Part II: Biochemical changes after pituitary adenylate cyclase-activating polypeptide-38 infusion in migraine patients

Cephalalgia ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 136-147 ◽  
Author(s):  
Song Guo ◽  
Anne Luise Haulund Vollesen ◽  
Young Bae Lee Hansen ◽  
Erik Frandsen ◽  
Malene Rohr Andersen ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Plasma Levels ◽  
Intravenous Infusion ◽  
Plasma Concentrations ◽  
Pituitary Hormones ◽  
Control Group ◽  
Gene Variant ◽  
Biochemical Variables ◽  
Increased Risk ◽  
Pituitary Adenylate Cyclase

Background Intravenous infusion of pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine attacks in 65–70% of migraine without aura (MO) patients. We investigated whether PACAP38 infusion causes changes in the endogenous production of PACAP38, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), tumour necrosis factor alpha (TNFα), S100 calcium binding protein B (S100B), neuron-specific enolase and pituitary hormones in migraine patients. Methods We allocated 32 previously genotyped MO patients to receive intravenous infusion PACAP38 (10 pmol/kg/minute) for 20 minutes and recorded migraine-like attacks. Sixteen of the patients were carriers of the risk allele rs2274316 ( MEF2D), which confers increased risk of MO and may regulate PACAP38 expression, and 16 were non-carriers. We collected blood samples at baseline and 20, 30, 40, 60 and 90 minutes after the start of the infusion. A control group of six healthy volunteers received intravenous saline. Results PACAP38 infusion caused significant changes in plasma concentrations of VIP ( p = 0.026), prolactin ( p = 0.011), S100B ( p < 0.001) and thyroid-stimulating hormone (TSH; p = 0.015), but not CGRP ( p = 0.642) and TNFα ( p = 0.535). We found no difference in measured biochemical variables after PACAP38 infusion in patients who later developed migraine-like attacks compared to those who did not ( p > 0.05). There was no difference in the changes of biochemical variables between patients with and without the MEF2D-associated gene variant ( p > 0.05). Conclusion PACAP38 infusion elevated the plasma levels of VIP, prolactin, S100B and TSH, but not CGRP and TNFα. Development of delayed migraine-like attacks or the presence of the MEF2D gene variant was not associated with pre-ictal changes in plasma levels of neuropeptides, TNFα and pituitary hormones.

Part I: Pituitary adenylate cyclase-activating polypeptide-38 induced migraine-like attacks in patients with and without familial aggregation of migraine

Cephalalgia ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 125-135 ◽  
Author(s):  
Song Guo ◽  
Anne Luise Haulund Vollesen ◽  
Rikke Dyhr Hansen ◽  
Ann-Louise Esserlind ◽  
Faisal Mohammed Amin ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Intravenous Infusion ◽  
Migraine Without Aura ◽  
Risk Allele ◽  
Familial Aggregation ◽  
Induced Response ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Pituitary Adenylate Cyclase ◽  
To Receive

Background Intravenous infusion of adenylate cyclase-activating polypeptide-38 (PACAP38) provokes migraine-like attacks in 65–70% of migraine sufferers. Whether aggregation of migraine in first-degree relatives contributes to this discrepancy in PACAP38-induced response is unknown. We hypothesized that genetic enrichment plays a role in triggering of migraine and that migraine without aura patients with a high family load ( ≥ 2 first-degree relatives with migraine) would report more migraine-like attacks after intravenous infusion of human PACAP38. Methods In this study, we allocated 32 previously genotyped migraine without aura patients to receive intravenous infusion of 10 pmol/kg/min PACAP38 and recorded migraine-like attacks including headache characteristics and associated symptoms. Information of familial aggregation was obtained by telephone interview of first-degree relatives using a validated semi-structured questionnaire. Results PACAP38 infusion induced a migraine-like attack in 75% (nine out of 12) of patients with high family load compared to 70% (14 out of 20) with low family load ( P = 0.761). In an explorative investigation, we found that the migraine response after PACAP38 was not associated with the risk allele of rs2274316 ( MEF2D), which confers increased risk of migraine without aura and may regulate PACAP38 expression. Conclusion Migraine response to PACAP38 infusion in migraine without aura patients is not associated with high family load or the risk allele of rs2274316 ( MEF2D).

scholarly journals Stress-related disorders, pituitary adenylate cyclase—activating peptide (PACAP)ergic system, and sex differences

