The Experts below are selected from a list of 128400 Experts worldwide ranked by ideXlab platform
C.j. Kenyon - One of the best experts on this subject based on the ideXlab platform.
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Regulation of adrenocortical steroidogenesis by Benzodiazepines
The Journal of Steroid Biochemistry and Molecular Biology, 1995Co-Authors: I. Thomson, Robert Fraser, C.j. KenyonAbstract:Abstract Benzodiazepines affect steroidogenesis in at least four ways depending on concentration and adrenocortical cell type. Firstly, at micromolar concentrations, they inhibit steroidogenic enzymes. Competition for microsomal 17- and 21-hydroxylase activity explains the inhibition of ACTH-stimulated aldosterone and cortisol synthesis by diazepam and midazolam. At slightly higher concentrations, we have evidence that 11β-hydroxylase activity is also inhibited. Secondly, at sub-micromolar concentrations, calcium influx is inhibited. T-type and L-type calcium channels appear to be blocked, this impairs signal response coupling and, in particular, decreases angiotensin-and K + -stimulated aldosterone synthesis in zona glomerulosa cells. Thirdly, the mitochondrion of steroidogenic tissues is a sensitive site for the stimulatory effects of Benzodiazepines. Aldosterone synthesis from added HDL-cholesterol by cultured bovine zona glomerulosa cells is stimulated by diazepam, RO5-4864 and PK11195. The fourth site of benzodiazepine's effect on steroidogenesis is particular to zona glomerulosa cells. In addition to cholesterol side chain cleavage, the final part of the aldosterone biosynthetic pathway, the conversion from deoxycorticosterone is controlled. Although high micromolar concentrations of diazepam appear to be inhibitory, lower nanomolar concentrations stimulate the synthesis of aldosterone from added deoxycorticosterone. In vivo , a fifth site of benzodiazepine activity may influence plasma steroid concentrations. Competition between steroids and Benzodiazepines for hepatic clearance enzymes may affect half lives of both drugs and hormones.
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Regulation of adrenocortical steroidogenesis by Benzodiazepines.
The Journal of steroid biochemistry and molecular biology, 1995Co-Authors: I. Thomson, Robert Fraser, C.j. KenyonAbstract:Benzodiazepines affect steroidogenesis in at least four ways depending on concentration and adrenocortical cell type. Firstly, at micromolar concentrations, they inhibit steroidogenic enzymes. Competition for microsomal 17- and 21-hydroxylase activity explains the inhibition of ACTH-stimulated aldosterone and cortisol synthesis by diazepam and midazolam. At slightly higher concentrations, we have evidence that 11 beta-hydroxylase activity is also inhibited. Secondly, at sub-micromolar concentrations, calcium influx is inhibited. T-type and L-type calcium channels appear to be blocked, this impairs signal response coupling and, in particular, decreases angiotensin- and K(+)-stimulated aldosterone synthesis in zona glomerulosa cells. Thirdly, the mitochondrion of steroidogenic tissues is a sensitive site for the stimulatory effects of Benzodiazepines. Aldosterone synthesis from added HDL-cholesterol by cultured bovine zona glomerulosa cells is stimulated by diazepam, RO5-4864 and PK11195. The fourth site of benzodiazepine's effect on steroidogenesis is particular to zona glomerulosa cells. In addition to cholesterol side chain cleavage, the final part of the aldosterone biosynthetic pathway, the conversion from deoxycorticosterone is controlled. Although high micromolar concentrations of diazepam appear to be inhibitory, lower nanomolar concentrations stimulate the synthesis of aldosterone from added deoxycorticosterone. In vivo, a fifth site of benzodiazepine activity may influence plasma steroid concentrations. Competition between steroids and Benzodiazepines for hepatic clearance enzymes may affect half lives of both drugs and hormones.
Di Liang - One of the best experts on this subject based on the ideXlab platform.
