, whereas patients with atrial fibrillation (AF) or multiple or global infarct were treated with anticoagulants. Estimated Glomerular Filtration Rate (eGFR) referring to renal functions was determined by the Modification of Diet in Renal Disease (MDRD) formula. Twenty-seven renal units of 23 patients with acute RI were identified. The mean age was 59.7 ± 15.7 years. Fourteen patients (60.8%) with RI had atrial fibrillation (AF) as an etiologic factor of which four had concomitant mesenteric ischemia at diagnosis. At presentation, 20 patients (86.9%) had elevated serum lactate dehydrogenase (LDH), 18 patients (78.2%) had leukocytosis, and 16 patients (69.5%) had microscopic hematuria. Two patients with concomitant mesenteric ischemia and AF passed away during follow up. Mean eGFR was 70.8 ± 23.2 mL/min/1.73 m(2) at admission and increased to 82.3 ± 23.4 mL/min/1.73 m(2) at 1 year follow up. RI should be considered in patients with persistent flank or abdominal pain, particularly if they are at high risk of thromboembolism. Antiplatelet and/or anticoagulant drugs are both effective treatment options according to the amplitude of the infarct for preserving kidney functions.

  11. Gastric relaxation induced by hyperglycemia is mediated by vagal afferent pathways in the rat.

    Zhou, Shi-Yi; Lu, Yuan-Xu; Owyang, Chung


    Hyperglycemia has a profound effect on gastric motility. However, little is known about the site and mechanism that sense alteration in blood glucose level. The identification of glucose-sensing neurons in the nodose ganglia led us to hypothesize that hyperglycemia acts through vagal afferent pathways to inhibit gastric motility. With the use of a glucose-clamp rat model, we showed that glucose decreased intragastric pressure in a dose-dependent manner. In contrast to intravenous infusion of glucose, intracisternal injection of glucose at 250 and 500 mg/dl had little effect on intragastric pressure. Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg/dl), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia. In contrast, hyperglycemia had no effect on the gastric contraction induced by electrical field stimulation or carbachol (10(-5) M). To rule out involvement of serotonergic pathways, we showed that neither granisetron (5-HT(3) antagonist, 0.5 g/kg) nor pharmacological depletion of 5-HT using p-chlorophenylalanine (5-HT synthesis inhibitor) affected gastric relaxation induced by hyperglycemia. Lastly, N(G)-nitro-L-arginine methyl ester (L-NAME) and a VIP antagonist each partially reduced gastric relaxation induced by hyperglycemia and, in combination, completely abolished gastric responses. In conclusion, hyperglycemia inhibits gastric motility through a capsaicin-sensitive vagal afferent pathway originating from the gastroduodenal mucosa. Hyperglycemia stimulates vagal afferents, which, in turn, activate vagal efferent cholinergic pathways synapsing with intragastric nitric oxide- and VIP-containing neurons to mediate gastric relaxation.

  12. Increasing cutaneous afferent feedback improves proprioceptive accuracy at the knee in patients with sensory ataxia.

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Goulding, Niamh; Palma, Jose-Alberto; Fuente Mora, Cristina; Kaufmann, Horacio


    Hereditary sensory and autonomic neuropathy type III (HSAN III) features disturbed proprioception and a marked ataxic gait. We recently showed that joint angle matching error at the knee is positively correlated with the degree of ataxia. Using intraneural microelectrodes, we also documented that these patients lack functional muscle spindle afferents but have preserved large-diameter cutaneous afferents, suggesting that patients with better proprioception may be relying more on proprioceptive cues provided by tactile afferents. We tested the hypothesis that enhancing cutaneous sensory feedback by stretching the skin at the knee joint using unidirectional elasticity tape could improve proprioceptive accuracy in patients with a congenital absence of functional muscle spindles. Passive joint angle matching at the knee was used to assess proprioceptive accuracy in 25 patients with HSAN III and 9 age-matched control subjects, with and without taping. Angles of the reference and indicator knees were recorded with digital inclinometers and the absolute error, gradient, and correlation coefficient between the two sides calculated. Patients with HSAN III performed poorly on the joint angle matching test [mean matching error 8.0 ± 0.8° (±SE); controls 3.0 ± 0.3°]. Following application of tape bilaterally to the knee in an X-shaped pattern, proprioceptive performance improved significantly in the patients (mean error 5.4 ± 0.7°) but not in the controls (3.0 ± 0.2°). Across patients, but not controls, significant increases in gradient and correlation coefficient were also apparent following taping. We conclude that taping improves proprioception at the knee in HSAN III, presumably via enhanced sensory feedback from the skin.

  13. BDNF released during neuropathic pain potentiates NMDA receptors in primary afferent terminals.

    Chen, Wenling; Walwyn, Wendy; Ennes, Helena S; Kim, Hyeyoung; McRoberts, James A; Marvizón, Juan Carlos G


    NMDA receptors in primary afferent terminals can contribute to hyperalgesia by increasing neurotransmitter release. In rats and mice, we found that the ability of intrathecal NMDA to induce neurokinin 1 receptor (NK1R) internalization (a measure of substance P release) required a previous injection of BDNF. Selective knock-down of NMDA receptors in primary afferents decreased NMDA-induced NK1R internalization, confirming the presynaptic location of these receptors. The effect of BDNF was mediated by tropomyosin-related kinase B (trkB) receptors and not p75 neurotrophin receptors (p75(NTR) ), because it was not produced by proBDNF and was inhibited by the trkB antagonist ANA-12 but not by the p75(NTR) inhibitor TAT-Pep5. These effects are probably mediated through the truncated form of the trkB receptor as there is little expression of full-length trkB in dorsal root ganglion (DRG) neurons. Src family kinase inhibitors blocked the effect of BDNF, suggesting that trkB receptors promote the activation of these NMDA receptors by Src family kinase phosphorylation. Western blots of cultured DRG neurons revealed that BDNF increased Tyr(1472) phosphorylation of the NR2B subunit of the NMDA receptor, known to have a potentiating effect. Patch-clamp recordings showed that BDNF, but not proBDNF, increased NMDA receptor currents in cultured DRG neurons. NMDA-induced NK1R internalization was also enabled in a neuropathic pain model or by activating dorsal horn microglia with lipopolysaccharide. These effects were decreased by a BDNF scavenger, a trkB receptor antagonist and a Src family kinase inhibitor, indicating that BDNF released by microglia potentiates NMDA receptors in primary afferents during neuropathic pain. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  14. Biochemical evidence that L-glutamate is a neurotransmitter of primary vagal afferent nerve fibers

    Perrone, M.H. (Cornell Univ., New York (USA). Medical Coll.)


    To determine in rat if vagal afferent fibers projecting into the intermediate one third of the nucleus tractus solitarius (NTS), the site of termination of baroafferents, utilize glutamate as a neurotransmitter, the high-affinity uptake of (/sup 3/H)L-glutamate and content of glutamate were analyzed in micropunches of rat brain stem. The intermediate NTS contains a high-affinity synaptosomal uptake system for (/sup 3/H)L-glutamate that is greater in capacity than that in areas adjacent to the NTS; it is almost two-fold higher than uptake in medial septum and nucleus accumbens and equal to that of hippocampal regions purportedly containing a rich glutamatergic innervation. Unilateral ablation of the nodose ganglion (i.e. cells of origin of vagal afferents) resulted, within 24 h in a prolonged significant reduction, to 56% of control, of (/sup 3/H)L-glutamate uptake, bilaterally in the NTS. The reduction of Na/sup +/-dependent synaptosomal uptake of (/sup 3/H)L-glutamate, resulted from a decrease in Vsub(max) without change in the Ksub(m) of the process, was anatomically restricted to the intermediate NTS, and was not associated with changes in (/sup 3/H)GABA uptake. The content of glutamate in the NTS was significantly (P < 0.01) decreased by 30% 7 days following unilateral extirpation of the nodose ganglion without changes in the concentrations of aspartate, glycine, glutamine, or GABA. A population of vagal afferent fibers projecting to NTS are glutamatergic. The results are consistent with the hypothesis obtained by physiological and pharmacological techniques that glutamate is a neurotransmitter of baroafferents.

  15. Contributions of skin and muscle afferent input to movement sense in the human hand.

    Cordo, Paul J; Horn, Jean-Louis; Künster, Daniela; Cherry, Anne; Bratt, Alex; Gurfinkel, Victor


    In the stationary hand, static joint-position sense originates from multimodal somatosensory input (e.g., joint, skin, and muscle). In the moving hand, however, it is uncertain how movement sense arises from these different submodalities of proprioceptors. In contrast to static-position sense, movement sense includes multiple parameters such as motion detection, direction, joint angle, and velocity. Because movement sense is both multimodal and multiparametric, it is not known how different movement parameters are represented by different afferent submodalities. In theory, each submodality could redundantly represent all movement parameters, or, alternatively, different afferent submodalities could be tuned to distinctly different movement parameters. The study described in this paper investigated how skin input and muscle input each contributes to movement sense of the hand, in particular, to the movement parameters dynamic position and velocity. Healthy adult subjects were instructed to indicate with the left hand when they sensed the unseen fingers of the right hand being passively flexed at the metacarpophalangeal (MCP) joint through a previously learned target angle. The experimental approach was to suppress input from skin and/or muscle: skin input by anesthetizing the hand, and muscle input by unexpectedly extending the wrist to prevent MCP flexion from stretching the finger extensor muscle. Input from joint afferents was assumed not to play a significant role because the task was carried out with the MCP joints near their neutral positions. We found that, during passive finger movement near the neutral position in healthy adult humans, both skin and muscle receptors contribute to movement sense but qualitatively differently. Whereas skin input contributes to both dynamic position and velocity sense, muscle input may contribute only to velocity sense.

  16. Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats.

    Nelson, David W; Liu, Xiaowen; Holst, Jens J; Raybould, Helen E; Ney, Denise M


    Small bowel resection stimulates intestinal adaptive growth by a neuroendocrine process thought to involve both sympathetic and parasympathetic innervation and enterotrophic hormones such as glucagon-like peptide-2 (GLP-2). We investigated whether capsaicin-sensitive vagal afferent neurons are essential for maximal resection-induced intestinal growth. Rats received systemic or perivagal capsaicin or ganglionectomy before 70% midjejunoileal resection or transection and were fed orally or by total parenteral nutrition (TPN) for 7 days after surgery. Growth of residual bowel was assessed by changes in mucosal mass, protein, DNA, and histology. Both systemic and perivagal capsaicin significantly attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein, and DNA in rats fed orally. Villus height was significantly reduced in resected rats given capsaicin compared with vehicle. Sucrase specific activity in jejunal mucosa was not significantly different; ileal mucosal sucrase specific activity was significantly increased by resection in capsaicin-treated rats. Capsaicin did not alter the 57% increase in ileal proglucagon mRNA or the 150% increase in plasma concentration of bioactive GLP-2 resulting from resection in orally fed rats. Ablation of spinal/splanchnic innervation by ganglionectomy failed to attenuate resection-induced adaptive growth. In TPN rats, capsaicin did not attenuate resection-induced mucosal growth. We conclude that vagal afferents are not essential for GLP-2 secretion when the ileum has direct contact with luminal nutrients after resection. In summary, vagal afferent neurons are essential for maximal resection-induced intestinal adaptation through a mechanism that appears to involve stimulation by luminal nutrients.

  17. Decoding of the spike timing of primary afferents during voluntary arm movements in monkeys

    Tatsuya eUmeda


    Full Text Available Understanding the mechanisms of encoding forelimb kinematics in the activity of peripheral afferents is essential for determining the optimal parameters of afferent stimulation to transmit proprioceptive signals in neuroprosthetics. To investigate whether the spike timing of dorsal root ganglion (DRG neurons could be estimated from the forelimb kinematics of behaving monkeys, we implanted two multi-electrode arrays chronically in the DRGs at the level of the cervical segments in two monkeys. Neuronal activity during voluntary reach-to-grasp movements were recorded simultaneously with the trajectories of hand/arm movements, which were tracked in three-dimensional space using a motion capture system. Sixteen and 13 neurons, including muscle spindles, skin receptors, and tendon organ afferents, were recorded in the two monkeys, respectively. We were able to reconstruct forelimb joint kinematics from the temporal firing pattern of a subset of DRG neurons using sparse linear regression (SLiR analysis, suggesting that DRG neuronal ensembles encoded information about joint kinematics. Furthermore, we estimated the spike timing of the DRG neuronal ensembles from joint kinematics using an integrate-and-fire model (IF incorporating the SLiR algorithm. The temporal change of firing frequency of a subpopulation of neurons was reconstructed precisely from forelimb kinematics using the SLiR. The spike timing of the DRG neurons was calculated using an IF model, in which a spike occurs if the cumulative sum of the firing frequency value exceeded a constant threshold. The estimated firing pattern of the DRG neuronal ensembles encoded forelimb joint angles and velocities as precisely as the originally recorded neuronal activity. These results suggest that the simple model can be used to generate an accurate estimate of the spike timing of DRG neuronal ensembles from forelimb joint kinematics, and is useful for designing a proprioceptive decoder in a brain machine

  18. Lactulose and renal failure.

    Vogt, B; Frey, F J


    The introduction of lactulose as a new therapeutic agent for treatment of hepatic encephalopathy was a major breakthrough in this field. It was hypothesized that lactulose might prevent postoperative renal impairment after biliary surgery in patients with obstructive jaundice. The presumable mechanism purported was the diminished endotoxinemia by lactulose. Unfortunately, such a reno-protective effect has not been shown conclusively until now in clinical studies. In chronic renal failure lactulose is known to promote fecal excretion of water, sodium, potassium, amonium, urea, creatinine and protons. Thus, lactulose could be useful for the treatment of chronic renal failure. However, compliance to the therapy represents a major problem.

  19. Renal tubule cell repair following acute renal injury.

    Humes, H D; Lake, E W; Liu, S


    Experimental data suggests the recovery of renal function after ischemic or nephrotoxic acute renal failure is due to a replicative repair process dependent upon predominantly paracrine release of growth factors. These growth factors promote renal proximal tubule cell proliferation and a differentiation phase dependent on the interaction between tubule cells and basement membrane. These insights identify the molecular basis of renal repair and ischemic and nephrotoxic acute renal failure, and may lead to potential therapeutic modalities that accelerate renal repair and lessen the morbidity and mortality associated with these renal disease processes. In this regard, there is a prominent vasoconstrictor response of the renal vasculature during the postischemic period of developing acute renal failure. The intravenous administration of pharmacologic doses of atrial natriuretic factor (ANF) in the postischemic period have proven efficacious by altering renal vascular resistance, so that renal blood flow and glomerular filtration rate improve. ANF also appears to protect renal tubular epithelial integrity and holds significant promise as a therapeutic agent in acute renal failure. Of equal or greater promise are the therapeutic interventions targeting the proliferative reparative zone during the postischemic period. The exogenous administration of epidermal growth factor or insulin-like growth factor-1 in the postischemic period have effectively decreased the degree of renal insufficiency as measured by the peak serum creatinine and has hastened renal recovery as measured by the duration of time required to return the baseline serum creatinine values. A similarly efficacious role for hepatocyte growth factor has also been recently demonstrated.