2016 ◽  
Vol 18 (4) ◽  
pp. 403-413 ◽  
Keyword(s):  
Sex Differences ◽  
Stress Response ◽  
Adenylate Cyclase ◽  
Messenger Rna ◽  
Human Subjects ◽  
Psychological Trauma ◽  
Blood Levels ◽  
Increased Risk ◽  
Pituitary Adenylate Cyclase ◽  
Specific Association

Trauma-related disorders, such as posttraumatic stress disorder (PTSD) are remarkably common and debilitating, and are often characterized by dysregulated threat responses. Across numerous epidemiological studies, females have been found to have an approximately twofold increased risk for PTSD and other stress-related disorders. Understanding the biological mechanisms of this differential risk is of critical importance. Recent data suggest that the pituitary adenylate cyclase-activating polypeptide (PACAP) pathway is a critical regulator of the stress response across species. Moreover, increasing evidence suggests that this pathway is regulated by both stress and estrogen modulation and may provide an important window into understanding mechanisms of sex differences in the stress response. We have recently shown that PACAP and its receptor (PAC1R) are critical mediators of abnormal processes after psychological trauma. Notably, in heavily traumatized human subjects, there appears to be a robust sex-specific association of PACAP blood levels and PAC1R gene variants with fear physiology, PTSD diagnosis, and symptoms, specifically in females. The sex-specific association occurs within a single-nucleotide polymorphism (rs2267735) that resides in a putative estrogen response element involved in PAC1R gene regulation. Complementing these human data, the PAC1R messenger RNA is induced with fear conditioning or estrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1R pathway are regulated by estrogen and are involved in abnormal fear responses underlying PTSD.

scholarly journals Plasma Concentrations of Matrilysins MMP-7 and MMP-26 as Diagnostic Biomarkers in Breast Cancer

2021 ◽  
Vol 10 (7) ◽  
pp. 1436
Author(s):  
Barbara Maria Piskór ◽  
Andrzej Przylipiak ◽  
Emilia Dąbrowska ◽  
Iwona Sidorkiewicz ◽  
Marek Niczyporuk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Plasma Levels ◽  
Proteolytic Enzymes ◽  
Plasma Concentrations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Diagnostic Utility ◽  
Study Results ◽  
Advanced Stages ◽  
Disease Study

Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are members of the MMPs group that show promise as potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the diagnostic utility of studied matrilysins in patients with BC. The study group consisted of 120 patients with BC, and the control group consisted of 40 subjects with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by enzyme-linked immunosorbent assay, and CA 15-3 by chemiluminescent microparticle immunoassay. Plasma levels of MMP-7 were significantly higher in the BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were highest in stages II and IV of the disease. The highest diagnostic sensitivity was observed in stages III and IV BC for the combination of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters combined in the BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) for the combination of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in stages III and IV. Individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of the disease. Study results indicate that MMP-7 could be used as an additional marker that would improve the diagnostic utility of CA 15-3 in early stages of BC. Therefore, the combined assessment of MMP-7 and MMP-26 with CA 15-3 might be useful in determining disease progression. Further studies are needed to evaluate whether matrilysins show promise as potential markers for improving the diagnosis of BC.

Imatinib Plasma Levels and Its Correlation with Response in Chronic-Phase Chronic Myeloid Leukemia: Experience of One Centre.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4284-4284
Author(s):  
J. Valentin Garcia. Gutierrez ◽  
Jesús Odriozola ◽  
Pilar Herrera ◽  
Javier Lopez ◽  
Maria Calbacho ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Plasma Levels ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Plasma Concentrations ◽  
Chronic Phase ◽  
Control Group ◽  
Treatment Optimisation ◽  
Number Of Patients

