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Biomedical subjects

J A Blair

Publications and source records attributed to J A Blair.

At least 19 recordsLinked to original sources
PubMed2003

Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs.

Hyaluronic acid (HA) and recombinant human insulin were co-spray dried to form a dry powder suitable for inhalation (Mass Median Aerodynamic Diameter, MMAD=1 to 4 microm). Insulin systemic levels and corresponding glucose levels were monitored following administration of the microparticles to the lungs of male Beagle dogs. Release kinetics were modified by addition of excess zinc ions (Zn2+) or hydroxypropyl cellulose (HPC). HA formulations containing insulin (10%w/w) were found to extend the mean residence time (MRT) and terminal half-life (t(1/2)) when compared to spray dried pure insulin. Addition of Zn2+ also improved MRT (>9 fold), AUC/dose (2.5 fold) and Tmax (by a factor of 3) when compared to spray dried pure insulin. Addition of HPC improved MRT (>7 fold), AUC/dose (5 fold) and Tmax (by a factor of 3) when compared to spray dried pure insulin. Our results demonstrate the potential of HA-based dry powder drug delivery systems in the pulmonary controlled release of insulin.

Administration, Inhalation↗
PubMed2002

Modifying the release of leuprolide from spray dried OED microparticles.

A range of oligosaccharide ester derivatives (OEDs) have been designed as drug delivery matrices for controlled release. The synthetic hormone analogue, leuprolide, was encapsulated within these matrices using hydrophobic ion pairing and solvent spray drying. The particles produced modified the release of leuprolide in vitro (dissolution in phosphate buffered saline) and in vivo (subcutaneous and pulmonary delivery in the rat). Release rate was dependent on drug loading and could be manipulated by choice of OED and by combining different OEDs in different ratios. Leuprolide encapsulated in the OEDs retained biological activity as evidenced by elevation in plasma luteinising hormone levels following subcutaneous injection of leuprolide recovered from OED particles in vitro prior to in vivo administration.

Administration, Inhalation↗
PubMed1997

Gallium-transferrin binding in treated and untreated Parkinson's disease.

The binding of gallium (Ga) to transferrin (Tf) was studied in plasma from control patients, in patients with untreated Parkinson's disease (PD) and in patients with PD treated either with levodopa (L-dopa) alone or in combination with selegiline. Mean percentage Ga-Tf binding was significantly reduced in untreated and treated PD compared with controls. Binding, however, was significantly greater in treated than in untreated patients. There was no difference in binding between patients treated with L-dopa alone and those treated with L-dopa and selegiline. The data support the hypothesis that oxidation reactions may be of pathogenic significance in PD.

Adult↗
PubMed1997

Mechanisms of pediatric electrical injury. New implications for product safety and injury prevention.

OBJECTIVES: To determine age-specific mechanisms of electrical injury in children, to examine product safety regulation of the major sources of electrical injury hazard, and to assess the adequacy of current prevention strategies. DESIGN: Case series of 144 pediatric and adolescent electrical injuries in patients seen in the specialized burn center and tertiary care hospital between 1970 and 1995, examination of Consumer Product Safety Commission product recall reports for electrical injury hazards between 1973 and 1995, and review of the National Electric Code. RESULTS: Eighty-six cases of electrical injuries resulted from low-voltage (< 1000-V) exposures, all occurring within the home. In children aged 12 years and younger, household appliance electrical cords and extension cords caused more than 64 (63%) of 102 injuries, whereas wall outlets were responsible for only 14 (15%) of injuries. Fifty-eight cases resulted from high-voltage exposures, accounting for 38 (90%) of 42 injuries in children older than 12 years. No federal safety regulations for electrical cords exist, although voluntary standards have been adopted by many manufacturers. Among 383 consumer products identified by the Consumer Product Safety Commission to be electrical injury hazards, 119 were appliance cords, extension cords, or holiday stringed light sets. Several products numbered more than 1.5 million units in US household distribution prior to the investigation by the Consumer Product Safety Commission. CONCLUSIONS: Household electrical cords are the major electrocution hazard for children younger than 12 years, yet no federal safety mandates exist. Despite voluntary standards, noncompliant manufacturers can introduce vast numbers of unsafe cords onto the US household market every year. Conversion of existing voluntary safety guidelines into federally legislated standards may be the most effective intervention against pediatric electrocutions.

