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Biomedical subjects

C M Dawson

Publications and source records attributed to C M Dawson.

At least 19 recordsLinked to original sources
PubMed1991

Use of a non-extraction HPLC technique for measuring angiotensin-converting enzyme under optimum conditions.

A non-extraction high performance liquid chromatography assisted method for the measurement of angiotensin-converting enzyme in serum has been developed. Serum containing the enzyme was incubated with the synthetic substrate, furylacryloylphenylalanylglycylglycine at a concentration approaching 10 times the apparent Km, prior to injection onto a shielded hydrophobic reverse phase high performance liquid chromatography column. This allowed the product to be separated and measured directly without the need for a time consuming protein extraction step. The method is enzymatically sound and avoids the methodological problems associated with automated kinetic assays.

Chlorides↗
PubMed1990

Direct serum injection high-performance liquid chromatographic method for the simultaneous determination of phenobarbital, carbamazepine and phenytoin.

A method is described for the simultaneous measurement of serum levels of three antiepileptic drugs, phenobarbital, phenytoin and carbamazepine, by direct injection high-performance liquid chromatography on a 25-cm Pinkerton internal surface reversed-phase (ISRP) column. Several commonly available compounds were tested and found not to co-chromatograph with the three drugs of interest or the internal standard, 5-(p-methylphenyl)-5-phenylhydantoin. Results obtained on patients' samples with this method compared well with those from enzyme-multiplied immunoassay technique (EMIT).

Carbamazepine↗
PubMed1990

4-Hydroxyanisole: human pharmacokinetics.

The pharmacokinetic behaviour of 4-hydroxyanisole (4HA) has been studied in ten female patients with recurrent malignant melanoma confined to the lower limb. Ten grams of 4HA was infused twice each day via a catheter placed in the common femoral artery for a maximum of 4 days. Blood samples were collected after the first and fourth infusions in all patients and the serum 4HA concentration assayed. Following infusion, the serum 4HA concentration declined in two phases, the half-lives (t1/2) of the distribution and elimination phases being 6.3 and 70.9 min, respectively. The serum 4HA concentrations and area under the curve (AUC) declined significantly between the first and fourth infusions. There was a significant rise in the apparent volume of distribution (VD) of 4HA between these times but no change in the t1/2 of the elimination phase or the clearance rate. It is concluded that there is no evidence that enzyme induction influences the clearance of 4-hydroxyanisole from the bloodstream in the short-term. However, it may be appropriate to adjust dosage regimens to take account of the change in VD that occurs with time.

Aged↗
PubMed1989

Non-extraction HPLC method for the simultaneous measurement of theophylline and caffeine in human serum.

A non extraction HPLC method is described for the simultaneous measurement of theophylline and caffeine in human serum using a Pinkerton ISRP column and u.v. detection at 275 nm. The method is suitable for therapeutic monitoring of theophylline levels in adults and, in particular, quantitation of both theophylline and caffeine in premature neonates where as little as 10 microL of sample can be used. Comparison of theophylline levels obtained by this method with EMIT analysis show a correlation coefficient of 0.97 (n = 37) in adults and 0.79 (n = 16) in premature neonates. There was no correlation between serum theophylline and caffeine levels in premature neonates receiving theophylline therapy. No interference was encountered from endogenous plasma components or other drugs in the 53 patients studied. Precision of the assays compares well with reported values for extraction HPLC and immunochemical analyses.

Caffeine↗
PubMed1989

Investigation of a persistently raised serum AST.

The AST responsible for a raised enzyme activity, with otherwise normal biochemistry, in a single individual over a 16-month period has been characterized as an IgG (lambda)-AST complex by (i) estimation of the molecular size by gel exclusion chromatography on Sephadex G200, (ii) agarose gel electrophoresis, (iii) immunoprecipitation by anti-immunoglobulin antisera and (iv) adsorption on to protein A-agarose.

Adsorption↗
PubMed1988

A non-extraction HPLC method for the simultaneous determination of serum paracetamol and salicylate.

A direct injection HPLC method for the sumultaneous measurement of serum paracetamol and salicylate is described using a Pinkerton internal surface reversed-phase column with benzoic acid as internal standard. The method is linear to at least 1000 mg/L for both drugs and shows good precision at levels of 62-500 mg/L. None of the drugs tested for interference affected the quantitation of either drug. In patient samples, the values obtained with this method correlated well with those from enzymatic paracetamol and Trinder salicylate methods.

Acetaminophen↗
PubMed1986

Effect of temperature upon potassium-stimulated insulin release and calcium entry in mouse and rat islets.

The effect of cooling to 27 degrees C was studied in islets of Langerhans exposed to 5 and 50 mM potassium in the absence of glucose. Membrane potential and insulin release were measured simultaneously from microdissected mouse islets while 45Ca outflow and insulin release were measured from collagenase-isolated rat islets. Cooling inhibited potassium-induced insulin release in both preparations. However, calcium entry estimated from electrical records and from 45Ca outflow experiments was only slightly affected by decreasing the temperature to 27 degrees C. It is concluded that the inhibition of insulin release caused by cooling to 27 degrees C can, within limits, be dissociated from calcium influx.

