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Biomedical subjects

A D Wright

Publications and source records attributed to A D Wright.

At least 19 recordsLinked to original sources

Balanitoside, a furostanol glycoside, and 6-methyldiosgenin from Balanites aegyptiaca.

In addition to a known spirostanol glycoside, balanitin-3, and a new sapogenol, 6-methyldiosgenin, a new furostanol saponin, balanitoside has been isolated from the fruits (mesocarp) of Balanites aegyptiaca. The structure of the glycoside has been determined as 26-O-beta-D-glucopyranosyl-3 beta, 22,26-trihydroxy-furost-5-ene 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D- glucopyranosyl-(1-->4)-beta-D-glucopyranoside, on the basis of spectroscopic and chemical evidence.

Carbohydrate Sequence

Four new antibacterial sesterterpenes from a marine sponge of the genus Luffariella.

The structures of four new sesterterpenoid compounds 1-4 isolated from a marine sponge of the genus Luffariella, collected from The Great Barrier Reef, Australia, have been determined by analysis of their 1H-nmr, 13C-nmr, ir, uv, and eims spectral data. The new metabolites 1-4 were found to co-occur with the compounds manoalide, secomanoalide, Z-neomanolaide [5], and E-neomanoalide.

Animals

Antimalarial activity of sesquiterpenes from the marine sponge Acanthella klethra.

Five sesquiterpenoids containing isonitrile or isothiocyanate groups were isolated from the sponge Acanthella klethra. Compounds 1 and 2 were identified as axisonitrile 3 and the corresponding isothiocyanate derivative, respectively. Compounds 3-5 were found to be eudesmane sesquiterpenes. None of these compounds was cytotoxic toward cultured KB-3 cells, but varying degrees of activity were observed with cultured Plasmodium falciparum. Compound 1 demonstrated greatest promise as an antimalarial agent.

Animals

Acetazolamide and high altitude diseases.

Acetazolamide is a useful prophylactic for acute mountain sickness causing marked reduction in headache, nausea, vomiting, weakness, etc. Improvements correlate with increased arterial oxygen concentrations, reduction in proteinuria and peripheral oedema and other objective measures of acute mountain sickness. Evidence that Acetazolamide is beneficial for pulmonary oedema or cerebral oedema is scanty because of the lower frequency of these severe forms of mountain sickness. Dexamethasone, used prophylactically, also reduces the symptoms of acute mountain sickness partly due to its euphoric effect. Use of Acetazolamide as a treatment for established acute mountain sickness has been investigated. Large doses of Acetazolamide increase arterial oxygen levels over a few hours and this leads to a reduction of symptoms but data is limited and faster acting carbonic anhydrides inhibitors such as Methazolamide may be preferable in an emergency situation. There is no comparison of the effectiveness of Acetazolamide with other drugs used for treating acute mountain sickness such as steroids and calcium channel blocking drugs. Also, there is no data on drug combinations which could have additive effects and thereby be more beneficial than individual drugs.

Acetazolamide

The maize auxotrophic mutant orange pericarp is defective in duplicate genes for tryptophan synthase beta.

orange pericarp (orp) is a seedling lethal mutant of maize caused by mutations in the duplicate unlinked recessive loci orp1 and orp2. Mutant seedlings accumulate two tryptophan precursors, anthranilate and indole, suggesting a block in tryptophan biosynthesis. Results from feeding studies and enzyme assays indicate that the orp mutant is defective in tryptophan synthase beta activity. Thus, orp is one of only a few amino acid auxotrophic mutants to be characterized in plants. Two genes encoding tryptophan synthase beta were isolated from maize and sequenced. Both genes encode polypeptides with high homology to tryptophan synthase beta enzymes from other organisms. The cloned genes were mapped by restriction fragment length polymorphism analysis to approximately the same chromosomal locations as the genetically mapped factors orp1 and orp2. RNA analysis indicates that both genes are expressed in all tissues examined from normal plants. Together, the biochemical, genetic, and molecular data verify the identity of orp1 and orp2 as duplicate structural genes for the beta subunit of tryptophan synthase.

Amino Acid Sequence

Growth hormone secreting pituitary carcinoma: a case report and literature review.

Only five cases of growth hormone secreting pituitary carcinoma have been documented. We present a 49-year-old West Indian male with grossly elevated plasma growth hormone (760-10,400 mU/l), and a large aggressive pituitary tumour that continued to grow despite repeated pituitary surgery, radiotherapy and medical therapy (bromocriptine and somatostatin analogue). Thirteen years after diagnosis the patient died secondary to left ventricular failure. A post-mortem revealed a large locally invasive pituitary tumour, but in addition numerous tumour seedlings within the cerebrospinal fluid space, and a solitary intraparenchymal tumour deposit within the right temporal lobe, clearly separate from the primary tumour. Pituitary carcinoma should be considered in any acromegalic with grossly elevated plasma growth hormone levels who fails to respond to conventional therapy.

