scholarly journals The vasodilatory mechanism of nitric oxide and hydrogen sulfide in human mesenteric artery of colorectal cancer patients: role of potassium channels

2019 ◽  
Author(s):  
Awat Y. Hassan ◽  
Ismail M. Maulood ◽  
Abbas Salihi
Keyword(s):  
Cancer Progression ◽  
Mesenteric Artery ◽  
Serum Levels ◽  
Mesenteric Arteries ◽  
Relaxation Rates ◽  
Time Intervals ◽  
Vasodilator Activity ◽  
Colorectal Cancer Patients ◽  
And Oxidative Stress

AbstractRecent studies focused on the role of gasotransmitters in cancer progression and prevention. Therefore, this study was designed to explore the vasodilator activity of NO and H2S in human mesenteric artery of CRC patients via activation of K+ channels. For this purpose, two sets of experiments were established. The blood samples from CRC patients were obtained to detect serum levels of Endocan and MDA. Moreover, the role of K+ channels were assessed in mediating vasodilation of human mesenteric artery in response to SNP and Na2S. The level of serum Endocan was decreased in CRC patients compared to healthy individuals, while serum MDA was not changed. The arterial rings precontracted with NE were first relaxed by cumulative addition of increasing concentrations of either SNP (30nM-30μM) or Na2S (1-6mM). Then maximal relaxation rates were calculated for four times at each 15min intervals. Preincubation of arterial rings for 20min with individual K+ channels blockers were significantly reduced relaxation caused by SNP and Na2S at different time intervals. Furthermore, pretreatment of L-NAME did not change the vasodilation induced by Na2S. Vasodilation of CRC mesenteric unchanged by synergistic application of SNP and Na2S. While preincubation of arterial rings with PAG significantly enhanced vasodilation induced by SNP. In conclusion, these results indicate that endothelial dysfunction and oxidative stress do not take part in the pathogenesis of CRC. The dilatory mechanisms of NO and H2S in mesenteric arteries of CRC patients are K+ channels and time dependent, and the activity of CSE enzyme slows down the vasodilator ability of exogenous NO.

Modulatory role of a constitutively active population of α1D-adrenoceptors in conductance arteries

2002 ◽  
Vol 282 (2) ◽  
pp. H475-H481 ◽  
Author(s):  
Khalid Ziani ◽  
Regina Gisbert ◽  
Maria Antonia Noguera ◽  
Maria Dolores Ivorra ◽  
Pilar D'Ocon
Keyword(s):  
Mesenteric Artery ◽  
Functional Role ◽  
Mesenteric Arteries ◽  
The Other ◽  
Active Population ◽  
Abrupt Changes ◽  
Resting Tone ◽  
Constitutively Active

A constitutively active population of α1D-adrenoceptors in iliac and proximal, distal, and small mesenteric rat arteries was studied. The increase in resting tone (IRT) that evidences it was observed only in iliac and proximal mesenteric and was inhibited by prazosin (pIC50 = 9.57), 5-methylurapidil (pIC50 = 7.61), and BMY 7378 (pIC50 = 8.77). Chloroethylchlonidine (100 μmol/l) did not affect IRT, but when added before the other antagonists it blocked their effect. The potency shown by BMY 7378 confirms the α1D-subtype as responsible for IRT. BMY 7378 displayed greater inhibition of adrenergic responses in iliac (pIC50 = 7.57 ± 0.11) and proximal mesenteric arteries (pIC50 = 8.05 ± 0.2) than in distal (pIC50 = 6.94 ± 0.13) or small mesenteric arteries (pIC50 = 6.30 ± 0.14), which confirms the functional role of the α1D-adrenoceptor in iliac and proximal mesenteric arteries. This subtype prevents abrupt changes in iliac and proximal mesenteric artery caliber when the agonist disappears, and this modulatory role is evidenced by the slower decay in the response to norepinephrine after removal.

