Hierarchical sparse coding in the sensory system of Caenorhabditis elegans

Animals with compact sensory systems face an encoding problem where a small number of sensory neurons are required to encode information about its surrounding complex environment. Using Caenorhabditis elegans worms as a model, we ask how chemical stimuli are encoded by a small and highly connected sensory system. We first generated a comprehensive library of transgenic worms where each animal expresses a genetically encoded calcium indicator in individual sensory neurons. This library includes the vast majority of the sensory system in C. elegans. Imaging from individual sensory neurons while subjecting the worms to various stimuli allowed us to compile a comprehensive functional map of the sensory system at single neuron resolution. The functional map reveals that despite the dense wiring, chemosensory neurons represent the environment using sparse codes. Moreover, although anatomically closely connected, chemo- and mechano-sensory neurons are functionally segregated. In addition, the code is hierarchical, where few neurons participate in encoding multiple cues, whereas other sensory neurons are stimulus specific. This encoding strategy may have evolved to mitigate the constraints of a compact sensory system.To forage for resources and avoid harm, living organisms must obtain information about their environment and map it onto their sensory system. Natural environments often contain rich information consisting of many different stimuli. Nonetheless, various sensory systems use only a small fraction of the neurons for the encoding task, a principle also known as sparse coding (1–8). Encoding capacity can be significantly large in sensory systems consisting of many thousands of neurons, but animals with a compact neural network face an encoding problem. For example, nematodes, which inhabit a very broad range of environments and which account for nearly 80% of all individual animals on earth, have a small compact neural network; specifically, Caenorhabditis elegans hermaphrodites have 302 neurons (9), Ascaris suum females have 298 neurons (10), and other species have a similar number of neurons. Moreover, the C. elegans connectome shows that the neural network is highly connected, as over 90% of the network is linked due to gap junctions (11). This feature of the network further accentuates the encoding capacity problem that these animals face.Here we use the nematode C. elegans as experimental preparation, making use of their essentially invariant anatomy, fully mapped connectome (9, 12), and well-characterized chemosensory system (13) to understand how environmental cues are encoded by a compact sensory system. We begin by introducing our comprehensive library of transgenic worms, where each line reports activity in individual sensory neurons. Subjecting this library to various stimuli, we reveal that even small compact neural systems use “sparse coding.” In addition, we find a hierarchical functional organization as well as functional segregation between the two main sensory modalities: chemo- and mechano-sensation.     

T current potentiation increases the occurrence and temporal fidelity of synaptically evoked burst firing in sensory thalamic neurons

A growing number of in vivo experiments shows that high frequency bursts of action potentials can be recorded in thalamocortical neurons of awake animals. The mechanism underlying these bursts, however, remains controversial, because they have been proposed to depend on T-type Ca(2+) channels that are inactivated at the depolarized membrane potentials usually associated with the awake state. Here, we show that the transient potentiation of the T current amplitude, which is induced by neuronal depolarization, drastically increases the probability of occurrence and the temporal precision of T-channel-dependent high frequency bursts. The data, therefore, provides the first biophysical mechanism that might account for the generation of these high frequency bursts of action potentials in the awake state. Remarkably, this regulation finely tunes the response of thalamocortical neurons to the corticofugal excitatory and intrathalamic inhibitory afferents but not to sensory inputs.     

Cortical network models of impulse firing in the resting and active states predict cortical energetics

