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2021 ◽  
Vol 12 ◽  
Author(s):  
Ioanna Katsiadaki ◽  
Tamar I. Schwarz ◽  
Alex R. O. Cousins ◽  
Alexander P. Scott

Previous toxicokinetic studies have shown that mussels (Mytilus spp.) can readily absorb the three main mammalian sex steroids, estradiol (E2), testosterone (T) and progesterone (P) from water. They also have a strong ability to store E2 and the 5α-reduced metabolites of T and P in the form of fatty acid esters. These esters were shown to have half-lives that were measured in weeks (i.e. they were not subject to fast depuration). The present study looked at the toxicokinetic profile of two other common steroids that are found in water, the potent synthetic oestrogen, (ethinyl-estradiol) (EE2; one of the two components of ‘the pill’), and cortisol, a natural stress steroid in vertebrates. In the first three hours of uptake, tritiated EE2 was found to be taken up at a similar rate to tritiated E2. However, the levels in the water plateaued sooner than E2. The ability of the animals to both esterify and sulphate EE2 was found to be much lower than E2, but nevertheless did still take place. After 24 h of exposure, the majority of radiolabelled EE2 in the animals was present in the form of free steroid, contrary to E2, which was esterified. This metabolism was reflected in a much lower half-life (of only 15 h for EE2 in the mussels as opposed to 8 days for E2 and >10 days for T and P). Intriguingly, hardly any cortisol (in fact none at all in one of the experiments) was absorbed by the mussels. The implications of this finding in both toxicokinetic profiling and evolutionary significance (why cortisol might have evolved as a stress steroid in bony fishes) are discussed.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
H Y E M Elalfy ◽  
S M Rashad ◽  
A M Shafek ◽  
M A Alsamkary

Abstract Background Acquired inflammatory punctual stenosis is a disease commonly presented with epiphora and most common cause is long term treatment with preservative containing topical eye drops. The inflammation causes a decrease in the clearance of the medication and preservative, and their continued use will result in more inflammation and stenosis, and therefore a longer clearance time resulting in a higher concentration and longer transit time, leading to a vicious cycle. Objective This study was conducted to compare between the effectiveness of topical preservative free steroids eye drops and preservative free artificial tears in treatment of punctal edema in Egypt. Methods This prospective comparative study comprised 40 eyes with punctal edema. Group A: 20 eyes Patients in this group received preservative free hydrocortisone 2.5% eye drops 4 times daily for 1 week with tapering over 3 weeks and followed up after 1 month. And after 3 months. Group B: 20 eyes Patients in this group received one of the preservative free artificial tears available in market 4 times/day for 1 month. All subjects were subjected to history taking, slit lamp examination, Flourescene dye disappearance test for diagnosis and follow up once/month for 3 months and measuring the punctual diameter pretreatment, after 1 month and after 3 months. From treatment. Results Comparing the two groups, the study found that there was no statistically significant difference found between the two studied groups regarding punctual diameter pretreatment, at 1 month and at 3 months and a highly statistically significant symptomatic improvement after 3 months in preservative free steroids group more than the preservative free artificial tears group. Conclusion The present study compared the effectiveness of topical preservative free steroid eye drops and preservative free artificial tears as regards increase in punctual diameter and symptomatic improvement and found a statistically significant increase in symptomatic improvement in preservative free steroid group more than the preservative free artificial tears group as after 3 months and statistically significant increase in punctual diameters in both groups in comparison to control group.


2020 ◽  
Vol 17 (1) ◽  
pp. 56-60
Author(s):  
Keith Ong ◽  
Leonard Ong

Two patients with presumed benzalkonium chloride (BAK) corneal toxicity after routine cataract surgery are presented. Patient 1 had corneal stroma and Descemet’s membrane folds. Patient 2 had moderate superficial punctate epithelial erosions (SPEE). They were on Chlorsig, Maxidex, and Acular eye drops tds postoperatively. The corneas of these two patients improved when BAK was removed or minimized from the postoperative eye drop regimen. Two vials of 1 ml dexamethasone 4mg/ml for injection were added to Chlorsig 10 ml bottle to substitute for Maxidex eye drops. BAK toxicity should be suspected when the cornea is not as clear as expected postoperatively. A practical way to eliminate BAK from postoperative eye drops is described, and would be useful until pharmaceuticals mass-produce BAK-free steroid eye drops economically.


