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Journal of Biosciences 2024Noradrenaline (NA) and serotonin (5-HT) induce nociception and antinociception. This antagonistic effect can be explained by the dose and type of activated receptors. We...
Noradrenaline (NA) and serotonin (5-HT) induce nociception and antinociception. This antagonistic effect can be explained by the dose and type of activated receptors. We investigated the existence of synergism between the noradrenergic and serotonergic systems during peripheral antinociception. The paw pressure test was performed in mice that had increased sensitivity by intraplantar injection of prostaglandin E (PGE). Noradrenaline (80 ng) administered intraplantarly induced an antinociceptive effect, that was reversed by the administration of selective antagonists of serotoninergic receptors 5-HT isamoltan, 5-HT BRL15572, 5-HT ketanserin, 5-HT ondansetron, but not by selective receptor antagonist 5-HT SB-269970. The administration of escitalopram, a serotonin reuptake inhibitor, potentiated the antinociceptive effect at a submaximal dose of NA. These results, indicate the existence of synergism between the noradrenergic and serotonergic systems in peripheral antinociception in mice.
Topics: Animals; Mice; Norepinephrine; Serotonin; Serotonin Antagonists; Male; Receptors, Serotonin; Dinoprostone; Citalopram; Nociception; Analgesics; Ondansetron; Ketanserin; Pain; Selective Serotonin Reuptake Inhibitors
PubMed: 38920106
DOI: No ID Found -
PloS One 2024The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing cesarean section.
METHODS
Fifty-four women scheduled for elective cesarean section were, randomly allocated to ondansetron group (n = 27) or palonosetron group (n = 27). Ten minutes prior to the administration of spinal anesthesia, participants received an intravenous injection of either ondansetron or palonosetron. A prophylactic phenylephrine infusion was initiated immediately following the intrathecal administration of bupivacaine and fentanyl. The infusion rate was titrated to maintain adequate blood pressure until the time of fetal delivery. The primary outcome was total dose of phenylephrine administered. The secondary outcomes were nausea or vomiting, the need for rescue antiemetics, hypotension, bradycardia, and shivering. Complete response rate, defined as the absence of postoperative nausea and vomiting and no need for additional antiemetics, were assessed for up to 24 hours post-surgery.
RESULTS
No significant differences were observed in the total dose of phenylephrine used between the ondansetron and palonosetron groups (387.5 μg [interquartile range, 291.3-507.8 μg versus 428.0 μg [interquartile range, 305.0-507.0 μg], P = 0.42). Complete response rates also showed no significant differences between the groups both within two hours post-spinal anesthesia (88.9% in the ondansetron group versus 100% in the palonosetron group; P = 0.24) and at 24 hours post-surgery (81.5% in the ondansetron group versus 88.8% in the palonosetron group; P = 0.7). In addition, there was no difference in other secondary outcomes.
CONCLUSION
Prophylactic administration of palonosetron did not demonstrate a superior effect over ondansetron in mitigating hemodynamic changes or reducing phenylephrine requirements in patients undergoing spinal anesthesia with bupivacaine and fentanyl for cesarean section.
Topics: Humans; Female; Anesthesia, Spinal; Cesarean Section; Palonosetron; Adult; Hypotension; Pregnancy; Ondansetron; Antiemetics; Postoperative Nausea and Vomiting; Phenylephrine; Anesthesia, Obstetrical
PubMed: 38917195
DOI: 10.1371/journal.pone.0305913 -
PloS One 2024Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general...
Changes in blood catecholamines during induction of general anesthesia in patients with post-induction hypotension undergoing laparoscopic cholecystectomy: A single-center prospective cohort study.
BACKGROUND
Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general anesthesia in patients with PIH undergoing laparoscopic cholecystectomy.
METHODS
This prospective study included 557 adult patients who underwent laparoscopic cholecystectomy under general anesthesia. PIH was defined as a greater than 20% decrease in systolic blood pressure from the pre-induction value, a systolic arterial pressure of less than 90 mmHg, or both. Plasma concentrations of epinephrine and norepinephrine during the induction of general anesthesia were determined using enzyme-linked immunosorbent assay. Multivariate logistic regression analysis evaluated the association between the clinical factors and PIH.
