scholarly journals Electroacupuncture at ST25 Inhibits Cisapride-Induced Gastric Motility in an Intensity-Dependent Manner

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Tingting Pang ◽  
Chunxia Lu ◽  
Kaiyue Wang ◽  
Chao Liang ◽  
Zhi Yu ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Construct Validity ◽  
Therapeutic Effect ◽  
Drug Concentration ◽  
Gastric Motility ◽  
Similar Pattern ◽  
Dependent Manner ◽  
Response Relationship ◽  
Intensity Response ◽  
Relationship Of

Background.Previous studies have demonstrated the efficacy of frequency-specific EAS. However, evaluation of intensity-response effects is challenging and has yet to be addressed.Aims.Using cisapride to promote gastric emptying, we measured the intensity-response relationship of EA at ST25 on gastric motility.Methods.We determined the effects of EA at ST25 using intensities (0.5, 1, 3, 5, 7, and 9 mA) on gastric motility in rats injected with cisapride (0.2, 0.02, and 0.002 mg/kg).Results.Utilizing three concentrations of cisapride yielded significantly differing levels of gastric motility. Furthermore, log IC50values for EAS were different within each group. Given the same EA intensity, cisapride antagonism decreased progressively in each group as a function of drug concentration. The relative amount of cisapride antagonized by EAS did not change in a linear fashion. Finally, EAS at different intensities within the three groups induced a similar pattern of cisapride antagonism.Conclusions.The ability of EAS to elicit a decrease in cisapride-induced gastric motility pressure was demonstrated in this study. The study encompasses construct validity to mirror individualized treatment being based on patients’ subjective feelings, not on a set fixed EA intensity. Clinically utilizing EAS at the smallest intensity can achieve the desired therapeutic effect.

scholarly journals Effects of Different Local Moxibustion-Like Stimuli at Zusanli (ST36) and Zhongwan (CV12) on Gastric Motility and Its Underlying Receptor Mechanism

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Yang-Shuai Su ◽  
Juan-Juan Xin ◽  
Zhao-Kun Yang ◽  
Wei He ◽  
Hong Shi ◽  
...  
Keyword(s):  
Gastric Motility ◽  
Crucial Role ◽  
Pain Threshold ◽  
Facilitatory Effect ◽  
Response Relationship ◽  
Wild Type ◽  
Trpv1 Receptor ◽  
Thermal Pain ◽  
Intensity Response

The aim of this study was to explore the “intensity-response” relationship in local moxibustion-like stimuli- (LMS-) modulated gastric motility and its underlying receptor mechanism. Based on the thermal pain threshold (43°C), 41°C, 43°C, and 45°C LMS were separately applied to ST36 or CV12 for 180 s among ASIC3 knockout (ASIC3−/−) mice, TRPV1 knockout (TRPV1−/−) mice, and their homologous wild-type C57BL/6 mice (n=8in each group). Gastric motility was continuously measured by an intrapyloric balloon, and the amplitude, integral, and frequency of gastric motility during LMS were compared with those of initial activities. We found that both 43°C and 45°C LMS at ST36 induced significantly facilitated effect of gastric motilityP<0.05, while LMS at CV12 induced inhibited effectsP<0.05. 41°C LMS had no significant impact on gastric motility. Compared with C57BL/6 mice, the facilitatory effect at ST36 and inhibitive effect of LMS at CV12 were decreased significantly in TRPV1−/− mice (P<0.05;P<0.01) but not changed markedly in ASIC3−/− miceP>0.05. These results suggest that there existed an “intensity-response” relationship between temperature in LMS and its effects on gastric motility. TRPV1 receptor played a crucial role in the LMS-modulated gastric motility.

