Nervous Stimuli Research Articles

The Effect of Focused Vibration on Tibialis Anterior Function in Normal Subjects

Category: Basic Sciences/Biologics; Other Introduction/Purpose: Foot drop is a debilitating condition which may be caused by peripheral nerve pathology. Focused vibration therapy (FVT) is a novel treatment in this setting which aims to improve the response of muscle motor units to nervous stimuli, improving muscle function and rehabilitation potential. This study investigates the effect of FVT on tibialis anterior (TA) function in normal subjects to determine the optimal timing of application. Methods: Fifteen normal subjects with mean age 25.47±3.27 years and BMI of 21.93±1.54kg/m2 were recruited. Using surface electromyography (EMG), a rotary potentiometer, video analysis (KINOVEA software), and force gauges, the activity of TA, ankle range of movement (ROM), and force at maximal isometric voluntary contraction (MVC) in dorsiflexion were measured. Baseline TA strength was recorded, and participants then performed a series of dorsiflexion exercises to induce fatigue. Strength measurements were repeated after a 5-minute rest period (control). This process was repeated with FVT applied before exercise (FVBE) and after exercise (during the rest period, FVAE). FVT was delivered over the TA muscle belly at 75Hz / 0.4mm amplitude. Data was analysed using ANOVA. Results: There was no significant change in EMG readings or dorsiflexion ROM between baseline, control and FVBE/FVAE measurements. Compared to baseline, MVC increased by 10.87N (6.6%) after FVBE (p=0.034) and 13.87N (8.4%) after FVAE (p=0.034). Compared to control, MVC did not increase significantly with FVBE, but did increase by 7.70N (4.3%) following FVAE (p=0.049). Conclusion: FVT improved the MVC of TA - this was most pronounced when FVT was applied during the recovery phase, after exercise. The lack of EMG / ROM improvement is expected in normal subjects. Our results suggest that FVT is more effective than passive rest and may enhance muscle strength recovery. Further work will investigate the optimal dose of FVT and response in patients with pathology.

Caffeine in Pain Perception and Management

Introduction: Caffeine is considered to be one of the most frequently used pharmacologically active substances in the world. Caffeine is a psychoactive and central nervous system stimuli that has the ability to increase energy, decrease fatigue, promote alertness and wakefulness. Potential role of caffeine's nociceptive properties shows that it may play a relevant role in pain modulation. Although caffeine at dietary levels is not a sufficient analgesic in its own, it has been included in many over-the-counter and prescription drugs. This review addresses caffeine's analgesic properties in pain management. Results: Caffeine shows relevant role in pain modulation through blocking adenosine receptors which are involved in nociception. Studies show that habitual dietary caffeine consumption results in decreased pain sensitivity.As an adjuvant to commonly used analgesics, caffeine provides an important increase in pain relief in various types of pain such as postoperative dental pain, headaches, or fibromyalgia.Conclusions: In conclusion, caffeine is associated with decreased pain sensitivity. Addition of caffeine to analgesics has resulted in their enhanced analgesic efficacy in pain treatment.

Transcriptomics analysis of differentially expressed genes in subcutaneous and perirenal adipose tissue of sheep as affected by their pre- and early postnatal malnutrition histories