  20. PAD patterns of physiologically identified afferent fibres from the medial gastrocnemius muscle.

    Jiménez, I; Rudomin, P; Solodkin, M


    Intracellular recordings were made in the barbiturate-anesthetized cat from single afferent fibres left in continuity with the medial gastrocnemius muscle to document the transmembrane potential changes produced in functionally identified fibres by stimulation of sensory nerves and of the contralateral red nucleus (RN). Fifty five fibres from muscle spindles had conduction velocities above 70 m/s and were considered as from group Ia. Stimulation of group I afferent fibres of the posterior biceps and semitendinosus nerve (PBSt) produced primary afferent depolarization (PAD) in 30 (54%) Ia fibres. Stimulation of the sural (SU) nerve produced no transmembrane potential changes in 39 (71%) group Ia fibres and dorsal root reflex-like activity (DRRs) in 16 (29%) fibres. In 17 out of 28 group Ia fibres (60.7%) SU conditioning inhibited the PAD generated by stimulation of the PBSt nerve. Facilitation of the PBSt-induced PAD by SU conditioning was not seen. Repetitive stimulation of the RN had mixed effects: it produced PAD in 1 out of 8 fibres and inhibited the PAD induced by PBSt stimulation in 2 other fibres. Nine fibres connected to muscle spindles had conduction velocities below 70 m/s and were considered to be group II afferents. No PAD was produced in these fibres by SU stimulation but DRRs were generated in 5 of them. In 23 out of 31 fibres identified as from tendon organs group I PBSt volleys produced PAD. However, stimulation of the SU nerve produced PAD only in 3 out of 34 fibres, no transmembrane potential changes in 30 fibres and DRRs in 1 fibre. The effects of SU conditioning on the PAD produced by PBSt stimulation were tested in 19 Ib fibres and were inhibitory in 12 of them. In 9 of these fibres SU alone produced no transmembrane potential changes. Repetitive stimulation of the RN produced PAD in 3 out of 9 Ib fibres. SU conditioning inhibited the RN-induced PAD. The present findings support the existence of an alternative inhibitory pathway from cutaneous

  1. Cutaneous neurturin overexpression alters mechanical, thermal, and cold responsiveness in physiologically identified primary afferents.

    Jankowski, Michael P; Baumbauer, Kyle M; Wang, Ting; Albers, Kathryn M; Davis, Brian M; Koerber, H Richard


    Neurotrophic factors play an important role in the regulation of functional properties of sensory neurons under normal and pathological conditions. The GDNF family member neurturin is one such factor that has been linked to modulating responsiveness to peripheral stimuli. Neurturin binds to the GFRα2 receptor, a receptor found primarily in isolectin B4-expressing polymodal cutaneous nociceptors. Previous work has shown that knockout of GFRα2 alters heat, but not mechanical, responses in dissociated sensory neurons and reduces pain-related behaviors during the second phase of the formalin test. Research has also shown that overexpression of neurturin in basal keratinocytes increases behavioral responsiveness to mechanical stimulation and innocuous cooling of the skin without affecting noxious heat responses. Here we directly examined the impact of neurturin overexpression on cutaneous afferent function. We compared physiological responses of individual sensory neurons to mechanical and thermal stimulation of the skin, using an ex vivo skin-nerve-dorsal root ganglion-spinal cord preparation produced from neurturin-overexpressing (NRTN/OE) mice and wild-type littermate controls. We found that neurturin overexpression increases responsiveness to innocuous mechanical stimuli in A-fiber nociceptors, alters thermal responses in the polymodal subpopulation of C-fiber sensory neurons, and changes the relative numbers of mechanically sensitive but thermally insensitive C-fiber afferents. These results demonstrate the potential roles of different functional groups of sensory neurons in the behavioral changes observed in mice overexpressing cutaneous neurturin and highlight the importance of neurturin in regulating cutaneous afferent response properties.NEW & NOTEWORTHY GDNF family neurotrophic factors regulate the development and function of primary sensory neurons. Of these, neurturin has been shown to modulate mechanical and cooling sensitivity behaviorally. Here we show

  2. Contribution of afferent feedback to the soleus muscle activity during human locomotion

    Mazzaro, Nazarena; Grey, Michael James; Sinkjær, Thomas


    During the stance phase of the human step cycle, the ankle undergoes a natural dorsiflexion that stretches the soleus muscle. The afferent feedback resulting from this stretch enhances the locomotor drive. In this study a robotic actuator was used to slightly enhance or reduce the natural ankle...... dorsiflexion, in essence, mimicking the small variations in the ankle dorsiflexion movement that take place during the stance phase of the step cycle. The soleus (SOL) and tibialis anterior EMG were analyzed in response to the ankle trajectory modifications. The dorsiflexion enhancements and reductions...

  3. High-Fat Diet-Induced Obesity Ablates Gastric Vagal Afferent Circadian Rhythms.

    Kentish, Stephen J; Vincent, Andrew D; Kennaway, David J; Wittert, Gary A; Page, Amanda J


    Rats with high-fat diet (HFD)-induced obesity increase daytime eating, suggesting an alteration in circadian food intake mechanisms. Gastric vagal afferents (GVAs) respond to mechanical stimuli to initiate satiety. These signals are dampened in HFD mice and exhibit circadian variations inversely with food intake in lean mice. Furthermore, leptin shows circadian variation in its circulating level and is able to modulate GVA mechanosensitivity. However, whether leptin's ability to modulate GVAs occurs in a circadian manner is unknown. Therefore, we investigated whether changes in the circadian intake of food in HFD-induced obesity is associated with a disruption in GVA circadian rhythms. Eight-week-old male C57BL/6 mice were fed a standard laboratory diet (SLD) or a HFD for 12 weeks. A subgroup of SLD and HFD mice were housed in metabolic cages. After 12 weeks, ex vivo GVA recordings were taken at 3 h intervals starting at zeitgeber time 0 (ZT0) and stomach content was measured. After 12 weeks, HFD mice consumed more food during the light phase through larger and more frequent meals compared with SLD mice. SLD mice exhibited circadian fluctuation in stomach content, which peaked at ZT18 and reached a nadir at ZT9. At these time points, both tension and mucosal receptor mechanosensitivity were the lowest and highest, respectively. HFD mice exhibited little circadian variation in stomach content or GVA mechanosensitivity. Leptin potentiated mucosal receptor mechanosensitivity only in SLD mice and with reduced potency during the dark phase. In conclusion, loss of circadian variation in GVA signaling may underpin changes in eating behavior in HFD-induced obesity. Appropriate circadian control of food intake is vital for maintaining metabolic health. Diet-induced obesity is associated with strong circadian changes in food intake, but the contributing mechanisms have yet to be determined. Vagal afferents are involved in regulation of feeding behavior, particularly meal

  4. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons

    Kim, Sojin; Jin, Zhenhua; Lee, Goeun [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Park, Yong Seek; Park, Cheung-Seog [Department of Microbiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Jin, Young-Ho, E-mail: [Department of Physiology, School of Medicine, Kyung Hee University, Seoul 130-701 (Korea, Republic of)


    Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin

  5. Movement and afferent representations in human motor areas: a simultaneous neuroimaging and transcranial magnetic/peripheral nerve-stimulation study

    Hitoshi eShitara


    Full Text Available Neuroimaging combined with transcranial magnetic stimulation (TMS to primary motor cortex (M1 is an emerging technique that can examine motor-system functionality through evoked activity. However, because sensory afferents from twitching muscles are widely represented in motor areas the amount of evoked activity directly resulting from TMS remains unclear. We delivered suprathreshold TMS to left M1 or electrically stimulated the right median nerve (MNS in 18 healthy volunteers while simultaneously conducting functional magnetic resonance imaging and monitoring with electromyography (EMG. We examined in detail the localization of TMS-, muscle afferent- and superficial afferent-induced activity in M1 subdivisions. Muscle afferent- and TMS-evoked activity occurred mainly in rostral M1, while superficial afferents generated a slightly different activation distribution. In 12 participants who yielded quantifiable EMG, differences in brain activity ascribed to differences in movement-size were adjusted using integrated information from the EMGs. Sensory components only explained 10-20% of the suprathreshold TMS-induced activity, indicating that locally and remotely evoked activity in motor areas mostly resulted from the recruitment of neural and synaptic activity. The present study appears to justify the use of fMRI combined with suprathreshold TMS to M1 for evoked motor network imaging.

  6. Renal scintigraphy in veterinary medicine.

    Tyson, Reid; Daniel, Gregory B


    Renal scintigraphy is performed commonly in dogs and cats and has been used in a variety of other species. In a 2012 survey of the members of the Society of Veterinary Nuclear Medicine, 95% of the respondents indicated they perform renal scintigraphy in their practice. Renal scintigraphy is primarily used to assess renal function and to evaluate postrenal obstruction. This article reviews how renal scintigraphy is used in veterinary medicine and describes the methods of analysis. Species variation is also discussed.

  7. Primary renal synovial sarcoma

    Girish D. Bakhshi


    Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

  8. Renal protection in diabetes

    Parving, H H; Tarnow, L; Rossing, P


    BACKGROUND: The combination of diabetes and hypertension increases the chances of progressive renal disorder and, ultimately, renal failure. Roughly 40% of all diabetics, whether insulin-dependent or not, develop diabetic nephropathy. Diabetic nephropathy is the single most important cause of end......-stage renal disease in the Western world and accounts for more than a quarter of all end-stage renal diseases. Diabetic nephropathy is a major cause of increased morbidity and mortality in diabetic patients. Increased arterial blood pressure is an early and common phenomenon in incipient and overt diabetic...... nephropathy. The relationship between arterial blood pressure and diabetic nephropathy is a complex one, with diabetic nephropathy increasing blood pressure and blood pressure accelerating the course of nephropathy. OVERVIEW: Calcium antagonists antagonize preglomerular vasoconstriction. Additional putative...

  9. Renal primitive neuroectodermal tumors.

    Bartholow, Tanner; Parwani, Anil


    Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive neuroectodermal tumor family. These tumors most commonly arise in the chest wall and paraspinal regions; cases with a renal origin are rare entities, but have become increasingly reported in recent years. Although such cases occur across a wide age distribution, the average age for a patient with a renal primitive neuroectodermal tumor is the mid- to late 20s, with both males and females susceptible. Histologically, these tumors are characterized by pseudorosettes. Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these are aggressive tumors, with an average 5-year disease-free survival rate of only 45% to 55%. Given that renal primitive neuroectodermal tumor bears many similarities to other renal tumors, it is important to review the histologic features, immunostaining profile, and genetic abnormalities that can be used for its correct diagnosis.

  10. Renal vein thrombosis

    ... Saunders; 2012:chap 34. Read More Acute kidney failure Arteriogram Blood clots Dehydration Nephrotic syndrome Pulmonary embolus Renal Tumor Review Date 5/19/2015 Updated by: Charles Silberberg, ...

  11. Eligibility for renal denervation

    Persu, Alexandre; Jin, Yu; Baelen, Marie;


    -resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according......Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after...... undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility...

  12. Complete renal recovery from severe acute renal failure after thrombolysis of bilateral renal vein thrombosis.

    Ramadoss, Suresh; Jones, Robert G; Foggensteiner, Lukas; Willis, Andrew P; Duddy, Martin J


    A previously healthy young man presented with acute renal failure due to extensive spontaneous deep vein thrombosis, including the inferior vena cava (IVC) and both renal veins. The patient was treated with selectively delivered thrombolytic therapy over a 7-day-period, which resulted in renal vein patency and complete recovery of renal function. A stent was placed over a segment stenosis of the IVC. No thrombophilic factors were identified. Bilateral renal vein thrombosis in young fit individuals is an unusual cause of acute renal failure. Thrombolytic therapy, even with delay, can completely restore renal function.




    Full Text Available Renal failure in obstetrics is rare but important complication, associated with significant mortality and long term morbidity.1,2 It includes acute renal failure due to obstetrical complications or due to deterioration of existing renal disease. AIMS AND OBJECTIVES: To evaluate the etiology and outcome of renal failure in obstetric patients. METHODS: We prospectively analyzed 30 pregnant and puerperal women with acute renal failure or pre-existing renal disease developing renal failure during pregnancy between November 2007 to sep-2009. Patients who presented/developed ARF during the hospital stay were included in this study. RESULTS: Among 30 patients, mean age was 23 years and 33 years age group. 12 cases (40% patients were primigravidae and 9(30% patients were multigravidae and 9 cases (30% presented in post-partum period. Eighteen cases (60% with ARF were seen in third trimester, followed by in postpartum period 9 cases (30%. Most common contributing factors to ARF were Pre-eclampsia, eclampsia and HELLP syndrome 60%, sepsis 56.6%, post abortal ARF 10%. DIC 40%. Haemorrhage as the aetiology for ARF was present 46%, APH in 20% and PPH in 26.6%. The type of ARF was renal in (63% and prerenal (36%; Oliguric seen in 10 patients (33% and high mortality (30%. Among the 20 pregnant patients with ARF, The average period of gestation was 33±2 weeks (30 -36 weeks, 5 cases (25% presented with intrauterine fetal demise and 18 cases (66% had preterm vaginal delivery and 2 cases (10% had induced abortion. And the average birth weight was 2±0.5 kg (1.5 kg. Eight cases (26% required dialysis. 80% of patients recovered completely of renal functions. 63% patients recovered without renal replacement therapy whereas 17% required dialysis. the maternal mortality was 20%, the main reason for mortality was septic shock and multi organ dysfunction (66%. CONCLUSION: ARF related pregnancy was seen commonly in the primigravidae and in the third trimester, the most

  14. Renal papillary necrosis

    Stephen A. Geller


    Full Text Available In 1877, Dr. Nikolaus Friedreich (1825-1882; student of Virchow who became Professor of Pathology at Heidelberg and who also described Friedreich’s ataxia first described renal papillary necrosis (RPN in patients with prostatic hypertrophy and secondary hydronephrosis. Thereafter in 1937, Froboese and Günther emphasized the association of this entity with diabetes mellitus. These authors also observed renal papillary necrosis in cases of urinary tract obstruction even in the absence of diabetes mellitus.

  15. [Hyperuricemia and renal risk].

    Viazzi, Francesca; Bonino, Barbara; Ratto, Elena; Desideri, Giovambattista; Pontremoli, Roberto


    Recent studies have revealed an association between elevated levels of uric acid and conditions correlated to chronic kidney diseases such as hypertension, cardiovascular and cerebral disease, insulin resistance. Several pathogenetic mechanisms at cellular and tissue levels could justify a direct correlation between serum uric acid levels and renal damage. Growing evidence indicating a correlation between urate lowering therapy and renal morbidity could encourage the use of urate lowering therapy in primary or secondary prevention in chronic kidney disease.

  16. Laparoscopic Renal Cryoablation

    Schiffman, Marc; Moshfegh, Amiel; Talenfeld, Adam; Del Pizzo, Joseph J.