Correlation between mRNA levels and functional role of α1-adrenoceptor subtypes in arteries: evidence of α1L as a functional isoform of the α1A-adrenoceptor

2005 ◽  
Vol 289 (5) ◽  
pp. H1923-H1932 ◽  
Author(s):  
Daniel Martí ◽  
Raquel Miquel ◽  
Khalid Ziani ◽  
Regina Gisbert ◽  
M. Dolores Ivorra ◽  
...  
Keyword(s):  
Mesenteric Artery ◽  
Mesenteric Arteries ◽  
Main Role ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Response Curves ◽  
Inhibitory Potency ◽  
Adrenoceptor Antagonist ◽  
Relevant Role

The mRNA levels for the three α1-adrenoceptor subtypes, α1A, α1B, and α1D, were quantified by real-time RT-PCR in arteries from Wistar rats. The α1D-adrenoceptor was prominent in both aorta (79.0%) and mesenteric artery (68.7%), α1A predominated in tail (61.7%) and small mesenteric artery (73.3%), and both α1A- and α1D-subtypes were expressed at similar levels in iliac artery. The mRNA levels of the α1B-subtype were a minority in all vessels (1.7–11.1%). Concentration-response curves of contraction in response to phenylephrine or relaxation in response to α1-adrenoceptor antagonists on maximal sustained contraction induced by phenylephrine were constructed from control vessels and vessels pretreated with 100 μmol/l chloroethylclonidine (CEC) for 30 min. The significant decrease in the phenylephrine potency observed after CEC treatment together with the inhibitory potency displayed by 8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-8-azaspiro ( 4 , 5 ) decane-7-dionedihydrochloride} (BMY-7378, an α1D-adrenoceptor antagonist) confirm the relevant role of α1D-adrenoceptors in aorta and iliac and proximal mesenteric arteries. The potency of 5-methylurapidil (an α1A-adrenoceptor antagonist) and the changes in the potency of both BMY-7378 and 5-methylurapidil after CEC treatment provided evidence of a mixed population of α1A- and α1D-adrenoceptors in iliac and distal mesenteric arteries. The low potency of prazosin (pIC50 < 9) as well as the high 5-methylurapidil potency in tail and small mesenteric arteries suggest the main role of α1A/α1L-adrenoceptors with minor participation of the α1D-subtype. The mRNA levels and CEC treatment corroborated this pattern and confirmed that the α1L-adrenoceptor could be a functional isoform of the α1A-subtype.

LDH serum levels as a predictive factor for global outcome in pretreated colorectal cancer patients receiving regorafenib: Implications for clinical management.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 497-497 ◽  
Author(s):  
Michela Del Prete ◽  
Mario Scartozzi ◽  
Tiziana Prochilo ◽  
Luca Faloppi ◽  
Riccardo Giampieri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Roc Curve Analysis ◽  
Group A ◽  
Group B ◽  
Colorectal Cancer Patients

497 Background: Although a demonstrated clinical efficacy, a non negligible proportion of colorectal cancer patients does not seem to benefit from regorafenib and are consequently exposed to unnecessary toxicity. LDH serum levels represent an indirect marker of tumour hypoxia, neo-angiogenesis and worse prognosis in many tumour types. In colorectal cancer LDH showed a correlation with treatment outcome for patients receiving antiangiogenetic treatment, thus suggesting a possible interaction with the activity profile of these drugs. We analyzed the role of LDH serum levels in predicting clinical outcome for pre-treated metastatic colorectal cancer patients receiving regorafenib. The final aim was to individuate a potentially reliable and easy to use marker for patients stratification. Methods: 118 colorectal cancer patients treated with regorafenib were available for our analysis. For all patients, LDH values were collected within one month before the procedure and after treatment end. LDH cutoff value was determined by ROC curve analysis, patients were then divided into two groups (A and B, below and above cut-off level respectively). Patients were also classified according to the variation in LDH serum levels pre- and post-treatment (increased patients vs. decreased patients). Results: Patients in group A and B proved homogeneous for all clinical characteristics analyzed. In group A patients median progression free survival (PFS) was 3.18 months, whereas it was 1.87 months in group B patients (p = 0.0018). Median overall survival (OS) was 6.23 months and 3.28 months in group A and B respectively (p = 0.048). Significant differences were not noted among the 2 groups for response rate. All the other clinical variables analyzed failed to show any correlation with patients outcome. Conclusions: Our observations seem to suggest a role of LDH as a marker of clinical outcome in colorectal cancer patients receiving regorafenib. We can then speculate that high LDH patients may not be optimal candidates for regorafenib. After further confirmation in larger trial, these findings may be relevant for a better patients stratification and selection.