BackgroundEarly life malnutrition is known to target adipose tissue with varying impact depending on timing of the insult. This study aimed to identify differentially expressed genes in subcutaneous (SUB) and perirenal (PER) adipose tissue of 2.5-years old sheep to elucidate the biology underlying differential impacts of late gestation versus early postnatal malnutrition on functional development of adipose tissues. Adipose tissues were obtained from 37 adult sheep born as twins to dams fed either NORM (fulfilling energy and protein requirements), LOW (50% of NORM) or HIGH (110% of protein and 150% of energy requirements) diets in the last 6-weeks of gestation. From day 3 to 6 months of age, lambs were fed high-carbohydrate-high-fat (HCHF) or moderate low-fat (CONV) diets, and thereafter the same moderate low-fat diet.ResultsThe gene expression profile of SUB in the adult sheep was not affected by the pre- or early postnatal nutrition history. In PER, 993 and 186 differentially expressed genes (DEGs) were identified in LOW versus HIGH and NORM, respectively, but no DEG was found between HIGH and NORM. DEGs identified in the mismatched pre- and postnatal nutrition groups LOW-HCHF (101) and HIGH-HCHF (192) were largely downregulated compared to NORM-CONV. Out of 831 DEGs, 595 and 236 were up- and downregulated in HCHF versus CONV, respectively. The functional enrichment analyses revealed that transmembrane (ion) transport activities, motor activities related to cytoskeletal and spermatozoa function (microtubules and the cytoskeletal motor protein, dynein), and responsiveness to the (micro) environmental extracellular conditions, including endocrine and nervous stimuli were enriched in the DEGs of LOW versus HIGH and NORM. We confirmed that mismatched pre- and postnatal feeding was associated with long-term programming of adipose tissue remodeling and immunity-related pathways. In agreement with phenotypic measurements, early postnatal HCHF feeding targeted pathways involved in kidney cell differentiation, and mismatched LOW-HCHF sheep had specific impairments in cholesterol metabolism pathways.ConclusionsBoth pre- and postnatal malnutrition differentially programmed (patho-) physiological pathways with implications for adipose functional development associated with metabolic dysfunctions, and PER was a major target.

Association of remote imaging photoplethysmography and cutaneous perfusion in volunteers

Remote imaging photoplethysmography (iPPG) senses the cardiac pulse in outer skin layers and is responsive to mean arterial pressure and pulse pressure in critically ill patients. Whether iPPG is sufficiently sensitive to monitor cutaneous perfusion is not known. This study aimed at determining the response of iPPG to changes in cutaneous perfusion measured by Laser speckle imaging (LSI). Thirty-seven volunteers were engaged in a cognitive test known to evoke autonomic nervous activity and a Heat test. Simultaneous measurements of iPPG and LSI were taken at baseline and during cutaneous perfusion challenges. A perfusion index (PI) was calculated to assess iPPG signal strength. The response of iPPG to the challenges and its relation to LSI were determined. PI of iPPG significantly increased in response to autonomic nervous stimuli and to the Heat test by 5.8% (p = 0.005) and 11.1% (p < 0.001), respectively. PI was associated with LSI measures of cutaneous perfusion throughout experiments (p < 0.001). iPPG responses to study task correlated with those of LSI (r = 0.62, p < 0.001) and were comparable among subjects. iPPG is sensitive to autonomic nervous activity in volunteers and is closely associated with cutaneous perfusion.

Optimal solid state neurons

Bioelectronic medicine is driving the need for neuromorphic microcircuits that integrate raw nervous stimuli and respond identically to biological neurons. However, designing such circuits remains a challenge. Here we estimate the parameters of highly nonlinear conductance models and derive the ab initio equations of intracellular currents and membrane voltages embodied in analog solid-state electronics. By configuring individual ion channels of solid-state neurons with parameters estimated from large-scale assimilation of electrophysiological recordings, we successfully transfer the complete dynamics of hippocampal and respiratory neurons in silico. The solid-state neurons are found to respond nearly identically to biological neurons under stimulation by a wide range of current injection protocols. The optimization of nonlinear models demonstrates a powerful method for programming analog electronic circuits. This approach offers a route for repairing diseased biocircuits and emulating their function with biomedical implants that can adapt to biofeedback.

Rehabilitation team approach for the treatment in facial palsy in a multicentric clinical practice. Consensus guide

The treatment for facial palsy is complex and requires specialized units as well as a multidisciplinary team to assess the patient globally and respond to the problems of each phase. To unify criteria and define the best treatment for each phase of the facial palsy, to improve facial function and quality of life. Both doctors and physical therapists from the Facial Palsy Units from the Rehabilitation Services of two university hospitals in Barcelona, Spain, got together to revise scientific articles, share clinical experiences and introduce new technique for facial palsy management. Afterwards, a consensus document was created as a protocol for both medical centers. Consensus on best treatment for each phase was achieved, as follows: – hypotonic phase: neurosensory stimulation through Perfetti method, proprioceptive and cognoscitive activities with neurosensory feedback, and movement induction by neuromuscular training (ill side). Treatment with botulinum toxin helps diminish hypercontractility of the sound side; – initiation of movement: neuromuscular training and Perfetti's neuromuscular stimulation; – synkinetic phase: neuromuscular retraining with dissociated movements of the synkinetic muscles. Relaxation treatment of the maintained muscle contractures. Treatment with botulinum toxin helps control aberrant movements and induces facial symmetry. Myofascial techniques (dry needling and mesotherapy) may help diminish maintained muscular contraction. After dynamic surgery, treatment must be based on the physiology of the reconstruction implemented, inducing movement according to the given nervous stimuli. In congenital/obstetric palsies, treatment will be similar to that of adults’ Bell's palsy, adjusting treatment to patient's age. We believe this consensus will allow for a better clinical practice, to offer the patient the best treatment to improve functionally, mentally and socially, thus improving quality of life.