RESULTS
Of the 557 patients, 390 had PIH, and the remaining 167 were allocated to the non-PIH group. Changes in blood adrenaline, noradrenaline levels, or both were more pronounced in the PIH than in the non-PIH group (p<0.05). Age, body mass index, a history of hypertension, preoperative systolic blood pressure, and propofol or sufentanil dose were independent predictors of PIH.
CONCLUSION
The changes of blood catecholamines in patients with more stable hemodynamics during the induction of general anesthesia are smaller than that in patients with post-induction hypotension.
TRIAL REGISTRATION
ChiCTR2200055549, 12/01/2022.
Topics: Humans; Cholecystectomy, Laparoscopic; Male; Female; Anesthesia, General; Middle Aged; Prospective Studies; Hypotension; Adult; Catecholamines; Blood Pressure; Aged; Norepinephrine; Epinephrine
PubMed: 38917102
DOI: 10.1371/journal.pone.0305980 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jun 2024VD is a crucial vitamin for human health, as it enhances calcium absorption in the intestines and prevent rickets. Calcifediol (25(OH)VD) and calcitriol (1α,25(OH)VD)... (Review)
Review
VD is a crucial vitamin for human health, as it enhances calcium absorption in the intestines and prevent rickets. Calcifediol (25(OH)VD) and calcitriol (1α,25(OH)VD) are two derivatives of vitamin D that play an important role in preventing and treating osteoporosis, as well as regulating human physiological functions. Currently, the production of calcifediol, and calcitriol primarily relies on chemical synthesis, which has disadvantages such as low product yield, numerous by-products, and environmental unfriendliness. Therefore, developing a green, safe, and environmentally friendly biocatalytic synthesis pathway is of utmost importance. This article mainly reviews the biocatalytic synthesis pathways of calcifediol, and calcitriol. The P450 enzymes, including P450 monooxygenases (cytochrome P450 monooxygenases, CYPs) and P450 peroxygenases (unspecific peroxygenases, UPOs), are crucial for the production of calcifediol and calcitriol. The catalytic mechanism of the extensively studied P450 monooxygenases, the selection of suitable redox partners, and the key residues involved in the enzyme's catalytic activity are analyzed. In addition, the review explores HO-driven UPOs, including their catalytic mechanism, strategies for high heterologous expression, and regeneration of HO. UPOs are regarded as highly promising biocatalysts because they can facilitate reactions without the need for expensive cofactors and redox partners. This review offers insights into the engineering of P450 for the efficient production of vitamin D derivatives.
Topics: Calcitriol; Cytochrome P-450 Enzyme System; Calcifediol; Humans; Biocatalysis
PubMed: 38914482
DOI: 10.13345/j.cjb.230664 -
Science Advances Jun 2024The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the...
The suprachiasmatic nucleus (SCN) sets the phase of oscillation throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the organum vasculosum of the lamina terminalis (OVLT), begging the question of the direction of blood flow and the nature of diffusible signals that flow in this specialized vasculature. Using a combination of anatomical and in vivo two-photon imaging approaches, we unequivocally show that blood flows unidirectionally from the SCN to the OVLT, that blood flow rate displays daily oscillations with a higher rate at night than in the day, and that circulating vasopressin can access portal vessels. These findings highlight a previously unknown central nervous system communication pathway, which, like that of the pituitary portal system, could allow neurosecretions to reach nearby target sites in OVLT, avoiding dilution in the systemic blood. In both of these brain portal pathways, the target sites relay signals broadly to both the brain and the rest of the body.
Topics: Suprachiasmatic Nucleus; Animals; Mice; Hypothalamus; Brain; Portal System; Male; Vasopressins; Cerebrovascular Circulation; Circadian Rhythm
PubMed: 38905332
DOI: 10.1126/sciadv.adn8350 -
International Journal of Medical... 2024Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against...
Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca(PO)) , which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.
Topics: Animals; Aortic Aneurysm, Abdominal; Apoptosis; Mice; Glutamine; Angiotensin II; Macrophage Activation; Muscle, Smooth, Vascular; Humans; Myocytes, Smooth Muscle; Oxidative Stress; Reactive Oxygen Species; Disease Models, Animal; Male; Macrophages; Aorta, Abdominal; Matrix Metalloproteinase 9; Matrix Metalloproteinase 2; Tumor Necrosis Factor-alpha; Interleukin-6; Calcium Phosphates
PubMed: 38903916
DOI: 10.7150/ijms.96395 -
PloS One 2024Arginine vasopressin (AVP) and oxytocin (OT) are well-known as neuropeptides that regulate various social behaviors in mammals. However, little is known about their role...