    In light of evidence linking radical nephrectomy and consequent suboptimal renal function to adverse cardiovascular events and increased mortality, research into nephron-sparing techniques for renal masses widely expanded in the past two decades. The American Urological Association (AUA) guidelines now explicitly list partial nephrectomy as the standard of care for the management of T1a renal tumors. Because of the increasing utilization of cross-sectional imaging, up to 70% of newly detected renal masses are stage T1a, making them more amenable to minimally invasive nephron-sparing therapies including laparoscopic and robotic partial nephrectomy and ablative therapies. Cryosurgery has emerged as a leading option for renal ablation, and compared with surgical techniques it offers benefits in preserving renal function with fewer complications, shorter hospitalization times, and allows for quicker convalescence. A mature dataset exists at this time, with intermediate and long-term follow-up data available. Cryosurgical recommendations as a first-line therapy are made at this time in limited populations, including elderly patients, patients with multiple comorbidities, and those with a solitary kidney. As more data emerge on oncologic efficacy, and technical experience and the technology continue to improve, the application of this modality will likely be extended in future treatment guidelines. PMID:24596441

  17. Neonatal renal vein thrombosis.

    Brandão, Leonardo R; Simpson, Ewurabena A; Lau, Keith K


    Neonatal renal vein thrombosis (RVT) continues to pose significant challenges for pediatric hematologists and nephrologists. The precise mechanism for the onset and propagation of renal thrombosis within the neonatal population is unclear, but there is suggestion that acquired and/or inherited thrombophilia traits may increase the risk for renal thromboembolic disease during the newborn period. This review summarizes the most recent studies of neonatal RVT, examining its most common features, the prevalence of acquired and inherited prothrombotic risk factors among these patients, and evaluates their short and long term renal and thrombotic outcomes as they may relate to these risk factors. Although there is some consensus regarding the management of neonatal RVT, the most recent antithrombotic therapy guidelines for the management of childhood thrombosis do not provide a risk-based algorithm for the acute management of RVT among newborns with hereditary prothrombotic disorders. Whereas neonatal RVT is not a condition associated with a high mortality rate, it is associated with significant morbidity due to renal impairment. Recent evidence to evaluate the effects of heparin-based anticoagulation and thrombolytic therapy on the long term renal function of these patients has yielded conflicting results. Long term cohort studies and randomized trials may be helpful to clarify the impact of acute versus prolonged antithrombotic therapy for reducing the morbidity that is associated with neonatal RVT.

  18. Myelinated Afferents Are Involved in Pathology of the Spontaneous Electrical Activity and Mechanical Hyperalgesia of Myofascial Trigger Spots in Rats

    Fei Meng


    Full Text Available Myofascial trigger points (MTrPs are common causes for chronic pain. Myelinated afferents were considered to be related with muscular pain, and our clinical researches indicated they might participate in the pathology of MTrPs. Here, we applied myofascial trigger spots (MTrSs, equal to MTrPs in human of rats to further investigate role of myelinated afferents. Modified pyridine-silver staining revealed more nerve endings at MTrSs than non-MTrSs (P0.05. 30 min after the injection, MPTs at MTrSs were significantly lower than those of non-MTrSs (P<0.01. Therefore, we concluded that proliferated myelinated afferents existed at MTrSs, which were closely related to pathology of SEA and mechanical hyperalgesia of MTrSs.

  19. Afferent projections from the brainstem to the area hypothalamica dorsalis: a horseradish peroxidase study in the cat.

    Aguirre, J A; Coveñas, R; Alonso, J R; Lara, J M; Aijón, J


    Experiments using the retrograde transport of horseradish peroxidase were performed in order to identify the cells of origin the ascending projections from different brainstem regions to the area hypothalamica dorsalis (aHd) in the cat. The afferent inputs to this area originate mainly from the midbrain and medulla oblongata regions. The main afferent source of the area hypothalamica dorsalis arises from the substantia grisea centralis, where a large number of labeled cells were observed bilaterally, although more abundant on the ipsilateral side. Substantial afferents reach the aHd from the nuclei vestibularis medialis and inferior and the formatio reticularis mesencephali. A modest number of peroxidase-labeled neurons were observed in the nuclei ruber, interpeduncularis, substantia nigra, reticularis gigantocellularis, vestibularis lateralis, cuneatus and gracilis. From the pons, the nucleus raphe magnus sends a weak projection to the aHd. These anatomical data suggest that such area could be involved in visceral, sexual, nociceptive somatosensorial, sleep-waking and motor mechanisms.

  20. The urodelean Mauthner cell. Morphology of the afferent synapses to the M-cell of larval Salamandra salamandra

    Cioni, C.; De Palma, F.; De Vito, L.; Stefanelli, A. [Rome, Univ. (Italy). Dipt. di Biologia Animale e dell`Uomo


    In the present work the fine morphology and the distribution of the afferent synapses to the Mauthner cell of larval Salamandra salamandra are described. The aim of the study is to characterize the synaptic bed in the larvae of this terrestrial salamander in order to compare it with that of larval axolotl and larval anurans. Four main types of afferent endings have been identified: myelinated club endings, round-vesicle end bulbs, flattened-vesicle end bulbs and spiral fibers endings. The M-cell afferent synaptology of larval stages of terrestrial amphibians is quite similar to that previously observed in larval stages of aquatic species. This fact can be related to the fundamental similarities between the larval lifestyles.

  1. Interpretation of muscle spindle afferent nerve response to passive muscle stretch recorded with thin-film longitudinal intrafascicular electrodes.

    Djilas, Milan; Azevedo-Coste, Christine; Guiraud, David; Yoshida, Ken


    In this study, we explored the feasibility of estimating muscle length in passive conditions by interpreting nerve responses from muscle spindle afferents recorded with thin-film longitudinal intrafascicular electrodes. Afferent muscle spindle response to passive stretch was recorded in ten acute rabbit experiments. A newly proposed first-order model of muscle spindle response to passive sinusoidal muscle stretch manages to capture the relationship between afferent neural firing rate and muscle length. We demonstrate that the model can be used to track random motion trajectories with bandwidth from 0.1 to 1 Hz over a range of 4 mm with a muscle length estimation error of 0.3 mm (1.4 degrees of joint angle). When estimation is performed using four-channel ENG there is a 50% reduction in estimate variation, compared to using single-channel recordings.

  2. An in vitro method for recording single unit afferent activity from mesenteric nerves innervating isolated segments of rat ileum.

    Sharkey, K A; Cervero, F


    A technique has been developed for recording single unit afferent activity from mesenteric nerves in isolated segments of rat distal ileum in vitro. The preparation consists of a 3-cm segment of ileum, containing a single neurovascular bundle, held horizontally in an organ bath. One end of the segment is attached to a tension transducer to record changes in longitudinal tension of the gut muscle and the other is connected to a pressure transducer to record changes in intra-luminal pressure. Electromyographic activity of the smooth muscle is recorded using glass-insulated tungsten microelectrodes inserted in the wall of the gut. Afferent nerve activity is recorded with a monopolar platinum wire electrode from filaments of the mesenteric nerves that run between the artery and vein supplying the segment. This preparation permits the detailed analysis of the electrical activity of intestinal afferent nerve fibres correlated with mechanical and chemical events occurring naturally in the gut or imposed experimentally on it.

  3. Group II muscle afferents probably contribute to the medium latency soleus stretch reflex during walking in humans

    Grey, Michael James; Ladouceur, Michel; Andersen, Jacob B.


    1. The objective of this study was to determine which afferents contribute to the medium latency response of the soleus stretch reflex resulting from an unexpected perturbation during human walking. 2. Fourteen healthy subjects walked on a treadmill at approximately 3.5 km h(-1) with the left ankle...... component (P = 0.004), whereas the medium latency component was unchanged (P = 0.437). 6. Two hours after the ingestion of tizanidine, an alpha(2)-adrenergic receptor agonist known to selectively depress the transmission in the group II afferent pathway, the medium latency reflex was strongly depressed (P...... = 0.007), whereas the short latency component was unchanged (P = 0.653). 7. An ankle block with lidocaine hydrochloride was performed to suppress the cutaneous afferents of the foot and ankle. Neither the short (P = 0.453) nor medium (P = 0.310) latency reflexes were changed. 8. Our results support...

  4. Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal Cancer Stem Cells

    Zhi-xiang Yuan; Jingxin Mo; Guixian Zhao; Gang Shu; Hua-lin Fu; Wei Zhao


    Renal cell carcinoma (RCC) is a common form of urologic tumor that originates from the highly heterogeneous epithelium of renal tubules. Over the last decade, targeting therapies to renal cancer cells have transformed clinical care for RCC. Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal carcinomas were responsible for driving tumor growth and resistance to conventional chemotherapy and radiotherapy, according to the theory of CSCs; this has provided the rati...


    Elisangela Giachini


    Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

  6. Gentamicin induced nitric oxide-related oxidative damages on vestibular afferents in the guinea pig.

    Hong, Sung Hwa; Park, Sook Kyung; Cho, Yang-Sun; Lee, Hyun-Seok; Kim, Ki Ryung; Kim, Myung Gu; Chung, Won-Ho


    Gentamicin is a well-known ototoxic aminoglycoside. However, the mechanism underlying this ototoxicity remains unclear. One of the mechanisms which may be responsible for this ototoxicity is excitotoxic damage to hair cells. The overstimulation of the N-methyl-d-aspartate (NMDA) receptors increases the production of nitric oxide (NO), which induces oxidative stress on hair cells. In order to determine the mechanism underlying this excitotoxicity, we treated guinea pigs with gentamicin by placing gentamicin (0.5 mg) pellets into a round window niche. After the sacrifice of the animals, which occurred at 3, 7 and 14 days after the treatment, the numbers of hair cells in the animals were counted with a scanning electron microscope. We then performed immunostaining using neuronal nitric oxide synthase (nNOS), inducible NOS (iNOS) and nitrotyrosine antibodies. The number of hair cells in the animals was found to decrease significantly after 7 days. nNOS and iNOS expression levels were observed to have increased 3 days after treatment. Nitrotyrosine was expressed primarily at the calyceal afferents of the type I hair cells 3 days after treatment. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining revealed positive hair cells 3 days after treatment. Our results suggest that inner ear treatment with gentamicin may upregulate nNOS and iNOS to induce oxidative stress in the calyceal afferents of type I hair cells, via nitric oxide overproduction.

  7. Physiological recruitment of motor units by high-frequency electrical stimulation of afferent pathways.

    Dideriksen, Jakob L; Muceli, Silvia; Dosen, Strahinja; Laine, Christopher M; Farina, Dario


    Neuromuscular electrical stimulation (NMES) is commonly used in rehabilitation, but electrically evoked muscle activation is in several ways different from voluntary muscle contractions. These differences lead to challenges in the use of NMES for restoring muscle function. We investigated the use of low-current, high-frequency nerve stimulation to activate the muscle via the spinal motoneuron (MN) pool to achieve more natural activation patterns. Using a novel stimulation protocol, the H-reflex responses to individual stimuli in a train of stimulation pulses at 100 Hz were reliably estimated with surface EMG during low-level contractions. Furthermore, single motor unit recruitment by afferent stimulation was analyzed with intramuscular EMG. The results showed that substantially elevated H-reflex responses were obtained during 100-Hz stimulation with respect to a lower stimulation frequency. Furthermore, motor unit recruitment using 100-Hz stimulation was not fully synchronized, as it occurs in classic NMES, and the discharge rates differed among motor units because each unit was activated only after a specific number of stimuli. The most likely mechanism behind these observations is the temporal summation of subthreshold excitatory postsynaptic potentials from Ia fibers to the MNs. These findings and their interpretation were also verified by a realistic simulation model of afferent stimulation of a MN population. These results suggest that the proposed stimulation strategy may allow generation of considerable levels of muscle activation by motor unit recruitment that resembles the physiological conditions.

  8. Peripheral afferent mechanisms underlying acupuncture inhibition of cocaine behavioral effects in rats.

    Seol Ah Kim

    Full Text Available Administration of cocaine increases locomotor activity by enhancing dopamine transmission. To explore the peripheral mechanisms underlying acupuncture treatment for drug addiction, we developed a novel mechanical acupuncture instrument (MAI for objective mechanical stimulation. The aim of this study was to evaluate whether acupuncture inhibition of cocaine-induced locomotor activity is mediated through specific peripheral nerves, the afferents from superficial or deep tissues, or specific groups of nerve fibers. Mechanical stimulation of acupuncture point HT7 with MAI suppressed cocaine-induced locomotor activity in a stimulus time-dependent manner, which was blocked by severing the ulnar nerve or by local anesthesia. Suppression of cocaine-induced locomotor activity was elicited after HT7 stimulation at frequencies of either 50 (for Meissner corpuscles or 200 (for Pacinian corpuscles Hz and was not affected by block of C/Aδ-fibers in the ulnar nerve with resiniferatoxin, nor generated by direct stimulation of C/Aδ-fiber afferents with capsaicin. These findings suggest that HT7 inhibition of cocaine-induced locomotor activity is mediated by A-fiber activation of ulnar nerve that originates in superficial and deep tissue.

  9. Transient, afferent input-dependent, postnatal niche for neural progenitor cells in the cochlear nucleus.

    Volkenstein, Stefan; Oshima, Kazuo; Sinkkonen, Saku T; Corrales, C Eduardo; Most, Sam P; Chai, Renjie; Jan, Taha A; van Amerongen, Renée; Cheng, Alan G; Heller, Stefan


    In the cochlear nucleus (CN), the first central relay of the auditory pathway, the survival of neurons during the first weeks after birth depends on afferent innervation from the cochlea. Although input-dependent neuron survival has been extensively studied in the CN, neurogenesis has not been evaluated as a possible mechanism of postnatal plasticity. Here we show that new neurons are born in the CN during the critical period of postnatal plasticity. Coincidently, we found a population of neural progenitor cells that are controlled by a complex interplay of Wnt, Notch, and TGFβ/BMP signaling, in which low levels of TGFβ/BMP signaling are permissive for progenitor proliferation that is promoted by Wnt and Notch activation. We further show that cells with activated Wnt signaling reside in the CN and that these cells have high propensity for neurosphere formation. Cochlear ablation resulted in diminishment of progenitors and Wnt/β-catenin-active cells, suggesting that the neonatal CN maintains an afferent innervation-dependent population of progenitor cells that display active canonical Wnt signaling.

  10. Afferent electrical stimulation during cycling improves spinal processing of sensorimotor function after incomplete spinal cord injury.

    Piazza, Stefano; Serrano-Muñoz, Diego; Gómez-Soriano, Julio; Torricelli, Diego; Segura-Fragosa, Antonio; Pons, José Luis; Taylor, Julian


    Appropriate afferent feedback delivery during the execution of motor tasks is important for rehabilitation after incomplete spinal cord injury (iSCI). However, during leg-cycling therapy, the plantar afferent feedback is minimal. We hypothesize that the augmentation of sensory input by combining cycling with a locomotor-like stimulation of plantar cutaneous innervations (ES-cycling), might help to restore proper spinal processing of sensorimotor function. Thirteen non-injured subjects and 10 subjects with iSCI performed 10 minutes of cycling and, on another session, of ES-cycling. To assess spinal processing of sensorimotor function, soleus H-reflex response was tested following a conditioning plantar electrical stimulation applied at 25-100 ms inter-stimulus intervals (ISI's), measured before and after the execution of the tasks. Before tasks execution, the conditioned H-reflex response was modulated in non-injured subjects, and absent in subjects with iSCI; after cycling, modulation profiles were unchanged. However, after ES-cycling a significant increase in H-reflex excitability was observed in the non-injured group at 100 ms ISI (p spinal processing of sensorimotor function. Reflex modulation recovery after ES-cycling may indicate the partial reactivation of these mechanisms.

