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General and Comparative Endocrinology Aug 2024Fecal samples are a non-invasive and relatively accessible matrix for investigating physiological processes in resident killer whale (Orcinus orca) populations. The high... (Review)
Review
Fecal samples are a non-invasive and relatively accessible matrix for investigating physiological processes in resident killer whale (Orcinus orca) populations. The high lipid content of the diet (primarily salmonids) leads to lower density fecal material and slower dispersion, facilitating sample collection. As fecal discharge is relatively infrequent and the volume of sample is variable, maximizing analytical options is an important consideration. Here we present an extraction methodology to measure hormones and lipid content from the same fecal aliquot. Lipid extractions are commonly conducted using chloroform and methanol from Folch or Bligh and Dyer (B&D), while alcohol is the primary solvent for hormone extraction. We evaluated the possibility of using the methanol layer from lipid extractions to assess fecal steroid hormone levels. Folch and B&D methanol residues were assayed form metabolites of progesterone (PMs) and corticosterone (GCs), and results were compared to aliquots extracted in 70 % ethanol. Hormone concentrations measured in the methanol layer from Folch and B&D extractions were 55 % to 79 % lower than concentrations in 70 % ethanol. We developed mathematical corrections, using linear regression models fitted to Folch or B&D methanol vs 70 % ethanol hormone concentrations (p < 0.01). Fecal concentrations of PMs and GCs from methanol extractions were biologically validated and are significantly higher in confirmed pregnant females compared to non-pregnant individuals (p < 0.05). This study demonstrates that lipid extraction protocols may be used for the analysis of multiple biomarkers, maximizing the use of small-volume samples.
Topics: Animals; Feces; Whale, Killer; Corticosterone; Progesterone; Female; Lipids
PubMed: 38705419
DOI: 10.1016/j.ygcen.2024.114544 -
NEJM Evidence Feb 2023Adrenal insufficiency is a common and potentially life-threatening endocrine disorder that can be drug induced or endogenous and of adrenal (primary) or...
Adrenal insufficiency is a common and potentially life-threatening endocrine disorder that can be drug induced or endogenous and of adrenal (primary) or pituitary/hypothalamic (secondary/tertiary) origin. Of particular concern in drug-induced disease is the patient with glucocorticoid- or opioid-induced adrenal insufficiency. Adrenal insufficiency of any cause is typically diagnosed biochemically with a subnormal morning serum cortisol (the circadian, awakening peak) and serum dehydroepiandrosterone sulfate, followed by or simultaneously with an assessment of the acute (30 and 60 minutes) serum cortisol response to injected synthetic corticotropin (ACTH), if clinically indicated.
Topics: Humans; Hydrocortisone; Cortisone; Adrenal Insufficiency; Adrenocorticotropic Hormone; Glucocorticoids
PubMed: 38320042
DOI: 10.1056/EVIDe2200306 -
The American Journal of Psychiatry Sep 2023
Topics: Humans; Depression; Pregnanes; Pyrazoles
PubMed: 37654113
DOI: 10.1176/appi.ajp.20230537 -
General and Comparative Endocrinology Sep 2023The alligator snapping turtle (Macrochelys temminckii) is a species for which captive propagation and reintroduction programs are well established; however, little is...
The alligator snapping turtle (Macrochelys temminckii) is a species for which captive propagation and reintroduction programs are well established; however, little is known about its reproductive behavior and physiology. In this study, we measured monthly plasma sex steroid hormone concentrations of androgen (T + DHT) estradiol-17B (E2), and progesterone (P4), and used ultrasonography to monitor annual reproductive cycles of a captive population of alligator snapping turtles that is maintained under semi-natural conditions in southeastern Oklahoma. Concurrently, we used automated radio telemetry to measure the relative activity levels of male and female alligator snapping turtles and examine these activity patterns in the context of their reproductive cycles. We also measured monthly concentrations of the glucocorticoid (GC) corticosterone (CORT). Seasonal variation was only detected for T in males, but was observed for T, E2, and P4 in females. Vitellogenesis began in August and ended in April and coincided with elevated E2. Ovulation took place 10-29 April and the nesting period lasted from 11 May - 3 June. Males exhibited greater relative activity levels than females in the fall, winter, and early spring, which coincided with the period when mature sperm would be available for mating. Females were more active than males during the peri-nesting period in the spring. Seasonal changes in CORT were detected and did not differ between males and females. CORT concentrations were elevated in the late spring and summer, coincident with the foraging season, and depressed in the fall, and winter, and at their nadir in the early spring.
