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Polimery W Medycynie 2016The aim of this work was to compare different chemical substances used in the treatment of ganglions located in the hand and wrist region. Their basic properties and... (Review)
Review
The aim of this work was to compare different chemical substances used in the treatment of ganglions located in the hand and wrist region. Their basic properties and mechanisms of action have been described. Moreover, the risks associated with the use of particular substances have been highlighted and potential complications connected with their administration have been discussed. On the basis of the available literature, the results of ganglion aspiration treatment followed by an injection of a chemical substance into the cyst cavity have been assessed. In the authors' opinion, due to the existing risk of complications associated with this treatment, as well as the relatively high rate of ganglion recurrence, this procedure should only be performed by qualified medical personnel. The authors recommend observation in cases of asymptomatic ganglions of the hand and wrist, and operative treatment in cases in which pain, restriction of limb mobility and weakening of handgrip strength are observed.
Topics: Anti-Inflammatory Agents; Ganglion Cysts; Hand; Humans; Hyaluronoglucosaminidase; Pregnanes; Recurrence; Sodium Tetradecyl Sulfate; Treatment Outcome; Wrist
PubMed: 28397424
DOI: 10.17219/pim/64803 -
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 -
Drug Metabolism and Disposition: the... Oct 2017The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that regulate the expression of...
The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are closely related transcription factors that regulate the expression of phase I (cytochrome P450s) and phase II metabolizing enzymes and transporter genes in response to stimulation from xenobiotics, including prescription drugs. PXR and CAR knockout and humanized mouse models have proven useful. However, the rat being bigger in size is a preferred model system for studying drug metabolism and pharmacokinetics. Here, we report the creation and preliminary characterization of PXR and CAR knockout rats and PXR/CAR double knockout rats. Whereas the expression of phase I and II enzymes and transporter genes were not upregulated by nuclear receptor-specific agonists pregnenlone-16-carbonitrile and 1,4-bis-[2-(3,5-dichloropyridyloxy)] benzene in the knockout rats, confirming the disruption of respective nuclear receptor(s), our data demonstrate that PXR appears to suppress the basal expression levels of Cyp2b2, Cyp3a23/3a1, Cyp3a2, Cyp3a18, and Ugt2b1 genes, while CAR maintains Cyp2b2 and Ugt2b1 and suppresses Cyp3a9 basal expression levels. In wild-type rats, agonist binding of the nuclear receptors relieves the suppression, and target genes are expressed at levels comparable to knockout rats, with or without drug treatment. Overall, our findings are in good agreement with data obtained from human primary hepatocytes, nuclear receptor knockout cell lines, and mouse knockout models. We believe these models are a useful complement to their mouse counterparts for drug development and as importantly, for functional studies on metabolic pathways involving nuclear receptors.
Topics: Animals; Constitutive Androstane Receptor; Cytochrome P-450 Enzyme System; Female; Gene Knockout Techniques; Hepatocytes; Liver; Male; Metabolic Detoxication, Phase I; Metabolic Detoxication, Phase II; Pregnane X Receptor; Pregnenolone Carbonitrile; Rats; Rats, Sprague-Dawley; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid
PubMed: 28716828
DOI: 10.1124/dmd.117.075788 -
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 -
Phytochemistry Jun 2023Phytochemical investigation on the stems of Strophanthus divaricatus led to the isolation of four undescribed cardiac glycosides and one undescribed C pregnane, together...
Phytochemical investigation on the stems of Strophanthus divaricatus led to the isolation of four undescribed cardiac glycosides and one undescribed C pregnane, together with eleven known steroids. Their structures were elucidated by a comprehensive analysis of HRESIMS, 1D and 2D NMR spectra. The absolute configuration of 16 was determined by comparison of the experimental and computed ECD spectra. Compounds 1-13 and 15 displayed potent to significant cytotoxicity against human cancer cell lines K562, SGC-7901, A549 and HeLa with IC values of 0.02-16.08, 0.04-23.13, 0.06-22.31 and 0.06-15.13 μM, respectively.
