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Biomedical subjects

J Hawkes

Publications and source records attributed to J Hawkes.

At least 19 recordsLinked to original sources

In vivo absorption, metabolism, and urinary excretion of alpha,beta-unsaturated aldehydes in experimental animals. Relevance to the development of cardiovascular diseases by the dietary ingestion of thermally stressed polyunsaturate-rich culinary oils.

Thermal stressing of polyunsaturated fatty acid (PUFA)- rich culinary oils according to routine frying or cooking practices generates high levels of cytotoxic aldehydic products (predominantly trans-2-alkenals, trans,trans-alka-2,4-dienals, cis,trans-alka-2, 4-dienals, and n-alkanals), species arising from the fragmentation of conjugated hydroperoxydiene precursors. In this investigation we demonstrate that typical trans-2-alkenal compounds known to be produced from the thermally induced autoxidation of PUFAs are readily absorbed from the gut into the systemic circulation in vivo, metabolized (primarily via the addition of glutathione across their electrophilic carbon-carbon double bonds), and excreted in the urine as C-3 mercapturate conjugates in rats. Since such aldehydic products are damaging to human health, the results obtained from our investigations indicate that the dietary ingestion of thermally, autoxidatively stressed PUFA-rich culinary oils promotes the induction, development, and progression of cardiovascular diseases.

Aldehydes↗

Metabolism of glycoprotein-derived sialic acid and N-acetylglucosamine by Streptococcus oralis.

Nine strains of Streptococcus oralis, isolated from blood cultures of patients with infective endocarditis or from the oral cavity as part of the normal flora, were examined for their ability to elaborate sialidase (neuraminidase) and N-acetylglucosaminidase, enzymes which are involved in the degradation of glycoproteins. Both glycosidases were induced when bacteria were grown in a minimal medium supplemented with porcine gastric mucin, a model glycoprotein, and repressed when growth occurred in the presence of glucose. Cell-free extracts mucin-grown cultures expressed elevated levels of N-acetylneuraminate pyruvate-lyase (the first intracellular enzyme in the pathway of N-acetylneuraminate catabolism), N-acetylglucosamine (glcNAc)-6-phosphate deacetylase and glucosamine-6-phosphate deaminase (enzymes involved in the intracellular catabolism of GlcNAc 6-phosphate); activity of each of these intracellular enzymes was markedly repressed when bacteria were grown in media supplemented with alpha 1-acid glycoprotein, a major component of human plasma. Cells from these cultures expressed high levels of sialidase, N-acetylglucosaminidase, and the intracellular enzymes involved in the catabolism of N-acetyl-sugars released by action of these glycosidases. High-resolution 1H-NMR spectroscopy of spent culture supernatants revealed that sialic acid and GlcNAc residues of the molecularly mobile oligosaccharide side-chains of alpha 1-acid glycoprotein had been hydrolysed and the released sugars internalized by the bacteria. These data indicate that S. oralis has the ability to hydrolyse constituents of oligosaccharide side-chains of host-derived glycoproteins and to utilize simultaneously these released carbohydrates. The biochemical characteristics induced by the growth of S. oralis on glycoproteins may play a role in the survival and persistence of these bacteria at the infection site in vivo.

Acetylglucosamine↗

Detection of aldehydes and their conjugated hydroperoxydiene precursors in thermally-stressed culinary oils and fats: investigations using high resolution proton NMR spectroscopy.

High field (400 and 600 MHz) proton NMR spectroscopy has been employed to investigate the thermally-induced autoxidation of glycerol-bound polyunsaturated fatty acids present in intact culinary frying oils and fats. Heating of these materials at 180 degrees C for periods of 30, 60 and 90 min. generated a variety of peroxidation products, notably aldehydes (alkanals, trans-2-alkenals and alka-2,4-dienals) and their conjugated hydroperoxydiene precursors. Since such aldehydes appear to be absorbed into the systemic circulation from the gut in vivo, the toxicological significance of their production during standard frying practices is discussed.

Aldehydes↗

Molecular mechanisms of the bleaching actions associated with commercially-available whitening oral health care products.