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Prescription drug monitoring programs and drug overdose deaths involving Benzodiazepines and prescription opioids
Drug and Alcohol Review, 2019Co-Authors: Di LiangAbstract:BACKGROUND AND AIMS: In the US, benzodiazepine overdose deaths increased at an alarming rate in the past two decades. Benzodiazepines were also the most common drugs involved in prescription opioid overdose deaths. Benzodiazepine prescribing has been monitored by Prescription Drug Monitoring Programs (PDMPs), but little was known about whether PDMPs reduced drug overdose deaths involving Benzodiazepines. DESIGN AND METHODS: This study used a difference-in-difference design with state-quarter aggregate data on drug overdose deaths. The primary data source was Mortality Multiple Cause Files in 1999-2016. Three age-adjusted rates of drug overdose deaths were examined, including those involving Benzodiazepines, those involving prescription opioids, and those involving both Benzodiazepines and prescription opioids. The policy variables included PDMP data access for Benzodiazepines and mandatory use of PDMP data for Benzodiazepines. Linear multivariable regressions were used to assess the associations of PDMP policies specific to Benzodiazepines with drug overdose death rates, controlling for other state-level policy and socioeconomic factors, state and time fixed effects, and state-specific time trends. RESULTS: No significant associations were found between PDMP data access for Benzodiazepines and changes in drug overdose death rates involving Benzodiazepines and/or prescription opioids. Similarly, no significant associations were found between mandatory use of PDMP data for Benzodiazepines and changes in drug overdose death outcomes. DISCUSSION AND CONCLUSIONS: This study suggested no evidence that PDMP policies specific to Benzodiazepines were associated with reduction in benzodiazepine overdose death rates. Future research is warranted to examine detailed features of PDMPs and continuously monitor the impacts of PDMP policies on benzodiazepine-related consequences.
Vassilios Papadopoulos - One of the best experts on this subject based on the ideXlab platform.
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peripheral type benzodiazepine diazepam binding inhibitor receptor biological role in steroidogenic cell function
Endocrine Reviews, 1993Co-Authors: Vassilios PapadopoulosAbstract:I. Introduction Benzodiazepines, a class of drugs that includes compounds such as diazepam (Valium), are frequently prescribed because of their anxiolytic, anticonvulsant, musclerelaxant, and hypnotic properties. It has been shown that the pharmacological effects of Benzodiazepines are mediated via a specific receptor complex located in the central nervous system (CNS); Benzodiazepines bind to a domain that allosterically regulates chloride channel gating by γ-aminobutyric acid (GABA), on GABAA receptors (1–3). In 1977, while searching for specific benzodiazepine receptors, Braestrup and Squires (4) observed the presence of high density radiolabeled diazepam binding sites in the kidney. Since then, numerous papers have reported that this class of benzodiazepine binding sites is present apparently in all tissues examined including the CNS (Section III). Because of their abundance in peripheral tissues and in order to distinguish them from the GABAA or central benzodiazepine receptors, this class of benzodi...
Nikole Pecora - One of the best experts on this subject based on the ideXlab platform.
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endogenous benzodiazepine like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy
Gut, 1998Co-Authors: Rossella Avallone, Ilaria Venturini, Claudia Baraldi, Maria Luisa Zeneroli, Franco Farina, M. Kleinschnitz, Carlo Ferrarese, Lorenzo Corsi, Peter Schreier, Nikole PecoraAbstract:Background/Aim—Despite some controversy, it has been suggested that endogenous benzodiazepine plays a role in the pathogenesis of hepatic encephalopathy. The aim of the present study was to evaluate the concentrations of endogenous Benzodiazepines and the peptide, diazepam binding inhibitor, in the blood of patients with liver cirrhosis with and without overt encephalopathy, and to compare these levels with those of consumers of commercial Benzodiazepines. Subjects—Normal subjects (90), benzodiazepine consumers (14), and cirrhotic patients (113) were studied. Methods—Endogenous Benzodiazepines were measured by the radioligand binding technique after high performance liquid chromatography (HPLC) purification. The presence of diazepam and N-desmethyldiazepam was assayed by HPLC-electrospray tandem mass spectrometry. Diazepam binding inhibitor was studied in serum by radioimmunoassay. Results—Endogenous Benzodiazepines were below the limit of detection in 7% of patients with encephalopathy. When detectable, their levels were at least comparable with those of benzodiazepine consumers and correlated with the liver dysfunction but not the stage of encephalopathy. Serum levels of diazepam binding inhibitor tended to decrease when endogenous Benzodiazepines levels increased. Conclusions—Endogenous Benzodiazepines may accumulate in patients with liver cirrhosis during the course of the disease, and the phenomenon appears to be independent of the presence or absence of encephalopathy. Keywords: benzodiazepine consumers; diazepam binding inhibitor; endogenous Benzodiazepines; liver cirrhosis; overt hepatic encephalopathy