Animals↗
PubMed1986

Potassium and rubidium permeability and potassium conductance of the beta-cell membrane in mouse islets of Langerhans.

The efflux of 42K+ and 86Rb+ has been studied in collagenase-isolated normal mouse islets of Langerhans. In double-labelled experiments, the ratio of efflux rate constants of Rb+ and K+ (kRb/kK) was 0.80 in 5 mM-K+ and 0 glucose. The ratio was unaffected by glucose concentrations up to 22.2 mM. In the presence of 50 mM-K+, 0 glucose, the ratio increased to 0.91 and in 50 mM-Rb+, 0 glucose and 0 K+, the ratio was 1.06. With these limitations, the results indicate that 86Rb+ is an acceptable isotope for K+. Using the Goldman model, K+ and Rb+ permeability coefficients and K+ slope and chord conductances were computed. The permeabilities decreased in glucose and in high K+ or high Rb+. In the case of high external K+, the K+ conductances increased. Also there may be more than one type of K+ channel with differing selectivities to K+ and Rb+. The addition of glucose in the presence of 50 mM-K+ had no further effect on Rb+ permeability. It is suggested that there are about ten small K+ channels open in the resting beta-cell and that progressive closure of these channels is involved in the depolarization of the cell membrane that initiates spike activity.

Animals↗
PubMed1985

Comparison of glucose-induced changes in electrical activity, insulin release, lactate output and potassium permeability between normal and ob/ob mouse islets: effects of cooling.

A comparison has been made between the glucose-induced changes in electrical activity, insulin release, lactate output and potassium permeability in normal and ob/ob obese (Norwich strain) mice. The electrical response of the islet membrane to high glucose (22.2 mmol/l) stimulation was different in the two types of mice, generating continuous spike activity in normal but producing bursts of activity in ob/ob mouse islets. The absolute amounts of insulin and lactate produced by ob/ob islets in response to both basal and high glucose concentrations were greater than the absolute amounts produced by normal islets, though the ratio of the amount produced in high glucose concentrations to the amount produced in basal glucose concentrations was not significantly different between normal and ob/ob islets for both parameters. Glucose-induced changes in potassium permeability were smaller in ob ob than in normal mice. Cooling from 37 to 27 degrees C, during steady-state glucose stimulation, reduced both lactate output and insulin release, the temperature coefficients being similar in both types of mice. The effect of temperature reduction on electrical activity was more marked in the islets of ob/ob mice than in those of normal mice; spike frequency was unaffected in normal but reduced in ob/ob mice, whereas spike amplitude was decreased in both. Cooling-induced inhibition of potassium permeability was greater in the islets of ob/ob mice than in those of normal mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

The response of pancreatic beta-cell membrane potential to potassium-induced calcium influx in the presence of glucose.

Membrane potential measurements were made in pancreatic beta-cells from microdissected islets from normal mice. In the presence of 11 mM glucose, depolarization of the membrane for 1 min with 50 mM potassium is followed by an inhibition of electrical activity before the normal burst pattern resumes. This inhibitory period, called the recovery time, is steady for each beta-cell after three consecutive pulses of 50 mM potassium. The mean recovery time is 109 s. During the recovery time, the membrane is hyperpolarized and the input resistance is decreased, indicating that potassium permeability is high over this period. The recovery time is dependent on the size of the depolarization: 1 min exposure to potassium concentrations below 50 mM reduces the recovery time with a half-maximal effect at 38.5 mM potassium, corresponding to -27 mV. Also, increasing the extracellular calcium concentration lengthens the recovery time. Increasing the glucose concentration, however, shortens the recovery time. It is postulated that the recovery time represents activation of the calcium-gated potassium permeability and is a reflexion of the time taken for the beta-cell to buffer the increased intracellular calcium resulting from the potassium depolarization.

Animals↗
PubMed1984

Effects of Zn2+ on glucose-induced electrical activity and insulin release from mouse pancreatic islets.

The effects of Zn2+ and CO2+ on glucose-induced beta-cell electrical activity and on insulin release from microdissected mouse pancreatic islets were studied. In 11 mM glucose the electrical activity is characterized by a burst pattern with a bimodal distribution of spike amplitudes along the plateau phase. Zn2+ at 0.05 mM induced a reduction in the number of spikes during the bursts and preferentially blocked the large action potentials. Zn2+ at 0.1 mM and CO2+ at 1.0 mM completely inhibited the electrical activity in response to glucose. Zn2+ inhibition of electrical activity was poorly reversible, whereas CO2+ inhibition was rapidly and completely reversible. Zn2+ and CO2+ inhibited the glucose-stimulated insulin release from microdissected perifused islets. Half-maximal inhibition occurred at about 0.3 mM for both metals. Zn2+ also inhibited K+-induced insulin release in the absence of glucose, indicating that Zn2+ inhibition does not involve glucose metabolism. It is proposed that Zn2+ blocks the voltage-gated Ca2+ channels in pancreatic beta-cells.

Action Potentials↗