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At least 19 recordsLinked to original sources
PubMed1992

Clinical distinctions between long-acting and short-acting benzodiazepines.

After their clinical introduction in the 1960s, the benzodiazepines rapidly became the most widely prescribed sedative/hypnotics because of their many advantages over barbiturates and other older agents. Along with this popularity came controversy, which has continued to this day. The most recent form this has taken has been the concern that the short-acting benzodiazepines may have a predisposition to induce certain forms of clinical complications. The author reviews the historical framework in which this controversy arose. In the late 1970s and early 1980s, it became increasingly clear that long-acting agents were associated with daytime sedation as well as cognitive and psychomotor impairment, particularly in the elderly. The short-acting benzodiazepines, which greatly reduced the frequency of these types of effects, rapidly became the most widely prescribed agents. A growing body of data indicates that the short-acting hypnotics are less likely to be associated with falls and hip fractures in the elderly and also have less respiratory depressant qualities, compared with the older long-acting agents. The short-acting compounds may also be more efficacious in inducing sleep during the first night of administration. In contrast, the long-acting agents may be more desirable in those cases in which daytime sedation is desired and may be associated with a delayed and milder withdrawal sleep disturbance. With the short-acting agents, however, sleep disturbance upon drug cessation is dose dependent and may be greatly reduced by tapering the dose.

Accidental Falls↗
PubMedDate not supplied

Improved phenotyping of alpha 1-antichymotrypsin (ACT) by isoelectric focusing and immunoprinting: first demonstration of a deficient protein variant in the ACT system.

Genetic variation of human alpha 1-antichymotrypsin (ACT) was investigated in sera using thin-layer polyacrylamide gel isoelectric focusing (pH range 4.0-6.5) followed by immunoprinting with a monospecific anti-human ACT antibody. Sialidase-treated samples showed a microheterogeneous banding pattern which consisted of two major and several additional minor components with isoelectric points between pH 5.0 and 5.3. A population study of 200 unrelated individuals from southern Germany revealed no genetic variation. In a clinical investigation, however, we found a unique banding pattern in a female patient suffering from chronic obstructive pulmonary disease. In comparison with the monomorphic normal type the detected variant phenotype shows two additional bands that have lower intensities and are located cathodically to their major bands. Inheritance of the deficient IEF variant "ACT Bochum" was confirmed by a family study. To our knowledge this is the first genetic ACT mutant to be observed at the protein level.

Female↗
PubMed1992

The pharmacokinetics of two different concentrations of short-acting insulin, intermediate-acting insulin, and an insulin mixture following subcutaneous injection.

To compare the pharmacokinetics of two different concentrations, containing either 40 or 100 IU/ml of short-acting human insulin (Velasulin HM), intermediate-acting human insulin (Insulatard HM), or an insulin mixture (25% short-acting insulin, 75% intermediate-acting insulin; Mixtard HM), three randomized, single-blind, crossover trials were performed using the euglycemic clamp technique. Eighteen healthy volunteers received insulin of either formulation subcutaneously in each of the studies (15 IU Velasulin, 20 IU Insulatard, or Mixtard). The blood glucose levels were maintained constant by glucose infusions. In the trial using Velasulin, the two different insulin concentrations were equivalent regarding the total absorption [area under the curve (AUC) of serum insulin: 126 +/- 28 and 123 +/- 35 mU/l x 12 h for U40 and U100 (mean +/- SD)], but not in regard to the rate of absorption (t max 1.3 +/- 0.4 and 2.4 +/- 1.0 h for U40 and U100). In the case of Insulatard, total absorption was not equivalent (AUC 153 +/- 35 and 128 +/- 37 ml/l x 24 h for U40 and U100), but the rate of absorption was equivalent (t max 4.8 +/- 2.9 and 5.3 +/- 4.6 h). In the Mixtard series, total absorption was equivalent (AUC 142 +/- 32 and 128 +/- 22 mU/l x 24 h), but the rate of absorption was not (t max 2.2 +/- 0.9 and 3.2 +/- 4.2 h for U40 and U100). The glucose requirement was not equivalent in each of the three series.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1976

Comparative efficacy of short-acting and long-acting quinidine for maintenance of sinus rhythm after electrical conversion of atrial fibrillation.

Forty patients with chronic atrial fibrillation, apparently unrelated to any overt heart disease, were randomly allocated to two groups after restoration of sinus rhythm by direct current shock. The patients in group A were given 4 daily doses of quinidine polygalacturonate, while those in group B were given 2 daily doses of a long-acting quinidine preparation, quinidine arabogalactan sulphate. The percentage of early relapses (within the first month following DC shock) was not significantly different in the two groups: 44-4% in group A and 35% in group B (P greater than 0-50). On the other hand, there were fewer late relapses with long-acting quinidine. After 18 months of treatment, 27-8% of patient in group A remained in sinus rhythm, compared with 61% in group B (P less than 0-05). The average amount of quinidine actually ingested by the patients in group A was smaller than that in group B. However, this could not entirely account for the difference observed in the incidence of relapse since with short-acting quinidine the proportion of patients remaining in sinu rhythm was similar whether the dose was decreased or not. The incidence of gastrointestinal side-effects was the same in the two groups and there were no seriou complications that could be attributed to treatment. It is concluded that long-acting quinidine preparations are more effective than conventional quinidine in preventing late relapses of atrial fibrillation.

Aged↗
PubMed1975

A radio-ligand receptor assay for the long-acting thyroid stimulator. Inhibition by the long-acting thyroid stimulator of the binding of radioiodinated thyroid-stimulating hormone to human thyroid membranes.