Measurements of the cortical metabolic rate of glucose oxidation [CMR_glc(ox)] have provided a number of interesting and, in some cases, surprising observations. One is the decline in CMR_glc(ox) during anesthesia and non-rapid eye movement (NREM) sleep, and another, the inverse relationship between the resting-state CMR_glc(ox) and the transient following input from the thalamus. The recent establishment of a quantitative relationship between synaptic and action potential activity on the one hand and CMR_glc(ox) on the other allows neural network models of such activity to probe for possible mechanistic explanations of these phenomena. We have carried out such investigations using cortical models consisting of networks of modules with excitatory and inhibitory neurons, each receiving excitatory inputs from outside the network in addition to intermodular connections. Modules may be taken as regions of cortical interest, the inputs from outside the network as arising from the thalamus, and the intermodular connections as long associational fibers. The model shows that the impulse frequency of different modules can differ from each other by less than 10%, consistent with the relatively uniform CMR_glc(ox) observed across different regions of cortex. The model also shows that, if correlations of the average impulse rate between different modules decreases, there is a concomitant decrease in the average impulse rate in the modules, consistent with the observed drop in CMR_glc(ox) in NREM sleep and under anesthesia. The model also explains why a transient thalamic input to sensory cortex gives rise to responses with amplitudes inversely dependent on the resting-state frequency, and therefore resting-state CMR_glc(ox).Classical measures of cortical activity, using cortical metabolic rate of glucose oxidation [CMR_glc(ox)], give results that are yet to be related in a mechanistic way with the underlying cortical excitability. There is a strict quantitative relationship between impulse and synaptic potential activity and CMR_glc(ox) necessary to maintain this activity (1). The recent establishment of this relationship allows for an inquiry into how cortical excitability might give rise to observed changes in CMR_glc(ox) in a number of different physiological conditions.Variation in impulse activity between modules in some networks would be expected to reflect the observed variation in CMR_glc(ox). Maximal reported differences of about 32% have been reported between different regions of cortex (2–4), but most cortical regions show much lower variations than this (3). The differences that do exist are not due to variations in thickness of cortex under consideration, nor to differences in the density of neurons (3). However, the differences may reflect that differences in the extent of cortico-cortical associational fiber connections for these are highest in posterior medial and parietal cortex (5), which have a relatively high oxidative demand (CMR_O2) and CMR_glc(ox) in the brain (see supplementary figure 5 in ref. 3). The question then arises as to whether it is possible that a quantitative relationship exists between the level of action potential and synaptic activity in a cortical area and the extent to which this area receives associational fiber connections.Correlations of signals between brain areas of subjects in the resting state have been taken to characterize resting-state functional networks (6), with the correlations probably mediated in many cases by synapses formed by associational fiber axons (7, 8). During sleep and anesthesia, some of these correlations are lost, indicating changes in synaptic transmission mediated by these fibers (9, 10). As there is concomitantly a significant decrease in CMR_glc(ox) and hence the average impulse frequency in these areas (1), the question arises as to whether the decrease in CMR_glc(ox) is due to a loss in average impulse frequency contingent on the loss of correlations. The cortical model presented here shows quantitatively that this is the case.If the average resting-state CMR_O2 is altered using anesthetics, then the changes in CMR_O2 (ΔCMR_O2) following forepaw stimulation in the rat are significantly smaller the higher the average resting-state CMR_O2 before stimulation (11, 12). Similar relationships are observed if impulse firing is measured rather than CMR_O2 (11, 12). Also, the ΔCMR_O2 spreads over a much larger area of cortex during the higher resting-state CMR_O2. Thus, for higher resting-state CMR_O2, the ΔCMR_O2 spreads over S1 and S2 somatosensory cortex and M1 and M2 motor regions as well as some lateral regions of the hippocampus and some secondary areas of the visual and auditory cortex. In contrast, at lower resting-state CMR_O2, when ΔCMR_O2 is comparatively large, it remains localized to the contralateral S1 and to an extent in S2 and M1 with no significant activation elsewhere (ref. 11; see also ref. 13). Even in awake primates, finger pad stimulation gives rise to a greater cortical spread of activation compared with anesthetized animals (14). Larger evoked signals are also recorded from cats and human visual cortex, with a clear quantitative inverse dependence of ΔCMR_O2 to a visual stimulus on the average resting-state CMR_O2 in this cortex: a 50% change in resting-state CMR_O2 gives a 60% change in ΔCMR_O2 (15). In addition, humans show both ΔCMR_O2 and change in cerebral blood flow, in response to a visual signal, that are inversely dependent on average resting-state values (16). As an inverse relationship of evoked impulse firing on resting-state firing is reproduced in our cortical model, it provides an opportunity to seek out a plausible mechanistic basis of how it arises.Although recent models of resting-state brain activity have used large-scale networks of cortico-cortical anatomical connectivity to analyze resting-state cortical activity (17–20), it is very useful to explore phenomenological models of lower complexity, for they allow insights concerning the important mechanisms that are active in the generation and dynamics of cortical activity (21). We have used such models, described in Materials and Methods and illustrated in Fig. 1, to provide plausible answers to the questions raised above concerning the relationships between CMR_glc(ox) and cortical impulse activity.Open in a separate windowFig. 1.Cortical network. (A) The basic model used in the present work. Shown are two modules (regions of interest, ROI₁ and ROI₂), represented by ellipses containing pools of excitatory neurons (red triangles) and inhibitory neurons (green circles), synaptically connected within and between pools (black arrows). The associational axons between ROI₁ and ROI₂ originate and end on single neurons and are either excitatory to excitatory (red arrows) or excitatory to inhibitory (green arrows). The input from the basal nucleus and thalamus is also excitatory; computationally, this input is represented by a Poisson train of impulses, the strength and frequency of which can be varied. (B) Intermodular connections in an eight-modular network (NI). The bold line within each module indicates separation of excitatory and inhibitory neurons within the module with all associational fibers between the modules forming excitatory synapses, primarily on excitatory neurons within the modules but not exclusively so. (C) Intermodular connections in a seven-modular network (NII). The connectivity due to the associational axons follows the criteria described in A above. NII may be taken to represent the default-mode network (DMN). In this case, the modules may be identified as follows: 1, rLTC; 2, rIPL; 3, lIPL; 4, PCC; 5, dMPFC; 6, vMPFC; 7, lLTC. The number and diversity of the associational fibers were chosen so as to reflect the reported weight of such connections between the modules of the DMN (see ref. 50, their figure 8 and associated table; also figure 4 A and 4C in ref. 51). Abbreviations are as follows: dMPFC and vMPFC, dorsal and ventral medial prefrontal cortex, respectively; PCC, posterior cingulate cortex; rIPL and lIPL, right and left inferior parietal lobe, respectively; and rLTC and lLTC, right and left lateral temporal cortex, respectively (from figure 8 in ref. 50).     

