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Domestic Animal Endocrinology Apr 2024Increased fetal cortisol is associated with catecholamine release, a primary factor for neonatal adaptive responses. However, relationship between canine peripartum...
Increased fetal cortisol is associated with catecholamine release, a primary factor for neonatal adaptive responses. However, relationship between canine peripartum cortisol and catecholamine is unknown. We aimed to compare serum adrenaline, noradrenaline and cortisol during peripartum in bitches and neonates of distinct obstetric conditions and to assess amniotic fluid cortisol concentration. Twenty females and maximum of three puppies per litter were allocated into Vaginal Eutocia (10 females; 17 neonates) and Elective C-section (10 females; 20 neonates) groups. Amniotic fluid was collected at delivery for cortisol concentration. Maternal and neonatal blood were collected prepartum, intrapartum, postpartum and 1h postpartum, and at birth, 30 and 60min, 12hs and 24hs, respectively, for cortisol, adrenaline and noradrenaline assessment. C-section determined higher noradrenaline throughout delivery and cortisol concentration from intrapartum through 1h postpartum, compared to vaginal birth. C-section maternal cortisol showed progressive increase from intrapartum onwards, while neonatal cortisol remained unchanged. No difference of maternal cortisol concentration occurred along whelping, whereas a significant decrease was verified for vaginal delivery puppies from birth until the 12hs. Puppies delivered vaginally had higher cortisol concentration at birth and 30min, compared to c-section puppies. There was a higher concentration of amniotic fluid cortisol in vaginal eutocia. In conclusion, c-section induces higher maternal stress during and after surgery, whilst vaginal delivery is a more neonatal physiologically stressful condition, contributing to better adaptation during transition.
Topics: Pregnancy; Female; Dogs; Animals; Hydrocortisone; Catecholamines; Amniotic Fluid; Norepinephrine; Epinephrine
PubMed: 38401307
DOI: 10.1016/j.domaniend.2024.106838 -
Hepatology (Baltimore, Md.) May 2024Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefits, but may be associated with cardiopulmonary...
BACKGROUND AND AIMS
Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefits, but may be associated with cardiopulmonary complications. We analyzed the predictors of terlipressin response and mortality using point-of-care echocardiography (POC-Echo) and cardiac and renal biomarkers.
APPROACH
Between December 2021 and January 2023, patients with HRS-AKI were assessed with POC-Echo and lung ultrasound within 6 hours of admission, at the time of starting terlipressin (48 h), and at 72 hours. Volume expansion was done with 20% albumin, followed by terlipressin infusion. Clinical data, POC-Echo data, and serum biomarkers were prospectively collected. Cirrhotic cardiomyopathy (CCM) was defined per 2020 criteria.
RESULTS
One hundred and forty patients were enrolled (84% men, 59% alcohol-associated disease, mean MELD-Na 25±SD 5.6). A median daily dose of infused terlipressin was 4.3 (interquartile range: 3.9-4.6) mg/day; mean duration 6.4 ± SD 1.9 days; the complete response was in 62% and partial response in 11%. Overall mortality was 14% and 16% at 30 and 90 days, respectively. Cutoffs for prediction of terlipressin nonresponse were cardiac variables [ratio of early mitral inflow velocity and mitral annular early diastolic tissue doppler velocity > 12.5 (indicating increased left filling pressures, C-statistic: 0.774), tissue doppler mitral velocity < 7 cm/s (indicating impaired relaxation; C-statistic: 0.791), > 20.5% reduction in cardiac index at 72 hours (C-statistic: 0.885); p < 0.001] and pretreatment biomarkers (CysC > 2.2 mg/l, C-statistic: 0.640 and N-terminal proBNP > 350 pg/mL, C-statistic: 0.655; p <0.050). About 6% of all patients with HRS-AKI and 26% of patients with CCM had pulmonary edema. The presence of CCM (adjusted HR 1.9; CI: 1.8-4.5, p = 0.009) and terlipressin nonresponse (adjusted HR 5.2; CI: 2.2-12.2, p <0.001) were predictors of mortality independent of age, sex, obesity, DM-2, etiology, and baseline creatinine.
CONCLUSIONS
CCM and reduction in cardiac index, reliably predict terlipressin nonresponse. CCM is independently associated with poor survival in HRS-AKI.
