The purpose of this study was to explore the effects of calcitonin gene-related peptide (CGRP) on the long-term depression (LTD) of hippocampus in mice. Sixty C57BL/6J mice (30 days old) were randomly divided into control group, three CGRP (50, 100, and 200 nmol/L) groups, CGRP + CGRP group and CGRP + APV group (10 mice for each group). The effects of exogenous application of different concentrations of CGRP on synaptic plasticity and LTD in hippocampus of mice were detected by in vitro recording of local field potential. The results showed that higher doses (100 and 200 nmol/L) of CGRP significantly enhanced the induction of LTD in the hippocampus. Moreover, CGRP increased the magnitude of N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents. The above-mentioned effects of CGRP were blocked by either CGRP selective antagonist CGRP or NMDA receptor antagonist APV. These results suggest that CGRP can dose-dependently enhance the induction of LTD in hippocampus of mice, and the underlying mechanism involves the mediation of NMDA receptor function.
Animals ; Calcitonin Gene-Related Peptide ; pharmacology ; Hippocampus ; drug effects ; Long-Term Synaptic Depression ; drug effects ; Mice ; Mice, Inbred C57BL ; Random Allocation

OBJECTIVETo observe preventive and therapeutic effects of Tanshinone IIA (T II A) on oxaliplatin induced peripheral neuropathy (OlPN) and to explore its effects on the expression of calcitonin gene related peptide (CGRP) and never growth factor (NGF).

METHODSTotally 36 phase II - III patients with malignant tumor of digestive tract undergoing chemotherapy program with oxaliplatin, were equally assigned to the T II A group (using THA at 80 mg/day 1 day before oxaliplatin chemotherapy for 3 successive days) and the control group (using chemotherapy program with oxaliplatin alone) by segmented randomization. After 4 cycles of chemotherapy, the incidence degree and incidence of OlPN were evaluated. Sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity ( MNCV) were tested by EMG evoked potential device. Serum levels of CGRP and NGF were also detected in the two groups before and after chemotherapy. The correlation of serum levels of CGRP and NGF to OIPN was assessed using linear correlation analysis.

RESULTSAfter chemotherapy the OlPN incidence was 27.8% (5/18 cases) in the T II A group, obviously lower than that in the control group (55.6%, 10/18 cases; P < 0.05). Compared with before treatment in the same group, SNCV and MNCV of common peroneal nerve were slowed down, serum NGF levels decreased, and serum CGRP levels obviously increased in the two groups (all P < 0.05). Compared with the control group after treatment, SNCV and MNCV of common peroneal nerve were obviously accelerated, serum NGF levels increased, and serum CGRP levels obviously decreased in the THA group (all P < 0.05). Results of linear correlation analysis indicated serum NGF level was negatively correlated with peripheral neuropathy (PN), serum CGRP expression was positively correlated with neurotoxicity (P < 0.05).

CONCLUSIONT II A could reduce the incidence of OlPN, which might be associated with inhibiting the expression of CGRP and up-regulating NGF activities.

Calcitonin Gene-Related Peptide ; blood ; Diterpenes, Abietane ; therapeutic use ; Gastrointestinal Neoplasms ; drug therapy ; Humans ; Nerve Growth Factor ; blood ; Neural Conduction ; drug effects ; Organoplatinum Compounds ; adverse effects ; Peripheral Nervous System Diseases ; chemically induced ; drug therapy ; Up-Regulation