The role of sensory perception in the development and targeting of tobacco products

AIMS: To examine tobacco industry research on smoking-related sensory effects, including differences in sensory perception across smoker groups, and to determine whether this research informed targeted product development and impacted the development of commercial tobacco products. DESIGN: We searched previously secret internal tobacco industry documents available online through document databases housed at Tobacco Documents Online, the British American Tobacco Document Archive and the Legacy Tobacco Documents Library. We identified relevant documents using a snowball sampling method to first search the databases using an initial set of key words and to then establish further search terms. FINDINGS: Sensory research is a priority within the tobacco industry directly impacting commercial markets both in the United States and internationally. Sensory factors contribute to smoker satisfaction and product acceptance, and play an important role in controlling puffing behavior. Cigarette manufacturers have capitalized on distinct sensory preferences across gender, age and ethnic groups by tailoring products for specific populations. CONCLUSIONS: Regulation of tobacco products is needed to address product changes that are used to reinforce or contribute to tobacco dependence; for instance, the incorporation of additives that target attributes such as smoothness, harshness and aftertaste. Greater understanding of the role of sensory effects on smoking behavior may also help to inform the development of tobacco treatment options that support long-term tobacco abstinence.     

Diabetes-induced alterations in calcium homeostasis in sensory neurones of streptozotocin-diabetic rats are restricted to lumbar ganglia and are prevented by neurotrophin-3