scholarly journals Adamalysines as Biomarkers and a Potential Target of Therapy in Colorectal Cancer Patients: Preliminary Results

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Katarzyna Walkiewicz ◽  
Joanna Strzelczyk ◽  
Dariusz Waniczek ◽  
Krzysztof Biernacki ◽  
Małgorzata Muc-Wierzgoń ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Distant Metastases ◽  
Serum Levels ◽  
Control Group ◽  
Colorectal Cancer Patients ◽  
And Control ◽  
The Relationship ◽  
Increased Activity

Colorectal cancer is one of the most common cancers in the world. Due to its still undetermined pathogenesis, we are searching for signaling pathways that are important in the development of colorectal cancer. In this article, we present results of study on the role of ADAM proteins in colorectal cancer. The study included 85 adult colorectal cancer patients (48 men, 37 women) and 25 patients in the control group (after diagnostic colonoscopy—without cancer). During hospitalization, a serum sample (3 cm3) was collected from the study and control group, anthropometric measurements were conducted and others clinical data were analyzed. In the serum ADAM10, 12, 17, and 28, protein concentrations were determined and, in the next step, examined the relationship between ADAMs concentrations and selected clinical parameters in both groups. The analysis showed that serum levels of ADAM10 and ADAM28 are significantly higher in patients with colorectal cancer and correlate with histopathological grading and with presence of distant metastases. Moreover, noticed the trend to correlate concentrations of adamalysines with higher BMI score. One of the functions of adamalysines is the activation of growth factors involved in cancer, including IGF and TNFα. The increased activity of adamalysines in patients may play a role in the pathogenesis of colorectal cancer. Our study highlights the prevalence of metabolic disorders in the group of patients with diagnosed CRC, and this cancer seems to be a further complication of obesity.

scholarly journals The Role of Vascular Endothelial Growth Factorin Thrombocytosis in Colorectal Cancer Patients

2018 ◽  
Vol 2 (2) ◽  
pp. 1-7
Author(s):  
Subandrate Subandrate ◽  
Dwi Indira Setyorini ◽  
Mediarty Mediarty ◽  
Irsan Saleh
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Research Subjects ◽  
Elisa Technique ◽  
Average Serum ◽  
Colorectal Cancer Patients ◽  
Endothelial Growth Factor

Backgorund: Colorectal cancer was included in a group of cancer with various complications. One complication that was often a cause of morbidity and mortality was thrombocytosis. In colorectal cancer, the incidence of thrombocytosis associated with the formation of blood vessels around the tumor or angiogenesis. Factors that played an important role in angiogenesis was vascular endothelial growth factor (VEGF). Methods: This study was an observational analytic research in colorectal cancer patients to determine the correlation levels of platelets and serum VEGF levels. A total of 33 patients with colorectal cancer at the Palembang Mohammad Hoesin Hospital be research subjects to examine the levels of platelets and levels of VEGF. The level of serum VEGF was performed using ELISA technique from SIGMA®. Results: The average level of the patient's platelets was281,090.9±105,860.8/mm3.  In this study, two patients (6.06%) have thrombocytosis.The average serum levels of VEGF research subjects were 221.2 ± 152.8 pg/mL.Correlation test of levels of serum VEGF and platelets levels showed the value of p=0.040 (p> 0.05) and r = 0468. Conclusions: Thus, it can be concluded that in this research serum VEGF levels are almost always causes an increase in platelet levels in patients with colorectal cancer.