Topics: Male; Humans; Female; Terlipressin; Vasoconstrictor Agents; Hepatorenal Syndrome; Lypressin; Point-of-Care Systems; Acute Kidney Injury; Liver Cirrhosis; Albumins; Echocardiography; Biomarkers; Treatment Outcome
PubMed: 37976391
DOI: 10.1097/HEP.0000000000000691 -
Critical Care Medicine Aug 2023To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and...
OBJECTIVES
To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock.
DESIGN
Animal experimental study.
SETTING
University translational research laboratory.
SUBJECTS
Fifteen Landrace pigs.
INTERVENTIONS
Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance.
MEASUREMENTS AND MAIN RESULTS
Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively).
CONCLUSIONS
In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
Topics: Animals; Swine; Norepinephrine; Microcirculation; Splanchnic Circulation; Vasoconstrictor Agents; Shock, Septic; Hemodynamics; Lactates
PubMed: 37255347
DOI: 10.1097/CCM.0000000000005885 -
Journal of Cardiothoracic and Vascular... Sep 2023
Topics: Humans; Hydroxocobalamin; Shock; Hypotension; Vasodilation; Vasoconstrictor Agents
PubMed: 37225547
DOI: 10.1053/j.jvca.2023.05.001 -
Annals of Allergy, Asthma & Immunology... Aug 2023
Topics: Humans; Anaphylaxis; Epinephrine
PubMed: 37536870
DOI: 10.1016/j.anai.2023.05.024 -
Clinical Toxicology (Philadelphia, Pa.) Sep 2023
Topics: Humans; Epinephrine; Heart Arrest; Substance-Related Disorders
PubMed: 37988118
DOI: 10.1080/15563650.2023.2271652 -
Acta Biochimica Et Biophysica Sinica Jul 2023Intrahepatic cholangiocarcinoma (iCCA) is a highly fatal malignancy with rapidly increasing incidence and mortality worldwide. Currently, gemcitabine-based systemic...
Intrahepatic cholangiocarcinoma (iCCA) is a highly fatal malignancy with rapidly increasing incidence and mortality worldwide. Currently, gemcitabine-based systemic chemotherapy is the main clinical therapeutic regimen; however, its efficacy is poor, and its mechanism has not been elucidated. In this study, we use a Seahorse Extracellular Flux analyser to measure glycolysis capacity (extracellular acidification rate, ECAR) and oxygen consumption rate (OCR). The glucose uptake or lactic acid content is detected, and the effects of saikosaponin D, an active compound derived from (a traditional Chinese medicine for soothing the liver and relieving depression), on gemcitabine cytotoxicity in norepinephrine-stimulated iCCA cells are analysed. We find that adrenergic signaling plays a fundamental role in chronic stress-induced therapeutic resistance in iCCA. Norepinephrine (NE) and epinephrine (E) enhance the proliferation of iCCA cells and interfere with the response to gemcitabine through activation of the β2-adrenergic receptor (ADRB2). Furthermore, we find that NE upregulates the expressions of several drug efflux-related genes (such as and ) and promotes glycolysis in iCCA cells. In addition, saikosaponin D reverses the poor response of iCCA cells to gemcitabine by downregulating ADRB2 level. Furthermore, saikosaponin D inhibits drug efflux and glycolysis in iCCA cells by regulating the expressions of MDR1, ABCG2, HK2, and GLUT1. Collectively, saikosaponin D enhances the antitumor effect of gemcitabine by controlling glucose metabolism and drug efflux by inhibiting the ADRB2 signaling. Therefore, the combination of saikosaponin D and gemcitabine may be a potential therapeutic strategy for the treatment of iCCA.
Topics: Humans; Gemcitabine; Norepinephrine; Cholangiocarcinoma; Epinephrine; Bile Ducts, Intrahepatic; Bile Duct Neoplasms; Glycolysis; Receptors, Adrenergic, beta-2
PubMed: 37489008
DOI: 10.3724/abbs.2023040 -
BMJ Supportive & Palliative Care Oct 2023It is estimated that 5% of patients with heart failure (HF) will progress to end-stage disease refractory to medical therapy and might require prolonged hospitalisation...