Enhanced insulin sensitivity mediated by adipose tissue browning perturbs islet morphology and hormone secretion in response to autonomic nervous activation in female mice

Insulin resistance results in a compensatory increase in insulin secretion to maintain normoglycemia. Conversely, high insulin sensitivity results in reduced insulin secretion to prevent hypoglycemia. The mechanisms for this inverse adaptation are not well understood. We utilized highly insulin-sensitive mice, due to adipocyte-specific overexpression of the FOXC2 transcription factor, to study mechanisms of the reversed islet adaptation to increased insulin sensitivity. We found that Foxc2TG mice responded to mild hyperglycemia with insulin secretion significantly lower than that of wild-type mice; however, when severe hyperglycemia was induced, Foxc2TG mice demonstrated insulin secretion equal to or greater than that of wild-type mice. In response to autonomic nervous activation by 2-deoxyglucose, the acute suppression of insulin seen in wild-type mice was absent in Foxc2TG mice, suggesting impaired sympathetic signaling to the islet. Basal glucagon was increased in Foxc2TG mice, but they displayed severely impaired glucagon responses to cholinergic and autonomic nervous stimuli. These data suggest that the autonomic nerves contribute to the islet adaptation to high insulin sensitivity, which is compatible with a neuro-adipo regulation of islet function being instrumental for maintaining glucose regulation.

Facts, Challenges, Difficulties and Hopes in Single-Cell Biology: Physiopathological Studies

Single-cell approaches are being increasingly used to unravel the many diverse mechanisms underlying biological processes that characterize each cell irrespective of the influx of other cells even within the same tissue. Consequently, the interference of metabolites and nervous stimuli emanating from the circulatory or nervous system in a higher organism like man is avoided. However, while the single-cell approach yields a wealth of data about single-cell metabolism and internal regulatory mechanisms, information about interactions and interrelations among similar or dissimilar cells may remain obscure. Starting from these considerations, here we summarize, without attempting to be exhaustive, some areas in which we think single-cell biological studies could be effective in translational medicine and in other areas of applied sciences. In this short review we describe the facts, challenges and perspectives related to these issues.

Involvement of intracellular signaling in the IL-1β inhibitory effect on fructose intestinal absorption.

A variety of bacteria and their excreted/secreted products having direct effects on epithelial ion transport and permeability and the release of cytokines during bacterial infection may impact directly on epithelial function. Interleukin-1β (IL-1β) is a pleiotropic cytokine that affects the intestinal absorption of nutrients. The aim of this work was to study the intracellular signaling pathways involved in the inhibitory effect of IL-1β on D-fructose intestinal transport in rabbit jejunum and Caco-2 cells. The results show that the cytokine inhibitory effect was completely reversed in presence of proteasome or PKC selective inhibitors in IL-1β treated rabbits. In addition, the activation of PI3K abolished the IL-1β effect. Likewise, these results were confirmed in Caco-2 cells. In addition, p-PI3K expression was increased by IL-1β-treatment whereas the expression of p-PKCα was not significantly affected. In summary, the results suggest that IL-1β could regulate the activation of pPKCα 73, pPI3K 55, and NF-kB proteins. These events could exert an inhibitory effect on fructose intestinal absorption by a modification of GLUT5 insertion to brush-border membrane and/or the functional transporter activity. This effect is independent of hormonal milieu and nervous stimuli.

