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Biomedical subjects

P Cutler

Publications and source records attributed to P Cutler.

At least 19 recordsLinked to original sources
PubMed1997

Hemin and related porphyrins inhibit beta-amyloid aggregation.

Porphyrins related to the naturally occurring pigment heme were found to effectively interfere with the aggregation of beta-amyloid peptides as determined by an immunoassay configured for the detection of beta-amyloid oligomers. Oligomerisation of beta-amyloid is believed to be a key event in the progression of Alzheimer's disease. Inhibition of this aggregation is thus an important strategy in combating this commonest form of senile dementia. Evidence was also generated for hemin and hematin mediated protection of cultured cells against the neurotoxic effects of beta-amyloid. These data are discussed with reference to the known pathology of Alzheimer's disease and the chemistry of porphyrins.

Amyloid beta-Peptides↗
PubMed1997

The recognition of haemoglobin by antibodies raised for the immunoassay of beta-amyloid.

Canine and porcine cerebrospinal fluid (CSF) were fractionated by size exclusion chromatography and analysed by a luminescence enzyme linked immunosorbent assay (ELISA) configured to detect beta-amyloid. A peak of activity was observed in the CSF consistent with the molecular weight of beta-amyloid. When CSF contaminated with blood was analysed an additional peak of immunoreactivity at a higher molecular weight was observed. The peak of activity was found to be derived from cross-reactivity of the immunoglobulins employed in the ELISA with haemoglobin. These findings are discussed with reference to primary and structural sequence homology between beta-amyloid and haemoglobin from a number of species, the known properties of beta-amyloid and recent clinical reports.

Amyloid beta-Peptides↗
PubMed1994

Iron overload and psychiatric illness.

Seven patients with varying psychiatric disorders were found to have iron overload as manifested by abnormal serum ferritin, transferrin saturation index (TSI), or excessive urinary iron. All possible sources of secondary iron overload were ruled out. The patients were treated with the specific iron chelator, deferoxamine, given IM for seven to 22 weeks which resulted in significant clinical improvements. These cases indicate a need to be aware that disordered iron metabolism is a somatic cause of psychiatric illness and that there is clinical improvement upon lowering elevated iron levels in patients with iron overload.

Adult↗
PubMed1993

Trends in the structure, productivity, effectiveness and unit costs of the Hospital and Community Health Services workforce in England: 1979-1991.

In this paper it is shown that there have been significant structural changes in the composition of the Hospital and Community Health Services (HCHS) workforce over the 1980s. The number of doctors, nurses and other medical professionals has grown at the expense of support staff such as ancillaries and maintenance workers. The number of agency and contract staff has risen rapidly, partly offsetting the loss of directly-employed support staff. Changes in the workforce have been compared with changes in activity, as measured by the cost-weighted activity index. According to this measure labour productivity has grown by a compound rate of 1.9% annually. Adjusting the labour force index for the wage bill of each group reveals productivity growth of 1.5%. The effectiveness of treatment, as proxied by the decline in avoidable perinatal mortality, has grown by 3.4% annually. Unit labour costs have fallen over the period at an average annual rate of 0.3%. The trend conceals wide fluctuations, with labour costs falling slowly during the first half of the decade, and rising strongly during the second half. Medical professionals benefited disproportionately from wage increases in comparison with other HCHS groups during the mid to late 1980s.

Community Health Services↗
PubMed1989

Tetrahydrobiopterin metabolism in the streptozotocin induced diabetic state in rats.

Streptozotocin induced diabetes has been shown to have associated changes in the metabolism of tetrahydrobiopterin. De novo biosynthesis of tetrahydrobiopterin in the brain was reduced as was dihydropteridine reductase activity. Consequently there is a shift from fully reduced biopterins to more oxidised species. Both can cause reduced levels in the cofactor pool and may cause reduced levels of the associated neurotransmitters and neurological deficits.

Animals↗
PubMed1989

Deferoxamine therapy in high-ferritin diabetes.

Serum ferritin and diabetes control were evaluated in 18 White patients with poorly controlled type II (non-insulin-dependent) diabetes who had no known causes of iron-storage disorder. Serum ferritin levels were found to be elevated with normal serum iron and total iron-binding capacity in 9 of the 18 patients studied. Because excess iron, typified by hemochromatosis, is associated with diabetes, and diabetes has been shown to improve after lowering total-body iron load through repeat venesection, I investigated whether regulating elevated ferritin levels could facilitate diabetes control. Deferoxamine (DFO), a known specific chelator of iron, was used because of its capacity to correct excess iron stores. All 9 patients in the high-ferritin diabetic group and 7 of 9 diabetic control subjects with normal serum ferritin levels were given DFO (10 mg/kg i.v.) twice weekly. Diabetic control, fasting glucose, triglyceride, cholesterol, HbA1c, and serum ferritin levels were monitored. Data show that lowering elevated ferritin levels correlated well with diabetes control and improved fasting glucose, triglyceride, and HbA1c in 8 of 9 patients with high ferritin levels. Lowering normal ferritin levels had no effect on diabetes control or on any of the other parameters in the 7 control subjects. This study shows there is a need to study iron metabolism in poorly controlled diabetes and demonstrates the value of DFO in controlling high-ferritin diabetes.

Aged↗
PubMed1987

Serum aluminum levels and erythrocyte dihydropteridine reductase activity in patients on hemodialysis.

Aluminum intoxication due to aluminum-containing antacids or dialysate can cause encephalopathy in patients undergoing hemodialysis, but the biochemical mechanism has not been defined. The enzyme dihydropteridine reductase (DHPR) is essential for the maintenance of normal brain concentrations of tetrahydrobiopterin, which is itself required for the synthesis of specific neurotransmitters. This enzyme is also present in erythrocytes. We measured erythrocyte DHPR activity and concentrations of the biopterin derivatives of its substrate and of aluminum in 38 patients on hemodialysis who had no clinical evidence of encephalopathy. Serum aluminum levels ranged from 15 to 190 micrograms per liter (mean, 67.6 +/- 7.7) as compared with 4.9 +/- 0.99 micrograms per liter in normal subjects. DHPR activity was inversely related to the serum aluminum concentration (r = -0.61, P less than 0.001) and was less than the activity predicted from the hemoglobin concentration in these patients. Serum concentrations of biopterin derivatives were markedly elevated. Eighteen patients were given the aluminum-chelating agent deferoxamine in a single dose, after which DHPR activity doubled. These studies suggest that aluminum inhibits DHPR activity in erythrocytes and that aluminum chelation reverses this effect. Although we did not directly measure DHPR activity in the brains of dialysis patients without encephalopathy, we propose that the reduction in activity in erythrocytes may reflect a similar reduction in the brain. Our findings could help to explain the encephalopathy associated with aluminum intoxication.

Adult↗