Developing an Educator Network: The Effect of a Teaching Scholars Program in the Health Professions on Networking and Productivity

Background: Teaching Scholars Programs are designed to enhance productivity and faculty retention. The formation of an increased network may be a facilitative mechanism. Purposes: This study determined if participants increased their educational network and if the increase affected productivity. Methods: Researchers interviewed Teaching Scholars participants for pre- and postparticipation members of their educational network and issues related to network formation and conducted a structured vita analysis. Researchers used social network analysis (SNA) to describe the networks and regression to determine the relationship between network and productivity. Results: Educational networks increased with participation (p <.001) but showed little or no effect on productivity. SNA revealed a decrease of participants with no network, increase in connections among participants, and increase in connections to central services personnel. Researchers identified six themes from the participants' comments. Conclusions: This relatively modest program demonstrated a small effect on productivity through the increased network.     

Differentiated responses of renal and adrenal sympathetic nerve activity to intravenous morphine administration in anesthetized rats

The aim of this study was to examine the effect of i.v. morphine on sympathetic nerve activity (SNA) in the rat. Adrenal SNA and renal SNA were recorded simultaneously, together with mean arterial pressure and heart rate, in chloralose-anesthetized, artificially ventilated rats. Separate groups of rats were subjected to vagotomy. In intact rats, i.v. injection of morphine (1 mg/kg) caused an immediate transient depressor response. Within 1-3 sec, renal SNA was markedly inhibited in parallel with hypotension and bradycardia. After a few minutes, mean arterial pressure and renal SNA returned toward base-line levels, and subsequently they declined gradually again below base line. Adrenal SNA, however, showed an immediate brief increase. In the vagotomized rats, an extended renal SNA excitation occurred, accompanied by a rise in mean arterial pressure. After about 15 min, these variables returned toward base-line levels. The adrenal SNA excitation still occurred in the vagotomized rats. The renal depressor and the renal and adrenal pressor responses were all abolished by naloxone pretreatment. It is concluded that i.v. injection of morphine induces a highly differentiated response of SNA. A pronounced immediate increase in adrenal SNA occurs in parallel with renal SNA inhibition. The renal nerve inhibition is mainly reflexly obtained by opioid receptor-mediated activation of vagal afferents. The predominant central action of morphine seems to be sympathetic excitation which is also mediated through opioid receptors.     

Regional changes in sympathetic nerve activity and baroreceptor reflex function and arterial plasma levels of catecholamines, renin and vasopressin during naloxone-precipitated morphine withdrawal in rats

The aim of the study was to examine regional changes in sympathetic nerve activity (SNA) and baroreceptor function and arterial plasma catecholamines, arginine vasopressin (AVP) and plasma renin activity during morphine withdrawal in chloralose-anesthetized rats. Dependence was induced by s.c. morphine base pellets. Adrenal, renal and splanchnic SNA and SNA from the lumbar sympathetic chain were recorded before and after i.v. injections of naloxone. Baroreceptor function was examined with phenylephrine-induced increases in mean arterial pressure. In separate experiments, arterial plasma norepinephrine, epinephrine, dopamine, plasma renin activity and AVP were measured before and after naloxone-precipitated withdrawal. Naloxone administration elicited an increase in mean arterial pressure and heart rate. Although renal SNA was inhibited by approximately 50%, adrenal SNA and lumbar SNA increased by approximately 400 and 80%, respectively. Splanchnic SNA did not change significantly. The baroreceptor-mediated inhibition of adrenal SNA was facilitated while that for renal SNA was attenuated. The arterial plasma level of norepinephrine was doubled and epinephrine increased almost 20-fold. AVP increased about 15-fold, whereas plasma renin activity showed only a minor increase after naloxone. This study shows that a marked differentiation of the SNA response occurs during morphine withdrawal in rats, which suggests an interaction between opioid receptors and the control of regional sympathetic output. Furthermore, large amounts of AVP and epinephrine are released, which probably contribute to the cardiovascular changes seen in the withdrawal phase.     