Differential Effects of Variable Frequencies of Manual Acupuncture at St36 in Rats with Atropine-Induced Inhibition of Gastric Motility

2016 ◽  
Vol 34 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Li-Li Gao ◽  
Yi Guo ◽  
Tao Sha ◽  
Yang-Yang Liu ◽  
Jia-Bei Tang ◽  
...  
Keyword(s):  
Frequency Analysis ◽  
Gastric Motility ◽  
Control Model ◽  
Response Relationship ◽  
Manual Acupuncture ◽  
Sprague Dawley ◽  
Time Frequency ◽  
Sprague Dawley Rats ◽  
Intensity Response ◽  
Single Operator

Objective The ‘intensity-response’ relationship between acupuncture stimulation and therapeutic effect is currently the focus of much research interest. The same needling manipulation with different frequencies can generate differential levels of stimulus. This study aimed to examine the effects on gastric motility induced by four twirling frequencies based on relatively standardised manual acupuncture (MA) manipulations. Methods Twirling manipulations at 1, 2, 3, and 4 Hz were practised before the experiments by a single operator using an MA parameter measurement device and stability was evaluated through time-frequency analysis. Forty-eight Sprague-Dawley rats were randomly divided into six groups (n=8 each): Control, Model, Model+MA (1, 2, 3, and 4 Hz). Rats in the five Model groups received injections of atropine into the tail vein to inhibit gastric motility, which was continuously recorded by a balloon in the gastric antrum. Rats in the four Model+MA groups received MA at 1, 2, 3 and 4 Hz, respectively, for 70 s and needles were retained for a further 5 min. Results The amplitude of waveforms produced by the four twirling frequencies was relatively consistent and reproducible. The gastric motility amplitude in all groups decreased after modelling (injections of atropine) (p<0.01). Twirling manipulation at 1, 2, and 3 Hz (but not 4 Hz) increased gastric motility amplitude (p<0.05). The increase in gastric motility amplitude induced by MA at 2 Hz was greater than for all other frequencies (p<0.05). Conclusions Acupuncture at ST36 helped recover gastric motility amplitude in rats with atropine-induced gastric inhibition and the effects induced by 1–3 Hz frequency were greater than those induced by 4 Hz.

scholarly journals “Intensity-Response” Effects of Electroacupuncture on Gastric Motility and Its Underlying Peripheral Neural Mechanism

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yang-Shuai Su ◽  
Wei He ◽  
Chi Wang ◽  
Hong Shi ◽  
Yu-Feng Zhao ◽  
...  
Keyword(s):  
Adult Male ◽  
Gastric Motility ◽  
Neural Mechanism ◽  
Facilitatory Effect ◽  
Response Relationship ◽  
Sprague Dawley ◽  
Trpv1 Receptor ◽  
Intensity Response ◽  
C Fiber ◽  
The Difference

The aim of this study was to explore the “intensity-response” relationship between EAS and the effect of gastric motility of rats and its underlying peripheral neural mechanism by employing ASIC3 knockout (ASIC3−/−), TRPV1 knockout (TRPV1−/−), and C57BL/6 mice. For adult male Sprague-Dawley (n=18) rats, the intensities of EAS were 0.5, 1, 3, 5, 7, and 9 mA, respectively. For mice (n=8in each group), only 1 mA was used, by which C fiber of the mice can be activated. Gastric antrum motility was measured by intrapyloric balloon. Gastric motility was facilitated by EAS at ST36 and inhibited by EAS at CV12. The half maximal facilitation intensity of EAS at ST36 was 2.1–2.3 mA, and the half maximal inhibitory intensity of EAS at CV12 was 2.8 mA. In comparison with C57BL/6 mice, the facilitatory effect of ST36 and inhibitive effect of CV12 in ASIC3−/− mice decreased, but the difference was not statistically significant (P>0.05). However, these effects in TRPV1−/− mice decreased significantly (P<0.001). The results indicated that there existed an “intensity-response” relationship between EAS and the effect of gastric motility. TRPV1 receptor was involved in the regulation of gastric motility of EAS.

scholarly journals Combination of subtherapeutic anti-TNF dose with dasatinib restores clinical and molecular arthritogenic profiles better than standard anti-TNF treatment

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lydia Ntari ◽  
Christoforos Nikolaou ◽  
Ksanthi Kranidioti ◽  
Dimitra Papadopoulou ◽  
Eleni Christodoulou-Vafeiadou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Therapeutic Effect ◽  
Expression Analysis ◽  
Mode Of Action ◽  
Gene Expression Analysis ◽  
Kinase Inhibitors ◽  
High Dose ◽  
Dependent Manner ◽  
Combination Therapies ◽  
Number Of Patients