Accidental Falls↗
PubMed1997

Mechanisms of aluminum absorption in rats.

Aluminum has become a dietary toxin in modern times but its mechanism of absorption is poorly understood. After ingestion, the systemic transfer of aluminum is small but it is greatly affected by the coingestion of certain dietary agents, such as citrate, that complex with the metal in the intestinal lumen or transiently alter the permeability of the mucosa. Here, mechanisms of aluminum absorption were studied by using freshly prepared aluminum hydroxide and aluminum citrate. Everted sacs of rat gut were used to investigate the site of absorption, effect of chemical charge on absorption of aluminum citrate, and presence of active or passive absorption with use of the metabolic inhibitor ouabain. Absorption was biphasic with a large tissue uptake that was consistent with adhesion to mucus-mucosal surface but little tissue transport, which was consistent with passive paracellular permeation. Citrate reduced the uptake-transport ratio both by competing with the mucosal uptake and by increasing mucus-mucosal permeation but not by affecting the charge of the luminal aluminum species. Despite the potential for hydroxypolymerization of aluminum at intestinal pH, the small bowel and colon absorbed aluminum passively and paracellularly but the stomach did not. The predominantly proximal absorption of aluminum observed in vivo is a reflection of the proximal absorption, and therefore removal, of dietary constituents (eg, citrate) that enhance mucosal permeation of aluminum. The colon should be investigated further as a site of significant paracellular permeability.

Aluminum↗
PubMed1995

The role of pterins in depression and the effects of antidepressive therapy.

Urinary excretion of neopterins (N) and biopterins (B) was measured in 48 patients with depression before and after treatment with placebo, antidepressants, or electroconvulsive therapy (ECT), and in 26 healthy control subjects. Patients prior to and after treatment had a significantly greater neopterin/biopterin (N:B) ratio than control subjects. There was a significant correlation between N:B ratios and the severity of depression and plasma cortisol. As a raised N:B ratio implies failure to convert neopterin to biopterin, it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate-limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive illness.

Adult↗
PubMed1995

Hypothesis: is Alzheimer's disease a metal-induced immune disorder?

A hypothesis that a metal-induced immune disorder may be involved in the pathogenesis of some forms of Alzheimer's disease (AD) is presented. The classical complement pathway is activated in AD and T cells and reactive microglia appear in the brain. Studies of metal induced autoimmunity and the use of compounds containing aluminium as vaccine adjuvants suggest that metals can activate complement and can be taken up by antigen presenting cells. The consequent immune response could contribute to neuronal damage, beta-amyloid deposition and cell death. The strengths and weaknesses of this hypothesis are discussed and tests of some aspects are proposed.

Alzheimer Disease↗
PubMed1994

Pre-injury emotional trauma and chronic back pain. An unexpected finding.

STUDY DESIGN: A retrospective study investigated pre-injury emotional trauma in out-of-work, blue collar patients with chronic back pain (N = 27) who participated in a 30-hour workshop in which a wide range of cognitive skills was taught to help patients with rehabilitation and return them to work. OBJECTIVES: This study identified categories of pre-injury emotional trauma, calculated summary statistics, and performed category comparisons. METHODS: The categories of abandonment, emotional abuse, physical abuse, and sexual abuse emerged from the data. Frequencies and percentages in each category were calculated. Chi-square tests compared the differences in emotional trauma and gender. RESULTS: Statistically more patients reported abandonment and emotional abuse than physical and sexual abuse. There were no differences in trauma rates by gender. The results of the study revealed a high rate of pre-injury emotional trauma in patients with chronic back pain. CONCLUSION: Including pre-injury emotional trauma in psychologic evaluations of patients with chronic back pain and high psychologic test scores is recommended.

Back Pain↗
PubMed1994

5-Methyltetrahydrofolate level in the serum of depressed subjects and its relationship to the outcome of ECT.

Serum 5-MeTHF levels are reported in 26 subjects, before and after completing a course of ECT, and compared to 21 healthy volunteers. 5-MeTHF levels of depressed subjects were significantly lower than controls before and after ECT. There was no difference in 5-MeTHF levels between ECT responders and non-responders but folate deficiency was related to severity of depression before ECT. Serum 5-MeTHF was not related to treatment response and values remained markedly low even after a good response to treatment.