Aims/hypothesis. In diabetic sensory polyneuropathy the earliest and most severe pathophysiology occurs in neurones with the longest axons. The aim of this study was to characterise a diabetes-induced neurodegenerative marker that was selective for sensory neurones with the longest axons. We studied alterations in calcium homeostasis since this occurs in other neurodegenerative diseases. Methods. Sensory neurones were cultured from control and streptozotocin-diabetic rats, treated with or without human recombinant neurotrophin-3 (hrNT-3), and neurones from L4-L6 dorsal root ganglia (DRG) which exhibit the longest axons in vivo were compared with those from C5-L3 DRG. Fluorescent video-imaging was used to measure cytoplasmic calcium dynamics. Results. Streptozotocin diabetes of 8 to 14 weeks, induced an increase in resting internal Ca²⁺ concentration ([Ca²⁺]_i), from 67 ± 7 nmol/l in small neurones and 79 ± 9 nmol/l in big neurones obtained from control animals to 214 ± 19 nmol/l in small neurones and 273 ± 30 nmol/l in big neurones after 14 weeks of diabetes (p < 0.05) in L4-L6 DRG cultures. Neurones from C5-L3 ganglia and non-neuronal cells were not affected. Treatment of 14-week streptozotocin-diabetic rats with subcutaneous injection of 5 mg/kg NT-3 normalised the increase in resting [Ca²⁺]_i. The amplitudes induced by depolarisation, caffeine and ATP [Ca²⁺]_i responses were reduced in small ( < 30μm diameter) but not big ( > 35μm diameter) neurones of L4-L6 DRG from streptozotocin-diabetic animals; the C5-L3 DRG were not similarly affected and the changes in the L4-L6 DRG were corrected by NT-3 treatment. Conclusions/interpretation. Altered calcium homeostasis could be an early molecular marker linked to the onset of diabetic sensory neuropathy. This neurodegenerative index can be corrected by NT-3 therapy and should encourage further work aimed at understanding the mechanistic basis of these observations. [Diabetologia (2002) 45: ▪–▪] Received: 5 November 2001 and in revised form: 10 December 2001     

From the Cover: Cortical energy demands of signaling and nonsignaling components in brain are conserved across mammalian species and activity levels

The continuous need for ion gradient restoration across the cell membrane, a prerequisite for synaptic transmission and conduction, is believed to be a major factor for brain’s high oxidative demand. However, do energy requirements of signaling and nonsignaling components of cortical neurons and astrocytes vary with activity levels and across species? We derived oxidative ATP demand associated with signaling (P_s) and nonsignaling (P_ns) components in the cerebral cortex using species-specific physiologic and anatomic data. In rat, we calculated glucose oxidation rates from layer-specific neuronal activity measured across different states, spanning from isoelectricity to awake and sensory stimulation. We then compared these calculated glucose oxidation rates with measured glucose metabolic data for the same states as reported by 2-deoxy-glucose autoradiography. Fixed values for P_s and P_ns were able to predict the entire range of states in the rat. We then calculated glucose oxidation rates from human EEG data acquired under various conditions using fixed P_s and P_ns values derived for the rat. These calculated metabolic data in human cerebral cortex compared well with glucose metabolism measured by PET. Independent of species, linear relationship was established between neuronal activity and neuronal oxidative demand beyond isoelectricity. Cortical signaling requirements dominated energy demand in the awake state, whereas nonsignaling requirements were ∼20% of awake value. These predictions are supported by ¹³C magnetic resonance spectroscopy results. We conclude that mitochondrial energy support for signaling and nonsignaling components in cerebral cortex are conserved across activity levels in mammalian species.     

慢性酒精中毒患者定量感觉特点及影响因素

目的研究慢性酒精中毒患者的定量感觉特点,探讨定量感觉检查(QST)是否可作为早期提示神经损伤的指标,并对引起周围神经损伤的相关因素进行研究。方法选择2000年12月至2003年12月重庆医科大学附属第一医院神经内科收治的慢性酒精中毒患者(每天饮酒250mL以上,饮酒时间>5年且简易智能量表评分>27分)40例,分别测定左侧小鱼际区、食指、足背外侧、第1足趾皮区的温度觉及食指、第1足趾的振动觉阈值和胫、正中、尺神经传导速度。分析饮酒时间、全身营养状况、肝肾功能等对周围神经的影响。结果长期饮酒患者5种感觉阈值均较正常组增高(P<0·05)。有感觉异常组高于无感觉异常组(P<0·05)。QST检出的异常率较神经传导速度高。饮酒时间越长、全身营养状况越差越容易出现周围神经损害。结论QST可作为早期提示慢性酒精中毒性周围神经损害的指标。周围神经损伤与饮酒时间呈正相关,与营养状态成负相关。     

Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2

Mechanotransduction in the mammalian auditory system depends on mechanosensitive channels in the hair bundles that project from the apical surface of the sensory hair cells. Individual stereocilia within each bundle contain a core of tightly packed actin filaments, whose length is dynamically regulated during development and in the adult. We show that the actin-binding protein epidermal growth factor receptor pathway substrate 8 (Eps8)L2, a member of the Eps8-like protein family, is a newly identified hair bundle protein that is localized at the tips of stereocilia of both cochlear and vestibular hair cells. It has a spatiotemporal expression pattern that complements that of Eps8. In the cochlea, whereas Eps8 is essential for the initial elongation of stereocilia, Eps8L2 is required for their maintenance in adult hair cells. In the absence of both proteins, the ordered staircase structure of the hair bundle in the cochlea decays. In contrast to the early profound hearing loss associated with an absence of Eps8, Eps8L2 null-mutant mice exhibit a late-onset, progressive hearing loss that is directly linked to a gradual deterioration in hair bundle morphology. We conclude that Eps8L2 is required for the long-term maintenance of the staircase structure and mechanosensory function of auditory hair bundles. It complements the developmental role of Eps8 and is a candidate gene for progressive age-related hearing loss.     

Symptoms of depression are important to psychological adaptation and metabolic control in children with diabetes mellitus.

AIMS: Sixty-two children (37 girls, 25 boys) between 9 and 18 years of age were enrolled to investigate: (1) the relationship between adaptation to diabetes mellitus (DM) and psychological functioning; (2) if adaptation or psychological functioning was related to metabolic control; and (3) if the patients' ability to cope with diabetes as assessed by physicians, was correlated to adaptation or psychological functioning. METHODS: Psychological functioning was measured by three general psychological instruments for depressive symptoms, self-esteem and fear. Diabetes adaptation was evaluated by questionnaires and coping with diabetes by an assessment of the physicians. Metabolic control was expressed by the individual HbA1c measured during the last year. RESULTS: Adaptation to diabetes correlated to psychological functioning (depression, P<0.001; self-esteem, P<0.01; and fear, P<0.01). Multiple regression analyses showed that metabolic control was predicted by adaptation (P=0.0013) with monitoring of diabetes as the only significant aspect of the adaptation (P < or = 0.0001). In turn, adaptation was predicted by symptoms of depression and metabolic control (P<0.0001). In support of this observation, a depressed (n = 9) and a non depressed (n= 53) group showed significant differences in metabolic control (P < or = 0.01), adaptation (P < or = 0.001) and self-esteem (P < or = 0.001). The only significant variable for the physicians assessment was metabolic control, which explained 35 % of the variance (P < 0.001). CONCLUSIONS: The major conclusion is that symptoms of depression affect both adaptation and metabolic control. It should be of concern to identify patients with depressive symptoms, offer treatment for their emotional difficulties and increase the support for taking care of their diabetes.     

Role of sensory innervation and mast cells in neurogenic plasma protein exudation into the airway lumen

Abstract Neurogenic inflammation in the airways involves both mucosal oedema and plasma protein exudation into the airway lumen. We aimed to investigate the mechanism of exudation of plasma proteins into the airway lumen. Neurogenic inflammation was induced in anaesthetized Sprague-Dawley rats by electrical stimulation of both vagal nerves at 20 V, 10 Hz, 5 ms. Vascular permeability was measured as ¹²⁵I-albumin extravasation into both the airway wall and tracheobronchial lavage fluid. Following vagal stimulation, tracheobronchial lavages were analysed for albumin, total protein, histamine, immunoreactive substance P (SP), and immunoreactive calcitonin gene-related peptide (CGRP). Vagal stimulation rapidly increased vascular permeability in the airway mucosa and induced exudation of plasma proteins into the tracheobronchial fluid. Pretreatment with capsaicin inhibited both neurogenic vascular permeability and movement of albumin into the airway lumen. SP and CGRP were detectable in basal lavages (1.37 ± 0.12 ng/mL and 2.17 ± 0.21 ng/mL, respectively) and the concentration of SP fell by 43% following treatment with capsaicin. Following vagal stimulation, concentrations of both SP and CGRP decreased significantly. Although basal tracheobronchial lavages contained histamine, vagal stimulation did not increase the histamine concentration. These results indicate that both neurogenic vascular permeability and plasma protein exudation into the airway lumen results from activation of capsaicin-sensitive sensory nerves and the reaction is not associated with mast cell activation.     