PURPOSE: The pathophysiology of discogenic low back pain is not fully understood. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are associated with primary sensory nerve transmission, and the NaV1.7 channel has emerged as an analgesic target. Previously, we found increased NaV1.7 expression in dorsal root ganglion (DRG) neurons innervating injured discs. This study aimed to examine the effect of blocking NaV1.7 on sensory nerves after disc injury. MATERIALS AND METHODS: Rat DRG neurons innervating the L5/6 disc were labeled with Fluoro-Gold (FG) neurotracer. Twenty-four rats underwent intervertebral disc puncture (puncture group) and 12 rats underwent sham surgery (non-puncture group). The injury group was divided into a saline infusion group (puncture+saline group) and a NaV1.7 inhibition group, injected with anti-NaV1.7 antibody (puncture+anti-NaV1.7 group); n=12 per group. Seven and 14 days post-surgery, L1 to L6 DRGs were harvested and immunostained for calcitonin gene-related peptide (CGRP) (an inflammatory pain marker), and the proportion of CGRP-immunoreactive (IR) DRG neurons of all FG-positive neurons was evaluated. RESULTS: The ratio of CGRP-IR DRG neurons to total FG-labeled neurons in the puncture+saline group significantly increased at 7 and 14 days, compared with the non-puncture group, respectively (p<0.05). Application of anti-NaV1.7 into the disc significantly decreased the ratio of CGRP-IR DRG neurons to total FG-labeled neurons after disc puncture at 7 and 14 days (40% and 37%, respectively; p<0.05). CONCLUSION: NaV1.7 antibody suppressed CGRP expression in disc DRG neurons. Anti-NaV1.7 antibody is a potential therapeutic target for pain control in patients with lumbar disc degeneration.
Animals ; Antibodies ; Calcitonin Gene-Related Peptide/metabolism ; Disease Models, Animal ; Ganglia, Spinal/*metabolism ; Intervertebral Disc/*drug effects/*injuries ; Intervertebral Disc Degeneration/metabolism ; Low Back Pain/*physiopathology ; Lumbar Vertebrae/injuries ; Male ; NAV1.7 Voltage-Gated Sodium Channel/*metabolism ; Neurons/*metabolism ; Pain/metabolism ; Rats ; Rats, Sprague-Dawley ; Stilbamidines

OBJECTIVETo explore the effects of oral administration of mixed enteral nutritional agent on intestinal mucosal barrier of patients with severe burn injury at early stage.

METHODSTwenty-four patients with severe burn injury admitted to our burn ward from August 2013 to September 2014, conforming to the study criteria, were divided into conventional therapy group (n = 12) and early enteral feeding group (n = 12) according to the random number table. Patients in conventional therapy group received conventional treatment immediately after admission, while those in early enteral feeding group were orally given 100 mL of a mixture of glutamine, probiotics, and prebiotics once a day besides conventional treatment for 7 days. Serum levels of diamine oxidase (DAO) and procalcitonin (PCT) and plasma level of LPS were determined by ELISA before treatment and on treatment day (TD) 1, 3, 7, 14, and 21. Wound secretion and blood samples were collected for bacterial culture within the 21 TD. The incidence of MODS within the 21 TD was observed. Data were processed with Fisher's exact test, rank sum test, analysis of variance for repeated measurement, and LSD-t test.

RESULTS(1) Serum levels of DAO in patients of early enteral feeding group on TD 7, 14, and 21 were respectively (14.9 ± 3.7), (12.4 ± 3.1), and (9.5 ± 0.7) ng/mL, which were significantly lower than those of conventional therapy group [(17.5 ± 4.0), (16.3 ± 3.3), and (13.0 ± 1.1) ng/mL, with t values from 2.913 to 15.304, P values below 0.01]. Serum levels of DAO at the other time points were close between the two groups (with t values from -0.598 to 0.139, P values above 0.05). (2) Compared with serum levels of PCT in patients of conventional therapy group [(11.7 ± 20.9) and (12.9 ± 23.9) ng/mL], those of early enteral feeding group were significantly lower on TD 7 and 14 [(2.7 ± 8.1) and (2.0 ± 5.6) ng/mL, with Z values respectively -2.919 and -2.139, P < 0.05 or P < 0.01]. Serum levels of PCT at the other time points were close between the two groups (with Z values from -1.833 to -0.346, P values above 0.05). (3) Plasma level of LPS in patients of early enteral feeding group on TD 7 was (33 ± 56) pg/mL, which was significantly lower than that of conventional therapy group [(102 ± 108) pg/mL, Z = -2.046, P < 0.05]. Plasma levels of LPS at the other time points between the two groups showed no significant difference (with Z values from -2.003~-0.526, P values above 0.05). (4) Positive results in bacterial culture of wound secretion were approximately the same between the two groups (P > 0.05). Bacterial culture of blood was positive in 7 patients of conventional therapy group and 1 patient of early enteral feeding group, showing significantly statistical difference (P < 0.05). MODS was observed in 1 patient of conventional therapy group, showing no significantly statistical difference with that of early enteral feeding group (no patient, P > 0.05).

CONCLUSIONSEarly intestinal feeding of mixed enteral nutritional agent in addition to conventional therapy can effectively promote repair of the impairment of intestinal mucosal barrier, protect integrity of intestinal mucosa, reduce damage to intestines, and alleviate inflammatory response in patients suffering from severe burn injury.