I. Thomson - One of the best experts on this subject based on the ideXlab platform.
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Regulation of adrenocortical steroidogenesis by Benzodiazepines
The Journal of Steroid Biochemistry and Molecular Biology, 1995Co-Authors: I. Thomson, Robert Fraser, C.j. KenyonAbstract:Abstract Benzodiazepines affect steroidogenesis in at least four ways depending on concentration and adrenocortical cell type. Firstly, at micromolar concentrations, they inhibit steroidogenic enzymes. Competition for microsomal 17- and 21-hydroxylase activity explains the inhibition of ACTH-stimulated aldosterone and cortisol synthesis by diazepam and midazolam. At slightly higher concentrations, we have evidence that 11β-hydroxylase activity is also inhibited. Secondly, at sub-micromolar concentrations, calcium influx is inhibited. T-type and L-type calcium channels appear to be blocked, this impairs signal response coupling and, in particular, decreases angiotensin-and K + -stimulated aldosterone synthesis in zona glomerulosa cells. Thirdly, the mitochondrion of steroidogenic tissues is a sensitive site for the stimulatory effects of Benzodiazepines. Aldosterone synthesis from added HDL-cholesterol by cultured bovine zona glomerulosa cells is stimulated by diazepam, RO5-4864 and PK11195. The fourth site of benzodiazepine's effect on steroidogenesis is particular to zona glomerulosa cells. In addition to cholesterol side chain cleavage, the final part of the aldosterone biosynthetic pathway, the conversion from deoxycorticosterone is controlled. Although high micromolar concentrations of diazepam appear to be inhibitory, lower nanomolar concentrations stimulate the synthesis of aldosterone from added deoxycorticosterone. In vivo , a fifth site of benzodiazepine activity may influence plasma steroid concentrations. Competition between steroids and Benzodiazepines for hepatic clearance enzymes may affect half lives of both drugs and hormones.
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Regulation of adrenocortical steroidogenesis by Benzodiazepines.
The Journal of steroid biochemistry and molecular biology, 1995Co-Authors: I. Thomson, Robert Fraser, C.j. KenyonAbstract:Benzodiazepines affect steroidogenesis in at least four ways depending on concentration and adrenocortical cell type. Firstly, at micromolar concentrations, they inhibit steroidogenic enzymes. Competition for microsomal 17- and 21-hydroxylase activity explains the inhibition of ACTH-stimulated aldosterone and cortisol synthesis by diazepam and midazolam. At slightly higher concentrations, we have evidence that 11 beta-hydroxylase activity is also inhibited. Secondly, at sub-micromolar concentrations, calcium influx is inhibited. T-type and L-type calcium channels appear to be blocked, this impairs signal response coupling and, in particular, decreases angiotensin- and K(+)-stimulated aldosterone synthesis in zona glomerulosa cells. Thirdly, the mitochondrion of steroidogenic tissues is a sensitive site for the stimulatory effects of Benzodiazepines. Aldosterone synthesis from added HDL-cholesterol by cultured bovine zona glomerulosa cells is stimulated by diazepam, RO5-4864 and PK11195. The fourth site of benzodiazepine's effect on steroidogenesis is particular to zona glomerulosa cells. In addition to cholesterol side chain cleavage, the final part of the aldosterone biosynthetic pathway, the conversion from deoxycorticosterone is controlled. Although high micromolar concentrations of diazepam appear to be inhibitory, lower nanomolar concentrations stimulate the synthesis of aldosterone from added deoxycorticosterone. In vivo, a fifth site of benzodiazepine activity may influence plasma steroid concentrations. Competition between steroids and Benzodiazepines for hepatic clearance enzymes may affect half lives of both drugs and hormones.
