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International Journal of Environmental... Mar 2023Aluminum phosphide is a highly effective insecticide for fumigation in granaries and is often used in rural grain storage. However, people's awareness of its toxicity is...
Aluminum phosphide is a highly effective insecticide for fumigation in granaries and is often used in rural grain storage. However, people's awareness of its toxicity is not strong. A case of acute inhalation toxicity of phosphine caused by the use of aluminum phosphide to fumigate a granary is reported here. The case presented with aspiration pneumonia and acute left heart failure. The patient was cured using comprehensive life support treatment, including respiratory support, antiarrhythmic treatment, and blood pressure maintenance with vasoactive drugs. There is no specific antidote for phosphine poisoning at present, and the comprehensive application of restricted fluid resuscitation, high-dose glucocorticoid shock, vasoactive drugs and bedside hemofiltration is significant in improving the prognosis of patients. It is also important to remind people to pay attention to their own protection in the process of using aluminum phosphide.
Topics: Humans; Phosphines; Aluminum Compounds; Insecticides
PubMed: 36981930
DOI: 10.3390/ijerph20065021 -
Physiological Research Aug 2021The use of oxygen therapy (high doses of oxygen - hyperoxia) in the treatment of premature infants results in their survival. However, it also results in a high... (Review)
Review
The use of oxygen therapy (high doses of oxygen - hyperoxia) in the treatment of premature infants results in their survival. However, it also results in a high incidence of chronic lung disease known as bronchopulmonary dysplasia, a disease in which airway hyper-responsiveness and pulmonary hypertension are well known as consequences. In our previous studies, we have shown that hyperoxia causes airway hyper-reactivity, characterized by an increased constrictive and impaired airway smooth muscle relaxation due to a reduced release of relaxant molecules such as nitric oxide, measured under in vivo and in vitro conditions (extra- and intrapulmonary) airways. In addition, the relaxation pathway of the vasoactive intestinal peptide (VIP) and/or pituitary adenylate cyclase activating peptide (PACAP) is another part of this system that plays an important role in the airway caliber. Peptide, which activates VIP cyclase and pituitary adenylate cyclase, has prolonged airway smooth muscle activity. It has long been known that VIP inhibits airway smooth muscle cell proliferation in a mouse model of asthma, but there is no data about its role in the regulation of airway and tracheal smooth muscle contractility during hyperoxic exposure of preterm newborns.
Topics: Airway Remodeling; Animals; Animals, Newborn; Bronchopulmonary Dysplasia; Disease Models, Animal; Gestational Age; Humans; Hyperoxia; Infant, Newborn; Infant, Premature; Lung; Muscle, Smooth; Oxygen Inhalation Therapy; Pituitary Adenylate Cyclase-Activating Polypeptide; Premature Birth; Signal Transduction; Vasoactive Intestinal Peptide
PubMed: 34062074
DOI: 10.33549/physiolres.934638 -
Journal of Molecular Neuroscience : MN Nov 2022Rotenone is a commercial pesticide commonly used to model Parkinson's disease (PD) due to its ability to induce dopaminergic degeneration. Studies have confirmed that...
Rotenone is a commercial pesticide commonly used to model Parkinson's disease (PD) due to its ability to induce dopaminergic degeneration. Studies have confirmed that rotenone causes microglial activation, which seems to contribute to the toxic effects seen in rodent models. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally related neuropeptides that have robust neuroprotective and anti-inflammatory properties. However, their ability to regulate microglial activity in response to rotenone is not fully understood. Using rotenone as an inflammatory stimulus, we tested whether PACAP or VIP could mitigate microglial activation in BV2 microglial cells. Rotenone dose-dependently reduced cell viability and the percentage of apoptotic cells. It also increased the release of nitric oxide (NO) in culture media and the expression of microglial activation markers and pro-inflammatory markers, including CD11b, MMP-9 and IL-6, and heightened the endogenous levels of PACAP and its preferring receptor PAC1. Co-treatment with PACAP or VIP prevented rotenone-induced increase of NO, CD11b, MMP-9 and IL-6. These results indicate that both PACAP and VIP are able to prevent the pro-inflammatory effects of rotenone in BV2 cells, supporting the idea that these molecules can have therapeutic value in slowing down PD progression.
