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Biomedical subjects

J E Shaw

Publications and source records attributed to J E Shaw.

At least 91 records · Page 5Linked to original sources
PubMed1987

Testing of controlled-release transdermal dosage forms. Product development and clinical trials.

In vitro techniques have been developed that are predictive of drug permeation through skin. Methods also have been developed to determine the skin irritation potential of a drug substance during the preclinical stages of transdermal dosage form development. Clinical studies are performed to test for skin irritation, contact sensitization, plasma levels of drug, and efficacy of the dosage form. In theory, these studies should be predictive of a dosage form's performance in routine clinical use. This may not be the case, however; contact sensitization cannot be predicted with absolute certainty beforehand in animals. This article discusses various aspects of testing transdermal dosage forms and how the results of these tests correlate with what happens when a transdermal dosage form is put into routine clinical use.

Administration, Cutaneous↗
PubMed1986

Alleviation of induced vertigo. Therapy with transdermal scopolamine and oral meclizine.

Twelve healthy subjects received seven-day treatments on a randomized, double-blind, crossover basis, of a transdermal scopolamine system, oral meclizine, and placebo, separated by one-week intervals. Just prior to each treatment, and on days 1 and 7 of each treatment, subjects received two warm (44 degrees C) caloric irrigations of each external auditory canal. Following each irrigation, subjects rated their vertigo symptoms. Subjects reported on their side effects daily throughout each treatment period. Vertigo symptoms on day 1 of treatment were significantly less with transdermal scopolamine than oral meclizine or placebo and on day 7 were significantly less with both scopolamine and meclizine than the placebo. On day 1, meclizine did not reduce vertigo symptoms significantly when compared with the placebo. Drowsiness was greater with use of oral meclizine than transdermal scopolamine.

Dehydration↗
PubMed1985

The circular intracellular form of Epstein-Barr virus DNA is amplified by the virus-associated DNA polymerase.

Selective DNA extraction and hybridization procedures were used to estimate the relative number of covalently closed circular viral genomes in cultures of Epstein-Barr virus (EBV)-transformed cells. In virus-producing P3HR-1 cultures that were exposed for 11 days to phosphonoacetic acid or to acyclovir, the content of covalently closed circular EBV DNA was reduced ca. 70% relative to a control culture without drug. The EBV plasmid content of Raji, a virus nonproducer cell line, was not reduced by exposure to these compounds. When P3HR-1 cultures were exposed to 12-O-tetradecanoylphorbol-13-acetate, the number of circular genomes per cell increased. These findings indicate that two enzyme activities synthesize circular EBV DNA and that the virus-associated DNA polymerase synthesizes most of the circular EBV DNA in a virus producer culture. It is suggested that the circular genomes synthesized by the viral enzyme are intermediates in the syntheses of linear virus DNA.

Acyclovir↗
PubMed1985

Extrachromosomal DNA transformation of Caenorhabditis elegans.

DNA was introduced into the germ line of the nematode Caenorhabditis elegans by microinjection. Approximately 10% of the injected worms gave rise to transformed progeny. Upon injection, supercoiled molecules formed a high-molecular-weight array predominantly composed of tandem repeats of the injected sequence. Injected linear molecules formed both tandem and inverted repeats as if they had ligated to each other. No worm DNA sequences were required in the injected plasmid for the formation of these high-molecular-weight arrays. Surprisingly, these high-molecular-weight arrays were extrachromosomal and heritable. On average 50% of the progeny of a transformed hermaphrodite still carried the exogenous sequences. In situ hybridization experiments demonstrated that approximately half of the transformed animals carried foreign DNA in all of their cells; the remainder were mosaic animals in which some cells contained the exogenous sequences while others carried no detectable foreign DNA. The presence of mosaic and nonmosaic nematodes in transformed populations may permit detailed analysis of the expression and function of C. elegans genes.

Animals↗
PubMed1984

Expression of coliphage T7 in aging anucleate minicells of Escherichia coli.

Anucleate minicells produced by a mutated strain of Escherichia coli remain metabolically active for up to 48 h at 37 degrees C. Minicells of increasing age have been infected with the coliphage T7. Infection results in the onset of transcription and translation producing T7 encoded polypeptides. Quantitative and qualitative changes in T7 gene expression result from infection of increasingly old minicells. There is no detectable increase in the frequency of error occurrence in the synthesis of T7 polypeptides in infected old minicells as compared to infected young minicells.

Cell Nucleus↗
PubMed1984

Pharmacokinetics of nitroglycerin and clonidine delivered by the transdermal route.

This article describes in vitro and in vivo performance of two transdermal drug delivery systems. Transderm -Nitro delivers nitroglycerin for the treatment and prevention of angina for 24 hours following a single application. In a three-way crossover study comparing Transderm -Nitro with two other transdermal nitroglycerin products, mean plasma levels of drug were similar 0.5 and 6 hours after application; however, with Transderm -Nitro the area under the plasma concentration curve was highest and the coefficient of variation was least. A transdermal therapeutic system for delivering clonidine ( Catapres -TTS) is used for the treatment of hypertension. In a two-way crossover study comparing Catapres -TTS and oral Catapres , plasma levels of clonidine with use of the transdermal system reached a steady-state value in 2 to 3 days and remained steady for the duration of the wearing period; plasma levels with oral Catapres , however, fluctuated markedly. The ratio of maximum to minimum plasma levels during a dosing interval was 2 for oral Catapres and approximately 1 for Catapres -TTS. The potential use of intact skin as a route of entry for controlled delivery of drugs to the systemic circulation is promising.