Acromegaly

Control of diabetes mellitus in shift workers.

OBJECTIVE: To determine whether the control of diabetes is different in insulin treated diabetic subjects who work shifts compared with those who do not work shifts and whether control is related to the type of shift worked. DESIGN: Prospective controlled study of 32 diabetic subjects working either regular days or shifts in a large car assembly factory. Insulin treated subjects who underwent a change in their pattern of shift work had diabetic control assessed before and six months after a change in shifts. MAIN OUTCOME MEASURES: Random plasma glucose, serum fructosamine, and haemoglobin A1 while at work. RESULTS: Diabetic control of insulin treated subjects who worked shifts was not significantly different from insulin treated subjects who worked days only. Diabetic control was poor in both groups and similar to that of diabetic subjects treated with oral hypoglycaemic agents. In those subjects that moved to a more rapidly rotating shift pattern there was a significant deterioration in control (serum fructosamine concentration before, 405 (SD 68); after, 481 (SD 90) mumol/l, p less than 0.01). CONCLUSIONS: The control of diabetes in insulin treated diabetic subjects who worked shifts was no worse than those who worked days only. Slowly rotating shifts were associated with better diabetic control than more rapidly rotating shifts.

Blood Glucose

New indole alkaloid glycosides from Nauclea orientalis.

Two new indole alkaloid glycosides, 10-hydroxystrictosamide and 6'-O-acetylstrictosamide, as well as the known alkaloids strictosamide and vincosamide were isolated from the leaves of Nauclea orientalis L. The structures of the isolated compounds were determined using spectroscopic methods, mainly 1D- and 2D-NMR spectroscopy.

Animals

Metabolic effects of pharmacological adrenergic blockade in phaeochromocytoma.

Twelve-hour hormonal and metabolic profiles were performed in a 68-year-old woman with a benign adrenal phaeochromocytoma (a) prior to adrenergic blockade, (b) after the establishment of pharmacological alpha-blockade with phenoxybenzamine, (c) after combined alpha and beta-blockade with phenoxybenzamine and propranolol, and (d) after successful surgery and withdrawal of medication. Pretreatment, (a) vs (d), significant elevations (12-h mean +/- SD) were observed in the concentrations of noradrenaline (44.9 +/- 14.4 vs 2.3 +/- 0.7 nmol/l, P less than 0.01), glucose (6.9 +/- 1.9 vs 5.0 +/- 1.0 mmol/l, P less than 0.05), glycerol (0.22 +/- 0.02 vs 0.07 +/- 0.01 mmol/l, P less than 0.01), non-esterified fatty acids (0.71 +/- 0.28 vs 0.34 +/- 0.08 mmol/l, P less than 0.01), and total ketone bodies (0.08 +/- 0.03 vs 0.03 +/- 0.02 mmol/l, P less than 0.01). Alpha-blockade, (b) vs (a), was associated with an increase in noradrenaline levels (P less than 0.01) but not with any significant alterations in intermediary metabolite concentrations. Following the establishment of combined alpha and beta-blockade, (c) vs (b), plasma noradrenaline returned to its pretreatment level while the concentrations of glycerol, fatty acids and ketone bodies were normalized. A completely physiological 12-h blood glucose profile, however, was observed only post-operatively. No significant differences were observed in mean plasma insulin levels between the four studies. These results indicate impaired regulation of multiple aspects of carbohydrate, lipid and ketone body metabolism in our patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms

A comparison of the metabolic effects of flosequinan and propranolol in patients with non-insulin-dependent diabetes mellitus.

The effects of steady-state flosequinan, a new peripheral vasodilator, and propranolol on glucose tolerance and plasma lipids in 22 non-insulin-dependent diabetics were investigated in a randomized double-blind placebo-controlled, three-way crossover trial. Flosequinan produced no impairment of glucose tolerance compared with placebo. Propranolol produced significant increases in fasting plasma glucose (P less than 0.01) and increases in the area under the glucose tolerance curve (P less than 0.05) compared to placebo. No significant effects on cholesterol levels were seen on either treatment but triglyceride levels were significantly elevated on propranolol compared with placebo (P less than 0.01). These data suggest that flosequinan, used in therapeutic dosage, has no adverse metabolic effects on the non-insulin-dependent diabetic and this may be an advantage for a drug used in the treatment of hypertension or congestive heart failure.

Adult

Qualitative and quantitative abnormalities of von Willebrand antigen in patients with diabetes mellitus.

