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Expert Opinion on Drug Metabolism &... Jul 2015Drug-induced vascular injury (DIVI) is a serious problem in preclinical studies of vasoactive molecules and for survivors of pediatric cancers. DIVI is often observed in...
Drug-induced vascular injury (DIVI) is a serious problem in preclinical studies of vasoactive molecules and for survivors of pediatric cancers. DIVI is often observed in rodents and some larger animals, primarily with drugs affecting vascular tone, but not in humans; however, DIVI observed in animal studies often precludes a drug candidate from continuing along the development pipeline. Thus, there is great interest by the pharmaceutical industry to identify quantifiable human biomarkers of DIVI. Small-scale endothelialized tissue-engineered blood vessels using human cells represent a promising approach to screen drug candidates and develop alternatives to cancer therapeutics in vitro. We identify several technical challenges that remain to be addressed, including high-throughput systems to screen large numbers of candidates, identification of suitable cell sources and establishing and maintaining a differentiated state of the vessel wall cells. Adequately addressing these challenges should yield novel platforms to screen drugs and develop new therapeutics to treat cardiovascular disease.
Topics: Animals; Biomarkers; Blood Vessel Prosthesis; Blood Vessels; Drug Design; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Humans; Species Specificity; Tissue Engineering; Toxicity Tests; Vascular Diseases
PubMed: 26028128
DOI: 10.1517/17425255.2015.1047342 -
Birth Defects Research Aug 2020Amniotic band syndrome (ABS) includes limb deficiencies accompanied by fibrous strands originating from the amniotic lining. Terminal transverse limb deficiencies (TTLD)...
INTRODUCTION
Amniotic band syndrome (ABS) includes limb deficiencies accompanied by fibrous strands originating from the amniotic lining. Terminal transverse limb deficiencies (TTLD) appear to be similar but lack fibrous strands. Both are hypothesized to result from vascular disruption. For ABS, limb deficiencies are considered secondary to amnion rupture. We explored an alternative possibility-that TTLD is the primary defect and ABS is secondary.
METHODS
Using data from the National Birth Defects Prevention Study, we expanded on a previous study. We examined smoking, alcohol, and medications categorized by indicated vasoactivity as markers of vascular disruption. Logistic regression models with Firth's penalized likelihood were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).
RESULTS
Use of bronchodilators and aspirin appeared to increase the risk of ABS, while decongestants and nonaspirin NSAIDs increased the risk of TTLD. The risk of ABS was markedly increased in cases reporting combinations of vasoactive exposures, particularly alcohol and aspirin (aOR 3.7, 95% CI 1.6, 7.8), and alcohol and bronchodilators (aOR 3.4, 95% CI 1.4, 7.5). Increased risk of TTLD due to combinations of vasoactive exposures was only observed for smoking and decongestants (aOR 2.3, 95% CI 1.4, 3.6).
CONCLUSIONS
Exposures associated with increased risk of ABS had no apparent association with TTLD, supporting previous evidence that these may be distinct phenotypes. ABS appears to be associated with combined exposures with vasodilation properties, such as alcohol and bronchodilators, while increased risk of TTLD may be associated with smoking and decongestants, both vasoconstrictive exposures.
Topics: Amniotic Band Syndrome; Humans; Infant, Newborn; Odds Ratio; Smoking
PubMed: 32573119
DOI: 10.1002/bdr2.1740 -
Kidney360 Jan 2021
Topics: Arteriovenous Fistula; Arteriovenous Shunt, Surgical; Humans; Kidney Diseases; Renal Dialysis
PubMed: 35368825
DOI: 10.34067/KID.0006262020 -
Journal of Traditional Chinese Medicine... Aug 2022To investigate the influence of Qihuang decoction on enteric nervous system after gastrectomy in rats.
OBJECTIVE
To investigate the influence of Qihuang decoction on enteric nervous system after gastrectomy in rats.
METHODS
The morphology, distribution and number of intestinal neurons in enteric nervous system (ENS) were observed by immunofluorescence labeling and confocal laser scanning microscopy. Reverse transcription-polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of intestinal neurotransmitters and corresponding receptors in ENS.
RESULTS
The morphology and distribution of enteric neurons in ENS were changed after gastrectomy, and these neurons in Qihuang decoction group were similar with that of sham operation group. The number of ACh and SP positive neurons, mRNA and protein expression of excitatory neurotransmitters (AChE, SP) and receptors (M3R, NK1R) were decreased after gastrectomy. And the intervention of Qihuang decoction could increase the number of ACh and SP positive neurons and promote the expression of their mRNA and protein. For vasoactive intestinal peptide (VIP) and nitric oxide synthase (NOS), the number of neurons and mRNA and protein expression of inhibitory neurotransmitters (VIP and NOS) and receptors (VIP2R) were increased after gastrectomy. And these rising indexes fall back after the intervention of Qihuang decoction. Besides, the intestinal propulsion rate in QH group was significantly increased than that in SEN and IEN group.