Intestinal inflammation and activation of sensory nerve pathways: a functional and morphological study in the nematode infected rat

BACKGROUND: In the rat, gastric distension elicits an intensity dependent pseudoaffective bradycardia mediated via capsaicin sensitive afferent and cholinergic efferent vagal pathways. Inflammation alters visceral perception although the mediators responsible have not been identified. In the nematode infected rat, there is a substantial increase in neuronal substance P (SP) content of the gut. AIMS: To examine the effects of inflammation on perception of a noxious visceral stimulus and on SP and neurokinin 1 (NK-1) receptor immunoreactivity (IR) in visceral afferent pathways. METHODS: Immunohistochemistry was performed on sections from the jejunum, dorsal root ganglia (DRG), and spinal cord (T1-L1) using SP and NK-1 rabbit polyclonal antibodies. In the DRG, the number of SP-IR or NK-1-IR neurones per section was visually quantified. The pseudoaffective cardiac reflex response to gastric stimulation was compared in control and Trichinella spiralis infected rats. RESULTS: Intestinal inflammation induced a rightward shift in the intensity dependent bradycardic response to gastric distension. This was associated with a marked increase in SP-IR not only in the gut wall but also in the DRG and dorsal horn of the spine. In contrast, NK-1-IR was not increased in the gut wall. Moreover, inflammation evoked a decrease in NK-1-IR in the dorsal horn. No NK-1-IR was identified in the DRG of either control or infected animals. CONCLUSIONS: Intestinal inflammation modulates the capsaicin sensitive pseudoaffective autonomic response to gastric distension, increases SP-IR in afferent pathways, and downregulates dorsal horn NK-1-IR. As the pseudoaffective response is capsaicin sensitive, the rightward shift of the response is likely the consequence of the decrease in NK-1 receptors in the sensory pathways.     

Studies on the role of calcium and cyclic nucleotides in the control of TSH secretion.

The role of putative mediators in the control of thyrotropin (TSH) secretion has been investigated by monitoring hormone release from isolated anterior cells in response to agents and conditions which modify cyclic nucleotide concentrations or calcium fluxes. The secretory response to 5-min pulses of TRH, raised K⁺ concentration and A-23187 was diminished within 5 min when Ca²⁺-free perifusion was begun 80 sec prior to the pulse. In contrast, the response to theophylline and IBMX was unaffected under these conditions. Both IBMX and dibutyryl cyclic AMP potentiated the effects of TRH and raised K⁺concentration but not that of A-23187. Methoxyverapamil inhibited TSH secretion stimulated by TRH, raised K⁺ concentration and IBMX but not that induced by A-23187. Calcium efflux showed a similar temporal profile to hormone secretion in response to TRH, IBMX and raised K⁺ concentration. It is proposed that one interpretation of these findings is that there is an interrelationship between calcium ions and the cyclic nucleotides in the control of TSH secretion and that cyclic nucleotides may act at the level of the Ca²⁺ channel to modulate Ca²⁺ entry.     

Effect of palmitic acid and fatty acid binding protein on ventricular fibrillation threshold in the perfused rat heart

The effects of increased free fatty acid (FFA) levels on ventricular arrhythmias remain controversial. Using ventricular fibrillation threshold (VFT), we examined the relationship between FFA levels and ventricular arrhythmias. Isolated rat hearts were perfused with palmitate bound to either albumin or fatty acid binding protein (FABP) by Langendorf's method. The VFT was determined by electrical stimulation. Perfusion with 0.12 mM albumin alone, 0.12 mM palmitate bound to 0.12 mM albumin, and 0.36 mM palmitate bound to 0.12 mM albumin did not lower the VFT significantly. However, 0.60 mM palmitate bound to 0.12 mM albumin lowered VFT from 2.19 +/- 0.20 mA to 1.56 +/- 0.13 mA. The perfusion of 0.36 mM palmitate bound to 0.12 mM FABP lowered the VFT from 2.05 +/- to 0.19 mA to 1.47 +/- 0.23 mA, but 0.12 mM FABP alone did not affect the VFT. Perfusion with 0.36 mM palmitate bound to 0.12 mM FABP caused the VFT to fall more than perfusion with 0.36 mM palmitate bound to 0.12 mM albumin. Then the effects of verapamil perfusion or a low concentration of perfusate Ca2+ on VFT were examined. VFT was determined by electrical stimulation. Palmitate (0.6 mM) bound to 0.12 mM albumin lowered VFT. Verapamil 10(-7) M perfusion and a low concentration of Ca2+ (Ca2+ 1.67 mM) suppressed the FFA-induced fall of VFT. These results suggested that the arrhythmogenic action of FFA was related to Ca2+ overload in myocardial cells.     

