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Transplantation Apr 2024We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other perioperative outcomes in adult liver transplant recipients. We searched multiple electronic databases using words from the "liver transplantation" and "vasoactive drug" domains. We included all randomized controlled trials conducted in adult liver transplant recipients comparing 2 different intravenous vasoactive drugs or 1 against a standard of care that reported AKI, intraoperative blood loss, or any other postoperative outcome. We conducted 4 frequentist network meta-analyses using random effect models, based on the interventions' mechanism of action, and evaluated the quality of evidence (QoE) using Grading of Recommendations, Assessment, Development, and Evaluations recommendations. We included 9 randomized controlled trials comparing different vasopressor drugs (vasoconstrictor or inotrope), 3 comparing a somatostatin infusion (or its analogues) to a standard of care, 11 comparing different vasodilator infusions together or against a standard of care, and 2 comparing vasoconstrictor boluses at graft reperfusion. Intravenous clonidine was associated with shorter duration of mechanical ventilation, intensive care unit, and hospital length of stay (very low QoE), and some vasodilators were associated with lower creatinine level 24 h after surgery (low to very low QoE). Phenylephrine and terlipressin were associated with less intraoperative blood loss when compared with norepinephrine (low and moderate QoE). None of the vasoactive drugs improve any other postoperative outcomes, including AKI. There is still important equipoise regarding the best vasoactive drug to use in liver transplantation for most outcomes. Further studies are required to better inform clinical practice.
Topics: Adult; Humans; Liver Transplantation; Blood Loss, Surgical; Network Meta-Analysis; Vasoconstrictor Agents; Vasodilator Agents; Acute Kidney Injury
PubMed: 37525360
DOI: 10.1097/TP.0000000000004744 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Sep 2021The role of neuroimmunomodulation in allergic diseases is a research hotspot in recent years. Allergic rhinitis(AR) is caused by overactive immune response to a...
The role of neuroimmunomodulation in allergic diseases is a research hotspot in recent years. Allergic rhinitis(AR) is caused by overactive immune response to a foreign antigen in nasal mucosa. Immune cells release inflammatory mediators(including histamine, cytokines and neurotrophins), which directly activate peripheral neurons to mediate nasal congestion, itching, sneezing, and other hyperresponsive symptoms. Upon activation, these peripheral neurons release neurotransmitters (including acetylcholine and norepinephrine) and neuropeptides(including calcitonin gene-related peptide, substance P and vasoactive intestinal peptide) that directly act on immune cells to drive allergic inflammation. Neuro-immune signaling may play a significant role in the pathophysiology of AR. Therefore, a better understanding of these cellular and molecular neuro-immune interactions may inspire the discovery of new targets and novel therapies.
Topics: Humans; Nasal Mucosa; Neuroimmunomodulation; Neuropeptides; Rhinitis, Allergic; Vasoactive Intestinal Peptide
PubMed: 34628846
DOI: 10.13201/j.issn.2096-7993.2021.09.021 -
NeoReviews Mar 2020Failure of the normal transition from in utero to ex utero physiology leads to "" pulmonary hypertension of the newborn (PPHN). PPHN is frequently associated with low... (Review)
Review
Failure of the normal transition from in utero to ex utero physiology leads to "" pulmonary hypertension of the newborn (PPHN). PPHN is frequently associated with low systemic blood pressure and low cardiac output because of increased right ventricular afterload and myocardial dysfunction. The general management of newborns with PPHN is geared toward maintenance of normothermia, normal serum electrolytes, normal intravascular volume, correction of acidosis, adequate sedation/analgesia, adequate ventilation and oxygenation with optimal lung recruitment, and avoidance of hyperoxia. Inotropic and vasoactive agents are commonly initiated early to increase cardiac output, maintain adequate systemic blood pressure, and enhance oxygen delivery to the tissue. Unfortunately, there is not much evidence on the choice, timing of initiation, dosing, monitoring, and titrating of vasoactive agents in this patient population. In this review, we will discuss the pathophysiology of PPHN and review the use of inotropic, lusitropic, and vasoactive agents in the management of PPHN, with particular attention to milrinone.