Aged↗
PubMed1994

Recovery from depression after electroconvulsive therapy is accompanied by evidence of increased tetrahydrobiopterin-dependent hydroxylation.

Serum phenylalanine and tyrosine levels were measured in 26 patients with severe depression before and after receiving electroconvulsive therapy. The phenylalanine:tyrosine [P:T] ratio declined significantly for those responding to treatment but not for nonresponders. These findings are discussed in relation to tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, dopamine and serotonin and the hydroxylation of phenylalanine to tyrosine.

Aged↗
PubMed1993

Reduced transferrin binding in Down syndrome: a route to senile plaque formation and dementia.

Plasma transferrin binding in Down syndrome and Alzheimer's disease is significantly reduced compared with age matched controls and it was thought this may help elucidate a pathological time sequence for the onset of dementia in Down syndrome. In Down syndrome, there was a reduction in gallium and aluminium transferrin binding both with age and the onset of dementia. Non-transferrin bound gallium species were identified as non-transportable phosphate or silicate. Thus, the route of entry of metals into the brain must be via a transferrin mediated complex only. A clear sequence of pathological events has been demonstrated in Down syndrome which shows the pathway to development of plaques and dementia and this is believed to have an immunological origin.

Adolescent↗
PubMed1992

Pterin metabolism in depression: an extension of the amine hypothesis and possible marker of response to ECT.

Urinary excretion of neopterins and biopterins was measured in 23 patients with severe depression before and after receiving electroconvulsive therapy (ECT) and 26 healthy control subjects. Patients with psychotic depression and those responding to ECT had neopterin:biopterin (N:B) ratio significantly higher than controls before commencing ECT and positive therapeutic response was associated with reduction of N:B ratio towards control values. As a raised N:B ratio implies failure to convert neopterin to biopterin it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive disorders. The N:B ratio may be a marker for certain depressive subtypes and response to ECT.

Adult↗
PubMed1992

Aluminium administered in drinking water but not in the diet influences biopterin metabolism in the rodent.

To investigate the neurotoxic effects of aluminium (Al) Al was administered: 1) in the diet of the rat (30 mg Al/kg body weight for 6 weeks); 2) as a suspension of aluminium acetate in drinking water of the rat for 3 months and 3) in a long-term study in the mouse in which aluminosilicates were incorporated into a pelleted diet (1035 mg/kg of food over 23 months). In the latter treatment, increased Al was combined with a reduction in calcium and magnesium; a treatment designed to increase absorption of Al into the body. Administration of Al in the drinking water significantly reduced total brain biopterins and BH4 synthesis. However, no significant affect of Al in the diet on total biopterins or BH4 synthesis was found either in the rat or in the long-term study in the mouse. In addition, in the mouse no significant effects of the Al diet on levels of noradrenaline, serotonin, dopamine, 5-HIAA or CAT could be demonstrated. Hence, the occurrence of brain alterations may depend on the Al species present and the method of administration. Al salts in drinking water may increase brain tissue levels compared with the administration of a more insoluble species. Since alterations in biopterin metabolism are also a feature of Alzheimer's disease (AD) these results support the hypothesis that Al in the water supply may be a factor in AD.

Aluminum↗
PubMed1990

Defective gallium-transferrin binding in Alzheimer disease and Down syndrome: possible mechanism for accumulation of aluminium in brain.

The plasma distribution of gallium (as an analogue of aluminium) was investigated in patients with Alzheimer disease, Down syndrome, or stroke dementia, in subjects on haemodialysis for chronic renal failure, and in healthy controls. Gallium-transferrin binding was significantly lower in the Alzheimer (mean [SEM] 7.9 [1.1]%) and Down syndrome groups (6.9 [0.7]%) than in the controls (17.1 [1.6]%), whereas stroke dementia and haemodialysis patients had normal binding. There were no differences among the groups in plasma citrate concentration. The plasma transferrin concentration was slightly lower in the Alzheimer and Down syndrome groups than in the controls, but even lower in stroke dementia patients (1.74 [0.14] g/l vs 2.98 [0.18] g/l in controls). Transferrin iron saturation was higher in the Alzheimer (58.9%) and Down syndrome groups (81.6%) than in the controls (39.0%) or stroke dementia patients (33.4%). This deficiency of gallium/aluminium binding would leave more unbound aluminium which could move readily into the brain, where it has neurotoxic effects.

Adult↗
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↗