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Biomedical subjects

C M Perkins

Publications and source records attributed to C M Perkins.

At least 19 recordsLinked to original sources
PubMed1997

Biodegradation of [S,S], [R,R] and mixed stereoisomers of ethylene diamine disuccinic acid (EDDS), a transition metal chelator.

An in-depth biodegradation test program was executed on the hexadentate ligand Ethylene Diamine Di Succinate (EDDS). The EDDS structure contains two chiral carbon atoms, and has three stereoisomers ([R,R], [R,S]/[S,R], [S,S]). Our research has focused on the isomer mixture (i.e. 25%[S,S]; 25%[R,R]; 50%[S,R]/[R,S], as produced from the reaction of ethylene diamine with maleic anhydride) and on the single [S,S]- and [R,R]-isomers. Biodegradation screening of the 14C-labelled EDDS isomer mixture in a Batch Activated Sludge (BAS) test with various inocula revealed incomplete mineralization, up to ca. 65% after 28 days. N-(2-aminoethyl) aspartic acid (AEAA), probably the d-isomer, was identified as the major portion of the 14C-material remaining in solution. Further testing revealed that the [S,S]-isomer is rapidly and completely mineralized in all test systems. By contrast, [R,R]-EDDS remained undegraded in a Sturm (OECD 301B) test, but was very slowly biotransformed into the recalcitrant metabolite AEAA in a BAS test. The [S,R]/[R,S] form undergoes biotransformation to AEAA in both high and low biomass systems. In a sewage treatment simulation test (OECD 303) the steady state DOC removal of mixture-EDDS in a CAS test was limited to 25-35%, even after extensive pre-acclimation, while the [S,S]-isomer achieved nearly complete removal (96%). This study illustrates the importance stereospecificity may have on the biodegradation and metabolite formation of a chemical. A biodegradation scheme for the different EDDS stereoisomers is proposed.

Aspartic Acid↗
PubMed1989

The effect of aldose reductase inhibition on erythrocyte polyols and galactitol accumulation in diabetic patients.

Erythrocyte sorbitol level has previously been used as a measure of the efficacy of aldose reductase inhibitors, but its value is limited by fluctuations related to variations in blood glucose concentration. The aim of the study was to compare sorbitol content with the ability to accumulate galactitol during ex vivo incubation with galactose, of erythrocytes taken from diabetic patients following administration of a single 600 mg dose of the aldose reductase inhibitor, ponalrestat. Twelve patients were studied in a placebo-controlled crossover trial. Blood glucose levels were not statistically different during the placebo and ponalrestat treatment periods except at 1 h after the dose was taken (10.6 +/- 6.7 vs 7.7 +/- 4.6 mmol l-1 (+/- SD), p less than 0.05). Ponalrestat reduced erythrocyte sorbitol concentrations compared with placebo at 3, 5 and 7 h (0.82 +/- 0.36, 0.69 +/- 0.23, and 0.83 +/- 0.35 mg l-1 vs 1.79 +/- 0.67, 1.68 +/- 0.65, and 1.57 +/- 0.59 mg l-1 respectively, p less than 0.005) and 24 h post-dose (1.57 + 0.45 vs 2.01 + 0.73 mg l-1, p less than 0.05). Ponalrestat also reduced erythrocyte galactitol accumulation at 3, 5 and 24 h post-dose from 5.53 +/- 2.41, 5.43 +/- 1.89, and 5.42 +/- 1.96 mg l-1 2-h-1 to 1.47 +/- 0.30, 1.76 +/- 0.41, and 4.12 +/- 0.72 mg l-1 2-h-1 respectively, p less than 0.01. Galactitol accumulation rate appeared to be a less variable parameter than erythrocyte sorbitol and was not influenced by fluctuations in blood glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1987

Peripheral nerve concentrations of glucose, fructose, sorbitol and myoinositol in diabetic and non-diabetic patients.

Glucose, fructose, sorbitol and myoinositol concentrations were measured in biopsies of peripheral nerve obtained at above-knee or below-knee amputation. In diabetic patients nerve glucose (median [range]) (5.09 [1.62-12.82] vs 3.12 [1.81-4.01]) p less than 0.001, fructose (0.245 [0.060-1.280] vs 0.150 [0.053-0.385]) p less than 0.05, and sorbitol (0.028 [0.012-0.496] vs 0.016 [0.007-0.059] p less than 0.02, mumol/g wet weight) were significantly higher than in non-diabetic patients. No significant difference was found in myoinositol concentration (1.95 [1.00-3.55] vs 2.09 [1.27-5.40] mumol/g wet weight). Concentrations differed markedly from previously reported values in human nerve obtained at post-mortem.

Adult↗
PubMed1986

Diagnosis and treatment of heart failure in different European countries: a young AEMIE questionnaire.