Abstract Abstract 4284 Introduction Imatinib (IM), 400 mg/d. induces durable responses in chronic myeloid leukaemia (CML) in chronic phase (CP). However, although IM-biodisponibility is fairly good, its plasma levels are variable and can not be predicted. Recently, these plasma concentrations have been related both to the dose being administrated and to the cytogenetic and molecular responses. Thus, Imatinib pharmacokinetics could be an issue towards treatment optimisation in CML patients. Recent studies suggest that therapeutic IM plasma levels should be above 1040 ng/dl. Aims To evaluate the association between IM dose and throughout plasma levels with different clinical outcomes. Results In this study, we looked for an association between plasma concentrations and clinical outcomes in 16/86 CML chronic phase patients who did not achieve optimal responses following the European Leukemia Net guidelines (ELN) (table 1). Patients with optimal responses and treated with the same standard doses were also analysed as a control group. Patients receiving doses above 400 mg showed throughout plasma levels considered as appropriate. In 7 of 16 patients (47.5%) not achieving optimal responses (ELN criteria), plasma levels were below the supposed therapeutic ranges. We have found no evidence for a correlation between clinical risk factors at diagnosis and the measurement of optimal plasma levels. Conclusions IM plasma levels are well correlated with IM dose administrated in the patients studied. In almost 50% of patients who did not achieve optimal responses, IM plasma levels were under the ranges considered therapeutic. Probably these are the patients who may benefit of a dose increase. Obviously, to learn more about the practical value of these measurements a longer follow up with a larger number of patients is needed. Disclosures: No relevant conflicts of interest to declare.

Circulating Microparticles and Risk of Venous Thromboembolism.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3987-3987
Author(s):  
Paolo Bucciarelli ◽  
Emanuele Previtali ◽  
Ida Martinelli ◽  
Andrea Artoni ◽  
Serena M Passamonti ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Venous Thromboembolism ◽  
Body Mass ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Factor V Leiden ◽  
Control Group ◽  
Dependent Manner ◽  
Healthy Controls ◽  
Increased Risk

Abstract Abstract 3987 Poster Board III-923 Background Microparticles (MPs) are circulating, submicroscopic fragments (<1 μm of diameter) of membrane-bound cytoplasm that shed from the surface of an activated or apoptotic cell and play a role in coagulation, inflammation, cell remodelling and proliferation. There is increasing evidence that MPs are involved in thrombosis, but whether or not they are an independent risk factor for venous thromboembolism (VTE) is not established. Aim of the study To investigate the association between high plasma levels of MPs and risk of VTE Patients and Methods In a case-control study, 186 patients with a first episode of VTE (deep venous thrombosis and/or pulmonary embolism) and 418 healthy controls were included. MPs were analyzed by flow cytometry with a gate defined by a 1 μm beads and using APC-Annexin V together with FITC anti-CD41 or FITC anti-CD142 antibodies in order to identify platelet MPs (MP-Plts) and MPs exposing tissue factor (MP-TF), respectively. MPs levels were expressed as number/μL. Results Patients had significantly higher median plasma levels of both MPs-Plts and MPs-TF than controls [1942 vs 1519 (p<0.0001) and 579 vs 454 (p<0.0001)]. Higher median levels of MP-Plts and MP-TF were found in 41 patients who underwent blood sampling within 6 months from VTE than in those sampled later [2114 vs 1694 (p=0.086) and 652 vs 543 (p=0.120)]. Sex, age, body mass index and factor VIII plasma levels had no influence on MPs levels, as well as the use of oral contraceptives (this latter evaluated only in controls). In the whole study population, carriership of thrombophilia (antithrombin, protein C or protein S deficiency, factor V Leiden, prothrombin G20210A, antiphospholipid antibodies, hyperhomocysteinemia or combined abnormalities) had higher levels of MP-Plts and MP-TF than non-carriers [1907 vs 1565 (p=0.002) and 532 vs 468 (p=0.011)]. The odds ratio (OR) for VTE, adjusted for sex, age, body mass index and thrombophilia was 2.5-fold higher in individuals with MPs plasma levels >95th percentile of the control group (3633/μL for MPs-Plts and 1113/μL for MPs-TF) than in those with MPs levels ≤95th percentile [for MPs-Plts: OR=2.59 (95%CI 1.23 – 5.45); for MPs-TF: OR=2.38 (1.15 – 4.92)]. The risk increased in a dose-dependent manner for both MPs-Plts and MPs-TF, particularly above the 75th percentile of the distribution in controls. The exclusion of patients whose MPs levels were measured within 6 months from VTE (in order to avoid the possible effect of the acute phase on MPs measurements), did not change the results [adjusted OR: 2.63 (1.18 – 5.89) for MPs-Plts and 2.36 (1.10 – 5.19) for MPs-TF]. The Table shows the relative risks of VTE associated with the presence or absence of high MPs levels and thrombophilia. Individuals with MPs >95th percentile or thrombophilia alone had a 2 to 3-fold increased risk of VTE, whereas those with both MPs-Plts >95th percentile and thrombophilia had a 9-fold increased risk of VTE. This synergistic effect was confirmed also for MPs-TF and remained after the exclusion of patients whose blood sample was collected within 6 months from VTE [OR 7.72 (1.68-35.4) for MP-Plts and 8.14 (2.08-31.8) for MP-TF]. Conclusions Plasma levels of MPs are significantly higher in patients with VTE than in healthy controls. MPs levels >95th percentile are associated with a 2.5-fold increased risk of VTE. There is a synergistic interaction between high levels of MPs and thrombophilia on VTE risk. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Dietary Intake and Plasma Levels of Choline and Betaine in Children with Autism Spectrum Disorders