Abstract Background New medications for Rheumatoid Arthritis (RA) have emerged in the last decades, including Disease Modifying Antirheumatic Drugs (DMARDs) and biologics. However, there is no known cure, since a significant proportion of patients remain or become non-responders to current therapies. The development of new mode-of-action treatment schemes involving combination therapies could prove successful for the treatment of a greater number of RA patients. Methods We investigated the effect of the Tyrosine Kinase inhibitors (TKIs) dasatinib and bosutinib, on the human TNF-dependent Tg197 arthritis mouse model. The inhibitors were administered either as a monotherapy or in combination with a subtherapeutic dose of anti-hTNF biologics and their therapeutic effect was assessed clinically, histopathologically as well as via gene expression analysis and was compared to that of an efficient TNF monotherapy. Results Dasatinib and, to a lesser extent, bosutinib inhibited the production of TNF and proinflammatory chemokines from arthritogenic synovial fibroblasts. Dasatinib, but not bosutinib, also ameliorated significantly and in a dose-dependent manner both the clinical and histopathological signs of Tg197 arthritis. Combination of dasatinib with a subtherapeutic dose of anti-hTNF biologic agents, resulted in a synergistic inhibitory effect abolishing all arthritis symptoms. Gene expression analysis of whole joint tissue of Tg197 mice revealed that the combination of dasatinib with a low subtherapeutic dose of Infliximab most efficiently restores the pathogenic gene expression profile to that of the healthy state compared to either treatment administered as a monotherapy. Conclusion Our findings show that dasatinib exhibits a therapeutic effect in TNF-driven arthritis and can act in synergy with a subtherapeutic anti-hTNF dose to effectively treat the clinical and histopathological signs of the pathology. The combination of dasatinib and anti-hTNF exhibits a distinct mode of action in restoring the arthritogenic gene signature to that of a healthy profile. Potential clinical applications of combination therapies with kinase inhibitors and anti-TNF agents may provide an interesting alternative to high-dose anti-hTNF monotherapy and increase the number of patients responding to treatment.

scholarly journals Antimicrobial Peptide Modifications against Clinically Isolated Antibiotic-Resistant Salmonella

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4654
Author(s):  
Suthee Mangmee ◽  
Onrapak Reamtong ◽  
Thareerat Kalambaheti ◽  
Sittiruk Roytrakul ◽  
Piengchan Sonthayanon
Keyword(s):  
Antibacterial Activity ◽  
Hemolytic Activity ◽  
Multidrug Resistant ◽  
Terminal Group ◽  
Scorpion Venom ◽  
Antibiofilm Activity ◽  
Peptide Antibiotic ◽  
Dependent Manner ◽  
C Terminus ◽  
Relationship Of

Antimicrobial peptides are promising molecules to address the global antibiotic resistance problem, however, optimization to achieve favorable potency and safety is required. Here, a peptide-template modification approach was employed to design physicochemical variants based on net charge, hydrophobicity, enantiomer, and terminal group. All variants of the scorpion venom peptide BmKn-2 with amphipathic α-helical cationic structure exhibited an increased antibacterial potency when evaluated against multidrug-resistant Salmonella isolates at a MIC range of 4–8 µM. They revealed antibiofilm activity in a dose-dependent manner. Sheep red blood cells were used to evaluate hemolytic and cell selectivity properties. Peptide Kn2-5R-NH2, dKn2-5R-NH2, and 2F-Kn2-5R-NH2 (variants with +6 charges carrying amidated C-terminus) showed stronger antibacterial activity than Kn2-5R (a variant with +5 charges bearing free-carboxyl group at C-terminus). Peptide dKn2-5R-NH2 (d-enantiomer) exhibited slightly weaker antibacterial activity with much less hemolytic activity (higher hemolytic concentration 50) than Kn2-5R-NH2 (l-enantiomer). Furthermore, peptide Kn2-5R with the least hydrophobicity had the lowest hemolytic activity and showed the highest specificity to Salmonella (the highest selectivity index). This study also explained the relationship of peptide physicochemical properties and bioactivities that would fulfill and accelerate progress in peptide antibiotic research and development.