Topics: Vasoactive Intestinal Peptide; Pituitary Adenylate Cyclase-Activating Polypeptide; Microglia; Rotenone; Matrix Metalloproteinase 9; Interleukin-6
PubMed: 35199308
DOI: 10.1007/s12031-022-01968-1 -
Frontiers in Physiology 2022The process of matching skeletal muscle blood flow to metabolism is complex and multi-factorial. In response to exercise, increases in cardiac output, perfusion pressure... (Review)
Review
The process of matching skeletal muscle blood flow to metabolism is complex and multi-factorial. In response to exercise, increases in cardiac output, perfusion pressure and local vasodilation facilitate an intensity-dependent increase in muscle blood flow. Concomitantly, sympathetic nerve activity directed to both exercising and non-active muscles increases as a function of exercise intensity. Several studies have reported the presence of tonic sympathetic vasoconstriction in the vasculature of exercising muscle at the onset of exercise that persists through prolonged exercise bouts, though it is blunted in an exercise-intensity dependent manner (functional sympatholysis). The collective evidence has resulted in the current dogma that vasoactive molecules released from skeletal muscle, the vascular endothelium, and possibly red blood cells produce local vasodilation, while sympathetic vasoconstriction restrains vasodilation to direct blood flow to the most metabolically active muscles/fibers. Vascular smooth muscle is assumed to integrate a host of vasoactive signals resulting in a precise matching of muscle blood flow to metabolism. Unfortunately, a critical review of the available literature reveals that published studies have largely focused on bulk blood flow and existing experimental approaches with limited ability to reveal the matching of perfusion with metabolism, particularly between and within muscles. This paper will review our current understanding of the regulation of sympathetic vasoconstriction in contracting skeletal muscle and highlight areas where further investigation is necessary.
PubMed: 36171966
DOI: 10.3389/fphys.2022.980524 -
Frontiers in Medicine 2021Enteral nutrition (EN) is recommended within the first 24-48 h for patients with hemodynamic stability, following admission to an intensive care unit (ICU). However,...
Enteral nutrition (EN) is recommended within the first 24-48 h for patients with hemodynamic stability, following admission to an intensive care unit (ICU). However, for patients with approximate stable hemodynamics requiring mechanical circulatory support and vasoactive drugs, the application of early EN remains controversial. We sought to evaluate the tolerance of early EN in patients with cardiogenic shock who required vasoactive drugs and mechanical circulatory support after cardiac surgery. This single-center, prospective observational study included patients with cardiogenic shock, requiring vasoactive drugs and mechanical circulatory support after cardiac surgery, undergoing EN. The primary endpoint was EN tolerance and secondary endpoints were mortality, length of mechanical ventilation, and length of ICU stay. From February 2019 to December 2020, 59 patients were enrolled, of which 25 (42.37%) developed intolerance within 3 days of starting EN. Patients in the EN intolerant group had a longer median length of mechanical ventilation (380 vs. 128 h, = 0.006), a longer median ICU stay (20 vs. 11.5 days, = 0.03), and a higher proportion of bloodstream infections (44 vs. 14.71%, = 0.018). The median EN calorie levels for all patients in the first 3 days of EN were 4.00, 4.13, and 4.28 kcal/kg/day, respectively. Median protein intake levels of EN in the first 3 days were 0.18, 0.17, and 0.17 g/kg/day, respectively. No significant difference was observed in the median dose of vasoactive drugs between the groups (0.035 vs. 0.05 μg/kg/min, = 0.306). Patients with cardiogenic shock after cardiac surgery had a high proportion of early EN intolerance, and patients with EN intolerance had a worse prognosis, but no significant correlation was identified between EN tolerance and the dose of vasoactive drugs.