Molecular mechanisms and therapeutics of the deficit in specific force in ageing skeletal muscle

The age-related impairment in muscle force is only partially explained by the loss of muscle mass. The loss both in specific and absolute forces contributes to the muscle weakness measured in the elderly and in animal models of ageing. Successful interventions aimed at preventing age-associated functional deficits will require a better insight into the mechanisms underlying the decline in muscle-specific force. The present review article is focused on recent evidence supporting excitation-contraction uncoupling as a key factor underlying fast and slow muscle fiber impairment with ageing. The molecular, functional and structural factors supporting this theory and counteracting measures such as insulin-like growth factor 1 transgenic overexpression are discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Dysfunction of tubular phosphate reabsorption related to glomerular filtration and blood glucose control in diabetic children

Summary The renal handling of inorganic phosphate was studied by measuring the urinary excretion rate of phosphate ( ), phosphate-(Cr⁵¹) EDTA clearance ratio ( ) and maximal tubular reabsorption of phosphate per litre glomerular filtrate ( ) during fasting in 26 ambulatory Type 1 (insulin-dependent) diabetic children without clinical signs of microangiopathy (age: 7–14 years; duration of disease: 3–14 years). Similar measurements were made in 28 healthy schoolchildren (age: 8–14 years). and were significantly enhanced in the diabetic children (p<0.001) and correlated with the degree of hyperglycaemia (p<0.005). was significantly suppressed in the diabetic children (1.23 versus 1.73 mmol/1, p<0.001). This disturbance was neither related to changes in serum parathyroid hormone nor to growth hormone concentrations but was inversely correlated with the degree of hyperglycaemia (r=-0.61, p<0.001) and with tubular reabsorption of glucose in the diabetic subjects, the mean maximal ( ) and absolute tubular phosphate reabsorption rates were equal to those of the 28 healthy subjects. Both in the diabetic and healthy subjects, these parameters were positively correlated with glomerular filtration rate which was significantly elevated in the diabetic children (138 versus 109 ml/min per 1.73 m², p<0.01). The study demonstrates a dysfunction in tubular phosphate reabsorption in diabetic children which is related to glycaemic regulation.     

我院呼吸内科抗菌药物应用分析及药学服务模式探讨

目的分析我院呼吸内科抗菌药物的应用情况,并探讨临床药师参与临床药物治疗的服务模式。方法回顾性分析我院自2010年6月~2013年8月收治的呼吸内科患者临床资料。比较分析临床药师采用的3种不同的服务模式(分别为传统药学服务模式、间接药学服务模式干预以及直接药学服务模式干预)对呼吸内科患者抗菌药物使用强度、联合抗菌药物使用率、不良反应报告率、抗菌药物分级以及特殊使用级抗菌药物使用率、微生物标本送检率情况的影响。结果 (1)间接干预组和直接干预组患者在抗菌药物使用强度、联合抗菌药物使用情况、微生物标本送检率、不良反应报告率以及抗菌药物分级使用、特殊使用级抗菌药物使用情况等方面表现均显著优于传统组(P0.05),其中传统组的不良反应报告率为2.60%,间接干预组为9.38%,直接干预组为7.99%;(2)两组患者在微生物标本送检率、不良反应报告率、特殊使用级抗菌药物使用率、联合抗菌药物使用率以及抗菌药物分级使用情况方面比较差异无统计学意义(P0.05),而在抗菌药物使用强度方面,直接干预组患者表现显著优于间接干预组(P0.05)。结论临床药师所采用的药学服务模式能够显著提高呼吸内科患者抗菌药物的使用效率,相对间接干预而言,直接干预的效果更好,值得临床大力推广使用。