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Joanna C. Hamlin ◽  
Margaret Pauly ◽  
Stepan Melnyk ◽  
Oleksandra Pavliv ◽  
William Starrett ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Research Network ◽  
Control Group ◽  
Lower Plasma ◽  
One Carbon Metabolism ◽  
Positive Correlations

Abnormalities in folate-dependent one-carbon metabolism have been reported in many children with autism. Because inadequate choline and betaine can negatively affect folate metabolism and in turn downstream methylation and antioxidant capacity, we sought to determine whether dietary intake of choline and betaine in children with autism was adequate to meet nutritional needs based on national recommendations. Three-day food records were analyzed for 288 children with autism (ASDs) who participated in the national Autism Intervention Research Network for Physical Health (AIR-P) Study on Diet and Nutrition in children with autism. Plasma concentrations of choline and betaine were measured in a subgroup of 35 children with ASDs and 32 age-matched control children. The results indicated that 60–93% of children with ASDs were consuming less than the recommended Adequate Intake (AI) for choline. Strong positive correlations were found between dietary intake and plasma concentrations of choline and betaine in autistic children as well as lower plasma concentrations compared to the control group. We conclude that choline and betaine intake is inadequate in a significant subgroup of children with ASDs and is reflected in lower plasma levels. Inadequate intake of choline and betaine may contribute to the metabolic abnormalities observed in many children with autism and warrants attention in nutritional counseling.

Primary Headaches: Reduced Circulating β-Lipotropin and β-Endorphin Levels with Impaired Reactivity to Acupuncture

Cephalalgia ◽  
1981 ◽  
Vol 1 (4) ◽  
pp. 195-201 ◽  
Author(s):  
F. Facchinetti ◽  
G. Nappi ◽  
F. Savoldi ◽  
A. R. Genazzani
Keyword(s):  
Healthy Volunteers ◽  
Plasma Levels ◽  
Chronic Headache ◽  
Plasma Concentrations ◽  
Primary Headache ◽  
Control Group ◽  
Primary Headaches ◽  
Chinese Acupuncture ◽  
Daily Chronic Headache

Eleven patients affected by common migraine (CM), eleven affected by daily chronic headache (DCH), and eight healthy volunteers were studied. Plasma levels of β-endorphin (βEP), β-lipotropin (βLPH), ACTH and cortisol were measured in basal conditions and after traditional Chinese acupuncture (TCA). Basal βLPH and βEP plasma levels (pg/ml) in the DCH patients (57.6 ± 9.5 and 16.8 ± 2.5, respectively; M ± SE) were lower than those found in the controls (83.6 ± 13.7 and 26.0 ± 6.1; p < 0.001), while those found in the CM cases showed intermediate values (75.3 ± 12.0 and 24.4 ± 5.8). ACTH and cortisol concentrations in both the CM and DCH patients were in the same range as those of the control group. TCA caused an increase in βLPH and βEP plasma concentrations in the control group (βLPH: 117 ± 16.9; βEF: 44.6 ± 6.7). Opioid plasma levels, however, remained unmodified after TCA in both the CM and DCH groups. ACTH plasma levels remained stable after TCA in all three subject groups. Patients suffering from primary headache are characterized by low βLPH and βEP plasma levels and by a poor reactivity of circulating opioids to non-stressful stimuli.