Excitatory postsynaptic potentials recorded from regular-spiking cells in layers II/III of rat sensorimotor cortex

1992 ◽  
Vol 67 (3) ◽  
pp. 728-737 ◽  
Author(s):  
G. G. Hwa ◽  
M. Avoli
Keyword(s):  
Nmda Receptor Antagonist ◽  
Short Latency ◽  
Neuronal Membrane ◽  
Dependent Manner ◽  
Excitatory Postsynaptic Potentials ◽  
Normal Medium ◽  
Postsynaptic Potentials ◽  
Extracellular Stimuli ◽  
Relationship Of

1. Intracellular recording techniques were used to investigate the physiological and pharmacological properties of stimulus-induced excitatory postsynaptic potentials (EPSPs) recorded in regular-spiking cells located in layers II/III of rat sensorimotor cortical slices maintained in vitro. 2. Depending on the strength of the extracellular stimuli, a pure EPSP or an EPSP-inhibitory postsynaptic potential sequence was observed under perfusion with normal medium. The EPSPs displayed short latency of onset [2.4 +/- 0.7 (SD) ms] and were able to follow repetitive stimulation (tested less than or equal to 5 Hz). Variation of the membrane potential (Vm) revealed two types of voltage behavior for the short-latency EPSP. The first type decreased in amplitude with depolarization and increased in amplitude with hyperpolarization. In contrast, the second type behaved anomalously by increasing and decreasing in size after depolarization and hyperpolarization, respectively. 3. Several experimental procedures were carried out to investigate the mechanism underlying the anomalous voltage behavior of the EPSP. Results indicated that this type of Vm dependency could be mimicked by an intrinsic response evoked by a brief pulse of depolarizing current and could be abolished by N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (50 mM). Furthermore, the EPSP was not sensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP, 10 microM). Thus the anomalous voltage relationship of the neuronal membrane. 4. The involvement of non-NMDA receptors in excitatory synaptic transmission was investigated with their selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1-10 microM). This drug greatly reduced or completely blocked the EPSP in a dose-dependent manner (1-10 microM). The IC50 for the CNQX effect was approximately 2 microM. In the presence of CNQX (10 microM) and glycine (10 microM), synaptic stimulation failed to elicit firing of action potential. However, a CPP-sensitive EPSP was observed. 5. When synaptic inhibition was reduced by low concentration of bicuculline methiodide (BMI, 1-2 microM), extracellular stimulation revealed late EPSPs (latency to onset: 10-30 ms) that were not discernible in normal medium. Similar to the short-latency EPSP, the Vm dependency displayed by this late EPSP could be modified by inward membrane rectifications. The late EPSP appeared to be polysynaptic in origin because 1) its latency of onset was long and variable and 2) it failed to follow repetitive stimuli delivered at a frequency that did not depress the short-latency EPSP.(ABSTRACT TRUNCATED AT 400 WORDS)

Underestimation of Dose - Response Relationship with Particular Reference to the Relationship between the Dietary Intake of Mercury and its Concentration in Blood

1988 ◽  
Vol 7 (2) ◽  
pp. 129-132 ◽  
Author(s):  
J.C. Sherlock ◽  
M.J. Quinn
Keyword(s):  
Linear Regression ◽  
Dietary Intake ◽  
Dose Response ◽  
Mercury Concentration ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Blood Mercury ◽  
Relationship Of ◽  
The Relationship ◽  
Blood Mercury Concentration

Wide discrepancies have been observed between controlled and uncontrolled intake studies of the relationship of blood mercury concentration to intake of mercury. The probable reason for the apparent discrepancies is that the within-subject variation of mercury intake in the uncontrolled studies was almost certainly considerably larger than the within-subject variation in blood mercury concentration; in these circumstances, the apparent slope obtained from a linear regression of blood mercury on intake will invariably be much smaller than the true slope. Studies of the exposure or intake of any substance should therefore include a consideration of the likely within-subject variation in the exposure or intake relative to that in the effect.

A model analysis for dose–response relationship of warfarin in Japanese children: An introduction of the SIZE parameter

2016 ◽  
Vol 31 (3) ◽  
pp. 234-241 ◽  
Author(s):  
Saki Nakamura ◽  
Nao Watanabe ◽  
Naoki Yoshimura ◽  
Sayaka Ozawa ◽  
Keiichi Hirono ◽  
...  
Keyword(s):  
Dose Response ◽  
Model Analysis ◽  
Response Relationship ◽  
Size Parameter ◽  
Dose Response Relationship ◽  
Japanese Children ◽  
Relationship Of
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