PubMed: 34938748
DOI: 10.3389/fmed.2021.765424 -
No pain, no gain? The effects of pain-promoting neuropeptides and neurotrophins on fracture healing.Bone Feb 2020Neuropeptides and neurotrophins are key regulators of peripheral nociceptive nerves and contribute to the induction, sensitization, and maintenance of pain. It is now... (Review)
Review
Neuropeptides and neurotrophins are key regulators of peripheral nociceptive nerves and contribute to the induction, sensitization, and maintenance of pain. It is now known that these peptides also regulate non-neuronal tissues, including bone. Here, we review the effects of numerous neuropeptides and neurotrophins on fracture healing. The neuropeptides calcitonin-gene related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP) have varying effects on osteoclastic and osteoblastic activity. Ultimately, CGRP and SP both accelerate fracture healing, while VIP and PACAP seem to negatively impact healing. Unlike the aforementioned neuropeptides, the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have more uniform effects. Both factors upregulate osteoblastic activity, osteoclastic activity, and, in vivo, stimulate osteogenesis to promote fracture healing. Future research will need to clarify the exact mechanism by which the neuropeptides and neurotrophins influence fracture healing. Specifically, understanding the optimal expression patterns for these proteins in the fracture healing process may lead to therapies that can maximize their bone-healing capabilities and minimize their pain-promoting effects. Finally, further examination of protein-sequestering antibodies and/or small molecule agonists and antagonists may lead to new therapies that can decrease the rate of delayed union/nonunion outcomes and fracture-associated pain.
Topics: Fracture Healing; Humans; Nerve Growth Factors; Pain; Pituitary Adenylate Cyclase-Activating Polypeptide; Vasoactive Intestinal Peptide
PubMed: 31715336
DOI: 10.1016/j.bone.2019.115109 -
Journal of Smooth Muscle Research =... 2021Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are major cell types that control vascular function, and hence dysfunction of these cells plays a key...
Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are major cell types that control vascular function, and hence dysfunction of these cells plays a key role in the development and progression of vasculopathies. Abnormal vascular responsiveness to vasoactive substances including vasoconstrictors and vasodilators has been observed in various arteries in diseases including diabetes, hypertension, chronic kidney diseases, and atherosclerosis. Several substances derived from ECs tightly control vascular function, such as endothelium-derived relaxing and contracting factors, and it is known that abnormal vascular signaling of these endothelium-derived substances is often observed in various diseases. Derangement of signaling in VSMCs and altered function influence vascular reactivity to vasoactive substances and tone, which are important determinants of vascular resistance and blood pressure. However, understanding the molecular mechanisms underlying abnormalities of vascular functions in pathological states is difficult because multiple substances interact in the development of these processes. Advanced glycation end products (AGEs), a heterogeneous group of bioactive compounds, are thought to contribute to vascular dysfunction, which in turn cause the development of several diseases including diabetes, hypertension, stroke, and atherosclerosis. A growing body of evidence suggests that AGEs could affect these cells and modulate vascular function. This study is focused on the link between AGEs and functions of ECs and VSMCs, particularly the modulative effects of AGEs on vascular reactivities to vasoactive substances.
Topics: Atherosclerosis; Endothelial Cells; Endothelium, Vascular; Glycation End Products, Advanced; Humans; Hypertension
PubMed: 35095032
DOI: 10.1540/jsmr.57.94 -
Current Neuropharmacology 2022The blood-brain barrier inhibits the central nervous system penetration of 98% of small molecule drugs and virtually all biologic agents, which has limited progress in... (Review)
Review
BACKGROUND
The blood-brain barrier inhibits the central nervous system penetration of 98% of small molecule drugs and virtually all biologic agents, which has limited progress in treating neurologic disease. Vasoactive peptides have been shown in animal studies to transiently disrupt the blood-brain barrier and regadenoson is currently being studied in humans to determine if it can improve drug delivery to the brain. However, many other vasoactive peptides could potentially be used for this purpose.
METHODS
We performed a review of the literature evaluating the physiologic effects of vasoactive peptides on the vasculature of the brain and systemic organs. To assess the likelihood that a vasoactive peptide might transiently disrupt the blood-brain barrier, we devised a four-tier classification system to organize the available evidence.
RESULTS
We identified 32 vasoactive peptides with potential blood-brain barrier permeabilityaltering properties. To date, none of these are shown to open the blood-brain barrier in humans. Twelve vasoactive peptides increased blood-brain barrier permeability in rodents. The remaining 20 had favorable physiologic effects on blood vessels but lacked specific information on permeability changes to the blood-brain barrier.