An increased public awareness in dental aesthetics has resulted in the wide availability of techniques of tooth bleaching, both in the dental chair and at home. This article reviews the aetiology of tooth discolouration both at the clinical and the molecular level, together with methods of alleviating such discolouration. Much of the therapeutic and aesthetic actions of commercially-available tooth whiteners, gels, oral rinses and other dentifrices are predominantly dependent on their ability to act as oxidants. A novel method of evaluating these aspects of dentifrice activity is also described: high resolution proton nuclear magnetic resonance (NMR) spectroscopy is a virtually non-invasive, multi component bioanalytical technique that can be employed to study oxidation/reduction reactions at the molecular level and is utilised here to investigate the mechanisms of action of a newly developed dentifrice (Ultrawhite Opal, Janina International). Such methodology also offers much potential for studies concerning the numerous chemical reactions occurring within the oral environment.

Dentifrices↗

Degradation of hyaluronate by Streptococcus intermedius strain UNS 35.

Streptococcus intermedius strain UNS 35, a brain abscess isolate, produced extracellular hyaluronidase when grown in brain heart infusion broth. Chemical assays with this enzyme indicated that hyaluronate depolymerisation resulted in the formation of carbohydrate moieties with N-acetylglucosamine at the reducing terminal and containing an unsaturated carbon-carbon double bond. The nature of the products of this hyaluronidase were investigated further by high-field (400 MHz) proton (1H) NMR spectroscopy. Treatment of hyaluronate with the enzyme resulted in a series of new, sharp resonances in spectra (acetamido methyl group singlets located at 2.03 and 2.07 ppm, sugar ring proton multiplets in the 3.5-4.2 ppm chemical shift range, and doublets at 5.16 and 5.87 ppm) characteristic of low-M(r) oligosaccharide species, predominantly those containing glucuronosyl residues with delta 4,5-carbon-carbon double bonds. Comparison of spectra acquired from hyaluronidase-treated samples with that of an authentic sample of 4-deoxy-L-threo-hex-4-enopyranosyluronic-acid-N-acetylglucosamine (delta UA GlcNAc) indicated that this disaccharide was a major product arising from the actions of this enzyme. When used in minimal media, hyaluronate supported growth of S. intermedius, with lactate as the major metabolic end-product.

Carbohydrate Sequence↗

Mood swings in patients with panic disorder.

Depression is frequently found in patients with panic disorder. It is known that patients suffering from panic disorder and depression have more severe symptoms of anxiety and avoidance and respond less well to treatment with antidepressants. The General Behaviour Inventory, an instrument that identifies subjects with subsyndromal and syndromal recurrent mood disorders was completed by 108 patients in a panic disorder program. Thirty-four percent (n = 37) were classified as suffering from a mood disorder. Of the mood disordered patients, 25 of 37 (68%) (23% of the total) were classified as suffering from bipolar or cyclothymic mood disorder.

Adult↗

Phenelzine reduces plasma vitamin B6.

Plasma levels of the active form of vitamin B6 (pyridoxal phosphate) in 19 patients taking phenelzine were found to be reduced on the average to approximately 54% of the value in a control group. There was no correlation of pyridoxal phosphate level with phenelzine daily dosage over the range of 30 mg to 90 mg. No symptoms of vitamin B6 deficiency peripheral neuropathy were found.

Adolescent↗

Effect of lithium dosing schedule on urinary output.

Lithium has been reported to induce polyuria in up to 35% of patients receiving it. It has been suggested that polyuria may be reduced by using single rather than multiple daily dosing. However, this information is based on non-randomized studies, which used higher serum lithium levels than are currently used. In fact, the incidence of polyuria may be lower at currently used lithium levels, and the benefits of a single daily dose regimen on urine volume at these levels have not been assessed. We conducted a prospective randomized study to test the hypothesis that switching patients from multiple daily dose lithium to single daily dose lithium would significantly lower urine volume. Twenty-four patients previously stabilized on multiple daily dosing were randomly allocated to either single or multiple daily dose lithium. Twenty-four-hour urine volume, serum creatinine, creatinine clearance and serum lithium were measured at study entry and completion. Switching to single daily dose lithium did not significantly reduce the 24-h urine volume.