Topics: Humans; Strophanthus; Glycosides; Pregnanes; Antineoplastic Agents; Cell Line, Tumor; Molecular Structure
PubMed: 37019169
DOI: 10.1016/j.phytochem.2023.113668 -
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 -
Frontiers in Endocrinology 2023
Topics: Humans; Aldosterone; Hydrocortisone; Neurosecretory Systems; Cardiovascular Diseases
PubMed: 37964959
DOI: 10.3389/fendo.2023.1295655 -
Theriogenology Jul 2016Analytical advancements, especially methods using gas or liquid chromatography tandem mass spectrometry, have allowed more specific and reliable measurement of multiple... (Review)
Review
Analytical advancements, especially methods using gas or liquid chromatography tandem mass spectrometry, have allowed more specific and reliable measurement of multiple steroid hormones in the plasma of mares throughout gestation and the periparturient period. Data such as these will form the central focus of this review. The comprehensive analyses possible with liquid chromatography tandem mass spectrometry illuminate the key physiological and developmental transitions that make equine gestation unique. Weeks 6 to 20 encompass endometrial cup formation and equine chorionic gonadotropic secretion that stimulates primary corpora lutea and induces formation of secondary luteal structures. The period is defined by increased progesterone, 17OH-progesterone, and androstenedione secretion, providing substrate feeding the rise in estrone sulfate that can be used as an aid in the diagnosis of pregnancy. The 5α-reduced metabolite of progesterone, dihydroprogesterone (DHP), parallels progesterone secretion during this period at less than half the concentration. After week 12, progesterone declines, but DHP concentrations continue to increase, exceeding progesterone by week 16, thereby defining the luteo-placental shift in pregnane synthesis from ovarian to primarily placental thereafter. The growth of fetal gonads begins around week 14 and is defined by increasing dehydroepiandrosterone, among other androgens, which fuels placental estrogen secretion, functioning as a true fetoplacental unit. Metabolites of DHP (including allopregnanolone) dominate in late gestation, some exceeding DHP by 10-fold near term. However, all major pregnanes decrease from 3 days before foaling, when fetal cortisol is reportedly rising. Though unique, equine pregnancy and parturition share many features in common with those seen in human pregnancy and birth.
Topics: Animals; Female; Horses; Parturition; Pregnancy; Pregnancy, Animal; Progesterone
PubMed: 27156685
DOI: 10.1016/j.theriogenology.2016.04.049 -
Steroids Feb 2017Spironolactone is a well-known multi-target drug and is specifically used for the treatment of high blood pressure and heart failure. It is also used for the treatment... (Review)
Review
Spironolactone is a well-known multi-target drug and is specifically used for the treatment of high blood pressure and heart failure. It is also used for the treatment of edema, cirrhosis of the liver, malignant, pediatric, nephrosis and primary hyperaldosteronism. Spironolactone in association with thiazide diuretics treats hypertension and in association with furosemide treats bronchopulmonary dyspepsia. The therapeutic mechanism of action of spironolactone involves binding to intracellular mineralocorticoids receptors (MRs) in kidney epithelial cells, thereby inhibiting the binding of aldosterone. Since its first synthesis in 1957 there are several synthetic approaches have been reported throughout the years, Synthetic community has devoted efforts to improve the synthesis of spironolactone and to synthesize its analogues and derivatives. This review aims to provide comprehensive insight for the synthetic endeavors devoted towards the synthesis of a versatile drug spironolactone and its analogues/derivatives.
Topics: Aldosterone; Androstadienes; Androstenes; Animals; Canrenone; Chloranil; Dehydroepiandrosterone; Eplerenone; Humans; Molecular Structure; Receptors, Mineralocorticoid; Spironolactone
PubMed: 28041953
DOI: 10.1016/j.steroids.2016.12.010