Topics: Cardiotonic Agents; Humans; Infant, Newborn; Milrinone; Persistent Fetal Circulation Syndrome; Vasoconstrictor Agents
PubMed: 32123121
DOI: 10.1542/neo.21-3-e165 -
Nature Chemical Biology Oct 2023Despite wide appreciation of the biological role of nitric oxide (NO) synthase (NOS) signaling, questions remain about the chemical nature of NOS-derived bioactivity....
Despite wide appreciation of the biological role of nitric oxide (NO) synthase (NOS) signaling, questions remain about the chemical nature of NOS-derived bioactivity. Here we show that NO-like bioactivity can be efficiently transduced by mobile NO-ferroheme species, which can transfer between proteins, partition into a hydrophobic phase and directly activate the sGC-cGMP-PKG pathway without intermediacy of free NO. The NO-ferroheme species (with or without a protein carrier) efficiently relax isolated blood vessels and induce hypotension in rodents, which is greatly potentiated after the blockade of NOS activity. While free NO-induced relaxations are abolished by an NO scavenger and in the presence of red blood cells or blood plasma, a model compound, NO-ferroheme-myoglobin preserves its vasoactivity suggesting the physiological relevance of NO-ferroheme species. We conclude that NO-ferroheme behaves as a signaling entity in the vasculature.
Topics: Nitric Oxide; Erythrocytes; Heme; Signal Transduction
PubMed: 37710073
DOI: 10.1038/s41589-023-01411-5 -
Translational Stroke Research Feb 2023Therapeutic induction of collateral flow as a means to salvage tissue and improve outcome from acute ischemic stroke is a promising approach in the era in which... (Review)
Review
Therapeutic induction of collateral flow as a means to salvage tissue and improve outcome from acute ischemic stroke is a promising approach in the era in which endovascular therapy is no longer time-dependent but collateral-dependent. The importance of collateral flow enhancement as a therapeutic for acute ischemic stroke extends beyond those patients with large amounts of salvageable tissue. It also has the potential to extend the time window for reperfusion therapies in patients who are ineligible for endovascular thrombectomy. In addition, collateral enhancement may be an important adjuvant to neuroprotective agents by providing a more robust vascular route for which treatments can gain access to at risk tissue. However, our understanding of collateral hemodynamics, including under comorbid conditions that are highly prevalent in the stroke population, has hindered the efficacy of collateral flow augmentation for improving stroke outcome in the clinical setting. This review will discuss our current understanding of pial collateral function and hemodynamics, including vasoactivity that is critical for enhancing penumbral perfusion. In addition, mechanisms by which collateral flow can be increased during acute ischemic stroke to limit ischemic injury, that may be different depending on the state of the brain and vasculature prior to stroke, will also be reviewed.
Topics: Humans; Ischemic Stroke; Brain Ischemia; Stroke; Brain; Thrombectomy; Collateral Circulation; Cerebrovascular Circulation
PubMed: 35416577
DOI: 10.1007/s12975-022-01019-2 -
Current Opinion in Endocrinology,... Apr 2021To discuss recent advances of vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) receptors in pharmacology, cell biology, and... (Review)
Review
Pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide [Part 1]: biology, pharmacology, and new insights into their cellular basis of action/signaling which are providing new therapeutic targets.
PURPOSE OF REVIEW
To discuss recent advances of vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating polypeptide (PACAP) receptors in pharmacology, cell biology, and intracellular signaling in cancer.
RECENT FINDINGS
Recent studies provide new insights into the pharmacology, cell biology of the VIP/PACAP system and show they play important roles in a number of human cancers, as well as in tumor growth/differentiation and are providing an increased understanding of their signaling cascade that is suggesting new treatment targets/approaches.
SUMMARY
Recent insights from studies of VIP/PACAP and their receptors in both central nervous system disorders and inflammatory disorders suggest possible new treatment approaches. Elucidation of the exact roles of VIP/PACAP in these disorders and development of new therapeutic approaches involving these peptides have been limited by lack of specific pharmacological tools, and exact signaling mechanisms involved, mediating their effects. Reviewed here are recent insights from the elucidation of structural basis for VIP/PACAP receptor activation as well as the signaling cascades mediating their cellular effects (using results primarily from the study of their effects in cancer) that will likely lead to novel targets and treatment approaches in these diseases.