scholarly journals The Relationship between the Soluble Receptor for Advanced Glycation End Products and Oxidative Stress in Patients with Palmoplantar Warts

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 706 ◽  
Author(s):  
Cristina Iulia Mitran ◽  
Ilinca Nicolae ◽  
Mircea Tampa ◽  
Madalina Irina Mitran ◽  
Constantin Caruntu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Serum Levels ◽  
Soluble Receptor ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
The Relationship ◽  
And Oxidative Stress ◽  
Inflammation Parameters

Background and objectives: Warts are the most common lesions caused by human papillomavirus (HPV). Recent research suggests that oxidative stress and inflammation are involved in the pathogenesis of HPV-related lesions. It has been shown that the soluble receptor for advanced glycation end products (sRAGE) may act as a protective factor against the deleterious effects of inflammation and oxidative stress, two interconnected processes. However, in HPV infection, the role of sRAGE, constitutively expressed in the skin, has not been investigated in previous studies. Materials and Methods: In order to analyze the role of sRAGE in warts, we investigated the link between sRAGE and the inflammatory response on one hand, and the relationship between sRAGE and the total oxidant/antioxidant status (TOS/TAS) on the other hand, in both patients with palmoplantar warts (n = 24) and healthy subjects as controls (n = 28). Results: Compared to the control group, our results showed that patients with warts had lower levels of sRAGE (1036.50 ± 207.60 pg/mL vs. 1215.32 ± 266.12 pg/mL, p < 0.05), higher serum levels of TOS (3.17 ± 0.27 vs. 2.93 ± 0.22 µmol H2O2 Eq/L, p < 0.01), lower serum levels of TAS (1.85 ± 0.12 vs. 2.03 ± 0.14 µmol Trolox Eq/L, p < 0.01) and minor variations of the inflammation parameters (high sensitivity-CRP, interleukin-6, fibrinogen, and erythrocyte sedimentation rate). Moreover, in patients with warts, sRAGE positively correlated with TAS (r = 0.43, p < 0.05), negatively correlated with TOS (r = −0.90, p < 0.01), and there was no significant correlation with inflammation parameters. There were no significant differences regarding the studied parameters between groups when we stratified the patients according to the number of the lesions and disease duration. Conclusions: Our results suggest that sRAGE acts as a negative regulator of oxidative stress and could represent a mediator involved in the development of warts. However, we consider that the level of sRAGE cannot be used as a biomarker for the severity of warts. To the best of our knowledge, this is the first study to demonstrate that sRAGE could be involved in HPV pathogenesis and represent a marker of oxidative stress in patients with warts.

Alterations in EDHF-type relaxation and phosphodiesterase activity in mesenteric arteries from diabetic rats

2003 ◽  
Vol 285 (1) ◽  
pp. H283-H291 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Tsuneo Kobayashi ◽  
Katsuo Kamata
Keyword(s):  
Gap Junctions ◽  
Superior Mesenteric Artery ◽  
Mesenteric Artery ◽  
Matched Control ◽  
Diabetic Rats ◽  
Selective Inhibitor ◽  
Mesenteric Arteries ◽  
Phosphodiesterase Activity ◽  
Camp Phosphodiesterase