  11. Deletion of leptin signaling in vagal afferent neurons results in hyperphagia and obesity.

    de Lartigue, Guillaume; Ronveaux, Charlotte C; Raybould, Helen E


    The vagal afferent pathway senses hormones released from the gut in response to nutritional cues and relays these signals to the brain. We tested the hypothesis that leptin resistance in vagal afferent neurons (VAN) is responsible for the onset of hyperphagia by developing a novel conditional knockout mouse to delete leptin receptor selectively in sensory neurons (Nav1.8/LepR (fl/fl) mice). Chow fed Nav1.8/LepR (fl/fl) mice weighed significantly more and had increased adiposity compared with wildtype mice. Cumulative food intake, meal size, and meal duration in the dark phase were increased in Nav1.8/LepR (fl/fl) mice; energy expenditure was unaltered. Reduced satiation in Nav1.8/LepR (fl/fl) mice is in part due to reduced sensitivity of VAN to CCK and the subsequent loss of VAN plasticity. Crucially Nav1.8/LepR (l/fl) mice did not gain further weight in response to a high fat diet. We conclude that disruption of leptin signaling in VAN is sufficient and necessary to promote hyperphagia and obesity.

  12. Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

    May, Marcus; Gueler, Faikah; Barg-Hock, Hannelore; Heiringhoff, Karl-Heinz; Engeli, Stefan; Heusser, Karsten; Diedrich, André; Brandt, André; Strassburg, Christian P.; Tank, Jens; Sweep, Fred C. G. J.; Jordan, Jens


    Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (pwater drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. Trial Registration NCT01237431 PMID:22016786

  13. Transcriptional changes in sensory ganglia associated with primary afferent axon collateral sprouting in spared dermatome model

    Benjamin J. Harrison


    Full Text Available Primary afferent collateral sprouting is a process whereby non-injured primary afferent neurons respond to some stimulus and extend new branches from existing axons. Neurons of both the central and peripheral nervous systems undergo this process, which contributes to both adaptive and maladaptive plasticity (e.g., [1–9]. In the model used here (the “spared dermatome” model, the intact sensory neurons respond to the denervation of adjacent areas of skin by sprouting new axon branches into that adjacent denervated territory. Investigations of gene expression changes associated with collateral sprouting can provide a better understanding of the molecular mechanisms controlling this process. Consequently, it can be used to develop treatments to promote functional recovery for spinal cord injury and other similar conditions. This report includes raw gene expression data files from microarray experiments in order to study the gene regulation in spared sensory ganglia in the initiation (7 days and maintenance (14 days phases of the spared dermatome model relative to intact (“naïve” sensory ganglia. Data has been deposited into GEO (GSE72551.

  14. Liver afferents contribute to water drinking-induced sympathetic activation in human subjects: a clinical trial.

    Marcus May

    Full Text Available UNLABELLED: Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups after 30-40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects. TRIAL REGISTRATION: NCT01237431.

  15. Influences of laryngeal afferent inputs on intralaryngeal muscle activity during vocalization in the cat.

    Shiba, K; Yoshida, K; Nakajima, Y; Konno, A


    The present study was undertaken to elucidate the possible role of the laryngeal afferent inputs in the regulation of intralaryngeal muscle activity during vocalization. We studied the influences of airflow and/or pressure applied to the larynx on intralaryngeal muscle activity during vocalization in ketamine-anesthetized cats. Vocalization was induced by airflow applied to the upper airway, which was isolated from the lower airway, during pontine call site stimulation. When the upper airway was open to the atmosphere through the nostrils and mouth, the airflow increased not only the vocal fold adductor and tensor activities but also the duration of these activities. The adductor and tensor activities were increased suddenly at a critical subglottic pressure level equivalent to the subglottic pressure threshold for vocalization. These effects were significantly reduced by sectioning of the internal branch of the superior laryngeal nerve or by lidocaine application to the laryngeal mucosa. Sustained pressure applied to the isolated upper airway, when the mouth and nostrils were occluded, did not affect adductor or tensor activities. These results indicate that the afferent inputs evoked by vocal fold stretching or vibration play an important role in the motor control of intralaryngeal and respiratory muscles during vocalization.

  16. Effects of electrical and natural stimulation of skin afferents on the gamma-spindle system of the triceps surae muscle.

    Johansson, H; Sjölander, P; Sojka, P; Wadell, I


    The aim of the present study was to investigate the extent to which skin receptors might influence the responses of primary muscle spindle afferents via reflex actions on the fusimotor system. The experiments were performed on 43 cats anaesthetized with alpha-chloralose. The alterations in fusimotor activity were assessed from changes in the responses of the muscle spindle afferents to sinusoidal stretching of their parent muscles (triceps surae and plantaris). The mean rate of firing and the modulation of the afferent response were determined. Control measurements were made in absence of any cutaneous stimulation. Tests were made (a) during physiological stimulation of skin afferents of the ipsilateral pad or of the contralateral hindlimb, or (b) during repetitive electrical stimulation of the sural nerve in the ipsilateral hindlimb, or of sural or superficial peroneal nerve in the contralateral hindlimb. Of the total number of 113 units tested with repetitive electrical stimulation of the ipsilateral sural nerve (at 20 Hz), 24.8% exhibited predominantly dynamic fusimotor reflexes, 5.3% mixed or predominantly static fusimotor reflexes. One unit studied in a preparation with intact spinal cord exhibited static reflexes at low stimulation intensities and dynamic ones at higher stimulation strengths. The remaining units (69%) were uninfluenced. When the receptor-bearing muscle was held at constant length and a train of stimuli (at 20 Hz) was applied to the ipsilateral sural nerve, the action potentials in the primary muscle spindle afferent could be stimulus-locked to the 3rd or 4th pulse in the train (and to the pulses following thereafter), with a latency of about 24 ms from the effective pulse. This 1:1 pattern of driving seemed to be mediated via static and/or dynamic fusimotor neurons. Natural stimulation influenced comparatively few units (3 of 65 units tested from the ipsilateral pad and 10 of 98 tested from the contralateral hindlimb), but when the effects

  17. Non-peptidergic primary afferents are presynaptic to neurokinin-1 receptor immunoreactive lamina I projection neurons in rat spinal cord

    Saeed Abeer W


    Full Text Available Abstract Background Pain-related (nociceptive information is carried from the periphery to the dorsal horn of the spinal cord mostly by two populations of small diameter primary afferents, the peptidergic and the non-peptidergic. The peptidergic population expresses neuropeptides, such as substance P and calcitonin gene-related peptide, while the non-peptidergic fibers are devoid of neuropeptides, express the purinergic receptor P2X3, and bind the isolectin B4 (IB4. Although it has been known for some time that in rat the peptidergic afferents terminate mostly in lamina I and outer lamina II and non-peptidergic afferents in inner lamina II, the extent of the termination of the latter population in lamina I was never investigated as it was considered as very minor. Because our preliminary evidence suggested otherwise, we decided to re-examine the termination of non-peptidergic afferents in lamina I, in particular with regards to their innervation of projection neurons expressing substance P receptors (NK-1r. We used retrograde labeling of neurons from the parabrachial nucleus combined with lectin IB4 binding and immunocytochemistry. Samples were examined by confocal and electron microscopy. Results By confocal microscopy, we studied the termination of non-peptidergic afferents in lamina I using IB4 binding and P2X3 immunoreactivity as markers, in relation to CGRP immunoreactivy, a marker of peptidergic afferents. The number of IB4 or P2X3-labeled fibers in lamina I was higher than previously thought, although they were less abundant than CGRP-labeled afferents. There were very few fibers double-labeled for CGRP and either P2X3 or IB4. We found a considerable number of IB4-positive fiber varicosities in close apposition to NK-1r-positive lamina I projection neurons, which were distinct from peptidergic varicosities. Furthermore, we confirmed at the ultrastructural level that there were bona fide synapses between P2X3-immunoreactive non

  18. Malignant renal tumors in children

    Justin Scott Lee


    Full Text Available Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. 

  19. Percutaneous renal tumour biopsy.

    Delahunt, Brett; Samaratunga, Hemamali; Martignoni, Guido; Srigley, John R; Evans, Andrew J; Brunelli, Matteo


    The use of percutaneous renal tumour biopsy (RTB) as a diagnostic tool for the histological characterization of renal masses has increased dramatically within the last 30 years. This increased utilization has paralleled advances in imaging techniques and an evolving knowledge of the clinical value of nephron sparing surgery. Improved biopsy techniques using image guidance, coupled with the use of smaller gauge needles has led to a decrease in complication rates. Reports from series containing a large number of cases have shown the non-diagnostic rate of RTB to range from 4% to 21%. Re-biopsy has been shown to reduce this rate, while the use of molecular markers further improves diagnostic sensitivity. In parallel with refinements of the biopsy procedure, there has been a rapid expansion in our understanding of the complexity of renal cell neoplasia. The 2013 Vancouver Classification is the current classification for renal tumours, and contains five additional entities recognized as novel forms of renal malignancy. The diagnosis of tumour morphotype on RTB is usually achievable on routine histology; however, immunohistochemical studies may be of assistance in difficult cases. The morphology of the main tumour subtypes, based upon the Vancouver Classification, is described and differentiating features are discussed.

  20. Can renal infarction occur after renal cyst aspiration? Case report.

    Emre, Habib; Soyoral, Yasemin Usul; Tanik, Serhat; Gecit, Ilhan; Begenik, Huseyin; Pirincci, Necip; Erkoc, Reha


    Renal infarction (RI) is a rarely seen disorder, and the diagnosis is often missed. The two major causes of RI are thromboemboli originhating from a thrombus in the heart or aorta, and in-situ thrombosis of a renal artery. We report a case of RI that developed due to renal artery and vein thrombosis, as confirmed by pathological evaluation of the nephrectomy material, three weeks after renal cyst aspiration.

  1. Transient inflammation-induced ongoing pain is driven by TRPV1 sensitive afferents

    Mercado Ramon


    Full Text Available Abstract Background Tissue injury elicits both hypersensitivity to evoked stimuli and ongoing, stimulus-independent pain. We previously demonstrated that pain relief elicits reward in nerve-injured rats. This approach was used to evaluate the temporal and mechanistic features of inflammation-induced ongoing pain. Results Intraplantar Complete Freund's Adjuvant (CFA produced thermal hyperalgesia and guarding behavior that was reliably observed within 24 hrs and maintained, albeit diminished, 4 days post-administration. Spinal clonidine produced robust conditioned place preference (CPP in CFA treated rats 1 day, but not 4 days following CFA administration. However, spinal clonidine blocked CFA-induced thermal hyperalgesia at both post-CFA days 1 and 4, indicating different time-courses of ongoing and evoked pain. Peripheral nerve block by lidocaine administration into the popliteal fossa 1 day following intraplantar CFA produced a robust preference for the lidocaine paired chamber, indicating that injury-induced ongoing pain is driven by afferent fibers innervating the site of injury. Pretreatment with resiniferatoxin (RTX, an ultrapotent capsaicin analogue known to produce long-lasting desensitization of TRPV1 positive afferents, fully blocked CFA-induced thermal hypersensitivity and abolished the CPP elicited by administration of popliteal fossa lidocaine 24 hrs post-CFA. In addition, RTX pretreatment blocked guarding behavior observed 1 day following intraplantar CFA. In contrast, administration of the selective TRPV1 receptor antagonist, AMG9810, at a dose that reversed CFA-induced thermal hyperalgesia failed to reduce CFA-induced ongoing pain or guarding behavior. Conclusions These data demonstrate that inflammation induces both ongoing pain and evoked hypersensitivity that can be differentiated on the basis of time course. Ongoing pain (a is transient, (b driven by peripheral input resulting from the injury, (c dependent on TRPV1 positive

  2. Chronic recruitment of primary afferent neurons by microstimulation in the feline dorsal root ganglia

    Fisher, Lee E.; Ayers, Christopher A.; Ciollaro, Mattia; Ventura, Valérie; Weber, Douglas J.; Gaunt, Robert A.


    Objective. This study describes results of primary afferent neural microstimulation experiments using microelectrode arrays implanted chronically in the lumbar dorsal root ganglia (DRG) of four cats. The goal was to test the stability and selectivity of these microelectrode arrays as a potential interface for restoration of somatosensory feedback after damage to the nervous system such as amputation. Approach. A five-contact nerve-cuff electrode implanted on the sciatic nerve was used to record the antidromic compound action potential response to DRG microstimulation (2-15 µA biphasic pulses, 200 µs cathodal pulse width), and the threshold for eliciting a response was tracked over time. Recorded responses were segregated based on conduction velocity to determine thresholds for recruiting Group I and Group II/Aβ primary afferent fibers. Main results. Thresholds were initially low (5.1 ± 2.3 µA for Group I and 6.3 ± 2.0 µA for Group II/Aβ) and increased over time. Additionally the number of electrodes with thresholds less than or equal to 15 µA decreased over time. Approximately 12% of tested electrodes continued to elicit responses at 15 µA up to 26 weeks after implantation. Higher stimulation intensities (up to 30 µA) were tested in one cat at 23 weeks post-implantation yielding responses on over 20 additional electrodes. Within the first six weeks after implantation, approximately equal numbers of electrodes elicited only Group I or Group II/Aβ responses at threshold, but the relative proportion of Group II/Aβ responses decreased over time. Significance. These results suggest that it is possible to activate Group I or Group II/Aβ primary afferent fibers in isolation with penetrating microelectrode arrays implanted in the DRG, and that those responses can be elicited up to 26 weeks after implantation, although it may be difficult to achieve a consistent response day-to-day with currently available electrode technology. The DRG are compelling targets

  3. Cationic influences upon synaptic transmission at the hair cell-afferent fiber synapse of the frog

    Cochran, S. L.


    The concentrations of inorganic cations (K+, Na+, and Ca2+) bathing the isolated frog labyrinth were varied in order to assess their role in influencing and mediating synaptic transmission at the hair cell-afferent fiber synapse. Experiments employed intracellular recordings of synaptic activity from VIIIth nerve afferents. Recordings were digitized continuously at 50 kHz, and excitatory postsynaptic potentials were detected and parameters quantified by computer algorithms. Particular attention was focused on cationic effects upon excitatory postsynaptic potential frequency of occurrence and excitatory postsynaptic potential amplitude, in order to discriminate between pre- and postsynaptic actions. Because the small size of afferents preclude long term stable recordings, alterations in cationic concentrations were applied transiently and their peak effects on synaptic activity were assessed. Increases in extracellular K+ concentration of a few millimolar produced a large increase in the frequency of occurrence of excitatory postsynaptic potentials with little change in amplitude, indicating that release of transmitter from the hair cell is tightly coupled to its membrane potential. Increasing extracellular Na+ concentration resulted in an increase in excitatory postsynaptic potential amplitude with no significant change in excitatory postsynaptic potential frequency of occurrence, suggesting that the transmitter-gated subsynaptic channel conducts Na+ ions. Decreases in extracellular Ca2+ concentration had little effect upon excitatory postsynaptic potential frequency, but increased excitatory postsynaptic potential frequency and amplitude. These findings suggest that at higher concentrations Ca2+ act presynaptically to prevent transmitter release and postsynaptically to prevent Na+ influx during the generation of the excitatory postsynaptic potential. The influences of these ions on synaptic activity at this synapse are remarkably similar to those reported at the

  4. Variation in response dynamics of regular and irregular vestibular-nerve afferents during sinusoidal head rotations and currents in the chinchilla.