Administration, Oral ; Amine Oxidase (Copper-Containing) ; blood ; Burns ; metabolism ; therapy ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Enteral Nutrition ; methods ; Female ; Glutamine ; administration & dosage ; pharmacology ; Humans ; Intestinal Mucosa ; drug effects ; metabolism ; Protein Precursors ; blood ; Treatment Outcome ; Wound Healing

The increase of pronociceptive mediators in the dorsal root ganglia (DRG) and spinal dorsal horn is an important mechanism in the pathogenesis of inflammatory pain and opioid tolerance. Adrenomedullin (AM) belongs to calcitonin gene-related peptide (CGRP) family and has been recently demonstrated to be a pain-related peptide. It has also been shown that the expression and release of AM are increased in the DRG and spinal dorsal horn during inflammation and repeated use of morphine. Intrathecal administration of the selective AM receptor antagonist AM22-52 abolishes inflammatory pain and morphine tolerance, suggesting that enhanced AM receptor signaling in the DRG and spinal dorsal horn contributes to the induction of inflammatory pain and morphine tolerance. The present review highlights the recent developments regarding the involvement of AM in these two disorders. The neurological mechanisms of AM's actions are also discussed.
Adrenomedullin ; pharmacology ; Animals ; Calcitonin Gene-Related Peptide ; Drug Tolerance ; Ganglia, Spinal ; drug effects ; Inflammation ; drug therapy ; metabolism ; Morphine ; pharmacology ; Pain ; drug therapy ; metabolism ; Peptide Fragments ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenomedullin ; metabolism

BACKGROUND/AIMS: The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. METHODS: The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. RESULTS: All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. CONCLUSIONS: SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Arachidonate 5-Lipoxygenase/drug effects ; Calcitonin Gene-Related Peptide/drug effects ; Cyclooxygenase 1/drug effects ; Cyclooxygenase 2/drug effects ; Disease Models, Animal ; Gastric Mucosa/chemistry/drug effects ; Group IV Phospholipases A2/drug effects ; Male ; Momordica/*chemistry ; Peroxidase/drug effects ; Plant Extracts/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Seeds/*chemistry ; Stomach Ulcer/chemically induced/*prevention & control ; Treatment Outcome

OBJECTIVETo study the clinical characteristics of children who suffered from Streptococcus pneumoniae (SP) septicemia and the drug sensitivity of SP strains.

METHODSA retrospective analysis was performed on the clinical data of 25 children with SP septicemia between January 2009 and December 2012.

RESULTSOf the 25 cases, 16 (64%) were aged under 2 years, 5 (20%) were aged 2-5 years, and 4 (16%) were aged over 5 years. Fourteen cases (56%) were complicated by infection of other organs, and 5 cases (20%) had underlying chronic diseases. Fever was the most common clinical manifestation, and the majority presented with remittent fever. Eight patients with pneumonia or pyothorax had pulmonary symptoms. Five patients with purulent meningitis had neurological symptoms, five cases had hepatosplenomegaly and two cases had septic shock. Nineteen cases (76%, 19/25) had significantly elevated white blood cell (WBC) counts, twenty-one cases (84%, 21/25) had significantly elevated serum C-reactive protein (CRP) levels, and eight cases (50%, 8/16) had significantly elevated serum procalcitonin (PCT) levels. The drug sensitivity analysis showed that invasive SP had high resistance rates to penicillin (96%), clindamycin hydrochloride (88%) and erythromycin (84%), and it was completely sensitive to imipenem, vancomycin, levofloxacin and linezolid. The multi-drug resistance rate of invasive SP was up to 88%. Twenty-three cases (92%) were cured or improved after active treatment.

CONCLUSIONSSP septicemia is commonly seen in children aged under 2 years. The most common clinical manifestation is fever, accompanied by elevated WBC count, CRP level and PCT level, and it is usually complicated by pulmonary or brain infection. Resistance to multiple antibiotics is very common in SP strains, so it is important to properly use antibiotics according to drug sensitivity test results. Patients who receive active treatment have a good clinical outcome.

Anti-Bacterial Agents ; therapeutic use ; Bacteremia ; blood ; complications ; drug therapy ; C-Reactive Protein ; analysis ; Calcitonin ; blood ; Calcitonin Gene-Related Peptide ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Microbial Sensitivity Tests ; Pneumococcal Infections ; blood ; complications ; drug therapy ; Protein Precursors ; blood ; Retrospective Studies ; Streptococcus pneumoniae ; drug effects

OBJECTIVETo investigate the vasodilating effect of capsaicin (CAP) on rat mesenteric artery and its mechanism.