Arginine vasopressin (AVP) and oxytocin (OT) are well-known as neuropeptides that regulate various social behaviors in mammals. However, little is known about their role in mouse female sexual behavior. Thus, we investigated the role of AVP (v1a and v1b) and OT receptors on female sexual behavior. First, we devised a new apparatus, the bilevel chamber, to accurately observe female mouse sexual behavior. This apparatus allowed for a more precisely measurement of lordosis as receptivity and rejection-like behavior (newly defined in this study), a reversed expression of proceptivity. To address our research question, we evaluated female sexual behavior in mice lacking v1a (aKO), v1b (bKO), both v1a and v1b (dKO), and OT (OTRKO) receptors. aKO females showed decreased rejection-like behavior but a normal level of lordosis, whereas bKO females showed almost no lordosis and no change in rejection-like behavior. In addition, dKO females showed normal lordosis levels, suggesting that the v1b receptor promotes lordosis, but not necessarily, while the v1a receptor latently suppresses it. In contrast, although OTRKO did not influence lordosis, it significantly increased rejection-like behavior. In summary, the present results demonstrated that the v1a receptor inhibits proceptivity and receptivity, whereas the v1b and OT receptors facilitate receptivity and proceptivity, respectively.
Topics: Animals; Female; Receptors, Vasopressin; Receptors, Oxytocin; Sexual Behavior, Animal; Mice; Mice, Knockout; Male; Oxytocin; Mice, Inbred C57BL; Arginine Vasopressin
PubMed: 38900750
DOI: 10.1371/journal.pone.0304703 -
Biology of Sex Differences Jun 2024Prenatal hypoxia, a common pregnancy complication, leads to impaired cardiovascular outcomes in the adult offspring. It results in impaired vasodilation in coronary and...
BACKGROUND
Prenatal hypoxia, a common pregnancy complication, leads to impaired cardiovascular outcomes in the adult offspring. It results in impaired vasodilation in coronary and mesenteric arteries of the adult offspring, due to reduced nitric oxide (NO). Thromboxane A (TxA) is a potent vasoconstrictor increased in cardiovascular diseases, but its role in the impact of prenatal hypoxia is unknown. To prevent the risk of cardiovascular disease by prenatal hypoxia, we have tested a maternal treatment using a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ). We hypothesized that prenatal hypoxia enhances vascular TxA responses in the adult offspring, due to decreased NO modulation, and that this might be prevented by maternal nMitoQ treatment.
METHODS
Pregnant Sprague-Dawley rats received a single intravenous injection (100 µL) of vehicle (saline) or nMitoQ (125 µmol/L) on gestational day (GD)15 and were exposed to normoxia (21% O) or hypoxia (11% O) from GD15 to GD21 (term = 22 days). Coronary and mesenteric arteries were isolated from the 4-month-old female and male offspring, and vasoconstriction responses to U46619 (TxA analog) were evaluated using wire myography. In mesenteric arteries, L-NAME (pan-NO synthase (NOS) inhibitor) was used to assess NO modulation. Mesenteric artery endothelial (e)NOS, and TxA receptor expression, superoxide, and 3-nitrotyrosine levels were assessed by immunofluorescence.
RESULTS
Prenatal hypoxia resulted in increased U46619 responsiveness in coronary and mesenteric arteries of the female offspring, and to a lesser extent in the male offspring, which was prevented by nMitoQ. In females, there was a reduced impact of L-NAME in mesenteric arteries of the prenatal hypoxia saline-treated females, and reduced 3-nitrotyrosine levels. In males, L-NAME increased U46619 responses in mesenteric artery to a similar extent, but TxA receptor expression was increased by prenatal hypoxia. There were no changes in eNOS or superoxide levels.