Topics: Animals; Male; Female; Turtles; Alligators and Crocodiles; Semen; Gonadal Steroid Hormones; Progesterone; Corticosterone; Reproduction; Seasons
PubMed: 37244410
DOI: 10.1016/j.ygcen.2023.114310 -
Phytochemistry May 2024Steroids are farnesyl diphosphate-derived triterpene derivatives widely distributed in Meliaceae plants that can have several health benefits due to their biological... (Review)
Review
Steroids are farnesyl diphosphate-derived triterpene derivatives widely distributed in Meliaceae plants that can have several health benefits due to their biological activities. This literature survey on chemical and pharmacological studies of steroids from the Meliaceae plants indicates that 157 distinct steroids classified into six subclasses including (in decreasing number): pregnane-, stigmastane-, ergostane-, cholestane-, androstane- and ecdysterone-type steroids have been reported from a total of 49 plant species. This review aims to provide a reference document compiling information about the occurrence, chemistry and biological activities of meliaceous steroids for the period from 1988 to July 2023. In particular, generalities about the chemistry of steroids with unusual skeletons and underlying biosynthetic pathways are highlighted. In addition, some structural relationships between different compound types and their biological activities are presented. The information used during the writing of this paper was collected from the online libraries PubMed, Google Scholar and Scifinder using the keywords steroids and Meliaceae with no language restriction. This review points out new avenues for further investigations of steroids from plants of the Meliaceae family.
Topics: Meliaceae; Steroids; Pregnanes; Plant Extracts; Phytochemicals
PubMed: 38417722
DOI: 10.1016/j.phytochem.2024.114039 -
Steroids Aug 2021A preliminary chemical investigation on 70% MeOH extract of the roots of Asparagus cochinchinensis resulted in the isolation of nine steroids. These isolates comprised...
A preliminary chemical investigation on 70% MeOH extract of the roots of Asparagus cochinchinensis resulted in the isolation of nine steroids. These isolates comprised of four new C (1-4) and one new pregnane (5) glycosides, and four known C (6-9) spirostanol steroids. Their structures were identified via analysis of the spectroscopic data and the results of hydrolytic cleavage. The cytotoxic activities of the compounds were tested toward the human tumor cell line Hela (cervical cancer), and compounds 7 and 8 displayed moderate activity with IC values of 35.5 and 39.6 μM, respectively.
Topics: Antineoplastic Agents, Phytogenic; Apocynaceae; Cell Proliferation; Female; Glycosides; Humans; Molecular Structure; Plant Extracts; Plant Roots; Pregnanes; Steroids; Uterine Cervical Neoplasms
PubMed: 34102197
DOI: 10.1016/j.steroids.2021.108874 -
BMC Anesthesiology Dec 2022Alfaxalone is a fast acting intravenous anaesthetic with high therapeutic index. It is an analogue of the naturally-occurring neurosteroid allopregnanolone responsible... (Randomized Controlled Trial)
Randomized Controlled Trial
Alfaxalone anaesthesia increases brain derived neurotrophic factor levels and preserves postoperative cognition by activating pregnane-X receptors: an in vitro study and a double blind randomised controlled trial.
BACKGROUND
Alfaxalone is a fast acting intravenous anaesthetic with high therapeutic index. It is an analogue of the naturally-occurring neurosteroid allopregnanolone responsible for maintenance of cognition and neuroprotection by activation of brain pregnane X receptors and consequent increased production of mature brain-derived neurotrophic factor (m-BDNF). Two studies are reported here: an in vitro study investigated whether alfaxalone activates human pregnane X receptors (h-PXR) as effectively as allopregnanolone; and a clinical study that measured postoperative changes in serum m-BDNF and cognition in patients after alfaxalone anaesthesia compared with propofol and sevoflurane.
