Cholecystokinin/Cholecystokinin-1 Receptor-Mediated Peripheral Activation of the Afferent Vagus by Enteral Nutrients Attenuates Inflammation in Rats

2010 ◽  
Vol 252 (2) ◽  
pp. 376-382 ◽  
Author(s):  
Tim Lubbers ◽  
Jacco J. de Haan ◽  
Misha D. P. Luyer ◽  
Isabelle Verbaeys ◽  
Mʼhamed Hadfoune ◽  
...  
Keyword(s):  
Peripheral Activation ◽  
Enteral Nutrients ◽  
Afferent Vagus

scholarly journals CXCL10+ peripheral activation niches couple preferred sites of Th1 entry with optimal APC encounter

Cell Reports ◽  
2021 ◽  
Vol 36 (6) ◽  
pp. 109523
Author(s):  
Hen Prizant ◽  
Nilesh Patil ◽  
Seble Negatu ◽  
Noor Bala ◽  
Alexander McGurk ◽  
...  
Keyword(s):  
Peripheral Activation

Nociceptors and Chronic Pain

2021 ◽  
Author(s):  
Edgar T. Walters
Keyword(s):  
Chronic Pain ◽  
Spontaneous Activity ◽  
Intracellular Signaling ◽  
Chronic Conditions ◽  
Spontaneous Pain ◽  
Pain Pathways ◽  
Low Threshold ◽  
Highly Correlated ◽  
Hyperalgesic Priming ◽  
Peripheral Activation

Chronic pain lasting months or longer is very common, poorly treated, and sometimes devastating. Nociceptors are sensory neurons that usually are silent unless activated by tissue damage or inflammation. In humans their peripheral activation evokes conscious pain, and their spontaneous activity is highly correlated with spontaneous pain. Persistently hyperactive nociceptors mediate increased responses to normally painful stimuli (hyperalgesia) in chronic conditions and promote the sensitization of central pain pathways that allows low-threshold mechanoreceptors to elicit painful responses to innocuous stimuli (allodynia). Investigations of rodent models of neuropathic pain and hyperalgesic priming have revealed many alterations in nociceptors and associated cells that are implicated in the development and maintenance of chronic pain. These include chronic nociceptor hyperexcitability and spontaneous activity, sprouting, synaptic plasticity, changes in intracellular signaling, and modified responses to opioids, along with alterations in the expression and translation of thousands of genes in nociceptors and closely linked cells.

Abstract 400: Cannabinoid 1 Receptor Blockade Diminishes Obesity and Dyslipidemia via Peripheral Activation of Brown Adipose Tissue

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jimmy F Berbée ◽  
Mariëtte R Boon ◽  
Andrea D van Dam ◽  
Anita M van den Hoek ◽  
Marc Lombès ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Therapeutic Potential ◽  
Lipoprotein Metabolism ◽  
Special Focus ◽  
Cannabinoid 1 Receptor ◽  
Brown Adipose ◽  
Major Player ◽  
Peripheral Activation

Objectives: The endocannabinoid system is an important player in energy metabolism by regulating appetite, lipolysis and energy expenditure. Chronic blockade of the cannabinoid 1 receptor (CB1R) leads to long-term maintained weight loss and reduction of dyslipidemia in experimental and human obesity. Brown adipose tissue (BAT) that burns lipids towards heat using UCP1, recently emerged as a major player in lipoprotein metabolism and is present and active in human adults. The aim of the present study was to elucidate the mechanism by which CB1R blockade reverses dyslipidemia and obesity, with special focus on BAT. Methods and results: Diet-induced obese APOE*3-Leiden.CETP transgenic mice, a well-established model for human-like lipoprotein metabolism, were treated with the systemic CB1R blocker rimonabant (10 mg/kg/day) for 4 weeks. Rimonabant persistently decreased body weight (-25%, p<0.001), fat mass (-32%, p<0.001) and plasma triglyceride (TG) levels (-60%, p<0.05), despite a modest and transient reduction in food intake. Interestingly, rimonabant reduced plasma TG levels, not by affecting VLDL-TG production by the liver, but rather by selectively increasing VLDL-TG clearance by BAT (+40%, p<0.05). This was accompanied by increased energy expenditure (+20%, p<0.05), decreased lipid droplet size and increased UCP1 content in BAT (+28%, p<0.05), all pointing to increased BAT activity. Next, we demonstrated that the CB1R is highly expressed in BAT and that in vitro blockade of the CB1R in cultured brown adipocytes resulted in 2.5-fold upregulation of UCP1. Importantly, the in vivo results could be fully recapitulated using the strictly peripheral CB1R antagonist AM6545 (10 mg/kg/day) that does not induce hypophagia. Conclusion: CB1R blockade reduces dyslipidemia and obesity by peripheral activation of BAT. Selective targeting of peripheral CB1R in BAT has thus great therapeutic potential in decreasing dyslipidemia and obesity and ultimately cardiovascular diseases.