A review on digestive TAG-lipases of insects

Digestion in insects is a multi-step process to afford nutritional requirements of biological activities. The process starts with nervous stimuli and continues with biochemical activities of digestive enzymes as well as several pumps to digest and absorb the obtained molecules. Carbohydrases, lipases and proteases are the three main digestive enzymes involved in digestion process. Lipases seem to be very important not only for digestive role but also for esteratic activity so that some experts consider lipases as the Class 3 of general esterases. Digestive lipases divided into different groups based on their biological roles namely triacylglycerol lipases, phospholipases and two types of phosphatases. Briefly, triacylglycerol lipases (TAG-lipases) are the hydrolysing enzymes that affect the outer esteric links of triacylglycerols in ingested food. Phospholipases including PLA2 and PLA1 remove phosphatide fatty acids attached to the Position 2 and Position 1. Finally, Alkaline and acid phosphatases are the enzymes that hydrolyse phosphomonoesters under alkaline or acid conditions, respectively. In this review, presence and physiological role of digestive TAG-lipases are explained and their possible importance will be discussed in insect.

Influencing factors on iodine content of cow milk

Iodine is an essential trace element for humans and animals, and it is incorporated into the thyroid hormones such as thyroxine and triiodothyronine, which have multiple functions in energy metabolism and growth, but also as transmitter of nervous stimuli and as an important factor for brain development. Because of the small range between iodine requirements and the upper level for humans (between 1:2.5 and 3), the requirements should be met, but excesses should be avoided. One of the most important iodine sources for humans is milk of ruminants. Therefore, various influencing factors on the iodine content of milk of ruminants should be analyzed in the paper. The iodine content of milk depends on many factors, such as iodine content and level of iodine supplementation of feed, iodine source, iodine antagonists such as glucosinolates in the feed, farm management, teat dipping with iodine-containing substances, and milk processing in the dairy. The effects of some factors on the iodine content of milk are demonstrated and discussed. Feed iodine supplementation has the main effect on milk iodine. However, the iodine content of milk may vary considerably depending on many other influencing factors. As a consequence of preventive consumer protection, the European Food Safety Authority proposed a reduction in the iodine upper level for lactating ruminants from 5 to 2 mg/kg complete feed.

Interleukin-1beta reduces galactose transport in intestinal epithelial cells in a NF-kB and protein kinase C-dependent manner

Interleukins (IL), aside from their role in the regulation of the immune cascade, they have also been shown to modulate intestinal transport function. IL-1β is a potent inflammatory cytokine involved in many important cellular functions. The aim of this work was to study the in vitro effect of IL-1β on d-galactose transport across intestinal epithelia in rabbit jejunum and Caco-2 cells. The results showed that d-galactose intestinal absorption was diminished in IL-1β treated jejunum rabbits without affecting the Na+, K+-ATPase activity. The presence of IL-1 cell-surface receptors was confirmed by addition to tissue of a specific IL-1 receptor antagonist (IL-1ra). The cytokine did not inhibit either the uptake of d-galactose nor modified the sodium-glucose transport (SGLT1) protein levels in the brush border membrane vesicles, suggesting an indirect IL effect. The IL-inhibition was significantly reversed in the presence of inhibitors of protein kinase C (PKC) and mitogen-activated protein kinases (MAPKs). The proteasome selective inhibitor completely abolished the IL-effect. Furthermore, the cytokine inhibition on galactose transport related to NF-kB activation was also confirmed in Caco-2 cells. In summary, the direct addition of IL-1β to intestinal epithelia inhibits d-galactose transport by a possible reduction in the SGLT1 activity. This event may be mediated by several transduction pathways activated during the inflammatory processes related to several protein kinases and nuclear factor, NF-kB. The IL-effect is independent of hormonal milieu and nervous stimuli.