METHODS
In vitro Activation of h-PXR by allopregnanolone and alfaxalone solutions (206 - 50,000 nM) was measured using human embryonic kidney cells expressing h-PXR hybridised and linked to the firefly luciferase gene. Light emission by luciferase stimulated by each ligand binding with h-PXR was measured. Clinical A double blind prospective randomised study of patients undergoing hip arthroplasty anaesthetised with alfaxalone TIVA (n = 8) or propofol TIVA (n = 3) or propofol plus sevoflurane inhalational anaesthesia (n = 4). The doses of anaesthetics were titrated to the same depth of anaesthesia (BIS 40-60). Subjects' cognitive performance was assessed using the Grooved Pegboard Test, Digit Symbol Substitution Test (DSST) and Mini Mental State examination (MMSE) for 7 days postoperatively. Serum m-BDNF concentrations were measured for 7 postoperative days.
RESULTS
In vitro Allopregnanolone and alfaxalone both activated h-PXR, alfaxalone being more efficacious than allopregnanolone: 50,000 nM, p = 0.0019; 16,700 nM, p = 0.0472; 5600 nM, p = 0.0031. Clinical Alfaxalone treated subjects scored better than propofol and sevoflurane anaesthetised patients in the cognition tests: (MMSE p = 0.0251; Grooved Pegboard test dominant hand pre v post anaesthesia scores p = 0.8438 for alfaxalone and p = 0.0156 for propofol and propofol/sevoflurane combined). The higher cognition scores were accompanied by higher serum m-BDNF levels in the alfaxalone anaesthetised patients (p < 0.0001).
CONCLUSIONS
These results suggest that sedation and anaesthesia induced by the synthetic neuroactive steroid alfaxalone may be accompanied by effects normally caused by physiological actions of allopregnanolone at PXR, namely, increased secretion of m-BDNF and consequent neuroprotection and preservation of cognition.
TRIAL REGISTRATION
The clinical trial was registered on 17/01/2018 with the Australian New Zealand Clinical Trials Registry: registration number ACTRN12618000064202 [Universal Trial Number U1111-1198-0412].
Topics: Humans; Propofol; Sevoflurane; Brain-Derived Neurotrophic Factor; Prospective Studies; Pregnanolone; Australia; Anesthetics, Intravenous; Anesthetics, Inhalation; Cognition; Anesthesia, Inhalation; Double-Blind Method
PubMed: 36564723
DOI: 10.1186/s12871-022-01940-x -
Molecular and Biochemical Parasitology May 2022The rapid spread of drug resistant malaria parasites has necessitated the search for novel antimalarials and chemosensitizers capable of reversing drug resistance in the...
Iloneoside, an antimalarial pregnane glycoside isolated from Gongronema latifolium leaf, potentiates the activity of chloroquine against multidrug resistant Plasmodium falciparum.
The rapid spread of drug resistant malaria parasites has necessitated the search for novel antimalarials and chemosensitizers capable of reversing drug resistance in the parasites. A number of studies have revealed the resistance reversal activities of pregnane glycosides and the antimalarial activity of a pregnane glycoside obtained from Gongronema species. However, the pregnane (2) and pregnane glycosides (1, 3-4) isolated from Gongronema latifolium leaf have not been evaluated for these activities. This study was therefore carried out to evaluate the antiplasmodial and chloroquine resistance reversal activities of a pregnane and three pregnane glycosides isolated from G. latifolium leaf in vitro. The compounds were evaluated for their inhibitory activities against P. falciparum 3D7 (a chloroquine-sensitive strain) and P. falciparum W2 (a chloroquine-resistant clone) in vitro. The activities of chloroquine in separate combination with each of the compounds against P. falciparum W2 were also evaluated. Moreover, the interaction of the active compounds (1 and 4) with selected P. falciparum proteins (PfProteins) were evaluated in silico. The results revealed that only 1 and 4 were active against P. falciparum 3D7 and P. falciparum W2. Also, 2 and 3 did not exhibit chloroquine resistance reversal activity. Activity of chloroquine against P. falciparum W2 was potentiated by 1 by 3200% at concentrations higher than 0.625 µg/mL. Also, 1 and 4 demonstrated similar binding patterns and higher binding tendencies to the selected PfProteins compared to chloroquine. Thus, 1 (iloneoside) is an antimalarial pregnane glycoside which can potentiate the activity of chloroquine against multidrug resistant P. falciparum.