CONCLUSIONS
These experimental results showed that after gastrectomy, early intervention with Qihuang decoction in small intestine will contribute to the postoperative recovery of enteric nervous system and intestinal propulsion rate, and consequently enhance gastrointestinal motility.
Topics: Animals; Enteric Nervous System; Gastrectomy; Neurotransmitter Agents; RNA, Messenger; Rats; Vasoactive Intestinal Peptide
PubMed: 35848972
DOI: 10.19852/j.cnki.jtcm.20220519.004 -
Neurological Research Jan 2017Neurodegenerative disorders (NDDs) are characterized by neuronal death in the brain. The mechanism of the neuronal death is too complicated to be fully understood,... (Review)
Review
Neurodegenerative disorders (NDDs) are characterized by neuronal death in the brain. The mechanism of the neuronal death is too complicated to be fully understood, although in many NDDs, aging and neurotoxins are known risk factors. In the central and peripheral nervous system, vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide, is released to support neuronal survival in both physiological and pathological condition. VIP can inhibit the neurodegeneration induced by the loss of neurons. The indirect protection effect is mainly mediated by glial cells through the production of neurotrophic factor(s) and inhibition of proinflammatory mediators. By remolding the structure and improving the transfer efficiency of VIP, its nerve protective function could be further improved. Its neuroprotective action and efficacy in inhibiting a broad range of inflammatory responses make VIP or related peptides becoming a novel therapeutic method to NDDs. In this review, we aim to summarize the relationship between VIP and NDDs.
Topics: Animals; Humans; Neurodegenerative Diseases; Neuroprotective Agents; Vasoactive Intestinal Peptide
PubMed: 27786097
DOI: 10.1080/01616412.2016.1250458 -
The Journal of Headache and Pain Feb 2018In migraineurs pituitary adenylate cyclase activating peptide1-38 (PACAP1-38) is a potent migraine provoking substance and the accompanying long lasting flushing... (Review)
Review
BACKGROUND
In migraineurs pituitary adenylate cyclase activating peptide1-38 (PACAP1-38) is a potent migraine provoking substance and the accompanying long lasting flushing suggests degranulation of mast cells. Infusion of the closely related vasoactive intestinal peptide (VIP) either induces headache or flushing. This implicates the pituitary adenylate cyclase activating peptide type I receptor (PAC1) to be involved in the pathophysiology of PACAP1-38 provoked headaches. Here we review studies characterizing the effects of mainly PACAP but also of VIP on cerebral and meningeal arteries and mast cells.
DISCUSSION
PACAP1-38, PACAP1-27 and VIP dilate cerebral and meningeal arteries from several species including man. In rat cerebral and meningeal arteries the dilation seems to be mediated preferably via vasoactive intestinal peptide receptor type 1 (VPAC1) receptors while, in human, middle meningeal artery dilation induced via vasoactive intestinal peptide receptor type 2 (VPAC2) receptors cannot be ruled out. PACAP1-38 is a strong degranulator of peritoneal and dural mast cells while PACAP1-27 and VIP only have weak effects. More detailed characterization studies suggest that mast cell degranulation is not mediated via the known receptors for PACAP1-38 but rather via a still unknown receptor coupled to phospholipase C.
CONCLUSION
It is suggested that PACAP1-38 might induce migraine via degranulation of dural mast cells via a yet unknown receptor.
Topics: Animals; Cell Degranulation; Humans; Mast Cells; Meningeal Arteries; Migraine Disorders; Pituitary Adenylate Cyclase-Activating Polypeptide; Pituitary Gland; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; Signal Transduction; Vasoactive Intestinal Peptide
PubMed: 29460121
DOI: 10.1186/s10194-017-0822-2 -
Archives of Medical Research Nov 2021The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the latest threat to global health, causes overwhelming effects for the public... (Review)
Review
BACKGROUND
The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the latest threat to global health, causes overwhelming effects for the public healthcare systems worldwide. Of note, in addition to the respiratory complications, some patients with coronavirus disease 2019 (COVID-19) also develop serious cardiovascular injuries. Vasoactive peptides play an important role in a wide range of physiological and pathological conditions.
AIM
With the urgent need for exploring the specific therapeutic targets and biomarkers for the emerging COVID-19, the general aim of this review is to discuss the potentials of the vasoactive peptides including Angiotensin II (Ang II), vasoactive intestinal peptide (VIP), endothelin-1 (ET-1), calcitonin gene-related peptide (CGRP), natriuretic peptides, substance P (SP) and bradykinin (BK) as therapeutic targets and/or prognostic indicators for the COVID-19 pandemic.