Invited Commentary

Hundreds of articles have been published on primary hyperhidrosis, which affects approximately 3% of the general population, and despite decades of research we have no good pathophysiologic explanation for this disorder. We know that the sweat glands of patients with primary hyperhidrosis are normal in number and size but that hyperhidrotic patients have an abnormal sympathetic skin response. Few realize that the symptoms of primary hyperhidrosis, which may seem trivial to the general public, can cause so much social embarrassment in some patients that quality of life is reduced to a score comparable with that of end-stage renal disease, rheumatoid arthritis, or multiple sclerosis [1Cina C.S. Clase C.M. The Illness Intrusiveness Rating Scale: a measure of severity in individuals with hyperhidrosis.Qual Life Res. 1999; 8: 693-698Crossref PubMed Scopus (82) Google Scholar]. There are many surgical and nonsurgical ways to treat patients with primary hyperhidrosis and it is generally accepted that a sympathetic operation provides the only permanent treatment option. In the present study, de Moura Júnior and coauthors [2de Moura Júnior N.B. das-Neves-Pereira J.C. de Oliveira F.R.G. et al.Expression of acetylcholine and its receptor in human sympathetic ganglia in primary hyperhidrosis.Ann Thorac Surg. 2013; 95: 465-471Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar] used immunohistochemistry to evaluate the sympathetic ganglia from patients with palmar hyperhidrosis and used brain-dead organ donors with no history of hyperhidrosis as control individuals. They quantified the expression of primary antibodies against receptor subunits as well as acetylcholine, which is the primary neurotransmitter in sympathetic ganglia, and they found a significant difference between the two groups. The reason for this difference is speculative, but could it suggest that increased acetylcholine expression in the ganglia of patients may be related to hyperactivity of the central portion of the sympathetic nervous system, or that the sympathetic ganglia are able to modulate the nervous stimuli from the central nervous system and play a role in the pathophysiology of primary hyperhidrosis. The authors also made a new observation that the diameter of thoracic sympathetic chain ganglia was larger in hyperhidrotic patients. There are obvious limitations with the present study, because the two groups differed with respect to age and sex, and this should be addressed in future studies. Nevertheless, this article is a major contribution to our understanding of primary hyperhidrosis, providing a hint to its primary cause, and this is valuable information to thoracic surgeons and their patients. More importantly, this article points to where future research should be directed for complete elucidation and understanding of hyperhidrosis, which is such a frequent problem. Expression of Acetylcholine and Its Receptor in Human Sympathetic Ganglia in Primary HyperhidrosisThe Annals of Thoracic SurgeryVol. 95Issue 2PreviewThe pathophysiologic characteristics of primary hyperhidrosis are not well understood and seem to be related to a sympathetic nervous system dysfunction. The resection of thoracic sympathetic chain ganglia is the most effective treatment for hyperhidrosis; however sympathetic ganglia function in normal individuals and in patients with hyperhidrosis is unknown. Full-Text PDF

A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress

This presentation describes the “Stress Repair Mechanism”(SRM) that enables the “Universal Theory of Medicine” predicted by Hans Selye. It explains the nature of embryology, physiology, pathology, and stress. SRM function comprises the autonomic nervous system, the vascular endothelium, and the dynamic enzymatic interaction of blood‐borne hepatic Factors VII, VIIIC, IX and X that produces thrombin, soluble fibrin and insoluble fibrin, whose combined effects account for all SRM manifestations. The vascular endothelium is a diaphanous neuroendocrine organ that lines all blood vessels and is the sole constituent of capillary walls. It secretes tissue factor into extravascular tissues, and insulates those tissues from the hepatic enzymes. Tissue disruption exposes tissue factor to the enzymatic interaction and activates tissue repair. The vascular endothelium also releases nitric oxide and von Willebrand Factor into blood in accord with autonomic balance to regulate the enzymatic interaction to govern tissue perfusion and organ function. Therefore, continuously fluctuating combinations of nervous stimuli that affect autonomic balance and forces that disrupt tissues determine SRM activity.

Alcohol and hepatocyte-Kupffer cell interaction (Review)

Alcoholic liver disease accounts for 12,000 deaths per year in the United States and is the second leading indication for liver transplantation. It covers a spectrum of disease conditions ranging from steatosis and cirrhosis to hepatic malignancies. Epidemiological data clearly show a strong correlation between alcohol consumption and liver diseases. A large body of evidence has accumulated over the years in determining the molecular mediators of alcohol-induced liver injury. In this review, we provide an overview of such mediators, which include alcohol metabolites and reactive oxygen/nitrogen species, endotoxin via bacterial translocation from the gut and TNF-α, and highlight the role of the sympathetic nervous stimuli, norepinephrine and the α2A-adrenergic receptors in contributing to the deleterious effect observed in alcohol-induced hepatic dysfunction.