Previous reported studies of vVWf antigen (vWf:Ag) in patients with diabetes mellitus have not shown qualitative abnormalities despite frequent documentation of raised vWf:Ag. Twenty two patients with established diabetes mellitus have been studied and qualitative abnormalities of vWf:Ag multimers were found in 10 patients who had poorer glycaemic control (as judged by plasma fructosamine) than the other 12 patients. Seven of the 22 patients were restudied after a 3 month period of improved glycaemic control and the vWf:Ag multimer abnormalities disappeared in 6 of these. Some of the structural abnormalities were accompanied by loss of vWf functional activity. As vWf:Ag is synthesised in the endothelial cell, vWf:Ag abnormalities during periods of poor glycaemic control may reflect endothelial cell damage with vWf:Ag release and possibly subsequent proteolysis.

Antigens

Changing sex ratio in diabetic ketoacidosis.

An annual audit of diabetic ketoacidosis and hyperosmolar non-ketotic state was made in one hospital from 1971 to 1988. There were 846 episodes of ketoacidosis and 126 episodes of hyperosmolar state. A relative fall occurred in the number of episodes of ketoacidosis compared with hyperosmolar state over this time (p less than 0.05), and there was a change of female:male ratio for episodes of ketoacidosis occurring in established diabetes from 2.79 to 1.59 (p less than 0.01). In contrast the female:male ratio remained unchanged (mean 1.16) for episodes of hyperosmolar state and remained less than 1.0 for all episodes of ketoacidosis in previously undiagnosed diabetes mellitus. Among patients who suffered recurrent ketoacidosis there was a reduction in the number of episodes occurring in female patients and an increase in the number of episodes occurring in male patients in each successive 6-year period with consequent change in female:male ratio for this subgroup from 7.33 to 4.75 to 1.12 (p less than 0.001).

Adolescent

Cerebral blood flow in acute mountain sickness.

Changes in cerebral blood flow (CBF) were measured using the radioactive xenon technique and were related to the development of acute mountain sickness (AMS). In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased at 24 h [45.1 to 55.9 initial slope index (ISI) units] and 4% increased at 6 days (47.1 ISI units). Four subjects had similar increases of CBF when ascending to 3,200 m 3 mo later, indicating the reproducibility of the measurements. In nine subjects, ascending from 3,200 to 4,785-5,430 m, CBF increased to 76.4 ISI units, 53% above estimated sea-level values. CBF and increases in CBF were similar in subjects with or without AMS. In six subjects, CBF was measured before and after therapeutic intervention. At 2 h CBF increased 22% (71.3 to 87.3 ISI units) above pretreatment values in three subjects given 1.5 g acetazolamide, while three subjects given placebo showed no change. Symptoms remained unaltered in all subjects during the 2 h of the study. Overall, the results indicated that increases in CBF were similar in subjects with or without AMS while acetazolamide-provoked increases of CBF in AMS subjects caused no acute change in symptoms. Alterations in CBF cannot be directly implicated in the pathogenesis of AMS.

Acetazolamide

Xiaoke tea, a Chinese herbal treatment for diabetes mellitus.

Xiaoke tea, a traditional Chinese treatment for diabetes mellitus, lowered blood glucose concentrations in streptozotocin diabetic mice. To investigate Xiaoke clinically, a double-blind crossover study was undertaken in 12 non-insulin-treated diabetic patients. Xiaoke tea and ordinary tea (infusion of 2.72 g, 4 times daily) were consumed in random order for 4 weeks. A standard breakfast meal was taken before and after each treatment period. Xiaoke did not significantly affect glycosylated haemoglobin, basal or post-breakfast serum glucose and insulin concentrations, intermediary metabolite concentrations, triglyceride and cholesterol. No adverse side-effects of Xiaoke were evident.

Blood Glucose

The effects of verapamil, diltiazem, nifedipine and propranolol on metabolic control in hypertensives with non-insulin dependent diabetes mellitus.

The effects of one month's treatment with each of nifedipine, verapamil, diltiazem, propranolol and placebo, given in random order, on fasting plasma glucose, haemoglobin Alc, serum fructosamine, immunoreactive insulin, cholesterol, and triglyceride were studied in a group of 19 patients with hypertension and non-insulin dependent diabetes mellitus. The metabolic effects of the active drugs were generally small but fasting plasma glucose was increased by propranolol from 9.3 +/- 3.0 to 10.4 +/- 3.4 mmol/l (P less than 0.01) (mean +/- SD) and to 10.1 +/- 3.2 mmol/l (P less than 0.05) by nifedipine. Serum fructosamine was increased from 2.75 +/- 0.53 to 2.89 +/- 0.62 mmol/l (P less than 0.05) by diltiazem and to 2.91 +/- 0.65 (P less than 0.05) by propranolol. Verapamil increased fasting serum immunoreactive insulin: diltiazem and propranolol tended to reduce it. Propranolol but not the other drugs significantly increased serum triglyceride. Calcium antagonists may be preferable to beta adrenoceptor blockers for the treatment of hypertensive diabetics. Of the three calcium antagonists we studied, verapamil may have advantages over nifedipine and diltiazem.

Aged