scholarly journals Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside

2022 ◽  
Vol 23 (2) ◽  
pp. 673
Author(s):  
Vittoria Favero ◽  
Arianna Cremaschi ◽  
Chiara Parazzoli ◽  
Alberto Falchetti ◽  
Agostino Gaudio ◽  
...  
Keyword(s):  
Subclinical Atherosclerosis ◽  
Pituitary Tumors ◽  
Bone Fragility ◽  
Clinical Effects ◽  
Cortisol Secretion ◽  
Peripheral Tissues ◽  
Dehydrogenase Enzyme ◽  
Skin Fragility ◽  
Clinical Consequences ◽  
Peripheral Activation

Mild hypercortisolism is defined as biochemical evidence of abnormal cortisol secretion without the classical detectable manifestations of overt Cushing’s syndrome and, above all, lacking catabolic characteristics such as central muscle weakness, adipose tissue redistribution, skin fragility and unusual infections. Mild hypercortisolism is frequently discovered in patients with adrenal incidentalomas, with a prevalence ranging between 5 and 50%. This high variability is mainly due to the different criteria used for defining this condition. This subtle cortisol excess has also been described in patients with incidentally discovered pituitary tumors with an estimated prevalence of 5%. To date, the mechanisms responsible for the pathogenesis of mild hypercortisolism of pituitary origin are still not well clarified. At variance, recent advances have been made in understanding the genetic background of bilateral and unilateral adrenal adenomas causing mild hypercortisolism. Some recent data suggest that the clinical effects of glucocorticoid (GC) exposure on peripheral tissues are determined not only by the amount of the adrenal GC production but also by the peripheral GC metabolism and by the GC sensitivity. Indeed, in subjects with normal cortisol secretion, the combined estimate of cortisol secretion, cortisone-to-cortisol peripheral activation by the 11 beta-hydroxysteroid dehydrogenase enzyme and GC receptor sensitizing variants have been suggested to be associated with the presence of hypertension, diabetes and bone fragility, which are three well-known consequences of hypercortisolism. This review focuses on the pathophysiologic mechanism underlying both the different sources of mild hypercortisolism and their clinical consequences (bone fragility, arterial hypertension, subclinical atherosclerosis, cardiovascular remodeling, dyslipidemia, glucose metabolism impairment, visceral adiposity, infections, muscle damage, mood disorders and coagulation).

scholarly journals Peripheral activation of ACE2‐Ang‐(1–7)‐Mas axis reduces the cardiovascular reactivity to acute stress in rats

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Augusto Martins Lima ◽  
Carlos Henrique Xavier ◽  
Robson Augusto Souza Santos ◽  
Mohan K. Raizada ◽  
Anderson J. Ferreira ◽  
...  
Keyword(s):  
Cardiovascular Reactivity ◽  
Acute Stress ◽  
Peripheral Activation

Early enteral feeding of patients with multiple trauma

1999 ◽  
Vol 19 (6) ◽  
pp. 40-51 ◽  
Author(s):  
KH Cheever
Keyword(s):  
Multiple Trauma ◽  
Enteral Feeding ◽  
Clinical Course ◽  
Early Enteral Feeding ◽  
Effects Of Stress ◽  
Enteral Nutrients

The case study illustrates the recovery of a patient with multiple trauma who was fed a peptide-based formula via the enteral route soon after the trauma. Although the clinical course might have been worse if D.H. had not received this treatment, his generally excellent recovery might be partly attributable to this therapy. Although stress hypermetabolism occurs in most patients with multiple trauma within 48 hours after injury, no known treatment can arrest or reverse this problem. However, the lethal catabolic and septic effects of stress hypermetabolism can be at least partly thwarted through delivery of enteral nutrients within 72 hours after trauma.

Endoscopic Insertion of Nasojejunal Feeding Tube at Bedside for Critically Ill Patients: Relationship between Tube Position and Intragastric Countercurrent of Contrast Medium

2019 ◽  
Vol 75 (3) ◽  
pp. 163-167
Author(s):  
Hiroomi Tatsumi ◽  
Masayuki Akatsuka ◽  
Satoshi Kazuma ◽  
Yoichi Katayama ◽  
Yuya Goto ◽  
...  
Keyword(s):  
Contrast Medium ◽  
Feeding Tube ◽  
Tube Insertion ◽  
Abdominal Radiography ◽  
Feeding Tubes ◽  
Tube Position ◽  
Endoscopic Insertion ◽  
Endoscopic Placement ◽  
Nasojejunal Feeding ◽  
Enteral Nutrients