    Kim, Kyu-Sung; Minor, Lloyd B; Della Santina, Charles C; Lasker, David M


    In mammals, vestibular-nerve afferents that innervate only type I hair cells (calyx-only afferents) respond nearly in phase with head acceleration for high-frequency motion, whereas afferents that innervate both type I and type II (dimorphic) or only type II (bouton-only) hair cells respond more in phase with head velocity. Afferents that exhibit irregular background discharge rates have a larger phase lead re-head velocity than those that fire more regularly. The goal of this study was to investigate the cause of the variation in phase lead between regular and irregular afferents at high-frequency head rotations. Under the assumption that externally applied galvanic currents act directly on the nerve, we derived a transfer function describing the dynamics of a semicircular canal and its hair cells through comparison of responses to sinusoidally modulated head velocity and currents. Responses of all afferents were fit well with a transfer function with one zero (lead term). Best-fit lead terms describing responses to current for each group of afferents were similar to the lead term describing responses to head velocity for regular afferents (0.006 s + 1). This finding indicated that the pre-synaptic and synaptic inputs to regular afferents were likely to be pure velocity transducers. However, the variation in phase lead between regular and irregular afferents could not be explained solely by the ratio of type I to II hair cells (Baird et al 1988), suggesting that the variation was caused by a combination of pre- (type of hair cell) and post-synaptic properties.

  5. Imaging chronic renal disease and renal transplant in children

    Carmichael, Jim; Easty, Marina [Great Ormond Street Hospital, Radiology Department, London (United Kingdom)


    At Great Ormond Street Hospital we have the highest number of paediatric renal transplant patients in Europe, taking cases from across the United Kingdom and abroad. Our caseload includes many children with rare complicating medical problems and chronic renal failure related morbidity. This review aims to provide an overview of our experience of imaging children with chronic renal failure and transplants. (orig.)

  6. Renal sympathetic denervation: MDCT evaluation of the renal arteries.

    Hutchinson, Barry D


    Percutaneous transluminal renal sympathetic denervation is a new treatment of refractory systemic hypertension. The purpose of this study was to assess the clinical utility of MDCT to evaluate the anatomic configuration of the renal arteries in the context of renal sympathetic denervation.

  7. Screening renal stone formers for distal renal tubular acidosis

    Osther, P J; Hansen, A B; Røhl, H F


    A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted...

  8. Renal Tumor Biopsy Technique

    Lei Zhang; Xue-Song Li; Li-Qun Zhou


    Objective:To review hot issues and future direction of renal tumor biopsy (RTB) technique.Data Sources:The literature concerning or including RTB technique in English was collected from PubMed published from 1990 to 2015.Study Selection:We included all the relevant articles on RTB technique in English,with no limitation of study design.Results:Computed tomography and ultrasound were usually used for guiding RTB with respective advantages.Core biopsy is more preferred over fine needle aspiration because of superior accuracy.A minimum of two good-quality cores for a single renal tumor is generally accepted.The use of coaxial guide is recommended.For biopsy location,sampling different regions including central and peripheral biopsies are recommended.Conclusion:In spite of some limitations,RTB technique is relatively mature to help optimize the treatment of renal tumors.

  9. Dyslipoproteinemia in renal transplantation.

    Gunjotikar R


    Full Text Available Twenty-seven live related donor renal allograft recipients were evaluated for dyslipoproteinemia. Twenty-two patients received dual immunosuppression with prednisolone and azathioprine. Five patients received cyclosporin as well. Total cholesterol (Tch, triglycerides (TG, HDL cholesterol (HDLch, LDL cholesterol (LDLch and VLDL cholesterol (VLDLch levels were estimated. Fifteen (56% patients showed significant lipoprotein abnormalities. Renal allograft recipients showed significantly lower levels of Tch (p < 0.05 and LDLch (p < 0.05 and higher levels of TG (p < 0.005 and HDLch (p < 0.05. Diet and beta blockers did not influence lipoprotein levels. A significant negative correlation was noted between post-transplant duration and Tch, TG and VLDLch levels. Increased TG levels were associated with increase in weight and higher daily prednisolone dosage at the time of evaluation. The study confirms the existence of dyslipoproteinemia in renal allograft recipients.

  10. Renal (Kidney) Manifestations in TSC

    ... International TSC Research Conference Text Size Get Involved RENAL (KIDNEY) MANIFESTATIONS IN TSC Download a PDF of ... sclerosis complex (TSC) will develop some form of renal (kidney) disease during their lifetime. There are three ...

  11. Renal involvement in antiphospholipid syndrome.

    Pons-Estel, Guillermo J; Cervera, Ricard


    Renal involvement can be a serious problem for patients with antiphospholipid syndrome (APS). However, this complication has been poorly recognized and studied. It can be present in patients who have either primary or systemic lupus erythematosus-associated APS. Clinical and laboratory features of renal involvement in APS include hypertension, hematuria, acute renal failure, and progressive chronic renal insufficiency with mild levels of proteinuria that can progress to nephrotic-range proteinuria. The main lesions are renal artery stenosis, venous renal thrombosis, and glomerular lesions (APS nephropathy) that may be acute (thrombotic microangiopathy) and/or chronic (arteriosclerosis, arterial fibrous intimal hyperplasia, tubular thyroidization, arteriolar occlusions, and focal cortical atrophy). APS can also cause end-stage renal disease and allograft vascular thrombosis. This article reviews the range of renal abnormalities associated with APS, and their diagnosis and treatment options.

  12. [Renal transplantation and urinary lithiasis].

    Lechevallier, E; Saussine, C; Traxer, O


    Renal lithiasis in renal donors is rare. A renal stone in a donor, or in a renal transplant, is not a contraindication for harvesting nor transplantation. If possible, the stone must be removed at the time of the transplantation. The risk of lithiasis is increased in the renal transplant recipient, with a frequency of 2-6%. Metabolic abnormalities for lithiasis are frequent and can be induced by the immunosuppressive treatment, anticalcineurins. Lithiasis can have a poor prognosis in the renal recipient with a risk for infection or renal dysfunction. Small (renal transplant can be followed-up. Stones of 0.5-1.5cm need an extracorporeal lithotripsy with a previous safety JJ stent. Stones greater than 1.5cm can be treated by ureteroscopy or percutaneous surgery.

  13. Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells.

    Defourny, Jean; Poirrier, Anne-Lise; Lallemend, François; Mateo Sánchez, Susana; Neef, Jakob; Vanderhaeghen, Pierre; Soriano, Eduardo; Peuckert, Christiane; Kullander, Klas; Fritzsch, Bernd; Nguyen, Laurent; Moonen, Gustave; Moser, Tobias; Malgrange, Brigitte


    Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor among spiral ganglion neuron populations controls the targeting of type I and type II afferent fibres to inner and outer hair cells, respectively. In the absence of ephrin-A5 or EphA4 forward signalling, a subset of type I projections aberrantly overshoot the inner hair cell layer and invade the outer hair cell area. Lack of type I afferent synapses impairs neurotransmission from inner hair cells to the auditory nerve. By contrast, radial shift of type I projections coincides with a gain of presynaptic ribbons that could enhance the afferent signalling from outer hair cells. Ephexin-1, cofilin and myosin light chain kinase act downstream of EphA4 to induce type I spiral ganglion neuron growth cone collapse. Our findings constitute the first identification of an Eph/ephrin-mediated mutual repulsion mechanism responsible for specific sorting of auditory projections in the cochlea.

  14. Differential presynaptic control of the synaptic effectiveness of cutaneous afferents evidenced by effects produced by acute nerve section.

    Rudomin, P; Jiménez, I; Chávez, D


    In the anaesthetized cat, the acute section of the saphenous (Saph) and/or the superficial peroneal (SP) nerves was found to produce a long-lasting increase of the field potentials generated in the dorsal horn by stimulation of the medial branch of the sural (mSU) nerve. This facilitation was associated with changes in the level of the tonic primary afferent depolarization (PAD) of the mSU intraspinal terminals. The mSU afferent fibres projecting into Rexed's laminae III-IV were subjected to a tonic PAD that was reduced by the acute section of the SP and/or the Saph nerves. The mSU afferents projecting deeper into the dorsal horn (Rexed's laminae V-VI) were instead subjected to a tonic PAD that was increased after Saph and SP acute nerve section. A differential control of the synaptic effectiveness of the low-threshold cutaneous afferents according to their sites of termination within the dorsal horn is envisaged as a mechanism that allows selective processing of sensory information in response to tactile and nociceptive stimulation or during the execution of different motor tasks.

  15. Afferent-induced facilitation of primary motor cortex excitability in the region controlling hand muscles in humans.

    Devanne, H; Degardin, A; Tyvaert, L; Bocquillon, P; Houdayer, E; Manceaux, A; Derambure, P; Cassim, F


    Sensory inputs from cutaneous and limb receptors are known to influence motor cortex network excitability. Although most recent studies have focused on the inhibitory influences of afferent inputs on arm motor responses evoked by transcranial magnetic stimulation (TMS), facilitatory effects are rarely considered. In the present work, we sought to establish how proprioceptive sensory inputs modulate the excitability of the primary motor cortex region controlling certain hand and wrist muscles. Suprathreshold TMS pulses were preceded either by median nerve stimulation (MNS) or index finger stimulation with interstimulus intervals (ISIs) ranging from 20 to 200 ms (with particular focus on 40-80 ms). Motor-evoked potentials recorded in the abductor pollicis brevis (APB), first dorsalis interosseus and extensor carpi radialis muscles were strongly facilitated (by up to 150%) by MNS with ISIs of around 60 ms, whereas digit stimulation had only a weak effect. When MNS was delivered at the interval that evoked the optimal facilitatory effect, the H-reflex amplitude remained unchanged and APB motor responses evoked with transcranial electric stimulation were not increased as compared with TMS. Afferent-induced facilitation and short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) mechanisms are likely to interact in cortical circuits, as suggested by the strong facilitation observed when MNS was delivered concurrently with ICF and the reduction of SICI following MNS. We conclude that afferent-induced facilitation is a mechanism which probably involves muscle spindle afferents and should be considered when studying sensorimotor integration mechanisms in healthy and disease situations.

  16. NMClab, a model to assess the contributions of muscle visco-elasticity and afferent feedback to joint dynamics

    Schouten, Alfred C.; Mugge, Winfred; Helm, van der Frans C.T.


    The dynamic behavior of a neuromusculoskeletal system results from the complex mechanical interaction between muscle visco-elasticity resulting from (co-)contraction and afferent feedback from muscle spindles and Golgi tendon organs. As a result of the multiple interactions the individual effect of




    1. A muscle spindle model for primary afferent firing is presented that contains two components representing a gamma-d-dependent (bag1) and gamma-s-dependent (bag2/nuclear chain) intrafusal fiber. Each of the intrafusal fibers is composed of a linear elastic element representing the sensory part and

  18. Afferent facilitation of corticomotor responses is increased by IgGs of patients with NMDA-receptor antibodies.

    Manto, Mario; Dalmau, Josep; Didelot, Adrien; Rogemond, Véronique; Honnorat, Jérôme


    A severe subacute encephalitis associated with auto-antibodies to the NMDA receptor (NMDA-R) has been reported in humans. These antibodies are directed to NR1/NR2 heteromers of the NMDA receptor. We studied the effects of patients' cerebrospinal fluid (CSF) injected in rFr2 (the prefrontal area) on the afferent facilitation in a conditioning paradigm for corticomotor responses. The afferent facilitation was assessed in forelimbs and hindlimbs of rats, before and after application of trains of high-frequency stimulation (HFS) which are known to modulate the excitability of M1. Before HFS, patients' CSF did not modify afferent facilitation. After HFS, the amplitudes of corticomotor responses before conditioning were significantly larger in forelimbs and hindlimbs. There was an increase of the afferent facilitation in forelimbs. The same effect was observed after injection of purified IgGs from patients' sera. Our results highlight that IgGs of patients with NMDA-R antibodies induce a state of corticomotor hyperexcitability following application of HFS over the prefrontal area.

  19. Distinct target cell-dependent forms of short-term plasticity of the central visceral afferent synapses of the rat

    Watabe Ayako M


    Full Text Available Abstract Background The visceral afferents from various cervico-abdominal sensory receptors project to the dorsal vagal complex (DVC, which is composed of the nucleus of the solitary tract (NTS, the area postrema and the dorsal motor nucleus of the vagus nerve (DMX, via the vagus and glossopharyngeal nerves and then the solitary tract (TS in the brainstem. While the excitatory transmission at the TS-NTS synapses shows strong frequency-dependent suppression in response to repeated stimulation of the afferents, the frequency dependence and short-term plasticity at the TS-DMX synapses, which also transmit monosynaptic information from the visceral afferents to the DVC neurons, remain largely unknown. Results Recording of the EPSCs activated by paired or repeated TS stimulation in the brainstem slices of rats revealed that, unlike NTS neurons whose paired-pulse ratio (PPR is consistently below 0.6, the distribution of the PPR of DMX neurons shows bimodal peaks that are composed of type I (PPR, 0.6-1.5; 53% of 120 neurons recorded and type II (PPR, Conclusions These two general types of short-term plasticity might contribute to the differential activation of distinct vago-vagal reflex circuits, depending on the firing frequency and type of visceral afferents.

  20. Sensory Feedback in Interlimb Coordination: Contralateral Afferent Contribution to the Short-Latency Crossed Response during Human Walking

    Gervasio, Sabata; Voigt, Michael; Kersting, Uwe G.; Farina, Dario; Sinkjær, Thomas


    A constant coordination between the left and right leg is required to maintain stability during human locomotion, especially in a variable environment. The neural mechanisms underlying this interlimb coordination are not yet known. In animals, interneurons located within the spinal cord allow direct communication between the two sides without the need for the involvement of higher centers. These may also exist in humans since sensory feedback elicited by tibial nerve stimulation on one side (ipsilateral) can affect the muscles activation in the opposite side (contralateral), provoking short-latency crossed responses (SLCRs). The current study investigated whether contralateral afferent feedback contributes to the mechanism controlling the SLCR in human gastrocnemius muscle. Surface electromyogram, kinematic and kinetic data were recorded from subjects during normal walking and hybrid walking (with the legs moving in opposite directions). An inverse dynamics model was applied to estimate the gastrocnemius muscle proprioceptors’ firing rate. During normal walking, a significant correlation was observed between the magnitude of SLCRs and the estimated muscle spindle secondary afferent activity (P = 0.04). Moreover, estimated spindle secondary afferent and Golgi tendon organ activity were significantly different (P ≤ 0.01) when opposite responses have been observed, that is during normal (facilitation) and hybrid walking (inhibition) conditions. Contralateral sensory feedback, specifically spindle secondary afferents, likely plays a significant role in generating the SLCR. This observation has important implications for our understanding of what future research should be focusing on to optimize locomotor recovery in patient populations. PMID:28060839

  1. Afferent contribution to locomotor muscle activity during unconstrained overground human walking: an analysis of triceps surae muscle fascicles

    Klint, Richard af; Cronin, Neil J.; Ishikawa, Masaki


    Plantar flexor series elasticity can be used to dissociate muscle fascicle and muscle tendon behaviour and, therefore, afferent feedback during human walking. We used electromyography (EMG) and high speed ultrasonography concomitantly to monitor muscle activity and muscle fascicle behaviour in ni...