To compare diagnosis and treatment of heart failure among different European countries, an anonymous questionnaire was developed and sent to young AEMIE members all over Europe. 159 filled-in questionnaires were received: 30 p. 100 from France (F), 25 p. 100 from Great Britain (GB), 21 p. 100 from the Benelux countries (NL), 13 p. 100 from Italy (I) and 11 p. 100 from West-Germany (D). Baseline characteristics of the participating physicians (age, years of hospital training, available equipment, etc.) were comparable among the different countries. There was good agreement in the value of history, clinical examination, ECG and chest X-ray for the diagnosis of heart failure. In all countries breathlessness, basal crepitations and gallop rhythm were counted among the most important signs of left heart failure. Whereas the value of gated-blood-pool scanning and Holter monitoring as a first diagnostic approach was unanimously denied, the value of 2D-echocardiography in heart failure was discussed controversially: in I, F and D 50-80 p. 100 of the physicians thought echocardiography a first-hand diagnostic tool, whereas only 20-30 p. 100 of the physicians in GB and NL recommended echocardiography in the first place. Diuretics, sodium reduced diet and afterload reduction (in GB only) are the first therapeutic measures in GB, NL and F. However, in I and D digitalis is still the cornerstone of therapy (greater than or equal to 50 p. 100!). Physicians of all European countries with the exception of the physicians in D prefer pure digoxin as the first digitalis preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Furosemide-sensitive Na+-K+ cotransport and cellular metabolism in human erythrocytes.

Metabolic depletion of human red cells with 2-deoxy-D-glucose in the presence of EGTA decreased ATP to about 4% of the initial value and increased total ouabain- and furosemide-resistant Na+ and K+ effluxes by 20% and 100%, respectively, and furosemide-sensitive Na+ and K+ effluxes by 100% and 60%, respectively. When ATP was restored, all the components of Na+ and K+ fluxes measured returned to baseline levels suggesting a metabolic dependence.

Adenosine Triphosphate↗
PubMed1985

Cell volume and metabolic dependence of NEM-activated K+-Cl- flux in human red blood cells.

The effects of incubation in anisosmotic media and of metabolic depletion on ouabain-resistant (OR) Cl--dependent K+ influxes stimulated by N-ethylmaleimide (NEM) were studied in human red blood cells using Rb+ as K+ analogue. The NEM-stimulated but not the basal Rb+-Cl- influx measured in phosphate-buffered anisosmotic media was found to be cell volume dependent. When cellular ATP, [ATP]c, was lowered to less than 0.10 of its initial level by exposure to nonmetabolizable 2-deoxy-D-glucose, the NEM-stimulated but not the basal Cl--dependent Rb+ influxes were abolished. Metabolically depleted red blood cells subsequently repleted by incubation in glucose plus inosine regained the NEM-inducible Rb+ (K+) transport activity. The difference in the time course of ATP breakdown and Rb+ influx inhibition suggests that energization of the NEM-stimulated Rb+ flux by metabolism may involve factors additional to ATP.

Adenosine Triphosphate↗
PubMed1985

A sensitive high-temperature electrothermal atomic absorption analysis for Rb+ in erythrocytes and plasma of normal and hypertensive persons.

This method for determination of Rb+ in human plasma and erythrocytes by graphite-furnace atomic absorption spectrophotometry has a sensitivity of 29 nmol/L for plasma, 12 nmol/L for erythrocytes. The detection limit is 24 nmol/L for plasma, 4.8 nmol/L for erythrocytes. This assay is approximately 30-fold more sensitive than previously reported techniques involving atomic absorption spectrophotometry, enabling use of smaller samples. The rubidium signal is linear with concentration up to 1.2 mumol/L, and addition of other cations to the matrix produces only minor alterations in the Rb+ signal. We measured plasma and erythrocytic Rb+ concentrations in healthy subjects and in patients with untreated essential hypertension. In both, our values are similar to those previously reported for healthy individuals.

Adult↗
PubMed1984

A paradoxical fall in urine dopamine output when patients with essential hypertension are given added dietary salt.

The effect of dietary sodium on the urine dopamine excretion of eight hypertensive patients and six matched controls was studied under metabolic balance conditions over a 2 week period during which dietary sodium intake was increased from 20 to 220 mmol/day. The control group showed the expected increase in dopamine excretion in response to sodium but the hypertensive patients showed an initial fall followed by a return to baseline values. Neither group showed a rise in blood pressure but the hypertensive patients showed a greater weight gain on salt loading, although this change was not significant. The cumulative sodium balance was greater and more prolonged in the hypertensive patients, although this difference also did not attain statistical significance. This defect in dopamine mobilization may be important in relation to renal sodium handling by patients with essential hypertension.

Adult↗
PubMed1982

The Measurement of Haemoglobin A1c by isoelectric focussing in diabetic patients.

Incubation in vitro of human red cells in increasing glucose concentrations results in a rise in both haemoglobin A1c levels and an intermediate band when measured by an isoelectric focussing method. There are strong correlations between blood glucose levels, levels of haemoglobin A1c and the intermediate band both in vitro and in blood samples taken from diabetic patients. As the intermediate band is also included in the measurement of haemoglobin A1c by the usual analytical methods, this may lead to inaccurate results.