Sympathetic Neural Mechanisms in Human Cardiovascular Health and Disease

The sympathetic nervous system plays a key role in regulating arterial blood pressure in humans. This review provides an overview of sympathetic neural control of the circulation and discusses the changes that occur in various disease states, including hypertension, heart failure, and obstructive sleep apnea. It focuses on measurements of sympathetic neural activity (SNA) obtained by microneurography, a technique that allows direct assessment of the electrical activity of sympathetic nerves in conscious human beings. Sympathetic neural activity is tightly linked to blood pressure via the baroreflex for each individual person. However, SNA can vary greatly among individuals and that variability is not related to resting blood pressure; that is, the blood pressure of a person with high SNA can be similar to that of a person with much lower SNA. In healthy normotensive persons, this finding appears to be related to a set of factors that balance the variability in SNA, including cardiac output and vascular adrenergic responsiveness. Measurements of SNA are very reproducible in a given person over a period of several months to a few years, but SNA increases progressively with healthy aging. Cardiovascular disease can be associated with substantial increases in SNA, as seen for example in patients with hypertension, obstructive sleep apnea, or heart failure. Obesity is also associated with an increase in SNA, but the increase in SNA among patients with obstructive sleep apnea appears to be independent of obesity per se. For several disease states, successful treatment is associated with both a decrease in sympathoexcitation and an improvement in prognosis. This finding points to an important link between altered sympathetic neural mechanisms and the fundamental processes of cardiovascular disease.MI = myocardial infarction; MSNA = muscle sympathetic neural activity; OSA = obstructive sleep apnea; SA = sinoatrial; SNA = sympathetic neural activityThe sympathetic nervous system plays a vital role in the everyday lives of human beings. Sympathetic neural responses are essential to simple tasks such as changing posture. Movement from a supine or sitting position to an upright position requires complex adjustments in blood flow and blood pressure, and these adjustments are ultimately coordinated by sympathetic nerves in conjunction with parasympathetic modulation of heart rate. Without such adjustments, blood flow to the brain would fall below autoregulatory limits, and standing up would consistently cause syncope. Indeed, some persons with severe autonomic failure are unable to stand (or sometimes even to sit upright) without fainting.^1,2This article presents an overview of our current understanding of sympathetic neural mechanisms in human cardiovascular control. It focuses on measurements of sympathetic neural activity (SNA) that are obtained by microneurography, a technique that can directly measure the electrical activity of sympathetic nerves in intact, conscious human beings. During the past 3 decades, the information yielded by this technique has greatly increased our clinical and mechanistic understanding of sympathetic neural mechanisms in health and disease. Ongoing research using this technique continues to yield new insights into the pathophysiology of cardiovascular diseases, including hypertension, coronary artery disease, and heart failure, and into the cardiovascular risk associated with diseases such as obstructive sleep apnea (OSA) and obesity.     

Interaction of baroreceptor and chemoreceptor reflex control of sympathetic nerve activity in normal humans.

Animal studies have demonstrated that activation of the baroreflex by increases in arterial pressure inhibits cardiovascular and ventilatory responses to activation of peripheral chemoreceptors (PC) with hypoxia. In this study, we examined the influences of baroreflex activation on the sympathetic response to stimulation of PC and central chemoreceptors in humans. PC were stimulated by hypoxia (10% O2/90% N2) (n = 6) and central chemoreceptors by hypercapnia (7% CO2/93% O2) (n = 6). Responses to a cold pressor stimulus were also obtained as an internal reflex control to determine the selectivity of the interactive influence of baroreflex activation. Baroreflex activation was achieved by raising mean blood pressure by greater than 10 mmHg with intravenous infusion of phenylephrine (PE). Sympathetic nerve activity (SNA) to muscle was recorded from a peroneal nerve (microneurography). During hypoxia alone, SNA increased from 255 +/- 92 to 354 +/- 107 U/min (P less than 0.05). During PE alone, mean blood pressure increased and SNA decreased to 87 +/- 45 U/min (P less than 0.05). With hypoxia during baroreflex activation with PE, SNA did not increase (50 +/- 23 U/min). During hypercapnia alone, SNA increased from 116 +/- 39 to 234 +/- 72 U/min (P less than 0.01). Hypercapnia during baroreflex activation with PE increased SNA from 32 +/- 25 U/min during PE alone to 61 +/- 26 U/min during hypercapnia and PE (P less than 0.05). Like hypercapnia (but unlike hypoxia) the cold pressor test also increased SNA during PE. We conclude that baroreflex activation selectively abolishes the SNA response to hypoxia but not to hypercapnia or the cold pressor test. The inhibitory interaction of the baroreflex and the peripheral chemoreflex may be explained by convergence of baroreceptor and peripheral chemoreceptor afferents on neurons in the medulla.     