Topics: Antimalarials; Apocynaceae; Chloroquine; Drug Resistance; Folic Acid Antagonists; Glycosides; Malaria, Falciparum; Plant Leaves; Plasmodium falciparum; Pregnanes
PubMed: 35307401
DOI: 10.1016/j.molbiopara.2022.111474 -
Cells Aug 2022The aim of this study was to evaluate the effect of acute aldosterone (ALDO) administration on the vascular permeability of skin. ALDO was injected intradermally into...
The aim of this study was to evaluate the effect of acute aldosterone (ALDO) administration on the vascular permeability of skin. ALDO was injected intradermally into rats, and vascular permeability was measured. Eplerenone (EPL), a selective mineralocorticoid receptor (MR) antagonist, was used. Skin biopsies were carried out for immunohistochemical (IHC) staining, and polymerase chain reactions were performed to analyze the expression of MR, 11β-hydroxysteroid dehydrogenase type 2, von Willebrand factor (vWF), vascular endothelial growth factor (VEGF), and zonula occludens 1. Our study showed the presence of MR in the rat skin vasculature for the first time. It was found that ALDO injection resulted in a more than 30% increase in vascular permeability and enhanced the endothelial exocytosis of vWF. The effect of ALDO diminished after EPL administration. An accumulation of vWF and a reduction in VEGF IHC staining were observed following chronic EPL administration. No effect of ALDO or EPL on the mRNA expression of the studied genes or skin structure was observed. The results suggest that ALDO increases vascular permeability in the skin via an MR-dependent mechanism. This effect of ALDO on skin microcirculation may have important therapeutic implications for diseases characterized by increased levels of ALDO and coexisting skin microangiopathy.
Topics: Aldosterone; Animals; Capillary Permeability; Eplerenone; Mineralocorticoid Receptor Antagonists; Rats; Vascular Endothelial Growth Factor A; von Willebrand Factor
PubMed: 36078114
DOI: 10.3390/cells11172707 -
Steroids May 2023From the dichloromethane (DCM) fraction of the crude ethanolic extract of Caralluma awdeliana, four pregnane glycosides and a flavone glycoside were isolated using a...
From the dichloromethane (DCM) fraction of the crude ethanolic extract of Caralluma awdeliana, four pregnane glycosides and a flavone glycoside were isolated using a bio-guided isolation approach. The different extracts of C. awdeliana were subjected to in vitro enzyme inhibitory assays of anticholinesterases (AChE and BChE) and anti-inflammatory (COXs and 5-LOX). The highest inhibitory activity was exhibited by DCM fraction against COX-1, COX-2, and 5-LOX with IC of 4.8 ± 0.5 μg/mL, 0.68 ± 0.2 μg/mL, and 39.5 ± 3.0 μg/mL, respectively. The DCM showed also a moderate activity against AChE (IC 384.72 ± 3.6 μg/mL), and BChE (IC 384.72 ± 3.6 μg/mL). The repeated chromatography of DCM fraction resulted in the isolation of two new pregnane glycosides, namely awdeliosides A (1) and B (4), two known ones, namely caratuberosides B and D, along with the known flavone glycoside identified as luteolin 4 -O-neohesperidoside. All the isolated compounds were tested for their in vitro enzyme inhibitory assays. Among the isolated compounds, awdelioside B (4) showed the most potent effect against COX-1 with IC value of 10.99 ± 0.35 μM, compared to standard celecoxib (IC 230.74 ± 2.62 μM). All the isolated compounds showed weak anticholinesterase, except a moderate activity observed for awdelioside B (4) against BChE with IC value of 15.63 ± 3.5 μM, compared to standard donepezil (IC 0.77 ± 0.0088 μM).
Topics: Plants, Medicinal; Cholinesterase Inhibitors; Plant Extracts; Yemen; Glycosides; Anti-Inflammatory Agents; Pregnanes; Flavones; Apocynaceae
PubMed: 36780968
DOI: 10.1016/j.steroids.2023.109198