In isolated superior mesenteric artery rings from age-matched control rats and streptozotocin (STZ)-induced diabetic rats, we investigated the role of cAMP in endothelium-derived hyperpolarizing factor (EDHF)-type relaxation. The ACh-induced EDHF-type relaxation was significantly weaker in STZ-induced diabetic rats than in control rats, and in both groups of rats it was attenuated by 18α-glycyrrhetinic acid (18α-GA), an inhibitor of gap junctions, and enhanced by IBMX, a cAMP-phosphodiesterase (PDE) inhibitor. These enhanced EDHF-type responses were very similar in magnitude between diabetic and age-matched control rats. The EDHF-type relaxation was enhanced by cilostamide, a PDE3-selective inhibitor, but not by Ro 20–1724, a PDE4-selective inhibitor. The expression levels of the mRNAs and proteins for two cAMP PDEs (PDE3A, PDE3B) were significantly increased in STZ-induced diabetic rats, but those for PDE4D were not. We conclude that the impairment of EDHF-type relaxations in STZ-induced diabetic rats may be attributed to a reduction in the action of cAMP via increased PDE activity.

scholarly journals Evaluation of Apelin and Apelin Receptor Level in the Primary Tumor and Serum of Colorectal Cancer Patients

2019 ◽  
Vol 8 (10) ◽  
pp. 1513 ◽  
Author(s):  
Podgórska ◽  
Diakowska ◽  
Pietraszek-Gremplewicz ◽  
Nienartowicz ◽  
Nowak
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Serum Levels ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Protein Levels ◽  
Mrna And Protein Expression ◽  
Apelin Receptor ◽  
Colorectal Cancer Patients ◽  
The Relationship

Colorectal cancer is the second deadliest tumor, which has a positive correlation with obesity which led to increasing interest in the relationship between adipokines and cancer progression. Apelin is a secreted peptide involved in regulation of tumor progression and invasiveness. In this study, we examined apelin and apelin receptor expression level in colorectal cancer. Apelin, and its receptor mRNA, and protein expression levels were measured in tumor tissue of 56 surgically treated colorectal adenocarcinoma (CRC) patients. We also analyzed apelin and apelin receptor protein levels in sera of 56 CRC patients and 27 healthy controls. The mRNA and protein level of this peptide and its receptor was higher in tumors than that in control tissue. Serum levels of apelin and apelin receptor were increased in CRC patients in comparison to controls. The concentration of serum apelin level significantly increased in individuals with lymph node and distant metastasis. Obtained results suggest that apelin could be an important factor in progression of colorectal carcinoma.

Chewing and taste increase blood velocity in the celiac but not the superior mesenteric arteries

2008 ◽  
Vol 295 (6) ◽  
pp. R1921-R1925 ◽  
Author(s):  
Nami Someya ◽  
Naoyuki Hayashi
Keyword(s):  
Blood Flow ◽  
Superior Mesenteric Artery ◽  
Mesenteric Artery ◽  
Healthy Subjects ◽  
Celiac Artery ◽  
Blood Velocity ◽  
Mesenteric Arteries ◽  
Baseline Measurement ◽  
The Mean

To investigate the role of chewing and taste in the meal-induced rapid increase in splanchnic blood flow, we compared the blood flow responses in the celiac artery (CA) and superior mesenteric artery (SMA) to chewing solid food with a chocolate taste (FOOD) and paraffin wax without taste (WAX). After 5 min of baseline measurement, 15 healthy subjects repeated chewing and expectorating the FOOD or WAX every 20 s for 4 min followed by 10 min of recovery measurement. We measured the mean blood velocity (MBV) in the CA and SMA. The baseline MBVs in the CA and SMA did not differ between the FOOD and WAX trials. The MBV in the CA was lower than baseline at the 1st min of chewing in both trials. It was higher than baseline at the 3rd min of FOOD chewing, whereas it did not increase during and after WAX chewing. The MBV in the CA was higher in the FOOD trial than in the WAX trial at the 3rd min of chewing and thereafter. In contrast, the MBV in the SMA did not change throughout the protocols. These results suggest that the taste of food plays a role in meal-induced hyperemia in the CA but not the SMA.

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