A Stress Repair Mechanism That Maintains Vertebrate Structure During Stress

Based on Capillary Gate Theory and Tissue Repair Theory, this paper describes the "Stress Repair Mechanism" (SRM) that maintains and repairs vertebrate tissues. It accounts for most of the mysterious manifestations of allostasis that remain unexplained by Hypothalamic-Pituitary-Axis (HPA) hormones and thereby enables the Universal Theory of Medicine predicted by Hans Selye. SRM activity explains hemodynamic physiology, capillary hemostasis, infarction, Korotkoff sounds, blood pressure, hypertension, diabetes, allostasis, allostatic load, anesthesia, analgesia, atherosclerosis, apoptosis, malignancy, eclampsia, sepsis, Multi-System Organ Failure (MSOF), the surgical stress syndrome, the fight or flight response, and numerous other manifestations of physiology and pathology. SRM function comprises the autonomic nervous system, the vascular endothelium, and the dynamic enzymatic interaction of blood-borne hepatic Factors VII, VIIIC, IX and X that produces thrombin, soluble fibrin and insoluble fibrin, whose combined effects account for all SRM manifestations. The vascular endothelium is a diaphanous neuroendocrine organ that lines all blood vessels and is the sole constituent of capillary walls. It secretes tissue factor into extravascular tissues, and insulates those tissues from the hepatic enzymes, so that tissue disruption exposes tissue factor to the enzymatic interaction and activates tissue repair. The vascular endothelium also releases nitric oxide and von Willebrand Factor into blood in accord with autonomic balance to regulate the enzymatic interaction to govern tissue perfusion and organ function. Therefore, continuously fluctuating combinations of nervous stimuli that affect autonomic balance and forces that disrupt tissues determine SRM activity.

Carboxypeptidase E, an essential element of the regulated secretory pathway, is expressed and partially co-localized with chromogranin A in chicken thymus.

Although the functions of hormones and neuropeptides in the thymus have been extensively studied, we still do not know whether these intra-thymic humoral elements are released in a stimulated manner via the regulated secretory pathway or in a constitutive manner. Carboxypeptidase E (CpE) and chromogranin A (CgA) are functional and structural hallmarks of the regulated secretory pathway in (neuro)endocrine cells. Whereas we have previously shown a CgA-positive neuroendocrine population in the chicken thymus, the current study assesses the expression of CpE in the thymus, both at the mRNA and the protein level. Our immunohistochemical studies provide evidence for the co-existence of CgA and CpE in identical neuroendocrine cells in the thymus. CpE and CgA dual-positive cells have primarily been found in the transition zone between the cortex and medulla of the thymus, an area known to contain numerous arterioles and to be innervated by the autonomic nervous system. Our findings suggest that the diffuse neuroendocrine system serves as a relay for nervous stimuli delivered by the sympathetic and/or parasympathetic nervous system. Thus, these newly defined neuroendocrine cells might play an important role in the immuno-neuro-endocrine cross-talk in the thymus, potentially enabling thymopoiesis to be fine-tuned via the regulated secretory pathway by a variety of physical and environmental factors.

Commentary on Viewpoint: The human cutaneous circulation as a model of generalized microvascular function