Adolescent↗

Feed preferences of ponies.

Preference trials were conducted with mature ponies. In Trial 1, oats were compared with oats plus sucrose. Four of six pony geldings selected oats plus sucrose, but one pony demonstrated a dislike for sucrose and one selected from the bucket on the right side regardless of content. Oats, maize, barley, rye and wheat were compared in Trial 2 using six mature pony mares. Oats were the preferred grain, with maize and barley ranking second and third respectively. Wheat and rye were the least preferred. Even though the ponies demonstrated preference, the total intake at a given meal was not greatly depressed when only the less palatable grains were fed. In Trial 3, pony mares selected a diet containing 20 per cent dried distillers' grain and 80 per cent of a basal mixed diet of maize, oats, wheat bran, soybean meal, limestone and molasses over 100 per cent basal mixed diet, but selected the basal diet over diets containing 20 per cent blood meal, beet pulp or meat and bone meal and 80 per cent basal diet. They did not differentiate against diets containing 20 per cent alfalfa meal or 10 or 5 per cent meat and bone meal when the diets were compared to the basal mixed diet.

Animal Feed↗

The pathology of the human locus ceruleus.

The number of nerve cells of locus ceruleus and their nucleolar volume were determined in 63 normally aged individuals and in 41 cases with neurologic diseases. Pathologic alterations, such as a severe nerve cell loss and atrophy with or without extensive neurofibrillary degeneration or Lewy body formation, were generally seen in the nucleus locus ceruleus in Alzheimer's disease, Down's syndrome, dementia pugilistica, Parkinson's disease, and progressive supranuclear palsy, but such changes were only slight in normally aged individuals and minimal in motor neuron disease. Protein synthetic capacity was substantially reduced in the remaining nerve cells of the locus ceruleus, in Alzheimer's disease, Down's syndrome, and dementia pugilistica, but was unaltered in normally aged individuals (even in extreme old age), in motor neuron disease, and in the few remaining cells in Parkinson's disease and progressive supranuclear palsy. It is suggested that the pathologic alterations in the locus ceruleus found in these diseases, in conjunction with changes in the hypothalamus, lead to impairment of mental ability with eventual dementia through disturbance of the function of those pathways regulating homeostasis within the central nervous system.

Adult↗

The noradrenergic system in Alzheimer and multi-infarct dementias.

The number of melanin containing nerve cells of the locus coeruleus and vagus nucleus is reduced in Alzheimer's disease by 60% with decrease of 22% in the protein synthetic capability of remaining cells. These changes are matched by reductions in brain noradrenaline in eight regions, averaging 36%. In multi-infarct dementia, however, all three of these features are unchanged. These findings indicate that degeneration of central noradrenergic nerve cells is a specific aspect of the pathogenic process underlying Alzheimer's disease.

Aged↗

Low-dose insulin for treatment of diabetic ketoacidosis in a private community hospital.

We evaluated 21 patients with the diagnosis of diabetic ketoacidosis, involving 25 admissions to a large private community hospital, to evaluate the efficacy of low-dose insulin therapy by measuring time required for correction of hyperglycemia and acidosis, and to evaluate any associated morbidity or mortality. The protocols and laboratory tests were relatively loose and less stringent than our previous protocols, to permit flexibility of therapy by various physicians and to simulate the prevailing practice in such a hospital. All patients responded with correction of hyperglycemia within nine hours and acidosis within 12 hours, with averages of 5.61 and 6.8 hours, respectively. No deaths were recorded in the group. From these data, it is apparent that the low-dose insulin regimen is a safe, effective, and practical method for therapy of DKA in the private community hospital.

Adult↗

Immunoradiometric assay of salivary anti-c3 antibodies.

By an immunoradiometric assay IgA and IgG anti-C3 antibodies were found in adult parotid salivas. The binding of the IgA antibodies to complement coated red cells could be reversed by washing in buffer containing 0.01 M EDTA but IgG antibodies were unaffected. The binding of IgA antibodies was inhibited by small quantities of purified C3. This assay may prove useful in the detection of anti-C3 antibodies in other body fluids.

Adult↗