Obstructive sleep apnea and insight into mechanisms of sympathetic overactivity

Nearly two decades ago, we evaluated ten patients with obstructive sleep apnea (OSA). We determined that alarming nocturnal oscillations in arterial pressure and sympathetic nerve activity (SNA) were caused by regulatory coupling and neural interactions among SNA, apnea, and ventilation. Patients with OSA exhibited high levels of SNA when awake, during normal ventilation, and during normoxia, which contributed to hypertension and organ damage. Additionally, we achieved a beneficial and potentially lifesaving reduction in SNA through the application of continuous positive airway pressure (CPAP), which remains a primary therapeutic approach for patients with OSA. With these results in hindsight, we herein discuss three concepts with functional and therapeutic relevance to the integrative neurobiology of autonomic cardiovascular control and to the mechanisms involved in excessive sympathoexcitation in OSA.     

Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle.

Metabolic products of skeletal muscle contraction activate metaboreceptor muscle afferents that reflexively increase sympathetic nerve activity (SNA) targeted to both resting and exercising skeletal muscle. To determine effects of the increased sympathetic vasoconstrictor drive on muscle oxygenation, we measured changes in tissue oxygen stores and mitochondrial cytochrome a,a3 redox state in rhythmically contracting human forearm muscles with near infrared spectroscopy while simultaneously measuring muscle SNA with microelectrodes. The major new finding is that the ability of reflex-sympathetic activation to decrease muscle oxygenation is abolished when the muscle is exercised at an intensity > 10% of maximal voluntary contraction (MVC). During high intensity handgrip, (45% MVC), contraction-induced decreases in muscle oxygenation remained stable despite progressive metaboreceptor-mediated reflex increases in SNA. During mild to moderate handgrips (20-33% MVC) that do not evoke reflex-sympathetic activation, experimentally induced increases in muscle SNA had no effect on oxygenation in exercising muscles but produced robust decreases in oxygenation in resting muscles. The latter decreases were evident even during maximal metabolic vasodilation accompanying reactive hyperemia. We conclude that in humans sympathetic neural control of skeletal muscle oxygenation is sensitive to modulation by metabolic events in the contracting muscles. These events are different from those involved in either metaboreceptor muscle afferent activation or reactive hyperemia.     

Sphere of Nursing Advocacy Model

The Sphere of Nursing Advocacy (SNA) model explains and depicts nursing advocacy on behalf of a client. The SNA model views the client as continually protected from the external environment by a semipermeable sphere of nursing advocacy that allows clients to self advocate if the client is emotionally and physically able or to be advocated for by the nurse if the patient is unable to advocate for him- or herself. The SNA model can be used to guide research or it can provide the basis for instruction on the subject of nursing advocacy.     

Investigating online interprofessional learning and communication using social network analysis: a study protocol

ABSTRACT

Interprofessional education (IPE) via the use of online learning environments (OLEs) can help improve patient outcomes, interprofessional attitudes, and behaviors while providing education at a distance. Studies of interprofessional learning often examine communication and its relation to learning outcomes qualitatively. OLEs allow researchers to examine these communication patterns quantitatively, through social network analysis (SNA), and answer questions regarding the nature of communication between interprofessional learners and how this may impact interprofessional attitudes and behaviors. In this paper, we present a study that aims to track interprofessional communication within a cancer care course using SNA and examine how it relates to professional attitudes and collaboration. Using pre and post-course surveys as well as numerous SNA metrics derived from course discussion board posts, we hope to show how communication between interprofessional learners may mediate outcomes. This work will add to the existing IPE literature by providing an added quantitative layer to a largely qualitative literature and encourage future studies in this area.     