Plasma pancreatic trypsinogens in chronic renal failure and after nephrectomy

1982 ◽  
Vol 242 (2) ◽  
pp. G177-G182
Author(s):  
M. C. Geokas ◽  
R. Reidelberger ◽  
M. O'Rourke ◽  
E. Passaro ◽  
C. Largman
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Plasma Levels ◽  
Intravenous Infusion ◽  
Plasma Proteins ◽  
Plasma Concentrations ◽  
Normal Subjects ◽  
Cationic Trypsinogen ◽  
Anephric Patients ◽  
Highly Correlated

The kidney has previously been shown to be a major site for the plasma clearance of pancreatic trypsinogens in the rat. This study investigated plasma concentrations of anionic and cationic trypsinogen in chronic renal failure and anephric patients. Plasma concentrations were significantly elevated in both groups of patients. Hemodialysis did not change their plasma levels. The plasma levels of anionic and cationic trypsinogens were highly correlated in patients and normal subjects; however, the relative concentrations of anionic trypsinogen were significantly higher in renal failure patients. This suggests that in patients with renal failure the secondary clearance mechanisms for these plasma proteins more efficiently clear cationic molecules. In normal dogs, intravenous infusion of synthetic octapeptide of cholecystokinin (CCK-8) resulted in small transitory increases in plasma trypsinogen levels. After nephrectomy, basal levels of anionic and cationic trypsinogen were elevated, and intravenous infusion of CCK-8 resulted in prolonged, high levels of plasma trypsinogens.

scholarly journals Alterations in PACAP-38-like immunoreactivity in the plasma during ictal and interictal periods of migraine patients

Cephalalgia ◽  
2013 ◽  
Vol 33 (13) ◽  
pp. 1085-1095 ◽  
Author(s):  
Bernadett Tuka ◽  
Zsuzsanna Helyes ◽  
Adrienn Markovics ◽  
Teréz Bagoly ◽  
János Szolcsányi ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Healthy Subjects ◽  
Disease Duration ◽  
Animal Experiments ◽  
Control Group ◽  
Trigeminovascular System ◽  
Blood Samples ◽  
Calcitonin Gene ◽  
Pituitary Adenylate Cyclase ◽  
Healthy Control

Background Recent studies on migraineurs and our own animal experiments have revealed that pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) has an important role in activation of the trigeminovascular system. The aim of this study was to determine the PACAP-38-like immunoreactivity (LI) in the plasma of healthy subjects, and parallel with the calcitonin gene-related peptide (CGRP)-LI in migraine patients in the ictal and interictal periods. Methods A total of 87 migraineurs and 40 healthy control volunteers were enrolled in the examination. Blood samples were collected from the cubital veins in both periods in 21 patients, and in either the ictal or the interictal period in the remaining 66 patients, and were analysed by radioimmunoassay. Results A significantly lower PACAP-38-LI was measured in the interictal plasma of the migraineurs as compared with the healthy control group ( p < 0.011). In contrast, elevated peptide levels were detected in the ictal period relative to the attack-free period in the 21 migraineurs ( pPACAP-38 < 0.001; pCGRP < 0.035) and PACAP-38-LI in the overall population of migraineurs ( p < 0.009). A negative correlation was observed between the interictal PACAP-38-LI and the disease duration. Conclusion This is the first study that has provided evidence of a clear association between migraine phases (ictal and interictal) and plasma PACAP-38-LI alterations.

Vasopressin and oxytocin release evoked by NaCl loads are selectively blunted by area postrema lesions

2000 ◽  
Vol 278 (3) ◽  
pp. R732-R740 ◽  
Author(s):  
Wan Huang ◽  
Alan F. Sved ◽  
Edward M. Stricker
Keyword(s):  
Plasma Volume ◽  
Plasma Levels ◽  
Intravenous Infusion ◽  
Area Postrema ◽  
Hormone Secretion ◽  
Plasma Osmolality ◽  
Pituitary Hormones ◽  
Nacl Solution ◽  
Oxytocin Release ◽  
Nacl Load

The present study investigated the effect of area postrema lesions (APX) on stimulated neurohypophysial secretion of vasopressin (VP) and oxytocin (OT) in conscious rats. Blunted increases in plasma levels of both pituitary hormones were observed when rats with APX were infused intravenously with 1 M NaCl solution (2 ml/h for 6 h). In contrast, plasma VP and OT increased normally in rats with APX when equivalent increases in plasma osmolality (but not plasma Na+) resulted from intravenous infusion of an equiosmotic solution of 1 M mannitol and 0.5 M NaCl. Furthermore, APX did not affect increases in plasma VP and OT stimulated by plasma volume deficits, nor did APX disrupt OT secretion stimulated by intravenous injection of cholecystokinin. These findings suggest that the area postrema plays an important role in mediating secretion of VP and OT in response to an NaCl load, but not in response to an equiosmotic load that does not cause substantial hypernatremia, and not in response to other stimuli of neurohypophysial hormone secretion. Together with previous reports, these results suggest that APX impairs Na+ regulation in rats.

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