ABC of dermatology. Procedures.
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Biopsy↗
Biomedical subjects
D W Harris
Publications and source records attributed to D W Harris.
Renin inhibitors containing psi[CH2O] pseudopeptide inserts.
Renin inhibitors 2-4 with the D-Lys renin inhibitory peptide (RIP) sequence, but containing Leu psi[CH2O]Ala (2), Leu psi[CH2O]Val (3), and Leu psi[CH2O]Leu (4) at the P1-P1' site, were of a comparable potency to RIP. N-Terminal Boc-protected inhibitors containing Pro psi[CH2O]Phe in positions P4-P3 were potent inhibitors of renin, with Boc-Phe-Pro psi[CH2O]Phe-His-Leu psi[CH(OH)CH2]Val-Ile-(2-aminomethyl) pyridine (17) having an IC50 of 1.6 X 10(-9) M.
Amino Acid Sequence↗
The use and abuse of 0.05 per cent clobetasol propionate in dermatology.
In conclusion, there can be no doubt that CP is a remarkable local steroid with potency greater than anything previously available to the dermatologist. It may be useful for short-term (less than 2 weeks) and intermittent treatment of widespread inflammatory dermatoses. It is excellent for treating some stubborn localized inflammatory dermatoses before moving on to more dilute preparations. When prescribing CP, it is important to warn the patient of common side effects, such as atrophy and striae, and to instruct the patient carefully in its use, mentioning body areas that should be spared its application. CP should not be applied to flexural, scrotal, or, with a few exceptions such as discoid lupus erythematosus and actinic reticuloid, facial skin. Its use is contraindicated in infants, toddlers, and children under 12 years of age. In addition, adult patients must be told never to use more than 50 gm per week (the manufacturer's recommendation). The prescribing physician must monitor and regularly review the amount used per unit time. Treatment with CP beyond 2 weeks is not recommended in the product information on CP listed in the Physicians' Desk Reference (1988). Those few patients taking CP for a long period should be managed as though they are on systemic steroids. Episodes of acute stress, such as surgery and intercurrent infection, should be managed with supplemental, if necessary parenteral, glucocorticoid administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Topical↗
alpha-Methylproline-containing renin inhibitory peptides: in vivo evaluation in an anesthetized, ganglion-blocked, hog renin infused rat model.
A structure-activity analysis of peptides containing backbone C alpha-methyl modification at the P4 site of the angiotensinogen sequence led to the discovery of potent renin inhibitors with apparent in vitro metabolic stability. Boc-alpha-MePro-Phe-His-Leu psi[CHOHCH2]Val-Ile-Amp dicitrate (Va) is a potent inhibitor of human plasma renin with an IC50 value of 1.8 nM. This peptide was shown not to be degraded in vitro by chymotrypsin, elastase, pepsin, and a rat liver homogenate preparation. It is also a potent inhibitor of hog renin with an IC50 value of 1.6 nM and was shown to elicit in vivo activity and cause dose-dependent hypotensive responses when given intravenously to anesthetized ganglion-blocked, hog renin infused rats.
Amino Acid Sequence↗
Design and synthesis of a potent and specific renin inhibitor with a prolonged duration of action in vivo.
A structure-activity analysis of peptides containing backbone C alpha-methyl and N alpha-methyl modifications led to the discovery of potent renin inhibitors with high metabolic stability. In vitro, Boc-Pro-Phe-N alpha-MeHis-Leu psi-[CHOHCH2]Val-Ile-Amp (XII) is a potent inhibitor of human plasma renin with IC50 of 0.26 nM. It is a much weaker inhibitor of other aspartic proteases such as porcine pepsin or bovine cathepsin D (IC50 = 6 microM). It was shown not to be degraded by a rat liver homogenate preparation. In vivo, it inhibited plasma renin activity and lowered blood pressure of furosemide-treated cynomolgus monkeys. At a dose of 5 mg/kg iv, the pronounced hypotensive response persisted for greater than 3 h postinfusion.
Animals↗
An orally active inhibitor of renin.
A potent renin inhibitor, U-71038 (Boc-Pro-Phe-N-MeHis-Leu psi[CHOHCH2]Val-Ile-Amp), was tested for oral effectiveness. Enzyme kinetic studies indicated that U-71038 was a competitive inhibitor of hog renin with an inhibitor constant (Ki) value of 12 nM. Intravenous as well as oral administration of U-71038 to anesthetized, ganglion-blocked rats infused with hog renin elicited dose-related hypotensive responses. Intravenous administration of U-71038 to conscious, sodium-depleted monkeys caused dose-related decreases of blood pressure and plasma renin activity without affecting heart rate. Similarly, the oral administration of U-71038 at 50 mg/kg to conscious, sodium-depleted monkeys elicited a pronounced hypotension and decrease in plasma renin activity that persisted for 5 hours. The hypotensive responses elicited by intravenous and oral administration of U-71038 to hog renin-infused rats and sodium-depleted monkeys were shown to be due entirely to inhibition of the renin-angiotensin system. A comparison of the results obtained after the intravenous administration of U-71038 with the results obtained after the oral administration of U-71038 implied that at least 10% of the orally administered U-71038 must have been absorbed to cause the observed effects in hog renin-infused rats and sodium-depleted monkeys. The studies demonstrated that an inhibitor of renin with a long duration of action and with oral effectiveness is a feasible entity.
Administration, Oral↗
Marihuana use and personality.