CONCLUSION
Based on various observations some authors conclude that the assessment of vasoactive peptides shall be considered a routine part of COVID-19 patient monitoring, and they can serve as potential therapeutic targets for the disease management.
Topics: Biomarkers; COVID-19; Humans; Pandemics; Peptides; SARS-CoV-2
PubMed: 34134920
DOI: 10.1016/j.arcmed.2021.05.007 -
Peptides May 2022Neuropeptides are bioactive molecules, made up of small chains of amino acids, with many neuromodulatory properties. Several lines of evidence suggest that... (Review)
Review
Neuropeptides are bioactive molecules, made up of small chains of amino acids, with many neuromodulatory properties. Several lines of evidence suggest that neuropeptides, mainly expressed in the central nervous system (CNS), play an important role in the onset of Parkinson's Disease (PD) pathology. The wide spread disruption of neuropeptides has been excessively demonstrated to be related to the pathophysiological symptoms in PD where impairment in motor function per example was correlated with neuropeptides dysregulation in the substantia niagra (SN). Moreover, the levels of different neuropeptides have been found modified in the cerebrospinal fluid and blood of PD patients, indicating their potential role in the manifestation of PD symptoms and dysfunctions. In this review, we outlined the neuroprotective effects of neuropeptides on dopaminergic neuronal loss, oxidative stress and neuroinflammation in several models and tissues of PD. Our main focus was to elaborate the role of orexin, pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), opioids, angiotensin, carnosine and many others in the protection and/or involvement in the neurodegeneration of striatal dopaminergic cells. Further studies are required to better assess the mode of action and cellular mechanisms of neuropeptides in order to shift the focus from the in vitro and in vivo testing to applicable clinical testing. This review, allows a support for future use of neuropeptides as therapeutic solution for PA pathophysiology.
Topics: Central Nervous System; Humans; Parkinson Disease; Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide
PubMed: 34929264
DOI: 10.1016/j.peptides.2021.170713 -
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue Nov 2022The degree of hemodynamic support by vasoactive drugs in critically ill patients is often considered one of the markers of disease severity. The sequential organ failure... (Review)
Review
The degree of hemodynamic support by vasoactive drugs in critically ill patients is often considered one of the markers of disease severity. The sequential organ failure assessment (SOFA), European system for cardiac operative risk evaluation II (EuroScore II), and other scores only roughly quantify the drug support of cardiovascular system. When patients need large doses of vasoactive drugs, the mortality increases accordingly. The vasoactive-inotropic score (VIS) objectively quantifies the degree of cardiovascular support using a simple formula that standardizes the dose of different agents, and it is recommended as a simple, effective, and accurate prognostic indicator. In recent years, there are more and more clinical applications and related studies at home and abroad. This paper reviews the application and progress of VIS score in critically ill patients, providing help for doctors to judge the condition and prognosis of patients and guiding the decision-making of diagnosis and treatment.
Topics: Humans; Critical Illness; Prognosis; Heart; Retrospective Studies; Organ Dysfunction Scores
PubMed: 36567569
DOI: 10.3760/cma.j.cn121430-20211112-01686 -
Journal of Molecular Neuroscience : MN Sep 2018A bidirectional cross-talk is established between the nervous and immune systems through common mediators including neuropeptides, neurotransmitters, and cytokines.... (Review)
Review
A bidirectional cross-talk is established between the nervous and immune systems through common mediators including neuropeptides, neurotransmitters, and cytokines. Among these, PACAP and VIP are two highly related neuropeptides widely distributed in the organism with purported immunomodulatory actions. Due to their well-known anti-inflammatory properties, administration of these peptides has proven to be beneficial in models of acute and chronic inflammatory diseases. Nevertheless, the relevance of the endogenous source of these peptides in the modulation of immune responses remains to be elucidated. The development of transgenic mice with specific deletions in the genes coding for these neuropeptides (Vip and Adcyap1) or for their G-protein-coupled receptors VPAC1, VPAC2, and PAC1 (Vipr1, Vipr2, Adcyap1r1) has allowed to address this question, underscoring the complexity of the immunoregulatory properties of PACAP and VIP. The goal of this review is to integrate the existing information on the immune phenotypes of mice deficient for PACAP, VIP, or their receptors, to provide a global view on the roles of these endogenous neuropeptides during immunological health and disease.
Topics: Animals; Humans; Immunologic Factors; Mice; Mice, Knockout; Neuroimmunomodulation; Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Vasoactive Intestinal Peptide
PubMed: 30105629
DOI: 10.1007/s12031-018-1150-y