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  • Cell & Developmental Biology  (89)
  • Biochemistry and Biotechnology  (49)
  • Diazepam  (14)
  • 1
    ISSN: 0173-0835
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: A procedure for the isolation of protein markers of epidermal differentiation in vitro is described. Human epidermal keratinocytes were cultured and radiolabelled in vitro. Fractionation was performed according to buoyant density (which reflects the degree of terminal differentiation) using Percoll density gradient centrifugation. Subpopulations of keratinocytes were characterised using light and electron microscopy, and proteins fractionated using high resolution two-dimensional gel electrophoresis. Radio-labelled proteins were detected using autoradiography and fluorography. Integral membrane proteins were characterised using Triton X-114 phase shift extraction. Data from this in vitro study were compared to silver stained gels of samples from intact epidermis (in vivo). We report quantitative differences between 14 specific protein moieties expressed in subpopulations of keratinocytes and identify some of these proteins. The differential expression of these protein markers and their possible use in the interpretation of the keratinocyte maturation pathway in cultured cells from patients with skin diseases are discussed.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0173-0835
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: A procedure is described for the detection of keratinocyte specific proteins. Fibroblasts and keratinocytes were isolated from human skin and radiolabelled in vitro. Samples were separated by two-dimensional polyacrylamide gel electrophoresis to compare the proteins synthesised by the different types of cultured skin cells. Dual label autoradiography of samples radiolabelled with [35S]methionine and [75Se]selenomethionine was used to identify keratinocyte specific proteins. We report 45 keratinocyte-specific components and identify some of these proteins. The differential expression of these proteins and their relevance to epidermal differentiation are discussed.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Electrophoresis 12 (1991), S. 579-584 
    ISSN: 0173-0835
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Using histochemical techniques an abnormal programme of epidermal differentiation has been well documented in psoriasis. In order to characterise further the biochemistry of this process we have cultured dermal fibroblasts and epidermal keratinocytes from involved psoriatic skin. This has facilitated metabolic radiolabelling of skin cells and analysis of protein synthesis by two-dimensional polyacrylamide gel electrophoresis. The expression of keratin and differentiation markers was identical to that of normal keratinocytes, suggesting that psoriatic epidermal differentiation is not truncated in vitro as has been postulated to be the case in vivo. Low molecular mass components (5-8.5 kDa), previously shown to be upregulated in suprabasal keratinocytes, were detected in epidermal fractions from psoriatic skin enriched for basal cells. Of especial interest was a component of 26 kDa, pI 5.9, which was highly upregulated in psoriatic as compared to normal cultured keratinocytes and was not detected in fibroblasts. These findings are in accord with a qualitatively abnormal pattern of differentiation for keratinocytes in the involved psoriatic epidermis.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Pharmacokinetics ; Bioavailability ; Drug absorption ; Benzodiazepines ; Diazepam ; Ethanol ; Drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Six healthy male or female volunteers ingested a single 5-mg tablet of diazepam with a typical ethanol-containing cocktail (1.5 ounces of 80-proof vodka plus 4 ounces of orange juice plus ice) or with a similar ethanol-free mixture (4 ounces of orange juice plus ice) in the fasting state on two occasions separated by at least 1 week. Diazepam concentrations in multiple plasma samples drawn from 15 min to 24 h after each dose were determined by electron-capture gas-liquid chromatography. Mean values of pharmacokinetic variables for diazepam taken without and with ethanol, respectively, were: peak plasma diazepam concentration, 221 vs. 208 ng/ml; time of peak concentration, 0.79 vs. 1.79 h after dosing (P〈0.1); apparent lag time prior to start of absorption, 16.5 vs. 26.2 min; apparent first-order absorption half-life, 19.3 vs. 34.6 min. The completeness of diazepam absorption, judged by the area under the 24-h plasma concentration curve, was nearly identical for the two conditions. Thus, coadministration of diazepam with the ethanol cocktail tended to slow the rate of diazepam absorption, but did not influence the completeness of absorption. Pharmacodynamic synergism of ethanol and diazepam, if it exists, cannot be attributed to enhancement of the rate or completeness of diazepam absorption.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 75 (1981), S. 380-382 
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Diazepam ; Desmethyldiazepam ; Protein binding ; Equilibrium dialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The binding of diazepam (DZ) and its major metabolite desmethyldiazepam (DMDZ) to plasma protein was evaluated in a series of controlled in vitro studies using equilibrium dialysis. Free fraction (FF) of both drugs alone changed significantly with total plasma drug concentration, but the increased FF (reduction in binding) did not occur until concentrations considerably exceeded those encountered during typical therapeutic use. Increasing concentrations of one drug at a time tended to increase FF for the other, although the effects were, at most, of borderline significance. Simultaneously increasing concentrations of both drugs led to significantly increased FF for both. Thus, DZ and DMDZ appear to bind to the same site or sites on plasma albumin. Binding is concentration-independent within and considerably above the usual therapeutic range.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 70 (1980), S. 89-93 
    ISSN: 1432-2072