Erratum to “Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and non-nociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias” [Pain 153 (9) (2012) 1824–1836]

Partial nerve injury leads to peripheral neuropathic pain. This injury results in conducting/uninterrupted (also called uninjured) sensory fibres, conducting through the damaged nerve alongside axotomised/degenerating fibres. In rats seven days after L5 spinal nerve axotomy (SNA) or modified-SNA (added loose-ligation of L4 spinal nerve with neuroinflammation-inducing chromic-gut), we investigated (a) neuropathic pain behaviours and (b) electrophysiological changes in conducting/uninterrupted L4 dorsal root ganglion (DRG) neurons with receptive fields (called: L4-receptive-field-neurons). Compared to pretreatment, modified-SNA rats showed highly significant increases in spontaneous-foot-lifting duration, mechanical-hypersensitivity/allodynia, and heat-hypersensitivity/hyperalgesia, that were significantly greater than after SNA, especially spontaneous-foot-lifting. We recorded intracellularly in vivo from normal L4/L5 DRG neurons and ipsilateral L4-receptive-field-neurons. After SNA or modified-SNA, L4-receptive-field-neurons showed the following: (a) increased percentages of C-, Aδ-, and Aβ-nociceptors and cutaneous Aα/β-low-threshold mechanoreceptors with ongoing/spontaneous firing; (b) spontaneous firing in C-nociceptors that originated peripherally; this was at a faster rate in modified-SNA than SNA; (c) decreased electrical thresholds in A-nociceptors after SNA; (d) hyperpolarised membrane potentials in A-nociceptors and Aα/β-low-threshold-mechanoreceptors after SNA, but not C-nociceptors; (e) decreased somatic action potential rise times in C- and A-nociceptors, not Aα/β-low-threshold-mechanoreceptors. We suggest that these changes in subtypes of conducting/uninterrupted neurons after partial nerve injury contribute to the different aspects of neuropathic pain as follows: spontaneous firing in nociceptors to ongoing/spontaneous pain; spontaneous firing in Aα/β-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds to A-nociceptor sensitization, and greater evoked pain.     

Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias

Partial nerve injury leads to peripheral neuropathic pain. This injury results in conducting/uninterrupted (also called uninjured) sensory fibres, conducting through the damaged nerve alongside axotomised/degenerating fibres. In rats seven days after L5 spinal nerve axotomy (SNA) or modified-SNA (added loose-ligation of L4 spinal nerve with neuroinflammation-inducing chromic-gut), we investigated a) neuropathic pain behaviours and b) electrophysiological changes in conducting/uninterrupted L4 dorsal root ganglion (DRG) neurons with receptive fields (called: L4-receptive-field-neurons). Compared to pretreatment, modified-SNA rats showed highly significant increases in spontaneous-foot-lifting duration, mechanical-hypersensitivity/allodynia, and heat-hypersensitivity/hyperalgesia, that were significantly greater than after SNA, especially spontaneous-foot-lifting. We recorded intracellularly in vivo from normal L4/L5 DRG neurons and ipsilateral L4-receptive-field-neurons. After SNA or modified-SNA, L4-receptive-field-neurons showed the following: a) increased percentages of C-, Ad-, and Ab-nociceptors and cutaneous Aa/b-low-threshold mechanoreceptors with ongoing/spontaneous firing; b) spontaneous firing in C-nociceptors that originated peripherally; this was at a faster rate in modified-SNA than SNA; c) decreased electrical thresholds in A-nociceptors after SNA; d) hyperpolarised membrane potentials in A-nociceptors and Aa/b-low-threshold-mechanoreceptors after SNA, but not C-nociceptors; e) decreased somatic action potential rise times in C- and A-nociceptors, not Aa/b-low-threshold-mechanoreceptors. We suggest that these changes in subtypes of conducting/uninterrupted neurons after partial nerve injury contribute to the different aspects of neuropathic pain as follows: spontaneous firing in nociceptors to ongoing/spontaneous pain; spontaneous firing in Aa/b-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds to A-nociceptor sensitization, and greater evoked pain.     

Cocaine acts in the central nervous system to inhibit sympathetic neural activity