VIEWPOINTCommentary on Viewpoint: The human cutaneous circulation as a model of generalized microvascular functionDimitris Tousoulis, Kyriakoula Marinou, and Christodoulos StefanadisDimitris Tousoulis, Kyriakoula Marinou, and Christodoulos StefanadisPublished Online:01 Jul 2008https://doi.org/10.1152/japplphysiol.00165.2008This is the final version - click for previous versionMoreSectionsPDF (28 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat EVALUATING CUTANEOUS MICROCIRCULATION IN HUMANS: IS EXTRAPOLATION TO CARDIAC MICROCIRCULATION VALID?to the editor: Holowatz et al. (3) supported that the study of cutaneous microcirculation vasoreactivity (and especially the functional status of microvascular endothelium), provides important information regarding systemic microcirculation, including coronary microcirculation. But is this really valid? As cutaneous circulation is highly reactive to metabolic, thermal, and nervous stimuli, how easily can we study its vasoreactivity to an NO specific stimuli? And how similar is the pathophysiology of cutaneous and cardiac microcirculations?The widely used methods evaluating endothelial function in conduit arteries (e.g., flow mediated dilation in the brachial artery; Ref. 4) or forearm resistance vessels (by gauge-strain plethysmography; Ref. 4) are strongly correlated with endothelial function in coronary arteries (1) and most importantly, they predict clinical outcome in several populations (2). On the other hand, the vasoactive response of cutaneous microcirculation is not correlated with these markers of endothelial function in conduit arteries (5).As Holowatz et al. (3) stated, cutaneous vasoreactivity is impaired early in the progression of hypertensive vascular disease, despite the fact that it does not contribute significantly to the total increase of systemic vascular resistance, leading to hypertension. However, it remains to be proven whether the evaluation of vasoreactivity in cutaneous microcirculation may provide information regarding systemic peripheral microcirculation. Further clinical studies are required to determine this important issue and, most importantly, to validate the predictive value of the method for the clinical outcome in humans.REFERENCES1 Anderson TJ, Uehata A, Gerhard MD, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 26: 1235–1241, 1995.Crossref | PubMed | ISI | Google Scholar2 Brevetti G, Silvestro A, Schiano V, Chiariello M. Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease: additive value of flow-mediated dilation to ankle-brachial pressure index. Circulation 108: 2093–2098, 2003.Crossref | PubMed | ISI | Google Scholar3 Holowatz LA, Thompson-Torgerson CS, Kenney LW. Viewpoint: The human cutaneous circulation as a model of generalized microvascular function. J Appl Physiol; doi:10.1152/japplphysiol.00858.2007.Link | ISI | Google Scholar4 Tousoulis D, Antoniades C, Stefanadis C. Evaluating endothelial function in humans: a guide to invasive and non-invasive techniques. Heart 91: 553–558, 2005.Crossref | PubMed | ISI | Google Scholar5 Shamim-Uzzaman QA, Pfenninger D, Kehrer C, et al. Altered cutaneous microvascular responses to reactive hyperaemia in coronary artery disease: a comparative study with conduit vessel responses. Clin Sci (Lond) 103: 267–273, 2002.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: D. Tousoulis, Hippokration Hospital, Cardiology Dept., 5th Floor, Athens Univ. Medical School, Vasilissis Sofias 114, 115 28, Ampelokipi, Athens-Greece (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByIntroducing the Highlighted Topic seriesAndré De Troyer and Martin J. Tobin1 July 2009 | Journal of Applied Physiology, Vol. 107, No. 1 More from this issue > Volume 105Issue 1July 2008Pages 379-379 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00165.2008PubMed18292302History Published online 1 July 2008 Published in print 1 July 2008 Metrics

Incretins: Clinical Physiology and Bariatric Surgery –Correlating the Entero-endocrine System and a Potentially Anti-dysmetabolic Procedure

The digestive tract is well known for its endocrine functions. Recently, many studies have been reinforcing its role as a therapeutic target for both diabetes and obesity. Losing weight is clinically very difficult for most obese patients and the reason for this could be the effect of the physiological adipostatic system that triggers central nervous stimuli to compensate for variations in food intake and in physical activity. Gut hormones seem to have a key role in this complex, regulating body weight and satiety and contributing to glucose homeostasis. The enteroinsular axis appears to be impaired in both obese and diabetic patients. Recent data on bariatric surgery shows its striking effects on glucose control soon after the procedure, before a significant weight loss is achieved. The procedure appears to work beyond anti-obesity having a key metabolic impact possibly sharing a common mechanism with the new class of agents to treat type 2 diabetes mellitus: the incretin mimetics. This symposium discussed new data on the upcoming perspectives on both the pharmacological and the surgical approach to diabetes and obesity.

Ringing the dinner bell for insulin: Muscarinic M 3 receptor activity in the control of pancreatic β cell function

In this issue of Cell Metabolism, Gautam et al. (2006) show that pancreatic beta cell M3 muscarinic acetylcholine receptors control insulin secretion. Their results highlight the role of the M3 receptor subtype in integrating nervous stimuli with metabolic control of insulin secretion and glucose homeostasis.