Highly purified bovine TSH (thyroid-stimulating hormone) was labelled with 125I by using very low concentrations of chloramine-T. Human thyroid membranes prepared by discontinuous sucrose-density-gradient centrifugation were homogeneous on examination by electron microscopy. Incubation of radioiodinated TSH with the membranes showed that radioactivity could be bound to the membranes. Under the experimental conditions described here, binding was dependent on time and temperature and was a saturable phenomenon. Preincubation of the membranes with unlabelled hormone inhibited the subsequent binding of 125I-labelled TSH. Similarly, inhibition by the long-acting thyroid stimulator also showed a saturation behaviour. A rapid and sensitive method for the detection of the long-acting thyroid stimulator is described.

Cell Membrane↗
PubMed1992

The TACPyAT repeats in the chalcone synthase promoter of Petunia hybrida act as a dominant negative cis-acting module in the control of organ-specific expression.

Analysis of the expression of the GUS reporter gene driven by various regions of the Petunia hybrida chalcone synthase (chsA) promoter revealed that the developmental and organ-specific expression of the chsA gene is conferred by a TATA proximal module located between -67 and -53, previously designated as the TACPyAT repeats. Histochemical analysis of GUS reporter gene expression revealed that the organ-specific 67 bp promoter fragment directs the same cell-type specificity as a 530 bp promoter, whereas additional enhancer sequences are present within the more TATA distal region. Moreover, the region between -800 and -530 is also involved in extending the cell-type specificity to the trichomes of flower organs and of young seedlings. The mechanism by which the TACPyAT repeats modulate expression during plant development was studied by analysing the expression of the GUS gene driven by chimeric promoters consisting of the CaMV 35S enhancer (domain B, -750 to -90) fused to various chsA 5' upstream sequences. Detailed enzymatic and histochemical analysis revealed that in the presence of the TACPyAT module the CaMV 35S region only enhances GUS activity in those organs in which the chsA promoter is normally active. Furthermore, this analysis shows that enhancement in the presence of the CaMV 35S domain B is accomplished by increasing the number of cell types expressing the GUS gene within the organ, rather than enhancement of the chsA cell-type-specific expression within these organs. Deletion of the TACPyAT sequences in the chimeric promoter construct completely restores the well-documented CaMV 35S domain B cell-type specificity, showing that the TACPyAT module acts as a dominant negative cis-acting element which controls both organ and developmental regulation of the chsA promoter activity.

Acyltransferases↗
PubMed1979

Evidence that both long-acting thyroid stimulator and long-acting thyroid stimulator-protector stimulate the human thyroid gland.

Thyroid-stimulating immunoglobulins were prepared from two potent sera, one contained long-acting thyroid stimulator (LATS) and the other contained both LATS and LATS-protector (LATS-P). The potencies of the immunoglobulin G (IgG) preparations were estimated in the McKenzie assay. The accumulation of cyclic AMP in mouse thyroid lobes was stimulated only by LATS--IgG; LATS-P--IgG was inactive. In contrast, both LATS-IgG and LATS-P--IgG were equally effective in slices of human thyroid.

Animals↗
PubMed1992

Functional analysis of the true late human cytomegalovirus pp28 upstream promoter: cis-acting elements and viral trans-acting proteins necessary for promoter activation.

As a model for analyzing the regulation of human cytomegalovirus late genes, we investigated the 28-kDa phosphoprotein (pp28) gene region. Transcripts of 1.6 and 1.3 kb were expressed in wild-type human cytomegalovirus-infected cells but not in cells infected with a DNA-negative temperature-sensitive mutant (ts66), indicating that DNA replication is absolutely required for pp28 gene expression. Transient promoter activation studies revealed that the pp28 gene region upstream promoter (pp28US) functioned early when expressed independently of the viral genome. However, the promoter was not efficiently activated by immediate-early (IE) proteins but was activated equally well by both wild-type virus and ts66. Deletion analysis of the pp28US promoter indicated that sequences upstream of the CAP site between -107 and -32 were required for activation of the pp28 promoter. Within that region exist a 10-bp sequence at -90 (AGTGAT CGTG) and its inverted repeat at -32 which positively influence pp28 promoter function. Therefore, in the case of the pp28US promoter, viral proteins interact through discrete sequences to facilitate late gene expression.

Base Sequence↗
PubMed1992

Do centrally-acting antihypertensive drugs act at non-adrenergic as well as alpha-2 adrenoceptor sites?

Rabbits were treated with guanabenz, clonidine and rilmenidine for 6 days via osmotic minipumps. Blood pressure, heart rate and responses to intracisternal clonidine were measured after 1 and 6 days treatment. Radioligand binding to forebrain and hindbrain membranes after 6 days treatment was examined using [3H]yohimbine to measure the number of adrenergic binding sites and [3H]clonidine and [3H]idazoxan to assess nonadrenergic imidazoline sites. No change in nonadrenergic imidazoline binding was observed but adrenergic binding was decreased in forebrain and hindbrain by guanabenz and in hindbrain by clonidine treatment. Resting heart rate was decreased after 1 day's treatment with partial recovery by day 6. At this time heart rate significantly reduced in the clonidine and rilmenidine treated groups but not the guanabenz group. No significant change in baseline blood pressure was observed in normotensive rabbits. Both depressor and bradycardia responses to intracisternal clonidine were attenuated after 1 day's dosing but only depressor responses were influenced after 6 days. Blood pressure and heart rate thus appeared to be regulated independently. It is possible that imidazoline receptors predominate in the central control of blood pressure while central alpha-2 adrenoceptors play a greater part in heart rate regulation.

Animals↗