METHODSThe third branch of the superior mesenteric artery in male Sprague-Dawley rat (250-350 g) was excised, the periadventitial fat and connective tissue were removed and the mesenteric artery was dissected into 2 mm rings. Each ring was placed in a 5 ml organ bath of DMT 610M system and the tension was recorded.

RESULTSCAP (10(-9)-10(-5) mol/L) relaxed endothelium-intact and endothelium-denuded mesenteric artery pre-constricted by phenylephrine (10(-5) mol/L), and the vasodilation in endothelium-intact mesenteric artery was stronger than that in endothelium-denuded one. Pretreatment with either L-NAME (3 X10(-4) mol/L), an inhibitor of nitric oxide synthase(NOS), or CGRP8-37 (2 X 10(-6) mol/L), an antagonist of calcitonin gene-related peptide (CGRP), for 30 min significantly attenuated the relaxation of endothelium-intact mesenteric artery induced by CAP. CGRP (10(-10)-3 X10(-8) mol/L) relaxed endothelium-intact and endothelium-denuded mesenteric artery pre-constricted by phenylephrine, and the vasodilation in endothelium-intact mesenteric artery was stronger than that in endothelium-denuded one. Substance P did not relax the mesenteric artery pre-constricted by phenylephrine.

CONCLUSIONCAP has partial endothelium-dependent relaxation effect on rat mesenteric artery, which may be mediated by activating the endothelial NOS-NO pathway. The endothelium-independent relaxation in rat mesenteric artery induced by CAP may be mediated by CGRP.

Animals ; Calcitonin Gene-Related Peptide ; metabolism ; Capsaicin ; pharmacology ; In Vitro Techniques ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Peptide Fragments ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vasodilation ; drug effects

OBJECTIVE: To explore the inhibitory effect of calcitonin gene-related peptide (CGRP) on cardiac fibroblast proliferation and collagen synthesis induced by isoprenaline and the underlying mechanism. METHODS: The primary cultured cardiac fibroblasts were incubated with isoprenaline (10(-5) mol/L) for 48 h after pretreatment with CGRP (10(-8) or 10(-7) mol/L) for 1 h. Cell activity was detected by MTT. The mRNA expression of collagen (types I and III) and connective tissue growth factor (CTGF) was determined by RT-PCR, and the levels of intracellular ROS were determined by DCFH-DA fluorescent probe. RESULTS: Isoprenaline significantly promoted fibroblast proliferation and up-regulated collagen (types I and III) and CTGF mRNA expression concomitantly with an increase in ROS production, which were attenuated by CGRP. The effect of CGRP on cardiac fibroblasts was inhibited by CGRP8-37, a selective antagonist of CGRP receptor. CONCLUSION CGRP is able to protect cardiac fibroblasts against isoprenaline-induced proliferation and collagen expression, which might be related to the down-regulation of CTGF expression through inhibition of ROS production.
Animals ; Animals, Newborn ; Calcitonin Gene-Related Peptide ; pharmacology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Collagen Type I ; genetics ; metabolism ; Collagen Type III ; genetics ; metabolism ; Connective Tissue Growth Factor ; genetics ; metabolism ; Fibroblasts ; cytology ; Isoproterenol ; antagonists & inhibitors ; pharmacology ; Myocytes, Cardiac ; cytology ; Primary Cell Culture ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism

OBJECTIVETo discuss the effect of calcitonin gene-related peptides (CGRP) on epithelial cadherin (E-cd) expression in human bronchial epithelial cells (HBECs) in vitro.

METHODSThe effect of CGRP on E-cd protein and mRNA expression in both normal and O3-challenged HBECs were determined by immunocytochemistry and RT-PCR. The signal transduction pathways of CGRP were observed by using protein kinase C(PKC) inhibitor (H-7), calmodulin(CaM) inhibitor (W-7) and PKA inhibitor (H-89).

RESULTSCGRP increased E-cd mRNA and protein expressions of normal and O3-challenged HBECs in a dose-dependent manner. CGRP had no effect on cytoplasm E-cd expression. Pre-treatment with H-89, H-7 and W-7, the up-regulatory effect of CGRP on E-cd expression was partly abolished.

CONCLUSIONCGRP increased in cytomembrane E-cd expression of normal and O3-challenged HBECs in a dose-dependent manner. E-cd expression on HBECs was strengthened by CGRP via PKA, PKC and CaM pathways.

Bronchi ; cytology ; Cadherins ; metabolism ; Calcitonin Gene-Related Peptide ; administration & dosage ; pharmacology ; Cell Line ; Epithelial Cells ; drug effects ; metabolism ; Humans ; Ozone ; RNA, Messenger ; genetics