  2. Bilateral sensory deprivation of trigeminal afferent fibers on corticomotor control of human tongue musculature: A preliminary study

    Kothari, Mohit; Baad-Hansen, Lene; Svensson, Peter


    Background: Transcranial magnetic stimulation (TMS) has demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of sensory afferent inputs. Objective: The aim of the present study was to determine whether bilateral local anaesthesia (LA) of the lingual ne...

  3. Ultrasonography as a tool to study afferent feedback from the muscle-tendon complex during human walking

    Cronin, Neil J.; Klint, Richard af; Grey, Michael James


    In humans, one of the most common tasks in everyday life is walking, and sensory afferent feedback from peripheral receptors, particularly the muscle spindles and Golgi tendon organs (GTO), makes an important contribution to the motor control of this task. One factor that can complicate the abili...

  4. Renal denervation and hypertension.

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D


    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  5. Renal Artery Stent Outcomes

    Murphy, Timothy P.; Cooper, Christopher J.; Matsumoto, Alan H.; Cutlip, Donald E.; Pencina, Karol M.; Jamerson, Kenneth; Tuttle, Katherine R.; Shapiro, Joseph I.; D’Agostino, Ralph; Massaro, Joseph; Henrich, William; Dworkin, Lance D.


    BACKGROUND Multiple randomized clinical trials comparing renal artery stent placement plus medical therapy with medical therapy alone have not shown any benefit of stent placement. However, debate continues whether patients with extreme pressure gradients, stenosis severity, or baseline blood pressure benefit from stent revascularization. OBJECTIVES The study sought to test the hypothesis that pressure gradients, stenosis severity, and/or baseline blood pressure affects outcomes after renal artery stent placement. METHODS Using data from 947 patients with a history of hypertension or chronic kidney disease from the largest randomized trial of renal artery stent placement, the CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) study, we performed exploratory analyses to determine if subsets of patients experienced better outcomes after stent placement than the overall cohort. We examined baseline stenosis severity, systolic blood pressure, and translesion pressure gradient (peak systolic and mean) and performed interaction tests and Cox proportional hazards analyses for the occurrence of the primary endpoint through all follow-up, to examine the effect of these variables on outcomes by treatment group. RESULTS There were no statistically significant differences in outcomes based on the examined variables nor were there any consistent nonsignificant trends. CONCLUSIONS Based on data from the CORAL randomized trial, there is no evidence of a significant treatment effect of the renal artery stent procedure compared with medical therapy alone based on stenosis severity, level of systolic blood pressure elevation, or according to the magnitude of the transstenotic pressure gradient. (Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions [CORAL]; NCT00081731) PMID:26653621

  6. The role of resting frontal EEG asymmetry in psychopathology: afferent or efferent filter?

    Gatzke-Kopp, Lisa M; Jetha, Michelle K; Segalowitz, Sidney J


    Resting EEG asymmetry evident early in life is thought to bias affective behaviors and contribute to the development of psychopathology. However, it remains unclear at what stage of information processing this bias occurs. Asymmetry may serve as an afferent filter, modulating emotional reactivity to incoming stimuli; or as an efferent filter, modulating behavioral response tendencies under emotional conditions. This study examines 209 kindergarten children (M = 6.03 years old) to test predictions put forth by the two models. Resting asymmetry was examined in conjunction with electrodermal and cardiac measures of physiological reactivity to four emotion-inducing film clips (fear, sad, happy, anger) and teacher ratings of psychopathology. Results confirm an association between increased right side cortical activation and internalizing symptom severity as well as left activation and externalizing symptom severity. Significant interactions between resting asymmetry and physiological reactivity to emotion indicate that physiological reactivity moderates the association between resting asymmetry and symptoms of psychopathology.

  7. Whole-Brain Monosynaptic Afferent Inputs to Basal Forebrain Cholinergic System

    Hu, Rongfeng; Jin, Sen; He, Xiaobin; Xu, Fuqiang; Hu, Ji


    The basal forebrain cholinergic system (BFCS) robustly modulates many important behaviors, such as arousal, attention, learning and memory, through heavy projections to cortex and hippocampus. However, the presynaptic partners governing BFCS activity still remain poorly understood. Here, we utilized a recently developed rabies virus-based cell-type-specific retrograde tracing system to map the whole-brain afferent inputs of the BFCS. We found that the BFCS receives inputs from multiple cortical areas, such as orbital frontal cortex, motor cortex, and insular cortex, and that the BFCS also receives dense inputs from several subcortical nuclei related to motivation and stress, including lateral septum, central amygdala, paraventricular nucleus of hypothalamus, dorsal raphe, and parabrachial nucleus. Interestingly, we found that the BFCS receives inputs from the olfactory areas and the entorhinal–hippocampal system. These results greatly expand our knowledge about the connectivity of the mouse BFCS and provided important preliminary indications for future exploration of circuit function. PMID:27777554

  8. Endomorphins decrease heart rate and blood pressure possibly by activating vagal afferents in anesthetized rats.

    Kwok, E H; Dun, N J


    Endomorphin 1 (10, 30, 100 nmol/kg) administered intravenously (i.v. ) to urethane-anesthetized rats consistently and dose-dependently lowered heart rate (HR) and mean arterial pressure (MAP); the decrease in blood pressure recovered faster as compared to the HR. The effects of endomorphin 2 were qualitatively similar. Naloxone (2 mg/kg, i.v.) completely antagonized the bradycardia and hypotension caused by endomorphin 1. Pretreatment of the rats with atropine methylnitrate, atropine sulfate (2 mg/kg, i.v.) or bilateral vagotomy nearly abolished the bradycardia and attenuated the hypotensive effect of endomorphin 1. Our studies suggest that the bradycardia effect following systemic administration of the new opioid peptide may be explained by activation of vagal afferents and the hypotensive effect may be secondary to a reduction of cardiac output and/or a direct vasodilation.

  9. Phrenic nerve afferents elicited cord dorsum potential in the cat cervical spinal cord

    Davenport Paul W


    Full Text Available Abstract Background The diaphragm has sensory innervation from mechanoreceptors with myelinated axons entering the spinal cord via the phrenic nerve that project to the thalamus and somatosensory cortex. It was hypothesized that phrenic nerve afferent (PnA projection to the central nervous system is via the spinal dorsal column pathway. Results A single N1 peak of the CDP was found in the C4 and C7 spinal segments. Three peaks (N1, N2, and N3 were found in the C5 and C6 segments. No CDP was recorded at C8 dorsal spinal cord surface in cats. Conclusion These results demonstrate PnA activation of neurons in the cervical spinal cord. Three populations of myelinated PnA (Group I, Group II, and Group III enter the cat's cervical spinal segments that supply the phrenic nerve

  10. Afferent Inputs to Neurotransmitter-Defined Cell Types in the Ventral Tegmental Area

    Lauren Faget


    Full Text Available The ventral tegmental area (VTA plays a central role in the neural circuit control of behavioral reinforcement. Though considered a dopaminergic nucleus, the VTA contains substantial heterogeneity in neurotransmitter type, containing also GABA and glutamate neurons. Here, we used a combinatorial viral approach to transsynaptically label afferents to defined VTA dopamine, GABA, or glutamate neurons. Surprisingly, we find that these populations received qualitatively similar inputs, with dominant and comparable projections from the lateral hypothalamus, raphe, and ventral pallidum. However, notable differences were observed, with striatal regions and globus pallidus providing a greater share of input to VTA dopamine neurons, cortical input preferentially on to glutamate neurons, and GABA neurons receiving proportionally more input from the lateral habenula and laterodorsal tegmental nucleus. By comparing inputs to each of the transmitter-defined VTA cell types, this study sheds important light on the systems-level organization of diverse inputs to VTA.

  11. Renal Failure in Pregnancy.

    Balofsky, Ari; Fedarau, Maksim


    Renal failure during pregnancy affects both mother and fetus, and may be related to preexisting disease or develop secondary to diseases of pregnancy. Causes include hypovolemia, sepsis, shock, preeclampsia, thrombotic microangiopathies, and renal obstruction. Treatment focuses on supportive measures, while pharmacologic treatment is viewed as second-line therapy, and is more useful in mitigating harmful effects than treating the underlying cause. When supportive measures and pharmacotherapy prove inadequate, dialysis may be required, with the goal being to prolong pregnancy until delivery is feasible. Outcomes and recommendations depend primarily on the underlying cause.

  12. Renal lithiasis and nutrition.

    Grases, Felix; Costa-Bauza, Antonia; Prieto, Rafel M


    Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified through diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins) and each type of renal stone (calcium oxalate monohydrate papillary, calcium oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric acid, calcium oxalate/uric acid and cystine) is discussed.

  13. Pediatric Renal Neoplasms.

    Ranganathan, Sarangarajan


    Renal tumors in childhood consist of a diverse group of tumors ranging from the most common Wilms' tumor, to the uncommon and often fatal rhabdoid tumor. Diagnosis is based on morphologic features and aided by ancillary techniques such as immunohistochemistry and cytogenetics. Molecular techniques have helped identify a group of pediatric renal cell carcinomas that have specific translocations, called translocation-associated carcinomas. Differential diagnosis of the various tumors is discussed. Pathogenesis and nephroblastomatosis, the precursor lesions of Wilms tumor, also are discussed briefly, as are the handling of these tumor specimens and prognostic factors. Copyright © 2009 Elsevier Inc. All rights reserved.

  14. Gravidez e transplante renal

    Andrade, Joana Rita Ferreira


    Enquadramento: A gravidez é rara em mulheres com Doença Renal Crónica, sobretudo em estadio avançado, em virtude de várias condicionantes como a disfunção ovárica, hemorragias vaginais anovulatórias e amenorreia. Contudo, após transplante renal é possível alimentar o sonho de constituir família, mas é preciso considerar os riscos aumentados para o enxerto e a maior susceptibilidade para complicações da gravidez. Objectivo: Avaliar os riscos e identificar as variáveis que influenciam o suce...

  15. Renal lithiasis and nutrition

    Prieto Rafel M


    Full Text Available Abstract Renal lithiasis is a multifactorial disease. An important number of etiologic factors can be adequately modified trough diet, since it must be considered that the urine composition is directly related to diet. In fact, the change of inappropriate habitual diet patterns should be the main measure to prevent kidney stones. In this paper, the relation between different dietary factors (liquid intake, pH, calcium, phosphate, oxalate, citrate, phytate, urate and vitamins and each type of renal stone (calcium oxalate monohydrate papillary, calcium oxalate monohydrate unattached, calcium oxalate dihydrate, calcium oxalate dihydrate/hydroxyapatite, hydroxyapatite, struvite infectious, brushite, uric acid, calcium oxalate/uric acid and cystine is discussed.

  16. Effects of kappa opioid receptor-selective agonists on responses of pelvic nerve afferents to noxious colorectal distension.

    Su, X; Sengupta, J N; Gebhart, G F


    The aim of this study was to examine the effects of kappa-opioid receptor selective agonists on responses of mechanosensitive afferent fibers in the pelvic nerve. Single-fiber recordings were made from pelvic nerve afferents in the decentralized S1 dorsal root of the rat. A total of 572 afferent fibers in the S1 dorsal root were identified by electrical stimulation of the pelvic nerve; 252 (44%) responded to noxious colorectal distension (CRD; 80 mmHg). Of these 252 fibers that responded to CRD, 100 were studied further. All 100 fibers gave monotonic increases in firing to increasing pressures of CRD. Eighty-eight fibers had low thresholds for response (mean: 3 mmHg) and 12 fibers had high-thresholds for response (mean: 28 mmHg). Responses of 17 fibers also were tested after instillation of 5% mustard oil (MO) into the colon. The resting activity of 16/17 fibers significantly increased after MO instillation; 13 (77%) also exhibited sensitization of responses to graded CRD when tested 30 min after intracolonic MO instillation. The effects of kappa1-opioid receptor preferring agonists (U50,488H, U69,593 and U62,066), the kappa2-opioid receptor preferring agonist bremazocine, and the kappa3-opioid receptor preferring agonist naloxone benzoylhydrazone (nalBzoH) were tested on responses of 64 mechanosensitive afferent fibers to noxious CRD. All five agonists dose-dependently inhibited afferent fiber responses to noxious CRD. Doses producing inhibition to 50% of the control response to CRD did not differ among the five agonists, ranging from approximately 4 to 15 mg/kg. The effects of kappa1, kappa2, and kappa3 receptor agonists were attenuated by naloxone; two kappa-opioid receptor-selective antagonists were ineffective. There were no differences in the dose-response relationships of these drugs for fibers recorded from untreated and irritant-treated colons. Conduction velocities of the fibers remained unaffected after high doses of all tested agonists. In an in vitro

  17. Vagal and splanchnic afferent nerves are not essential for anorexia associated with abomasal parasitism in sheep.

    Fox, M T; Reynolds, G W; Scott, I; Simcock, D C; Simpson, H V


    Heavy burdens of the abomasal nematode, Ostertagia (Telodorsagia) circumcincta, in growing lambs result in a reduction in liveweight gain due largely to a drop in voluntary feed intake. The present study investigated: (1) the role of subdiaphragmatic vagal and non-vagal visceral afferent nerves in mediating a reduction in voluntary feed intake, using subdiaphragmatic vagal deafferentation (vagotomy) either alone or in combination with coeliac-superior mesenteric ganglionectomy (vagotomy and sympathectomy); and (2) the association between appetite, abomasal pH, selected blood values (amidated gastrin (G-17-amide), glycine-extended gastrin (G-17-Gly), pepsinogen and leptin) and worm burden, in sheep experimentally infected with 100,000 O. circumcincta infective larvae per os. Neither vagotomy alone nor vagotomy and sympathectomy in combination adversely affected the establishment or course of development of the parasite burden, when compared with a control group subject to sham surgery. Furthermore, neither surgical procedure prevented the drop in appetite seen 5-10 days post-infection, although combined vagotomy and sympathectomy did reduce voluntary feed intake prior to the start of the study. Ostertagia infection resulted in a significant increase in abomasal pH in all three groups, which was accompanied by an increase in blood G-17-amide and in G-17-Gly, the latter reported for the first time in parasitized ruminants. There were no significant differences in blood leptin, also reported for the first time in parasitized sheep, either between groups or in comparison with pre-infection levels, though weak negative correlations were established between blood leptin and appetite from day 5 to the end of the study in all three groups and a positive correlation with blood G-17-amide in the control group over the same period. These data suggest that neither intact subdiaphragmatic vagal afferent nerves or coeliac-superior mesenteric ganglion fibres, nor changes in

  18. CXCR4 is dispensable for T cell egress from chronically inflamed skin via the afferent lymph.

    Skye A Geherin

    Full Text Available T cell recirculation through extralymphoid tissues is essential to immune surveillance, host defense and inflammation. In this process, T cells enter the tissue from the blood and subsequently leave via the afferent lymph. In the absence of inflammation, T cells require CCR7 expression to egress from the skin or lung, which is consistent with the constitutive expression of the CCR7 ligand CCL21 on lymphatic endothelium. However, during chronic inflammation alternative chemoattractants come into play, allowing Ccr7-deficient (Ccr7-/- T cells to egress efficiently from affected skin. As T cell egress from inflamed sites is a potential control point of the inflammatory response, we aimed to determine alternative T cell exit receptors using a mouse and a sheep model. We show that CCR7+ and CCR7- T cells exiting from the chronically inflamed skin were highly responsive to the CXCR4 ligand CXCL12, which was induced in the lymphatics in the inflamed site. Based on these findings, we hypothesized that CXCR4 mediates T cell egress from inflamed skin. However, pharmacological inhibition of CXCR4 did not affect the tissue egress of wildtype or Ccr7-/- CD4 and CD8 T cells after adoptive transfer into chronically inflamed skin. Similarly, adoptively transferred Cxcr4-/- Ccr7-/- and Ccr7-/- T cells egressed from the inflamed skin equally well. Based on these data, we conclude that, while CXCR4 might play an essential role for other cell types that enter the afferent lymphatics, it is dispensable for T cell egress from the chronically inflamed skin.