2018 ◽  
Vol 9 (1) ◽  
pp. 138-143 ◽  
Author(s):  
Chareenun Chirapapaisan ◽  
Pinnita Prabhasawat ◽  
Sabong Srivannaboon ◽  
Vatookarn Roongpoovapatr ◽  
Piyada Chitsuthipakorn

Purpose: We report a rare case of ocular injury due to potassium permanganate (KMnO4) granules in a child. Methods: This is a retrospective case report. Results: A 2-year-old boy was transferred to our emergency room with severe pain in his right eye, inflamed eyelids, and brownish stains on his fingers. Chemical injury was suspected. Copious eye irrigation was immediately performed. Diffuse brownish splotches were then observed at the inferior bulbar conjunctiva. Otherwise, systemic organs were intact. Complete eye exam under general anesthesia revealed a 5-mm epithelial defect at the central cornea, along with generalized conjunctival injection and limbal ischemia, inferiorly. Multiple semi-dissolved granules of KMnO4 trapped in the inferior fornix were identified. The chemical particles were gradually washed out and removed; however, the brownish stains remained. The patient received preservative-free steroid, antibiotic eye drops, and lubricants as regular management for mild to moderate degree of ocular burn. Pseudomembrane developed early and transformed into symblepharon within a few days after the injury. Membrane adhesion was lysed, and more aggressive medications were then substituted. Commercial amniotic membrane (PROKERA®) was also applied to promote wound healing and to prevent recurrence of symblepharon. The ocular surface was eventually restored, and corneal transparency was preserved. Conclusion: Ocular injury with the granular form of KMnO4 is rare. Its toxicity is comparable to concentrated KMnO4 solution. However, the dissolved particles that had been absorbed in the stained conjunctiva were continuously released and damaged the ocular surface more than we primarily anticipated. Awareness of this condition and prompt management yield a good treatment outcome.


2015 ◽  
Vol 13 (1) ◽  
pp. nrs.13003 ◽  
Author(s):  
Gene A. Morrill ◽  
Adele B. Kostellow ◽  
Raj K. Gupta

Steroid receptors of the nuclear receptor superfamily are proposed to be either: 1) located in the cytosol and moved to the cell nucleus upon activation, 2) tethered to the inside of the plasma membrane, or 3) retained in the nucleus until free steroid hormone enters and activates specific receptors. Using computational methods to analyze peptide receptor topology, we find that the “classical” nuclear receptors for progesterone (PRB/PGR), androgen (ARB/AR) and estrogen (ER1/ESR1) contain two transmembrane helices (TMH) within their ligand-binding domains (LBD). The MEMSAT-SVM algorithm indicates that ARB and ER2 (but not PRB or ER1) contain a pore-lining (channel-forming) region which may merge with other pore-lining regions to form a membrane channel. ER2 lacks a TMH, but contains a single pore-lining region. The MemBrain algorithm predicts that PRB, ARB and ER1 each contain one TMH plus a half TMH separated by 51 amino acids. ER2 contains two half helices. The TM-2 helices of ARB, ER1 and ER2 each contain 9–13 amino acid motifs reported to translocate the receptor to the plasma membrane, as well as cysteine palmitoylation sites. PoreWalker analysis of X-ray crystallographic data identifies a pore or channel within the LBDs of ARB and ER1 and predicts that 70 and 72 residues are pore-lining residues, respectively. The data suggest that (except for ER2), cytosolic receptors become anchored to the plasma membrane following synthesis. Half-helices and pore-lining regions in turn form functional ion channels and/or facilitate passive steroid uptake into the cell. In perspective, steroid-dependent insertion of “classical” receptors containing pore-lining regions into the plasma membrane may regulate permeability to ions such as Ca2+, Na+ or K+, as well as facilitate steroid translocation into the nucleus.


2013 ◽  
Vol 70 (3) ◽  
pp. 393-400 ◽  
Author(s):  
Keith B. Tierney ◽  
Matthew Kereliuk ◽  
Yogesh Kumar Katare ◽  
Alexander P. Scott ◽  
Stephen J. Loeb ◽  
...  