Blood Glucose↗
PubMed1982

Urine dopamine in normal and hypertensive pregnancies.

Dopamine output in urine was determined in two groups of women with hypertension in pregnancy. A highly significant elevation of urine dopamine was detected in those women with pre-eclampsia compared with that in matched control subjects. In contrast, no difference in urine dopamine output was detected between a group of multigravidae with hypertension in pregnancy and matched control subjects.

Adolescent↗
PubMed1981

Urine free dopamine in normal primigravid pregnancy and women taking oral contraceptives.

1. Urine free dopamine was estimated at predetermined points of the menstrual cycle in normal volunteer subjects and in women taking a combined oral contraceptive. 2. There was no alteration in 24 h urine dopamine during the normal menstrual cycle but, in contrast, combined oral contraceptives produced a fall which recovered premenstrually. 3. In 19 primigravid subjects 24 h urine free dopamine was estimated at monthly intervals throughout pregnancy and at the time of the postnatal examination. 4. Urine dopamine was elevated throughout pregnancy when compared with postnatal values. Women receiving an oral progestogen contraceptive at the time of the postnatal examination showed a further fall in urine dopamine.

Adult↗
PubMed1981

The treatment of idiopathic orthostatic hypotension: a combined fludrocortisone and flurbiprofen regime.

We report our experience in the management of idiopathic orthostatic hypotension using the prostaglandin synthetase inhibitor, flurbiprofen. In five subjects with proven autonomic failure the effect on blood pressure of the addition of flurbiprofen (or fludrocortisone) to the previous drug regime was assessed. Both lying and standing blood pressure were seen to rise with fludrocortisone treatment although the change in standing blood pressure was not statistically significant. Flurbiprofen, in contrast, produced no change in lying blood pressure but a significant rise in standing blood pressure. Digital blood flow measurements were made on three subjects before and after flurbiprofen and a dose-related reduction in post-occlusive reactive hyperaemia was demonstrated suggesting an effect of this drug on precapillary smooth muscle tonus. Two patients failed to maintain a long-term response to treatment with flurbiprofen and fludrocortisone but have been helped by the addition of I) ephedrine or II) tyramine an monoamine oxidase inhibitor (phenelzine). We recommend a stepwise approach to treatment in this condition commencing with flurbiprofen and adding fludrocortisone later if necessary. This approach would appear to offer the maximum benefit with a minimum of side effects.

Adolescent↗
PubMed1980

Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells.

The plasma tripeptide glycyl-L-lysine (GHL), when added at nanomolar concentrations to a wide group of cultured systems, produces a disparate set of responses ranging from the stimulation of growth and differentiation to outright toxicity. Such diverse actions imply that this tripeptide mediates some basic biochemical function common to many types of cells and organisms. During the isolation of GHL we found the compound to co-isolate through a number of steps with approximately equimolar copper and about 1/5 molar iron. Maximal effects on hepatoma cells (HTC4) were seen when the peptide was added with copper and iron to the growth medium. Structure-function studies revealed that several tripeptides with a histidyl-lysyl linkage were nearly as active as GHL. The association of GHL with copper and a homology similarity between the tripeptide and the copper transport sites on albumin and alpha-fetoprotein, where the cupric atom is bound to a histidyl residue adjacent to a basic residue, suggested that GHL may act as a copper transport factor. We report here that the tripeptide readily forms complexes with copper(II) and enhances the uptake of the metal into cultured hepatoma cells.

Animals↗
PubMed1980

The effect of mineralocorticoid administration on urine free dopamine in man.

1. Five normal subjects were studied under metabolic conditions on a controlled sodium and potassium intake. 2. Plasma and urine free dopamine concentrations were measured in these subjects before, during and after 5 days administration of fludrocortisone (0.2 mg twice daily). 3. Urine free dopamine showed a tendency to fall during the early phase of fludrocortisone administration and then rose towards normal. 4. In a patient with primary hyperaldosteronism there was no evidence of increased renal production of dopamine. Urine dopamine fell when plasma renin activity rose as a result of spironolactone administration (200 mg three times a day for 5 days). 5. If renal dopamine has a role in mineralocorticoid 'escape' then it may be permissive only. The mechanisms of control of dopamine production could include tubular sodium concentration, tubular chloride concentration and intrarenal renin activity.

Adult↗
PubMed1979

Plasma and urine dopamine in man given sodium chloride in the diet.

1. Plasma and urine free dopamine were measured daily for 5 days in six normal subjects maintained on a low sodium diet. The subjects were then given dietary supplements of sodium chloride for 5 days and the measurements repeated. 2. Throughout the experiment the 24 h free dopamine excretion rates for all the subjects were higher than could be accounted for by renal clearance. Dopamine excretion increased significantly in response to the added sodium chloride whereas plasma dopamine remained unchanged. The rise in dopamine excretion preceded that of sodium excretion. 3. It is concluded that free dopamine is formed within the kidney in response to increased dietary sodium and may have a role in the control of sodium excretion.

Creatinine↗