  19. Evolution of a new sense for wind in flying phasmids? Afferents and interneurons

    Hustert, Reinhold; Klug, Rebecca


    The evolution of winged stick insects (phasmids) from secondarily wingless ancestors was proposed in recent studies. We explored the cuticle of flying phasmids for wind sensors that could be involved in their flight control, comparable to those known for locusts. Surprisingly, wind-sensitive hairs (wsH) occur on the palps of mouthparts and on the antennae of the winged phasmid Sipyloidea sipylus which can fly in tethered position only when air currents blow over the mouthparts. The present study describes the morphology and major functional properties of these “new” wsH with soft and bulging hair bases which are different from the beaker-like hair bases of the wsH on the cerci of phasmids and the wsH described in other insects. The most sensitive wsH of antennae and palps respond with phasic-tonic afferents to air currents exceeding 0.2 ms-1. The fields of wsH on one side of the animal respond mainly to ventral, lateral, and frontal wind on the ipsilateral side of the head. Afferent inputs from the wsH converge but also diverge to a group of specific interneurons at their branches in the suboesophageal ganglion and can send their integrated input from wsH fields of the palps and antennae to the thoracic central nervous system. Response types of individual wsH-interneurons are either phasic or phasic-tonic to air puffs or constant air currents and also, the receptive fields of individual interneurons differ. We conclude that the “new” wsH system and its interneurons mainly serve to maintain flight activity in airborne phasmids and also, the “new” wsH must have emerged together with the integrating interneurons during the evolution from wingless to the recent winged forms of phasmids.

  20. Muscle afferent receptors engaged in augmented sympathetic responsiveness in peripheral artery disease

    Jianhua eLi


    Full Text Available The exercise pressor reflex (EPR is a neural control mechanism responsible for the cardiovascular responses to exercise. As exercise is initiated, thin fiber muscle afferent nerves are activated by mechanical and metabolic stimuli arising in the contracting muscles. This leads to reflex increases in arterial blood pressure and heart rate primarily through activation of sympathetic nerve activity (SNA. Studies of humans and animals have indicated that the EPR is exaggerated in a number of cardiovascular diseases. For the last several years, studies have specifically employed a rodent model to examine the mechanisms at receptor and cellular levels by which responses of SNA and blood pressure to static exercise are heightened in peripheral artery disease (PAD, one of the most common cardiovascular disorders. A rat model of this disease has well been established. Specifically, femoral artery occlusion is used to study intermittent claudication that is observed in human PAD. The receptors on thin fiber muscle afferents that are engaged in this disease include transient receptor potential vanilloid type 1 (TRPV1, purinergic P2X and acid sensing ion channel (ASIC. The role played by nerve growth factor (NGF in regulating those sensory receptors in the processing of amplified EPR was also investigated. The purpose of this review is to focus on a theme namely that PAD accentuates autonomic reflex responses to exercise and further address regulatory mechanisms leading to abnormal sympathetic responsiveness. This review will present some of recent results in regard with several receptors in muscle sensory neurons in contribution to augmented autonomic reflex responses in PAD. Review of the findings from recent studies would lead to a better understanding in integrated processing of sympathetic nervous system in PAD.

  1. Intestinal epithelial stem/progenitor cells are controlled by mucosal afferent nerves.

    Ove Lundgren

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

  2. TRPM8 function and expression in vagal sensory neurons and afferent nerves innervating guinea pig esophagus.

    Yu, Xiaoyun; Hu, Youtian; Ru, Fei; Kollarik, Marian; Undem, Bradley J; Yu, Shaoyong


    Sensory transduction in esophageal afferents requires specific ion channels and receptors. TRPM8 is a new member of the transient receptor potential (TRP) channel family and participates in cold- and menthol-induced sensory transduction, but its role in visceral sensory transduction is still less clear. This study aims to determine TRPM8 function and expression in esophageal vagal afferent subtypes. TRPM8 agonist WS-12-induced responses were first determined in nodose and jugular neurons by calcium imaging and then investigated by whole cell patch-clamp recordings in Dil-labeled esophageal nodose and jugular neurons. Extracellular single-unit recordings were performed in nodose and jugular C fiber neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. TRPM8 mRNA expression was determined by single neuron RT-PCR in Dil-labeled esophageal nodose and jugular neurons. The TRPM8 agonist WS-12 elicited calcium influx in a subpopulation of jugular but not nodose neurons. WS-12 activated outwardly rectifying currents in esophageal Dil-labeled jugular but not nodose neurons in a dose-dependent manner, which could be inhibited by the TRPM8 inhibitor AMTB. WS-12 selectively evoked action potential discharges in esophageal jugular but not nodose C fibers. Consistently, TRPM8 transcripts were highly expressed in esophageal Dil-labeled TRPV1-positive jugular neurons. In summary, the present study demonstrated a preferential expression and function of TRPM8 in esophageal vagal jugular but not nodose neurons and C fiber subtypes. This provides a distinctive role of TRPM8 in esophageal sensory transduction and may lead to a better understanding of the mechanisms of esophageal sensation and nociception.

  3. Effects of acid on vagal nociceptive afferent subtypes in guinea pig esophagus.

    Yu, Xiaoyun; Hu, Youtian; Yu, Shaoyong


    Acid reflux-induced heartburn and noncardiac chest pain are processed peripherally by sensory nerve endings in the wall of the esophagus, but the underlying mechanism is still unclear. This study aims to determine the effects of acid on esophageal vagal nociceptive afferent subtypes. Extracellular single-unit recordings were performed in guinea pig vagal nodose or jugular C fiber neurons by using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. We recorded action potentials (AP) of esophageal nodose or jugular C fibers evoked by acid perfusion and compared esophageal distension-evoked AP before and after acid perfusion. Acid perfusion for 30 min (pH range 7.4 to 5.8) did not evoke AP in nodose C fibers but significantly decreased their responses to esophageal distension, which could be recovered after washing out acid for 90 min. In jugular C fibers, acid perfusion not only evoked AP but also inhibited their responses to esophageal distension, which were not recovered after washing out acid for 120 min. Lower concentration of capsaicin perfusion mimicked acid-induced effects in nodose and jugular C fibers. Pretreatment with TRPV1 antagonist AMG9810, but not acid-sensing ion channel (ASIC) inhibitor amiloride, significantly inhibited acid-induced effects in nodose and jugular C fiber. These results demonstrate that esophageal vagal nociceptive afferent nerve subtypes display distinctive responses to acid. Acid activates jugular, but not nodose, C fibers and inhibits both of their responses to esophageal distension. These effects are mediated mainly through TRPV1. This inhibitory effect is a novel finding and may contribute to esophageal sensory/motor dysfunction in acid reflux diseases.

  4. Phenylpyrazolone derivatives inhibit gastric emptying in rats by a capsaicin-sensitive afferent pathway

    A.M. Vinagre


    Full Text Available Dipyrone (Dp, 4-aminoantipyrine (AA and antipyrine (At administered iv and Dp administered icv delay gastric emptying (GE in rats. The participation of capsaicin (Cps-sensitive afferent fibers in this phenomenon was evaluated. Male Wistar rats were pretreated sc with Cps (50 mg/kg or vehicle between the first and second day of life and both groups were submitted to the eye-wiping test. GE was determined in these animals at the age of 8/9 weeks (weight: 200-300 g. Ten minutes before the study, the animals of both groups were treated iv with Dp, AA or At (240 μmol/kg, or saline; or treated icv with Dp (4 μmol/animal or saline. GE was determined 10 min after treatment by measuring % gastric retention (GR of saline labeled with phenol red 10 min after orogastric administration. Percent GR (mean ± SEM, N = 8 in animals pretreated with Cps and treated with Dp, AA or At (35.8 ± 3.2, 35.4 ± 2.2, and 35.6 ± 2%, respectively did not differ from the GR of saline-treated animals pretreated with vehicle (36.8 ± 2.8% and was significantly lower than in animals pretreated with vehicle and treated with the drugs (52.1 ± 2.8, 66.2 ± 4, and 55.8 ± 3%, respectively. The effect of icv administration of Dp (N = 6 was not modified by pretreatment with Cps (63.3 ± 5.7% compared to Dp-treated animals pretreated with vehicle (62.3 ± 2.4%. The results suggest the participation of capsaicin-sensitive afferent fibers in the delayed GE induced by iv administration of Dp, AA and At, but not of icv Dp.

  5. Can loss of muscle spindle afferents explain the ataxic gait in Riley-Day syndrome?

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Gutiérrez, Joel; Axelrod, Felicia B; Kaufmann, Horacio


    The Riley-Day syndrome is the most common of the hereditary sensory and autonomic neuropathies (Type III). Among the well-recognized clinical features are reduced pain and temperature sensation, absent deep tendon reflexes and a progressively ataxic gait. To explain the latter we tested the hypothesis that muscle spindles, or their afferents, are absent in hereditary sensory and autonomic neuropathy III by attempting to record from muscle spindle afferents from a nerve supplying the leg in 10 patients. For comparison we also recorded muscle spindles from 15 healthy subjects and from two patients with hereditary sensory and autonomic neuropathy IV, who have profound sensory disturbances but no ataxia. Tungsten microelectrodes were inserted percutaneously into fascicles of the common peroneal nerve at the fibular head. Intraneural stimulation within muscle fascicles evoked twitches at normal stimulus currents (10-30 µA), and deep pain (which often referred) at high intensities (1 mA). Microneurographic recordings from muscle fascicles revealed a complete absence of spontaneously active muscle spindles in patients with hereditary sensory and autonomic neuropathy III; moreover, responses to passive muscle stretch could not be observed. Conversely, muscle spindles appeared normal in patients with hereditary sensory and autonomic neuropathy IV, with mean firing rates of spontaneously active endings being similar to those recorded from healthy controls. Intraneural stimulation within cutaneous fascicles evoked paraesthesiae in the fascicular innervation territory at normal stimulus intensities, but cutaneous pain was never reported during high-intensity stimulation in any of the patients. Microneurographic recordings from cutaneous fascicles revealed the presence of normal large-diameter cutaneous mechanoreceptors in hereditary sensory and autonomic neuropathy III. Our results suggest that the complete absence of functional muscle spindles in these patients explains

  6. Decoding of the spike timing of primary afferents during voluntary arm movements in monkeys.

    Umeda, Tatsuya; Watanabe, Hidenori; Sato, Masa-Aki; Kawato, Mitsuo; Isa, Tadashi; Nishimura, Yukio


    Understanding the mechanisms of encoding forelimb kinematics in the activity of peripheral afferents is essential for developing a somatosensory neuroprosthesis. To investigate whether the spike timing of dorsal root ganglion (DRG) neurons could be estimated from the forelimb kinematics of behaving monkeys, we implanted two multi-electrode arrays chronically in the DRGs at the level of the cervical segments in two monkeys. Neuronal activity during voluntary reach-to-grasp movements were recorded simultaneously with the trajectories of hand/arm movements, which were tracked in three-dimensional space using a motion capture system. Sixteen and 13 neurons, including muscle spindles, skin receptors, and tendon organ afferents, were recorded in the two monkeys, respectively. We were able to reconstruct forelimb joint kinematics from the temporal firing pattern of a subset of DRG neurons using sparse linear regression (SLiR) analysis, suggesting that DRG neuronal ensembles encoded information about joint kinematics. Furthermore, we estimated the spike timing of the DRG neuronal ensembles from joint kinematics using an integrate-and-fire model (IF) incorporating the SLiR algorithm. The temporal change of firing frequency of a subpopulation of neurons was reconstructed precisely from forelimb kinematics using the SLiR. The estimated firing pattern of the DRG neuronal ensembles encoded forelimb joint angles and velocities as precisely as the originally recorded neuronal activity. These results suggest that a simple model can be used to generate an accurate estimate of the spike timing of DRG neuronal ensembles from forelimb joint kinematics, and is useful for designing a proprioceptive decoder in a brain machine interface.

  7. Cortico-muscular synchronization by proprioceptive afferents from the tongue muscles during isometric tongue protrusion.

    Maezawa, Hitoshi; Mima, Tatsuya; Yazawa, Shogo; Matsuhashi, Masao; Shiraishi, Hideaki; Funahashi, Makoto


    Tongue movements contribute to oral functions including swallowing, vocalizing, and breathing. Fine tongue movements are regulated through efferent and afferent connections between the cortex and tongue. It has been demonstrated that cortico-muscular coherence (CMC) is reflected at two frequency bands during isometric tongue protrusions: the beta (β) band at 15-35Hz and the low-frequency band at 2-10Hz. The CMC at the β band (β-CMC) reflects motor commands from the primary motor cortex (M1) to the tongue muscles through hypoglossal motoneuron pools. However, the generator mechanism of the CMC at the low-frequency band (low-CMC) remains unknown. Here, we evaluated the mechanism of low-CMC during isometric tongue protrusion using magnetoencephalography (MEG). Somatosensory evoked fields (SEFs) were also recorded following electrical tongue stimulation. Significant low-CMC and β-CMC were observed over both hemispheres for each side of the tongue. Time-domain analysis showed that the MEG signal followed the electromyography signal for low-CMC, which was contrary to the finding that the MEG signal preceded the electromyography signal for β-CMC. The mean conduction time from the tongue to the cortex was not significantly different between the low-CMC (mean, 80.9ms) and SEFs (mean, 71.1ms). The cortical sources of low-CMC were located significantly posterior (mean, 10.1mm) to the sources of β-CMC in M1, but were in the same area as tongue SEFs in the primary somatosensory cortex (S1). These results reveal that the low-CMC may be driven by proprioceptive afferents from the tongue muscles to S1, and that the oscillatory interaction was derived from each side of the tongue to both hemispheres. Oscillatory proprioceptive feedback from the tongue muscles may aid in the coordination of sophisticated tongue movements in humans.

  8. Branchio-oto-renal syndrome.

    Jalil, Jawad; Basheer, Faisal; Shafique, Mobeen


    The association of branchial arch anomalies (branchial cysts, branchial fistulas), hearing loss and renal anomalies constitutes the branchio-oto-renal (BOR) syndrome also known as Melnick Fraser syndrome. We present a case of this rare disorder in a girl child who presented with profound deafness, preauricular pits, branchial sinuses and renal hypoplasia.