CONCLUSION
Vasoactive peptides remain an understudied class of drugs with the potential to increase drug delivery and improve treatment in patients with brain tumors and other neurologic diseases. Dozens of vasoactive peptides have yet to be formally evaluated for this important clinical effect. This narrative review summarizes the available data on vasoactive peptides, highlighting agents that deserve further in vitro and in vivo investigations.
Topics: Animals; Blood-Brain Barrier; Central Nervous System; Central Nervous System Agents; Drug Delivery Systems; Humans; Peptides; Proteins
PubMed: 35100958
DOI: 10.2174/1570159X20999220131163504 -
International Journal of Molecular... Aug 2022Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide...
Vasoactive Effects of Chronic Treatment with Fructose and Slow-Releasing HS Donor GYY-4137 in Spontaneously Hypertensive Rats: The Role of Nitroso and Sulfide Signalization.
Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide (HS). We investigated whether a slow-releasing HS donor, GYY-4137, could exert beneficial activity in these conditions. We examined the effect of eight weeks of fructose intake on the blood pressure, biometric parameters, vasoactive responses, and NO and HS pathways in fructose-fed spontaneously hypertensive rats with or without three weeks of GYY-4137 i.p. application. GYY-4137 reduced triacylglycerol levels and blood pressure, but not adiposity, and all were increased by fructose intake. Fructose intake generally enhanced endothelium-dependent vasorelaxation, decreased adrenergic contraction, and increased protein expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and concentration of conjugated dienes in the left ventricle (LV). Although GYY-4137 administration did not affect vasorelaxant responses, it restored disturbed contractility, LV oxidative damage and decreased protein expression of TNFα in fructose-fed rats. While the participation of endogenous HS in vasoactive responses was not affected by fructose treatment, the expression of HS-producing enzyme cystathionine β-synthase in the LV was increased, and the stimulation of the NO signaling pathway improved endothelial function in the mesenteric artery. On the other hand, chronic treatment with GYY-4137 increased the expression of HS-producing enzyme cystathionine γ-lyase in the LV and stimulated the beneficial pro-relaxant and anti-contractile activity of endogenous HS in thoracic aorta. Our results suggest that sulfide and nitroso signaling pathways could trigger compensatory vasoactive responses in hypertensive rats with metabolic disorder. A slow HS-releasing donor could partially amend metabolic-related changes and trigger beneficial activity of endogenous HS.
Topics: Animals; Cystathionine gamma-Lyase; Fructose; Hydrogen Sulfide; Morpholines; Nitric Oxide; Organothiophosphorus Compounds; Rats; Rats, Inbred SHR; Sulfides; Tumor Necrosis Factor-alpha
PubMed: 36012477
DOI: 10.3390/ijms23169215 -
Journal of Biomechanical Engineering Apr 2022Albeit seldom considered explicitly, the vasoactive state of a central artery can contribute to luminal control and thereby affect the in vivo values of flow-induced...
Albeit seldom considered explicitly, the vasoactive state of a central artery can contribute to luminal control and thereby affect the in vivo values of flow-induced wall shear stress and pressure-induced intramural stress, which in turn are strong determinants of wall growth and remodeling. Here, we test the hypothesis that diminished vasoactive capacity compromises effective mechano-adaptations of central arteries. Toward this end, we use consistent methods to re-interpret published data on common carotid artery remodeling in a nonpharmacologic mouse model of induced hypertension and a model of connective tissue disorder that results in Marfan syndrome. The mice have identical genetic backgrounds and, in both cases, the data are consistent with the hypothesis considered. In particular, carotid arteries with strong (normal) vasoactive capacity tend to maintain wall thickness and in vivo axial stretch closer to homeostatic, thus resulting in passive circumferential wall stress and energy storage close to normal. We conclude that effective vasoactivity helps to control the biomechanical state in which the cells and matrix turnover, thus helping to delineate mechano-adaptive from maladaptive remodeling. Future analyses of experimental data and computational models of growth and remodeling should account for this strong coupling between smooth muscle contractile capacity and central arterial remodeling.
Topics: Animals; Carotid Artery, Common; Hypertension; Mice; Muscle Contraction; Muscle, Smooth, Vascular; Stress, Mechanical
PubMed: 34729580
DOI: 10.1115/1.4052888