Cocaine was administered i.v. to decerebrate cats while monitoring cardiac preganglionic sympathetic nerve activity (SNA), arterial blood pressure (BP) and heart rate (HR). Cocaine, 4 mg/kg i.v., reduced SNA by 55 +/- 6%, but did not significantly affect BP or HR. Cocaine, in doses that were ineffective by the i.v. route, was administered into the vertebral artery and produced decreases in SNA, BP and HR in anesthetized cats. Administration of cocaine into the carotid artery was without effect. Topical administration of cocaine to the intermediate area of the ventrolateral medullary surface (25 micrograms/side) evoked hypotension and bradycardia. Nisoxetine, an inhibitor of norepinephrine uptake, applied bilaterally to the intermediate area (30 micrograms/side) exerted a similar hypotensive effect. Lidocaine administered in doses equivalent to those of cocaine had no significant effect on SNA when given i.v. or on BP when given into the vertebral artery. These results indicate that cocaine inhibits central sympathetic outflow and that the site of action appears to be in the hindbrain at a site that is reached by placement of the drug at the intermediate area of the ventrolateral medulla. The data also indicate that the mechanism of action of cocaine to inhibit sympathetic outflow may be unrelated to its local anesthetic action and may involve inhibition of catecholamine uptake in the ventrolateral medulla.     

Differential cardiorespiratory and sympathetic reflex responses to microinjection of neuromedin U in rat rostral ventrolateral medulla

The rostral ventrolateral medulla (RVLM) regulates sympathetic vasomotor outflow and reflexes. Intracerebroventricular neuromedin U (NMU) increases sympathetic nerve activity (SNA), mean arterial pressure (MAP), and heart rate (HR), but the central nuclei that mediate these effects are unknown. In urethane-anesthetized, vagotomized, and artificially ventilated male Sprague-Dawley rats (n = 36) the effects of bilateral microinjection of NMU (50 nl, each side) into RVLM on cardiorespiratory variables, somatosympathetic reflex, arterial baroreflex, and chemoreflex were investigated. Microinjection of NMU into RVLM elicited a hypertension, tachycardia, and an increase in splanchnic SNA (SSNA) and lumbar SNA (LSNA) at lower doses (25 and 50 pmol). At higher dose (100 pmol), NMU caused a biphasic response, a brief hypertension and sympathoexcitation followed by prolonged hypotension and sympathoinhibition. The peak excitatory and inhibitory response was found at 100 pmol NMU with an increase in MAP, HR, SSNA, and LSNA of 36 mm Hg, 20 beats per minute, 34%, and 89%, respectively, and a decrease of 33 mm Hg, 25 beats per minute, 42%, and 52%, respectively, from baseline. NMU, in the RVLM, also increased phrenic nerve amplitude and the expiratory period and reduced the inspiratory period. NMU (100 pmol) attenuated the somatosympathetic reflex and the sympathoexcitatory and respiratory responses to hypoxia and hypercapnia. After NMU injection in RVLM, the maximum gain of the SSNA baroreflex function curve was increased, but that of the LSNA was reduced. The present study provides functional evidence for a complex differential modulatory activity of NMU on the cardiovascular and reflex responses that are integrated in the RVLM.     

Investigation of novel nanomaterial for the removal of toxic substances from contaminated water

Ligand-functionalized nanomaterials exhibit great potential for the removal of hazardous substances from the environment and industrial wastewater. In this work, a composite nanosphere material was fabricated using mesoporous silica and organic ligand, and employed for the efficient detection and subsequent removal of toxic sulfanilamide (SNA) from waste samples. The organic ligand 2-naphthol was successfully conjugated onto the mesoporous nanospheres, which then captured SNA under suitable conditions. A naked-eye color change was observed even when a trace amount of SNA interacted with the material, which is the most promising advantage of the fabricated material. A low limit of detection and quantification limit were also determined, and the new nanosphere material revealed the ultra-trace detection performance of 0.27 μg L⁻¹ of SNA in aqueous media. The effect of solution pH, competing ions, color optimization and initial concentration of SNA on the nanosphere material was investigated under the optimum conditions. The nanosphere material exhibited rapid adsorption properties, and its maximum adsorption capability approached 79.20 mg g⁻¹. Several compounds were examined as common interfering substances including vanillin, glucose, lactose, starch and sucrose, which did not adversely interfere in both the detection and adsorption systems using the proposed nanosphere material. The data emphasized that the proposed material is highly suitable for the capture of SNA from contaminated water based on its selectivity, sensitivity, cost-effectiveness and eco-friendly approach. The results also indicate that this nanosphere material will attract attention from researchers for the efficient and selective capture of the toxic SNA.

Preparation of novel nanosphere material for efficient capture of toxic substances. The nanosphere material was systematically investigated for the capture of a toxic substance. The material displayed high sensitivity with high adsorption efficiency.     