It is estimated that 5% of patients with heart failure (HF) will progress to end-stage disease refractory to medical therapy and might require prolonged hospitalisation with inotropic support. We present the case of a patient with end-stage HF who was admitted with cardiogenic shock. During his hospitalisation, he required prolonged intravenous vasopressor therapy due to refractory hypotension. He did not qualify for heart transplantation or left ventricular-assist device strategies. Midodrine was started as a last resort attempt to wean off vasopressors. After 5 days of therapy, the patient was weaned entirely off vasopressors and was discharged home for hospice care. By the time of discharge, he was tolerating low-dose carvedilol along with midodrine. We propose midodrine as a reasonable alternative for patients with end-stage HF with reduced ejection fraction and refractory hypotension, who are dependent on intravenous vasoactive drugs and are not candidates for advanced HF therapies.
Topics: Male; Humans; Midodrine; Vasoconstrictor Agents; Hospitalization; Heart Failure; Hypotension
PubMed: 32581003
DOI: 10.1136/bmjspcare-2020-002369 -
Biomolecules May 2024The active vitamin D metabolites, 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are produced by successive hydroxylation steps and play key roles in...
The active vitamin D metabolites, 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are produced by successive hydroxylation steps and play key roles in several cellular processes. However, alternative metabolic pathways exist, and among them, the 4-hydroxylation of 25D is a major one. This study aims to investigate the structure-activity relationships of 4-hydroxy derivatives of 1,25D. Structural analysis indicates that 1,4α,25(OH)D and 1,4β,25(OH)D maintain the anchoring hydrogen bonds of 1,25D and form additional interactions, stabilizing the active conformation of VDR. In addition, 1,4α,25D and 1,4β,25D are as potent as 1,25D in regulating the expression of VDR target genes in rat intestinal epithelial cells and in the mouse kidney. Moreover, these two 4-hydroxy derivatives promote hypercalcemia in mice at a dose similar to that of the parent compound.
Topics: Animals; Mice; Structure-Activity Relationship; Receptors, Calcitriol; Rats; Calcitriol; Male; Vitamin D; Hypercalcemia; Kidney
PubMed: 38785958
DOI: 10.3390/biom14050551 -
Resuscitation Oct 2023The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC)... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC) with no clear effect on long-term outcomes. The objective of the current manuscript was to evaluate the hemodynamic effects of intra-cardiac arrest vasopressin and methylprednisolone during the first 24 hours after ROSC.
METHODS
The VAM-IHCA trial randomized patients with in-hospital cardiac arrest to a combination of vasopressin and methylprednisolone or placebo during the cardiac arrest. This study is a post hoc analysis focused on the hemodynamic effects of the intervention after ROSC. Post-ROSC data on the administration of glucocorticoids, mean arterial blood pressure, heart rate, blood gases, vasopressor and inotropic therapy, and sedation were collected. Total vasopressor dose between the two groups was calculated based on noradrenaline-equivalent doses for adrenaline, phenylephrine, terlipressin, and vasopressin.
RESULTS
The present study included all 186 patients who achieved ROSC in the VAM IHCA-trial of which 100 patients received vasopressin and methylprednisolone and 86 received placebo. The number of patients receiving glucocorticoids during the first 24 hours was 22/86 (26%) in the placebo group and 14/100 (14%) in the methylprednisolone group with no difference in the cumulative hydrocortisone-equivalent dose. There was no significant difference between the groups in the mean cumulative noradrenaline-equivalent dose (vasopressin and methylprednisolone: 603 ug/kg [95CI% 227; 979] vs. placebo: 651 ug/kg [95CI% 296; 1007], mean difference -48 ug/kg [95CI% -140; 42.9], p = 0.30), mean arterial blood pressure, or lactate levels. There was no difference between groups in arterial blood gas values and vital signs.
CONCLUSION
Treatment with vasopressin and methylprednisolone during cardiac arrest caused no difference in mean arterial blood pressure, vasopressor use, or arterial blood gases within the first 24 hours after ROSC when compared to placebo.
Topics: Humans; Methylprednisolone; Cardiopulmonary Resuscitation; Heart Arrest; Vasopressins; Vasoconstrictor Agents; Hemodynamics; Norepinephrine; Hospitals; Gases
PubMed: 37543161
DOI: 10.1016/j.resuscitation.2023.109922