The round goby (Neogobius melanostomus) is an invasive fish in the Laurentian Great Lakes and beyond. Pheromones appear to be important for their reproductive success, as females are attracted to water in which reproductive males have resided (“conditioned water”). Previous investigation has shown conjugated and unconjugated forms of 3α-hydroxy-5β-androstane-11,17-dione (11-oxo-etiocholanolone; 11-O-ETIO) are released in the urine of these males. The goal of this study was to determine if the urine of reproductive males and fractionated extracts attract females. We found that reproductively active females were attracted to male urine and to isolates of male-conditioned water that contained conjugated 11-O-ETIO. The fractionated preparation that corresponded to unconjugated 11-O-ETIO (i.e., “free” steroid released via the gills of males) was not attractive to reproductive females, but curiously, it was attractive to nonreproductive females. Olfactory sensory deprivation confirmed that the behavioural responses were mediated by olfaction. These findings take us closer towards identifying the pheromone(s) that attract female gobies and, therefore, closer to having a method to limit this species' damaging invasion.


1992 ◽  
Vol 38 (9) ◽  
pp. 1830-1837 ◽  
Author(s):  
T Wong ◽  
C H Shackleton ◽  
T R Covey ◽  
G Ellis

Abstract Neonatal plasma contains interferents that increase the apparent 17 alpha-hydroxyprogesterone (17-OHP) content measured by direct (no-extraction) radioimmunoassay. We fractionated extracts from neonatal plasma pools by liquid chromatography with a Sephadex LH-20 column and measured 17-OHP immunoreactivity by a direct test kit. We found immunoreactivity in the free steroid and glucuronide fraction and also in the monosulfate fraction. We analyzed these two fractions by reversed-phase high-performance liquid chromatography (HPLC) and HPLC-mass spectrometry. We collected fractions and assayed for 17-OHP immunoreactivity. The HPLC fractions containing the interfering steroid monosulfates were analyzed by ion-spray mass spectrometry and, after solvolysis, by gas chromatography-mass spectrometry. Several monosulfates were identified, including those of 17 alpha-hydroxy-pregnenolone, 16 alpha-hydroxypregnenolone, pregnenolone, and several pregnenetriols. 17 alpha-Hydroxypregnenolone sulfate was the most significant interferent. Other commercially available 17-OHP assays showed similar interference when used without an extraction step. Kit manufacturers should select antibodies and protocols to minimize cross-reaction with sulfates, especially 17 alpha-hydroxypregnenolone sulfate.


1991 ◽  
Vol 69 (1) ◽  
pp. 104-110 ◽  
Author(s):  
A. P. Scott ◽  
Nancy M. Sherwood ◽  
A. V. M. Canario ◽  
Carol M. Warby

Milt from Pacific herring (Clupea harengus pallasi) was extracted and purified on reversed-phase high-performance liquid chromatography. The fractions were radioimmunoassayed for the following free and conjugated steroids: cortisol; 17α,20β-dihydroxy-4-pregnen-3-one; 17α,20α-dihydroxy-4-pregnen-3-one; 17α,21-dihydroxy-4-pregnene-3,20-dione; 17α,20β,21-trihydroxy-4-pregnen-3-one; 17α-hydroxy-4-pregnene-3,20-dione; 3α,17α,21-trihydroxy-5β-pregnan-20-one; testosterone; 11-ketotestosterone. Fractions containing significant amounts of immunoreactive material were subjected to further purification on thin-layer chromatography. Substantial amounts of cortisol (271 ng∙g−1 of milt) and 17α,20β-dihydroxy-4-pregnen- 3-one (ca. 38 ng∙g−1 of milt) were found in the free fractions of one of the extracts. Substantial amounts of cortisol (229 ng∙g−1 of milt), 17α,20β-dihydroxy-4-pregnen-3-one (25.7 ng∙g−1 of milt), and 3a, 17α,21-trihydroxy-5β-pregnan- 20-one (13 ng∙g−1 of milt) were found in the conjugated fractions of both extracts. Levels of the other steroids (free and conjugated) ranged from undetectable (<0.1) to 5.9 ng∙g−1 of milt. The possible reasons for the differences in free steroid levels between the extracts, and the potential role of the steroids as pheromones, are discussed.


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