Clinical relationship of myocardial sympathetic nervous activity to cardiovascular functions in chronic heart failure: assessment by myocardial scintigraphy with 123I-metaiodobenzylguanidine

The aim of this study was to clarify the relationship between cardiac sympathetic nervous activity (SNA) assessed by radioiodinated metaiodobenzylguanidine (123I-MIBG), an analogue of norepinephrine and cardiovascular functions in patients with chronic heart failure (CHF). Subjects were 17 patients with CHF. A dose of 111 MBq of 123I-MIBG was administered intravenously, and 5-minute anterior planar images were obtained 15 minutes (early image) and 3 hours (delayed image) after the injection. The heart/mediastinum (H/M) count ratio was defined to quantify cardiac 123I-MIBG uptake. The washout ratio (WR) of 123I-MIBG from the heart was calculated as follows: (early counts-delayed counts)/early counts x 100 (%). Echocardiography was performed on all patients within 1 week of 123I-MIBG scintigraphy to measure stroke volume index (SVI). Blood pressure and heart rate (HR) in the resting state were also recorded to calculate cardiovascular functions including cardiac output, pulse pressure (PP), and mean blood pressure. Significant linear correlations were found between the early H/M ratio of 123I-MIBG and SVI, and between the delayed H/M ratio of 123I-MIBG and SVI, respectively. WR of 123I-MIBG was correlated with HR, and was inversely correlated with SVI and with PP, respectively. It is likely that a decrease in SVI is associated with enhanced cardiac SNA in severe CHF. 123I-MIBG scintigraphy is effective in assessing the cardiac functional status and SNA in patients with CHF in vivo. Moreover, changes in PP and HR indicate well alteration in SNA.     

Detection of the sinus node artery using electron beam computed tomography of the heart

Background: Stenosis or obstruction of the sinus node artery (SNA) of the heart can cause cardiac arrhythmia and even sudden death. The purpose of this study was to evaluate the detectability of the SNA using electron beam computed tomography (EBCT). Material and methods: Eighty patients (mean age: 61 ± 10 years, range: 31–80 years) were examined with ECG-triggered EBCT (exposure time: 100 ms, slice thickness: 1.5 mm), using two different detector systems (n = 40; 9.5 line pairs/cm [Lp/cm]; n = 40; 7 Lp/cm) after intravenous contrast agent administration. Twenty-four out of 80 (30%) patients had supraventricular arrhythmia. Result: The SNA was detected in 60/80 (75%) of all patients with an average length of 16 ± 7 mm (3–35.2 mm). One additional branch of the SNA was detectable in 17/80 patients (21%), two branches in 6/80 (8%). There was no significant difference between the two used detector systems (p < 0.01) or between patients with or without supraventricular arrhythmia (71 vs. 77%; p = ns). Conclusion: EBCT allows to detect small coronary arteries such as the SNA of the heart.     

Gantrez AN as a new polymer for the preparation of ligand-nanoparticle conjugates.

The aim of this study was to evaluate the feasibility and in vitro activity of ligand-conjugates based on the use of poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA or Gantrez AN). Fluorescently labelled PVM/MA nanoparticles were prepared by desolvation and cross-linkage with 1,3-diaminopropane (DP). Conjugates were obtained by incubation between the carriers and Sambucus nigra agglutinin (SNA) for 1 h in an aqueous medium. The lectin binding to the surface of nanoparticles was increased by both increasing the bulk ligand concentration and decreasing the amount of cross-linker. However, a concentration of about 0.3-0.4 mg DP per mg polymer was necessary to obtain maximum agglutination activity. Under optimal conditions, the amount of fixed ligand was 46 microg/mg nanoparticle (binding efficiency of 86%); although the activity of SNA conjugates was 13.3 microg/mg particle. The activity of nanoparticles, measured by the association to Caco-2 monolayers, was higher when SNA was covalently bound onto their surface. The lectin-conjugate interaction was 6-fold higher than conventional nanoparticles. Moreover, energy-dependent mechanisms were only observed in SNA-PVM/MA particles. Finally, the decrease in association in the presence of lactose demonstrates that both SNA- and SNA-conjugate-binding was due to a true lectin-sugar interaction.     