  9. Drug-induced renal disease.

    Curtis, J R


    The clinical manifestations of drug-induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. It is therefore vital in any patient with renal disease whatever the clinical manifestations might be, to obtain a meticulous drug and toxin inventory. Withdrawal of the offending drug may result in amelioration or cure of the renal disorder although in the case of severe renal failure it may be necessary to utilise haemodialysis or peritoneal dialysis to tide the patient over the period of acute renal failure. Analgesic nephropathy is an important cause of terminal chronic renal failure and it is therefore vital to make the diagnosis as early as possible. The pathogenesis of some drug-induced renal disorders appears to be immunologically mediated. There are many other pathogenetic mechanisms involved in drug-induced renal disorders and some drugs may under appropriate circumstances be responsible for a variety of different nephrotoxic effects. For example, the sulphonamides have been incriminated in examples of crystalluria, acute interstitial nephritis, acute tubular necrosis, generalised hypersensitivity reactions, polyarteritis nodosa and drug-induced lupus erythematosus.

  10. Management of chronic renal failure.

    de Zeeuw, D.; Apperloo, AJ; de Jong, P.


    There is growing evidence that treatment of patients with renal function impairment will undergo a major shift within the next few years. Along with more or less successful attempts to alleviate the signs and symptoms of reduced renal function, new insights into renal pathophysiology as well as new

  11. Hyperpolarization-activated cyclic nucleotide-gated cation channel subtypes differentially modulate the excitability of murine small intestinal afferents

    Ying-Ping Wang; Bi-Ying Sun; Qian Li; Li Dong; Guo-Hua Zhang; David Grundy; Wei-Fang Rong


    AIM: To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels in regulating the excitability of vagal and spinal gut afferents.METHODS: The mechanosensory response of mesen-teric afferent activity was measured in an ex vivo murine jejunum preparation. HCN channel activity was recorded through voltage and current clamp in acutely dissociated dorsal root ganglia (DRG) and nodose ganglia (NG) neurons retrogradely labeled from the small intestine through injection of a fluorescent marker (DiI). The isoforms of HCN channels expressed in DRG and NG neurons were examined by immunohistochemistry.RESULTS: Ramp distension of the small intestine evoked biphasic increases in the afferent nerve activity, reflecting the activation of low- and high-threshold fibers.HCN blocker CsCl (5 mmol/L) preferentially inhibited the responses of low-threshold fibers to distension and showed no significant effects on the high-threshold responses. The effect of CsCl was mimicked by the more selective HCN blocker ZD7288 (10 ?mol/L). In 71.4% of DiI labeled DRG neurons (n = 20) and 90.9% of DiI labeled NG neurons (n = 10), an inward current (Ih current) was evoked by hyperpolarization pulses which was fully eliminated by extracellular CsCl. In neurons expressing Ih current, a typical "sag" was observed upon injection of hyperpolarizing current pulses in current-clamp recordings. CsCl abolished the sag entirely. In some DiI labeled DRG neurons, the Ih current was potentiated by 8-Br-cAMP, which had no effect on the Ih current of DiI labeled NG neurons. Immunohistochemistry revealed differential expression of HCN isoforms in vagal and spinal afferents, and HCN2 and HCN3 seemed to be the dominant isoform in DRG and NG, respectively.CONCLUSION: HCNs differentially regulate the excitability of vagal and spinal afferent of murine small intestine.

  12. Dopaminergic modulation of the voltage-gated sodium current in the cochlear afferent neurons of the rat.

    Catalina Valdés-Baizabal

    Full Text Available The cochlear inner hair cells synapse onto type I afferent terminal dendrites, constituting the main afferent pathway for auditory information flow. This pathway receives central control input from the lateral olivocochlear efferent neurons that release various neurotransmitters, among which dopamine (DA plays a salient role. DA receptors activation exert a protective role in the over activation of the afferent glutamatergic synapses, which occurs when an animal is exposed to intense sound stimuli or during hypoxic events. However, the mechanism of action of DA at the cellular level is still not completely understood. In this work, we studied the actions of DA and its receptor agonists and antagonists on the voltage-gated sodium current (INa in isolated cochlear afferent neurons of the rat to define the mechanisms of dopaminergic control of the afferent input in the cochlear pathway. Experiments were performed using the voltage and current clamp techniques in the whole-cell configuration in primary cultures of cochlear spiral ganglion neurons (SGNs. Recordings of the INa showed that DA receptor activation induced a significant inhibition of the peak current amplitude, leading to a significant decrease in cell excitability. Inhibition of the INa was produced by a phosphorylation of the sodium channels as shown by the use of phosphatase inhibitor that produced an inhibition analogous to that caused by DA receptor activation. Use of specific agonists and antagonists showed that inhibitory action of DA was mediated both by activation of D1- and D2-like DA receptors. The action of the D1- and D2-like receptors was shown to be mediated by a Gαs/AC/cAMP/PKA and Gαq/PLC/PKC pathways respectively. These results showed that DA receptor activation constitutes a significant modulatory input to SGNs, effectively modulating their excitability and information flow in the auditory pathway.

  13. Dopaminergic modulation of the voltage-gated sodium current in the cochlear afferent neurons of the rat.

    Valdés-Baizabal, Catalina; Soto, Enrique; Vega, Rosario


    The cochlear inner hair cells synapse onto type I afferent terminal dendrites, constituting the main afferent pathway for auditory information flow. This pathway receives central control input from the lateral olivocochlear efferent neurons that release various neurotransmitters, among which dopamine (DA) plays a salient role. DA receptors activation exert a protective role in the over activation of the afferent glutamatergic synapses, which occurs when an animal is exposed to intense sound stimuli or during hypoxic events. However, the mechanism of action of DA at the cellular level is still not completely understood. In this work, we studied the actions of DA and its receptor agonists and antagonists on the voltage-gated sodium current (INa) in isolated cochlear afferent neurons of the rat to define the mechanisms of dopaminergic control of the afferent input in the cochlear pathway. Experiments were performed using the voltage and current clamp techniques in the whole-cell configuration in primary cultures of cochlear spiral ganglion neurons (SGNs). Recordings of the INa showed that DA receptor activation induced a significant inhibition of the peak current amplitude, leading to a significant decrease in cell excitability. Inhibition of the INa was produced by a phosphorylation of the sodium channels as shown by the use of phosphatase inhibitor that produced an inhibition analogous to that caused by DA receptor activation. Use of specific agonists and antagonists showed that inhibitory action of DA was mediated both by activation of D1- and D2-like DA receptors. The action of the D1- and D2-like receptors was shown to be mediated by a Gαs/AC/cAMP/PKA and Gαq/PLC/PKC pathways respectively. These results showed that DA receptor activation constitutes a significant modulatory input to SGNs, effectively modulating their excitability and information flow in the auditory pathway.

  14. Dendritic HCN channels shape excitatory postsynaptic potentials at the inner hair cell afferent synapse in the mammalian cochlea.

    Yi, Eunyoung; Roux, Isabelle; Glowatzki, Elisabeth


    Synaptic transmission at the inner hair cell (IHC) afferent synapse, the first synapse in the auditory pathway, is specialized for rapid and reliable signaling. Here we investigated the properties of a hyperpolarization-activated current (I(h)), expressed in the afferent dendrite of auditory nerve fibers, and its role in shaping postsynaptic activity. We used whole cell patch-clamp recordings from afferent dendrites directly where they contact the IHC in excised postnatal rat cochlear turns. Excitatory postsynaptic potentials (EPSPs) of variable amplitude (1-35 mV) were found with 10-90% rise times of about 1 ms and time constants of decay of about 5 ms at room temperature. Current-voltage relations recorded in afferent dendrites revealed I(h). The pharmacological profile and reversal potential (-45 mV) indicated that I(h) is mediated by hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels. The HCN channel subunits HCN1, HCN2, and HCN4 were found to be expressed in afferent dendrites using immunolabeling. Raising intracellular cAMP levels sped up the activation kinetics, increased the magnitude of I(h) and shifted the half activation voltage (V(half)) to more positive values (-104 +/- 3 to -91 +/- 2 mV). Blocking I(h) with 50 microM ZD7288 resulted in hyperpolarization of the resting membrane potential (approximately 4 mV) and slowing the decay of the EPSP by 47%, suggesting that I(h) is active at rest and shortens EPSPs, thereby potentially improving rapid and reliable signaling at this first synapse in the auditory pathway.

  15. Significance of peripheral afferent input to the alpha-motoneurone pool for enhancement of tremor during an isometric fatiguing contraction.

    Cresswell, A G; Löscher, W N


    The objective of this study was to investigate the contribution of peripheral afferent input to the enhancement of isometric tremor during a sustained submaximal isometric contraction. It was hypothesised that during muscle fatigue, when excitatory drive is high, peripheral afferent input may augment oscillations in the stretch reflex arc and result in bursting motor-unit activity and increased tremor. Nine healthy subjects maintained isometric plantar flexions at 30% of their maximum voluntary contraction until the limit of endurance, under three test conditions. Two paradigms were used to reduce afferent input to the triceps surae alpha-motoneurone pool: (1) continued vibration of the Achilles tendon, and (2) ischaemic partial block of the tibial nerve. These were compared to a control experiment, in which there was no intervention. By recording H-reflexes from the gastrocnemius and soleus muscles, it was possible to assess the effectiveness of reducing the afferent input. When H-reflex suppression had stabilised, the fatiguing contraction was commenced and tremor was computed from the continuously recorded torque signal. Superimposed maximum twitches were elicited as indirect measures of excitatory drive. The increase in tremor root mean square throughout the fatiguing contraction was significantly less for both the vibration and ischaemic conditions. Furthermore, tremor mean power frequency decreased significantly with endurance time in the control experiment, while no significant change was seen in the other two experimental conditions. It is concluded that the enhancement of isometric tremor seen during a fatiguing submaximal isometric contraction is facilitated by peripheral afferent input to the alpha-motoneurone pool.

  16. Diverse firing properties and Aβ-, Aδ-, and C-afferent inputs of small local circuit neurons in spinal lamina I.

    Fernandes, Elisabete C; Luz, Liliana L; Mytakhir, Oleh; Lukoyanov, Nikolai V; Szucs, Peter; Safronov, Boris V


    Spinal lamina I is a key element of the pain processing system, which integrates primary afferent input and relays it to supraspinal areas. More than 90% of neurons in this layer are local circuit neurons, whose role in the signal processing is poorly understood. We performed whole-cell recordings in a spinal cord preparation with attached dorsal roots to examine morphological features and physiological properties of small local circuit neurons (n = 47) in lamina I. Cells successfully filled with biocytin (n = 17) had fusiform (n = 10), flattened (n = 4), and multipolar (n = 3) somatodendritic morphology; their axons branched extensively and terminated in laminae I-III. Intrinsic firing properties were diverse; in addition to standard tonic (n = 16), adapting (n = 7), and delayed (n = 6) patterns, small local circuit neurons also generated rhythmic discharges (n = 6) and plateau potentials (n = 10), the latter were suppressed by the L-type Ca(2+)-channel blocker nifedipine. The neurons received monosynaptic inputs from Aδ and C afferents and could generate bursts of spikes on the root stimulation. In addition, we identified lamina I neurons (n = 7) with direct inputs from the low-threshold Aβ afferents, which could be picked up by ventral dendrites protruding to lamina III. Stimulation of afferents also evoked a disynaptic inhibition of neurons. Thus, small local circuit neurons exhibit diverse firing properties, can generate rhythmic discharges and plateau potentials, and their dendrites extending into several laminae allow broad integration of Aβ-, Aδ-, and C-afferent inputs. These properties are required for processing diverse modalities of nociceptive inputs in lamina I and may underlie spinal sensitization to pain.

  17. [Hypertension and renal disease

    Kamper, A.L.; Pedersen, E.B.; Strandgaard, S.


    hypertension. Mild degrees of chronic kidney disease (CKD) can be detected in around 10% of the population, and detection is important as CKD is an important risk factor for atherosclerotic cardiovascular disease. Conversely, heart failure may cause an impairment of renal function. In chronic progressive...

  18. Insuficiencia renal aguda.

    Carlos Hernán Mejía


    Full Text Available La insuficiencia renal aguda se diagnostica aproximadamente en 5% de los pacientes hospitalizados. Sus principales causas se relacionan con la alteración del flujo sanguíneo renal, sea por depleción de volumen, baja perfusión renal o por distribución intrarrenal inadecuada y obstrucción del árbol urinario. El diagnóstico parte de la historia clínica y un buen examen físico que corrobore el estado de volemia del paciente y se complementa con el uso adecuado de los índices urinarios (excreción de sodio y osmolaridad, el uroanálisis y la ecografía renal. Su tratamiento consiste en una adecuada recuperación del volumen, manejo de los diuréticos, soporte nutricional, conservación del equilibrio hidroelectrolítico y brindar terapia de diálisis si hay toxicidad urémica, hipercaliemia severa (>6.5 mEq/l, acidosis metabólica o sobrecarga severa de volumen.

  19. Management of Renal Cysts

    Nalbant, Ismail; Can Sener, Nevzat; Firat, Hacer; Yeşil, Süleyman; Zengin, Kürşad; Yalcınkaya, Fatih; Imamoglu, Abdurrahim


    Background and Objectives: Renal cysts have a high prevalence in the general population, and their estimated incidence increases with age. Renal cyst aspiration (usually with sclerotherapy) or open/laparoscopic decortication is a generally effective and safe method in the treatment of symptomatic simple renal cysts. The success rates of laparoscopic decortication and percutaneous aspiration-sclerotherapy were compared to assist in the decision making for the procedure. Methods: A total of 184 patients with symptomatic simple renal cysts were treated with either laparoscopic decortication in 149 cases or percutaneous aspiration-sclerotherapy in 35 cases. The follow-up period was approximately 35 months, and the symptomatic and radiologic success rates of the 2 techniques were compared retrospectively. Results: Laparoscopic decortication was found to have high success rates, a low recurrence rate, and minimal morbidity. Percutaneous aspiration-sclerotherapy is an outpatient procedure with a minimally higher recurrence rate. Conclusion: When a symptomatic cyst is encountered and treatment of the cyst is indicated, laparoscopic decortication is a more efficient method that offers better results than percutaneous aspiration-sclerotherapy. PMID:25848184

  20. Rupture of Renal Transplant

    Shona Baker


    Full Text Available Background. Rupture of renal allograft is a rare and serious complication of transplantation that is usually attributed to acute rejection, acute tubular necrosis, or renal vein thrombosis. Case Presentation. LD, a 26-year-old male with established renal failure, underwent deceased donor transplantation using kidney from a 50-year-old donor with acute kidney injury (Cr 430 mmol/L. LD had a stormy posttransplant recovery and required exploration immediately for significant bleeding. On day three after transplant, he developed pain/graft swelling and another significant haemorrhage with cardiovascular compromise which did not respond to aggressive resuscitation. At reexploration, the renal allograft was found to have a longitudinal rupture and was removed. Histology showed features of type IIa Banff 97 acute vascular rejection, moderate arteriosclerosis, and acute tubular necrosis. Conclusion. Possible ways of avoiding allograft rupture include use of well-matched, good quality kidneys; reducing or managing risk factors that would predispose to delayed graft function; ensuring a technically satisfactory transplant procedure with short cold and warm ischemia times; and avoiding large donor-recipient age gradients.