Topics: Biology; Humans; Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Polypeptide, Type I; Vasoactive Intestinal Peptide
PubMed: 33449573
DOI: 10.1097/MED.0000000000000617 -
Scientific Reports Nov 2019A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and hypertensive rats has been described depending on the use of some...
A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and hypertensive rats has been described depending on the use of some vasoactive drugs and linked to certain mood disorders. Asymmetrical neuroperipheral connections involving neuropeptidases from the left or right hemisphere and aminopeptidases from the heart or plasma have been suggested to play a role in this asymmetry. We hypothesize that such asymmetries could be extended to the connection between the brain and physiologic parameters and metabolic factors from plasma and urine. To assess this hypothesis, we analyzed the possible correlation between neuropeptidases from the left and right frontal cortex with peripheral parameters in normotensive (Wistar Kyoto [WKY]) rats and hypertensive rats (spontaneously hypertensive rats [SHR]) untreated or treated with vasoactive drugs such as captopril, propranolol and L-nitro-arginine methyl ester. Neuropeptidase activities from the frontal cortex were analyzed fluorometrically using arylamide derivatives as substrates. Physiological parameters and metabolic factors from plasma and urine were determined using routine laboratory techniques. Vasoactive drug treatments differentially modified the asymmetrical neuroperipheral pattern by changing the predominance of the correlations between peripheral parameters and central neuropeptidase activities of the left and right frontal cortex. The response pattern also differed between SHR and WKY rats. These results support an asymmetric integrative function of the organism and suggest the possibility of a different neurometabolic response coupled to particular mood disorders, depending on the selected vasoactive drug.
Topics: Animals; Antihypertensive Agents; Blood Pressure; Captopril; Frontal Lobe; Humans; Hypertension; Male; NG-Nitroarginine Methyl Ester; Peptide Hydrolases; Propranolol; Rats; Rats, Inbred SHR; Rats, Inbred WKY
PubMed: 31695104
DOI: 10.1038/s41598-019-52658-9 -
Neuroscience May 2022Dendrites represent the "reception hub" of the neuron as they collect thousands of different inputs and send a coherent response to the cell body. A considerable portion... (Review)
Review
Dendrites represent the "reception hub" of the neuron as they collect thousands of different inputs and send a coherent response to the cell body. A considerable portion of these signals, especially in vivo, arises from neuromodulatory sources, which affect dendritic computations and cellular activity. In this context, acetylcholine (ACh) exerts a coordinating role of different brain structures, contributing to goal-driven behaviors and sleep-wake cycles. Specifically, cholinergic neurons from the medial septum-diagonal band of Broca complex send numerous projections to glutamatergic principal cells and GABAergic inhibitory neurons in the hippocampus, differentially entraining them during network oscillations. Interneurons display abundant expression of cholinergic receptors and marked responses to stimulation by ACh. Nonetheless, the precise localization of ACh inputs is largely unknown, and evidence for cholinergic modulation of interneuronal dendritic signaling remains elusive. In this article, we review evidence that suggests modulatory effects of ACh on dendritic computations in three hippocampal interneuron subtypes: fast-spiking parvalbumin-positive (PV) cells, somatostatin-expressing (SOM) oriens lacunosum moleculare cells and vasoactive intestinal polypeptide-expressing (VIP) interneuron-selective interneurons. We consider the distribution of cholinergic receptors on these interneurons, including information about their specific somatodendritic location, and discuss how the action of these receptors can modulate dendritic Ca signaling and activity of interneurons. The implications of ACh-dependent Ca signaling for dendritic plasticity are also discussed. We propose that cholinergic modulation can shape the dendritic integration and plasticity in interneurons in a cell type-specific manner, and the elucidation of these mechanisms will be required to understand the contribution of each cell type to large-scale network activity.