Human cardiovascular adjustments to acute hypoxaemia

Summary. Traditionally, cardiovascular adjustments to hypoxaemia are viewed as resultants of competing local vasodilation and vasoconstriction via arterial chemo-reflexes with net effects of increased cerebral and coronary blood flows (local) and reduced flow to visceral organs and muscle (reflex). Although true in asphyxia, breathing activates lung mechanoreceptors which reduce vagal outflow and apparently, in humans, abolishes sympathetic vasomotor activity (SNA). During rest, moderate to severe hypoxaemia (Pao₂= 35 to 27 mmHg) caused no splanchnic, cutaneous or muscle vasoconstriction. Local vasodilator effects of hypoxaemia were not sufficient to overwhelm vasoconstriction; splanchnic arterioles responded normally to infused noradrenalin (NA) during hypoxaemia. Possibly, central effects of hypoxaemia blunt SNA or peripheral, prejunctional effects impair neuronal release of NA. Persistent orthostatic tolerance with normal skeletal muscle vasoconstriction and retained spinal venomotor reflexes during hypoxaemia argue against prejunctional inhibition of NA release. Results so far suggest that beyond a certain threshold, hypoxaemia centrally inhibits SNA. In contrast to rest, even moderate hypoxaemia during exercise markedly increases plasma NA concentration (and SNA), but the usual relationship among splanchnic blood flow, plasma NA and heart rate was not observed—NA and heart rate rose together, whereas the predicted splanchnic vasoconstriction was not observed. In moderate hypoxaemia, muscle blood flow and cardiac output are greater than in normoxia at a given submaximal oxygen uptake; but at maximal oxygen uptake, blood pressure, total vascular conductance and maximal cardiac output are unaffected. Given the fixed upper limit to cardiac output and the greater capacity of active muscle to vasodilate and exceed cardiac pumping capacity during hypoxaemia, we conclude that blood pressure is maintained by baroreflex- (not chemoreflex-) mediated vasoconstriction in the active muscle which must be the primary target of increased SNA and the source of NA.     

Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedl syndrome

Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder characterized by many features, including obesity and cardiovascular disease. We previously developed knockout mouse models of 3 BBS genes: BBS2, BBS4, and BBS6. To dissect the mechanisms involved in the metabolic disorders associated with BBS, we assessed the development of obesity in these mouse models and found that BBS-null mice were hyperphagic, had low locomotor activity, and had elevated circulating levels of the hormone leptin. The effect of exogenous leptin on body weight and food intake was attenuated in BBS mice, which suggests that leptin resistance may contribute to hyperleptinemia. In other mouse models of obesity, leptin resistance may be selective rather than systemic; although mice became resistant to leptin's anorectic effects, the ability to increase renal sympathetic nerve activity (SNA) was preserved. Although all 3 of the BBS mouse models were similarly resistant to leptin, the sensitivity of renal SNA to leptin was maintained in Bbs4 -/- and Bbs6 -/- mice, but not in Bbs2 -/- mice. Consequently, Bbs4 -/- and Bbs6 -/- mice had higher baseline renal SNA and arterial pressure and a greater reduction in arterial pressure in response to ganglionic blockade. Furthermore, we found that BBS mice had a decreased hypothalamic expression of proopiomelanocortin, which suggests that BBS genes play an important role in maintaining leptin sensitivity in proopiomelanocortin neurons.     

Examining sympathetic nerve activity with microneurography during hypnosis: untangling the effects of central command

Using microelectrode recordings of postganglionic sympatheticaction potentials, the authors studied the effects of hypnotic suggestion on sympathetic outflow targeted to skin during static handgrip exercise. All subjects performed sustained handgrip at 33% maximal voluntary contraction (MVC) for 2 minutes during 3 consecutive trials. Two subjects randomly assigned to a hypnosis condition received suggestions that the 2nd trial was more difficult and the last trial was less difficult than the first trial. Two subjects randomly assigned to the control condition received no hypnosis or suggestions about task difficulty. In the nonhypnosis condition, skin sympathetic nerve activity (SNA) increased by 6% from baseline during the 2nd trial and 13% from baseline during the 3rd trial. In the hypnosis condition, skin SNA increased by 25% during the 2nd trial (suggestion of increased difficulty) and returned to baseline during the 3rd condition (suggestion of decreased difficulty). Therefore, the impact of central command on skin SNA is suggested by these results.