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Adolescent↗
Stimulation of cyclic GMP formation in smooth muscle cells by atriopeptin II.
Addition of synthesized atriopeptin II (AP-2), a 23 amino acid peptide of rat atria, to rat thoracic aorta smooth muscle cells results in the stimulation of cyclic GMP production by the cells. The EC50 for the effect is 81 nM and a 7 fold increase occurs at 10 microM AP-2. Cyclic GMP levels increased within 15 seconds after the addition of AP-2 and were maximal at 5 minutes. Cyclic GMP levels in primary rabbit kidney cells were increased 15 fold by 10 microM AP-2. However, no increase in cyclic GMP was detected in WI-38 fibroblast cells after the addition of 10 microM AP-2. Cyclic AMP levels were not affected by AP-2 in any of these cell systems. The effect upon cyclic GMP accumulation was specific for AP-2; none of the other compounds or peptides tested affected cyclic GMP levels.
Animals↗
Transcriptional activity in previtellogenic oocyte germinal vesicles from Xenopus laevis.
We have isolated germinal vesicles from previtellogenic Xenopus oocytes on a scale suitable for biochemical studies. The organelles were active in RNA synthesis, mainly mediated by endogenous RNA polymerase I. Nascent transcripts were 5-18S in size and complementary to DNA sequences present at intermediate reiteration frequency (several hundred copies per haploid genome). Hybridization to cloned 5S and 40S ribosomal genes demonstrated that the in vitro transcripts contained the latter, but not the former sequences in detectable amounts. The germinal vesicles also exhibited an ability to take up and retain UTP and a UTP-binding activity, probably protein(s), was extractable from the organelles with 0.35 M NaCl.
Animals↗
Use of a cell harvester for the collection of tissue fragments in receptor binding assays.
The use of a commercially available cell harvester in radioreceptor binding assays is described. Scatchard analyses of data acquired using the cell harvester is presented for [3H]clonidine, [3H]prazosin, [3H]quinuclidinyl benzilate (QNB), and [3H]flunitrazepam. Dissociation constants (Kd) and maximum number of binding sites (Bmax) obtained for each ligand are in good agreement with those published by others and there is excellent intra- and interassay agreement. Apparent inhibition constants for various common drugs are also included. Analyses of precision, efficiency, and cost support the use of this cell harvester in binding assays.
Animals↗
1-(alkylamino)isochromans: hypotensives with peripheral and central activities.
A series of 1-[1-(3,4-dimethoxy-1H-2-benzopyran-1-yl)alkyl]-4-arylpiperazines that shows hypotensive activity in the conscious rat has been investigated. Structure-activity relationships are described. A typical example that was investigated in greater detail is 1-[2-(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)ethyl]-4-(4-fluorophenyl)piperazine. This compound decreases sympathetic nerve activity recorded from the external carotid and splanchnic nerves of baroreceptor-denervated cats and, therefore, has a central component to its mechanism of action. It also blocks pressor effects of norepinephrine and phenylephrine and is thus an alpha-adrenergic antagonist. Binding data characterize this as alpha 1-adrenergic receptor blockade.
Adrenergic alpha-Antagonists↗
Determination of biological activity of alprazolam, triazolam and their metabolites.
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Alprazolam↗
Benzodiazepine receptor number after acute administration of alprazolam and diazepam.
Acute administration of alprazolam and diazepam (50 mg/kg i.p.) significantly increased benzodiazepine receptors in distilled water-washed rat brain membrane preparation. Similar effects were not observed when rat brain membranes were washed with phosphate-buffered saline. Results are discussed with respect to solubilization of benzodiazepine receptors in distilled water.
Alprazolam↗
Effect of norepinephrine uptake blocker on beta-adrenergic receptors of the rat cerebral cortex.
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Amphetamine↗
High affinity binding of [3H]ethylketocyclazocine to rat brain homogenate.
Ethylketocyclazocine (Ekc), a potent kappa-receptor agonist, binds to opiate receptor sites in rat brain tissue. The binding was saturable with respect to the concentration of [3H]Ekc. The dissociation constant of Ekc-receptor complex was 1.8 nM and the maximum number of binding sites in the whole brain was 9.6 pmol/g of tissue. Opiate agonists and antagonists have a high affinity for [3H]Ekc binding sites, but results of present investigations failed to differentiate opiates thought to be specific for the mu- and kappa-receptors.
Animals↗
Returned-medicines campaign in Birmingham, 1977.
In a returned-medicines campaign lasting 3 weeks 362000 tablets and capsules were returned in 11400 containers from a population of 1.05 million. This yield was considered low. A comparison of hospital admission figures for childhood poisoning before, during, and immediately after the campaign suggests that the publicity and the destruction of unwanted medicines had little preventive value. The quantities of different medicines returned were roughly proportional to the quantities prescribed.
Adolescent↗
Determination of prostaglandin synthetase activity in rectal biopsy material and its significance in colonic disease.
A method is described for determining prostaglandin synthetase activity in milligram amounts of tissue. The procedure is based on the conversion of 14C-arachidonic acid to prostaglandin E2 and F2alpha-like substances. High levels of prostaglandin synthetase activity occurred in the inflamed mucosa of patients with ulcerative colitis and fell during successful drug therapy, but it is not yet known whether the cause of the inflammation first involves increased PG synthetase activity, or whether inflammation caused increase of PG synthetase.
Colitis, Ulcerative↗