CONCLUSIONS
Prenatal hypoxia increased TxA vasoconstrictor capacity in the adult offspring in a sex-specific manner, via reduced NO modulation in females and increased TP expression in males. Maternal placental antioxidant treatment prevented the impact of prenatal hypoxia. These findings increase our understanding of how complicated pregnancies can lead to a sex difference in the programming of cardiovascular disease in the adult offspring.
Topics: Animals; Female; Rats, Sprague-Dawley; Pregnancy; Vasoconstriction; Male; Prenatal Exposure Delayed Effects; Thromboxane A2; Sex Characteristics; Antioxidants; Nitric Oxide; Mesenteric Arteries; Rats; Hypoxia; Fetal Hypoxia; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
PubMed: 38898532
DOI: 10.1186/s13293-024-00627-x -
International Journal of Molecular... May 2024Global warming has caused such problems as the poor coloration of grape skin and the decreased production of high-quality berries. We investigated the effect of...
Global warming has caused such problems as the poor coloration of grape skin and the decreased production of high-quality berries. We investigated the effect of synephrine (Syn) on anthocyanin accumulation. Anthocyanin accumulation in cultured grape cells treated with Syn at concentrations of 1 mM or higher showed no significant difference, indicating that the accumulation was concentration-independent. On the other hand, anthocyanin accumulation was dependent on the compound used for treatment. The sugar/acid ratio of the juice from berries treated with Syn did not differ from the control. The expression of anthocyanin-biosynthesis-related genes, but not phytohormones, was increased by the treatment with Syn at 24 h or later. The Syn treatment of cultured cells increased expression and hydrogen peroxide (HO) production from 3 to 24 h after treatment. Subsequently, the expression of and encoding HO-scavenging enzymes was also increased. Treatment of cultured cells with Syn and HO increased the expression of the HO-responsive gene and the anthocyanin-biosynthesis-related genes and 4 days after the treatment and increased anthocyanin accumulation 7 days after the treatment. On the other hand, the treatment of berries with Syn and HO increased anthocyanin accumulation after 9 days. These results suggest that Syn increases anthocyanin accumulation through HO production without changing phytohormone biosynthesis. Syn is expected to improve grape skin coloration and contribute to high-quality berry production.
Topics: Hydrogen Peroxide; Anthocyanins; Vitis; Plant Growth Regulators; Gene Expression Regulation, Plant; Synephrine; Fruit; Plant Proteins
PubMed: 38892099
DOI: 10.3390/ijms25115912 -
International Journal of Molecular... May 2024Human abdominal aortic aneurysms (AAAs) are characterized by increased activity of matrix metalloproteinases (MMP), including MMP-12, alongside macrophage accumulation...
Human abdominal aortic aneurysms (AAAs) are characterized by increased activity of matrix metalloproteinases (MMP), including MMP-12, alongside macrophage accumulation and elastin degradation, in conjunction with superimposed atherosclerosis. Previous genetic ablation studies have proposed contradictory roles for MMP-12 in AAA development. In this study, we aimed to elucidate if pharmacological inhibition of MMP-12 activity with a phosphinic peptide inhibitor protects from AAA formation and progression in angiotensin (Ang) II-infused Apoe mice. Complimentary studies were conducted in a human ex vivo model of early aneurysm development. Administration of an MMP-12 inhibitor (RXP470.1) protected hypercholesterolemia Apoe mice from Ang II-induced AAA formation and rupture-related death, associated with diminished medial thinning and elastin fragmentation alongside increased collagen deposition. Proteomic analyses confirmed a beneficial effect of MMP-12 inhibition on extracellular matrix remodeling proteins combined with inflammatory pathways. Furthermore, RXP470.1 treatment of mice with pre-existing AAAs exerted beneficial effects as observed through suppressed aortic dilation and rupture, medial thinning, and elastin destruction. Our findings indicate that pharmacological inhibition of MMP-12 activity retards AAA progression and improves survival in mice providing proof-of-concept evidence to motivate translational work for MMP-12 inhibitor therapy in humans.
Topics: Animals; Aortic Aneurysm, Abdominal; Angiotensin II; Matrix Metalloproteinase 12; Mice; Apolipoproteins E; Humans; Matrix Metalloproteinase Inhibitors; Male; Disease Models, Animal; Mice, Knockout; Mice, Inbred C57BL; Elastin; Proteomics
PubMed: 38891996
DOI: 10.3390/ijms25115809