Administration, Oral↗
PubMed1984

Free erythrocyte protoporphyrin as an index of perinatal iron status.

The relationship between free erythrocyte protoporphyrin and conventional indices of iron status was studied in 49 mothers and their infants. Maternal venous blood samples were collected at 34 weeks gestation and at delivery. The corresponding infant blood samples were collected from the umbilical cord and at age 6 weeks. In each case free erythrocyte protoporphyrin, serum iron, total iron binding capacity, and serum ferritin were determined. Cord free erythrocyte protoporphyrin was negatively correlated with maternal ferritin at 34 weeks gestation (p = 0.016) and at delivery (p = 0.014), and with transferrin saturation at delivery (p = 0.026). The infants' haemoglobin concentrations at 6 weeks were significantly negatively related to maternal free erythrocyte protoporphyrin at 34 weeks (p = 0.026) and at delivery (p = 0.026). Cord free erythrocyte protoporphyrin is an index of maternal iron status in the last trimester. Maternal free erythrocyte protoporphyrin in the last trimester predicts the magnitude of physiological anaemia of the infant at age 6 weeks.

Adult↗
PubMed1984

Identification of small DNA fragments synthesized in herpes simplex virus-infected cells in the presence of acyclovir.

The effect of acyclovir on DNA synthesized in cells infected with herpes simplex virus type 1 was examined. DNA that was synthesized in infected cells in the presence of acyclovir during a short pulse with [3H]thymidine remained near the top of an alkaline sucrose gradient after centrifugation. The sedimentation characteristics of labeled DNA were not changed after chasing in isotope-free medium. The slowly sedimenting DNA was identified as viral in origin by hybridization to purified herpes simplex virus nucleocapsid DNA. When cells were infected with acyclovir-resistant virus containing mutations in the polymerase gene, the viral DNA synthesized in the presence of acyclovir was chased into high-molecular-weight DNA. These findings are consistent with chain termination of herpes simplex virus DNA in virus-infected cells.

Acyclovir↗
PubMed1984

Nitroglycerin concentration in plasma: comparison between transdermal therapeutic system and ointment.

This double-blind cross-over study evaluates in 12 male volunteers the time course of nitroglycerin concentration in plasma with use of the TTS-nitroglycerin, a controlled-release transdermal dosage form for nitroglycerin, and compares the bioavailability of nitroglycerin delivered from the transdermal system with that from three successive applications of 0.5 inch of 2% nitroglycerin ointment placed at 8 hr intervals over 10 cm2 of skin. The mean amounts of nitroglycerin available when subjects wore the TTS-nitroglycerin or received successive applications of ointment were 15.8 mg +/- 1.8 (SE) and 9.8 mg +/- 0.8, respectively. Mean plasma concentrations for both treatments ranged from 10-18 pg/ml-cm2. The normalized areas under the curves--353 and 410 pg/hr/ml-cm2, respectively--did not differ significantly. The ratio of clearance from the two dosage forms was 0.98 +/- 0.12. All subjects experienced mild-to-moderate side effects of nitrate therapy with both dosage forms and also decrease in blood pressure and increase in heart rate.

Administration, Topical↗
PubMed1984

Survival in elderly patients presenting with uraemia.

A retrospective study was made of 93 patients aged 60 years or greater presenting with renal failure between 1976 and 1981 to assess survival and analyse the factors influencing it. Two-year survival of 28 patients with acute renal failure was 50 per cent and of 65 patients with chronic renal failure it was 40 per cent. Higher initial plasma urea and creatinine values and increasing age had a significantly adverse effect on survival. Patients requiring dialysis likewise fared less well although only one patient succumbed as a direct result of the dialysis procedure. The study reveals a worthwhile survival in both acute and chronic renal failure even though during the period under consideration long-term dialysis of patients in this age group with terminal chronic renal failure was rarely undertaken.

Acute Kidney Injury↗
PubMed1982

Treatment of life-threatening Epstein-Barr virus infection with acyclovir.

Two pediatric patients with life-threatening Epstein-Barr virus infections were studied immunologically and treated with acyclovir [9-(2-hydroxyethoxymethyl) guanine]. The patient with chronic active Epstein-Barr virus infection who experienced massive hepatosplenomegaly, pancytopenia, and failure to thrive demonstrated abnormalities of T and B lymphocytes. A second patient, with the X-linked lymphoproliferative syndrome, experienced a rapidly fatal course of acute Epstein-Barr virus infection which typifies this yet undefined immunodeficiency to Epstein-Barr virus. In each case, objective evidence for clinical improvement or antiviral effect of acyclovir treatment was not apparent. Abnormally productive Epstein-Barr virus infections did not appear to play a major role in the clinical syndromes observed. Current studies are focused on treatment of immunologically normal patients with early complicated Epstein-Barr virus infection.

Acyclovir↗
PubMed1982

Filamentous structures associated with Epstein-Barr virus-infected cells.

After the onset of Epstein-Barr virus DNA and protein synthesis 10 h after superinfection of Raji cells (a cell line containing Epstein-Barr virus DNA but not producing virus), filamentous structures 25 nm in diameter and 0.2 to 1.4 micrometers in length could be detected in the cell cytoplasm by electron microscopy. These structures banded in metrizamide gradients with viral DNA and proteins, but at a density different from that of virions or nucleocapsids. These filaments, enriched in a 155,000-dalton protein similar in size to a major nucleocapsid protein of Epstein-Barr virus, may represent intermediates in viral nucleocapsid assembly.

Acyclovir↗