Topics: Acetylcholine; Cholinergic Agents; Hippocampus; Interneurons; Parvalbumins; Receptors, Cholinergic; Vasoactive Intestinal Peptide
PubMed: 34129910
DOI: 10.1016/j.neuroscience.2021.06.011 -
Cells May 2024Heart failure is the common concluding pathway for a majority of cardiovascular diseases and is associated with cardiac dysfunction. Since heart failure is invariably... (Review)
Review
Heart failure is the common concluding pathway for a majority of cardiovascular diseases and is associated with cardiac dysfunction. Since heart failure is invariably preceded by adaptive or maladaptive cardiac hypertrophy, several biochemical mechanisms have been proposed to explain the development of cardiac hypertrophy and progression to heart failure. One of these includes the activation of different neuroendocrine systems for elevating the circulating levels of different vasoactive hormones such as catecholamines, angiotensin II, vasopressin, serotonin and endothelins. All these hormones are released in the circulation and stimulate different signal transduction systems by acting on their respective receptors on the cell membrane to promote protein synthesis in cardiomyocytes and induce cardiac hypertrophy. The elevated levels of these vasoactive hormones induce hemodynamic overload, increase ventricular wall tension, increase protein synthesis and the occurrence of cardiac remodeling. In addition, there occurs an increase in proinflammatory cytokines and collagen synthesis for the induction of myocardial fibrosis and the transition of adaptive to maladaptive hypertrophy. The prolonged exposure of the hypertrophied heart to these vasoactive hormones has been reported to result in the oxidation of catecholamines and serotonin via monoamine oxidase as well as the activation of NADPH oxidase via angiotensin II and endothelins to promote oxidative stress. The development of oxidative stress produces subcellular defects, Ca-handling abnormalities, mitochondrial Ca-overload and cardiac dysfunction by activating different proteases and depressing cardiac gene expression, in addition to destabilizing the extracellular matrix upon activating some metalloproteinases. These observations support the view that elevated levels of various vasoactive hormones, by producing hemodynamic overload and activating their respective receptor-mediated signal transduction mechanisms, induce cardiac hypertrophy. Furthermore, the occurrence of oxidative stress due to the prolonged exposure of the hypertrophied heart to these hormones plays a critical role in the progression of heart failure.
Topics: Heart Failure; Humans; Cardiomegaly; Signal Transduction; Animals; Angiotensin II; Oxidative Stress
PubMed: 38786079
DOI: 10.3390/cells13100856 -
Frontiers in Neural Circuits 2022Neuropeptides, a diverse class of signaling molecules in the nervous system, modulate various biological effects including membrane excitability, synaptic transmission... (Review)
Review
Neuropeptides, a diverse class of signaling molecules in the nervous system, modulate various biological effects including membrane excitability, synaptic transmission and synaptogenesis, gene expression, and glial cell architecture and function. To date, most of what is known about neuropeptide action is limited to subcortical brain structures and tissue outside of the central nervous system. Thus, there is a knowledge gap in our understanding of neuropeptide function within cortical circuits. In this review, we provide a comprehensive overview of various families of neuropeptides and their cognate receptors that are expressed in the prefrontal cortex (PFC). Specifically, we highlight dynorphin, enkephalin, corticotropin-releasing factor, cholecystokinin, somatostatin, neuropeptide Y, and vasoactive intestinal peptide. Further, we review the implication of neuropeptide signaling in prefrontal cortical circuit function and use as potential therapeutic targets. Together, this review summarizes established knowledge and highlights unknowns of neuropeptide modulation of neural function underlying various biological effects while offering insights for future research. An increased emphasis in this area of study is necessary to elucidate basic principles of the diverse signaling molecules used in cortical circuits beyond fast excitatory and inhibitory transmitters as well as consider components of neuropeptide action in the PFC as a potential therapeutic target for neurological disorders. Therefore, this review not only sheds light on the importance of cortical neuropeptide studies, but also provides a comprehensive overview of neuropeptide action in the PFC to serve as a roadmap for future studies in this field.
Topics: Neuropeptide Y; Neuropeptides; Prefrontal Cortex; Synaptic Transmission; Vasoactive Intestinal Peptide
PubMed: 35800635
DOI: 10.3389/fncir.2022.796443