Background and Oblectives: We evaluated the success rate of endoscopically positioned nasojejunal feeding tubes and the intragastric countercurrent of contrast medium thereafter. Method: This retrospective observational study investigated patients who were admitted to a single intensive care unit and required endoscopic placement of a post-pyloric feeding tube between January 2010 and June 2016. The feeding tube was grasped with forceps via a transoral endoscope and inserted into the duodenum or jejunum. Thereafter, we assessed the position of the tube and the intragastric countercurrent using abdominal radiography with contrast medium. Results: The tube tip was inserted at the jejunum and the duodenal fourth portion in 55.8 and 33.6% of patients, respectively. The tip of the inserted tube had moved into the jejunum of 71.7% of patients by the following day. The countercurrent rate was significantly lower among patients with a tube inserted into the duodenal fourth portion or more distal than among those with tubes inserted more proximally (8.4 vs. 45.4%, p = 0.0022). Conclusions: The endoscopic insertion and positioning of a nasojejunal feeding tube seemed effective because the rate of tube insertion into the duodenal fourth portion or more distal was about 90%. The findings of intragastric countercurrents indicated that feeding tubes should be inserted into the duodenal fourth portion or beyond to prevent vomiting and the aspiration of enteral nutrients.

The proinflammatory cytokine network: interactions in the CNS and blood of rhesus monkeys

1998 ◽  
Vol 274 (1) ◽  
pp. R139-R144 ◽  
Author(s):  
Teresa M. Reyes ◽  
Christopher L. Coe
Keyword(s):  
Rhesus Monkeys ◽  
Blood Levels ◽  
Brain Response ◽  
Cytokine Network ◽  
The Central Nervous System ◽  
Cytokine Cascade ◽  
Factor Α ◽  
Peripheral Activation ◽  
Necrosis Factor

Proinflammatory cytokines [interleukin (IL)-1 and -6 and tumor necrosis factor-α] function within a complex network, stimulating the release of one another, as well as other cytokine agonists and antagonists. These interactions have not been as widely studied in vivo. Therefore, the following studies measured cytokines in blood and cerebrospinal fluid (CSF) from juvenile rhesus monkeys after intravenous administration of cytokines. IL-1α and IL-1β were equally effective in elevating blood levels of IL-6. In contrast, IL-1β was the only cytokine that significantly elevated IL-6 levels in the CSF. Interestingly, both IL-1 and IL-6 increased levels of IL-1 receptor antagonist in the blood and comparably stimulated the release of cortisol. A second study confirmed that the IL-1-induced IL-6 in CSF was brain derived and not a result of diffusion from blood. This research extends studies of the cytokine cascade to the central nervous system (CNS), highlighting the brain response to peripheral activation.

scholarly journals Cortisol Secretion, Sensitivity, and Activity Are Associated With Hypertension in Postmenopausal Eucortisolemic Women

2019 ◽  
Vol 104 (10) ◽  
pp. 4441-4448 ◽  
Author(s):  
Iacopo Chiodini ◽  
Agostino Gaudio ◽  
Cristina Eller-Vainicher ◽  
Valentina Morelli ◽  
Carmen Aresta ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Postmenopausal Women ◽  
Fragility Fractures ◽  
Urinary Free Cortisol ◽  
Progressive Increase ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Heterozygous Variant ◽  
Free Cortisol ◽  
Peripheral Activation

Abstract Context Previous data suggest a possible association between type 2 diabetes (T2D) and fragility fractures (FX) with the degree of glucocorticoid suppressibility (GCS) and peripheral activation or sensitivity even in persons without hypercortisolemia. Objective To investigate whether the degree of GCS, GC sensitivity, and peripheral activation in persons without overt or mild hypercortisolism are associated with hypertension and with the number of the possible consequences of cortisol excess among patients with T2D, fragility FX, and hypertension. Design Case-control study. Setting Outpatient clinic. Patients A total of 216 postmenopausal women without hypercortisolemia (age, 50 to 80 years; 108 with hypertension); 68 and 99 patients had fragility FX and T2D, respectively Main outcome measures We assessed 24-hour urinary free cortisol (UFF), cortisone (UFE), their ratio (R-UFF/UFE), (F-1mgDST), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP). Results Hypertension was associated with F-1 mgDST [odds ratio (OR), 3.3; 95% CI, 1.5 to 7.5; P = 0.004) and R-UFF/UFE (OR, 101.7; 95% CI, 2.6 to 4004.1; P = 0.014), regardless of age, body mass index, and presence of the N363S single nucleotide polymorphism and of T2D. The progressive increase in the number of possible consequences of cortisol excess was significantly associated with F-1mgDST levels (R2 = 0.125; P = 0.04), R-UFF/UFE (R2 = 0.46; P = 0.02), and the prevalence of N363S heterozygous variant (T = 0.46; P = 0.015), after adjustment for age. Conclusions In postmenopausal women without hypercortisolemia, hypertension is associated with GCS and GC peripheral activation. The number of possible consequences of cortisol excess (among patients with hypertension, T2D, and fragility FX) is associated with GCS, GC peripheral activation, and the prevalence of the N363S heterozygous variant.

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