    Keywords: Diazepam ; Benzodiazepines ; Cerebrospinal fluid ; Blood-brain barrier ; Protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Five dogs received a single 1.0 mg/kg dose of diazepam (DZ) IV. Concentrations of DZ and its major metabolite desmethyldiazepam (DMDZ) were simultaneously measured in plasma and cisternal cerebrospinal fluid (CSF) for up to 8 h after the dose by electron-capture gas-liquid chromatography. DZ was rapidly eliminated from plasma (half-life 0.3–1.3 h); DZ disappearance was mirrored by formation of DMDZ, which in turn was eliminated slowly. Both DZ and DMDZ rapidly penetrated CSF and concentrations in CSF declined parallel with those in plasma. Despite rapid uptake, the extent of CSF transfer of DZ and DMDZ was limited by plasma protein binding. Mean CSF: plasma concentration ratios for DZ (range 0.023–0.137) and DMDZ (range 0.047–0.119) were highly correlated with the unbound fraction in plasma (r=0.95 and 0.80, respectively). Thus DZ and DMDZ concentrations in CSF, presumed to reflect concentrations at the site of action, are determined by unbound plasma concentrations. The intensity of pharmacologic action is more likely to correlate with unbound than with total plasma concentrations.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 73 (1981), S. 381-383 
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Diazepam ; Oxazepam ; Overdosage ; Plasma concentration ; Poisoning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Plasma concentrations and their relation to clinical outcome were evaluated in 21 patients who reached emergency treatment facilities following acute overdosage with benzodiazepine derivatives. Diazepam was implicated in 18 of the 21 cases, with plasma diazepam levels ranging from 585–8,635 ng/ml. In four cases of overdosage with diazepam alone, patients were minimally sedated and were discharged within 24 h, despite diazepam doses as high as 750 mg and plasma levels as high as 4,792 ng/ml. However, concurrent ingestion of diazepam together with other central depressant drugs (such as ethanol, barbiturates, analgesics, or tricyclic antidepressants) produced serious intoxication in 5 of the remaining 14 patients, regardless of the diazepam dosage or plasma concentration. Thus the severity of poisoning following benzodiazepine overdosage is determined largely by co-ingestion of other central depressants rather than the amount of benzodiazepine ingested or its concentration in plasma.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 87 (1985), S. 242-246 
    ISSN: 1432-2072
    Keywords: Diazepam ; Tolerance ; Initial treatment phenomenon ; Conflict behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The initial treatment phenomenon (ITP) to diazepam was investigated using a conditioned suppression of drinking (CSD) paradigm. Female Sprague-Dawley rats were trained to a stable baseline of punished and unpunished responses in the CSD paradigm. In Experiment 1, a control group (1) received vehicle after the CSD session on each of seven drug test days, while group 2 was treated with 3.0 mg/kg diazepam IP after each of these sessions. On drug test days 8–12, diazepam was administered to both groups before the CSD session. Drug test days were separated by 2–3 days when the animals were untreated but performed in the CSD. Prior exposure to diazepam in group 2 after sessions 1–7 conditioned the animals so that a greater release in punished behavior was seen during sessions 8–12 than in the control group (1). In Experiment 2, one group (3) of rats was administered diazepam vehicle after the CSD session for 4 drug test days and another group (4) was injected with 5.6 mg/kg diazepam after the CSD session on these same days. On the next 4 drug test days both groups received diazepam before they performed in the CSD. An ITP was observed in both the control (3) and the drug-conditioned (4) group, although the ITP was less obvious in the conditioned group. After a 28-day period of CSD exposure without vehicle or drug treatments, 5.6 mg/kg diazepam was administered to both groups before the CSD session for an additional 8 drug test days. During this last period both groups exhibited an ITP with no essential differences. These experiments demonstrate that the initial treatment phenomenon is complex, involving several components that include a behavioral tolerance to the disruptive effect of diazepam.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2072
    Keywords: Calcium antagonists ; Withdrawal ; Diazepam ; Dantrolene ; Nimodipine ; Brain concentration ; Tremor ; Vehicle effects ; Ethanol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The calcium antagonists nimodipine and dantrolene were compared with diazepam in an animal model of tolerance and physical dependence upon ethanol. Nimodipine and dantrolene were both effective in suppressing withdrawal tremors but diazepam was clearly superior to both agents. These results suggest that the ethanol with-drawal syndrome is only partially mediated by increased calcium flux.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Pharmacokinetics ; Diazepam ; Desmethyldiazepam ; Ratbrain ; Ratplasma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of diazepam (DZ) and its major metabolite desmethyldiazepam (DMDZ) in both plasma and brain after a single 5 mg/kg IP dose of diazepam were studied in rats. Four rats were sacrificed at 5 min, 15 min, 30 min, 1 h, 1.5, 2, 3, 4, 5 and 6 h after the dose. DZ rapidly disappeared from plasma and brain in parallel, with nearly identical overall half-lives of 0.88 and 0.89 h, respectively. Apparent volume of distribution was 19.3 1/kg and the apparent total clearance was 255 ml/kg/min. Free fractions were 19.6% and 15.8% for DZ and DMDZ, respectively. DMDZ rapidly appeared in both plasma and brain. Thereafter, DMDZ was likewise eliminated in parallel from both compartments, with nearly identical half-lives of disappearance from plasma (1.11 h) and brain (1.09 h). The rapid elimination of DZ was due to its very high clearance. Brain to plasma concentration ratios did not differ significantly over time either for DZ or for DMDZ. The overall ratios (mean±SE) were 4.5±0.1 for DZ and 3.5±0.2 for DMDZ. Equilibrium was attained at no more than 5 min after dose for both DZ and DMDZ. No evidence was found for persistence or sequestration of DZ or DMDZ in brain longer than could be predicted on the basis of first-order exponential disappearance.
    Type of Medium: Electronic Resource
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