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Biomedical subjects

R Gama

Publications and source records attributed to R Gama.

At least 19 recordsLinked to original sources

Diurnal variation in lipoprotein lipase activity.

BACKGROUND: We investigated whether variations in lipoprotein lipase activity, a key post-prandial enzyme involved in the removal of circulating dietary triglycerides, could contribute to the previously described nocturnal lipid intolerance. METHODS: We studied lipoprotein lipase activity in 12 healthy volunteers (five women, seven men) at 11:30 h and 23:30 h on two separate occasions. Subjects consumed a high-fat mixed meal at 07:30 h for the morning study or 19:30 h for the evening study. Then, after a 4-h fast, subjects were given an intravenous bolus of 7,500 U heparin. Blood samples were collected before and 15 min after heparin administration for measurement of lipoprotein lipase, hepatic lipase, triglycerides and non-esterified fatty acids concentrations. RESULTS: Post-prandial post-heparin lipoprotein lipase activity was greater in the morning than in the evening (16.5 +/- 1.4 versus 14.4 +/- 1.0 micromol oleate/mL/h; P< 0.05). Post-prandial post-heparin hepatic lipase activity was also greater in the morning than in the evening (8.7 +/- 1.5 versus 81 +/- 1.6 micromol oleate/mL/h; P= 0.002). There were no other significant diurnal differences. CONCLUSION: We report a diurnal variation in post-prandial lipoprotein lipase activity. This is consistent with the notion that decreased nocturnal insulin sensitivity extends to insulin's actions on lipoprotein lipase and provides a possible explanation for nocturnal lipid intolerance.

Adult↗

Analysis of cellular adhesion by microarray expression profiling.

Microarrays of oligonucleotides or cDNAs can be used to establish the expression profiles of numerous genes in a single experiment. We have established a microarray platform to identify genes in a number of different pathological conditions, particularly those with an inflammation component. This platform utilised the output of an eosinophil sequencing project in which 1069 sequences were identified that were not represented in the public domain. An eosinophil model cell line, AML14.3D10, was used to investigate cell adhesion. The transcription profile of adhered and non-adhered AML 14.3D10 cells was shown to be both technically and biologically reproducible. A number of genes were found differentially expressed in the adhered vs. non-adhered populations. In the adhered population, the expression of these genes was restricted compared to brain, lung, kidney and especially bone marrow. However, the differentially regulated genes were not among those genes most restricted to eosinophils. We discuss the implications of transcription profiling on gene annotation and its potential utility for the identification of targets for drug intervention.

Base Sequence↗

Herbal remedy poisoning presenting with acute abdomen and raised urine porphyrins.

We describe a case of lead poisoning due to herbal remedies, presenting with an acute abdomen, raised porphyrins and increased liver enzyme activities. We suggest that lead poisoning should be considered in the differential diagnosis of the 'acute abdomen', and that the presence of liver dysfunction points to the possibility of Asian herbal remedies as the source of the lead poisoning.

Abdomen, Acute↗

Changing clinicians' laboratory test requesting behaviour: can the poacher turn gamekeeper?

A major reason for the dramatic increase in laboratory costs is the increased number of laboratory investigations, many of which are perceived to be a waste of time and money. In consequence, several strategies, reviewed below, for curtailing clinicians' laboratory usage have been proposed but none has been universally successful. It is clear, however, that a combination of several strategies is likely to be more successful than any single approach. There may be several reasons why no single strategy has been widely adopted in routine practice. We suggest that modern computers have the ability to overcome these obstacles. We propose, therefore, that expert systems at the clinical-laboratory interface utilising a multifactorial approach within a framework of commitment from clinicians and laboratorians offer the best prospect for reducing inappropriate laboratory usage.

Clinical Laboratory Techniques↗

Hyperproinsulinaemia in elderly subjects: evidence for age-related pancreatic beta-cell dysfunction.

We investigated whether pancreatic beta-cell dysfunction has a role in the pathogenesis of glucose intolerance in the elderly by comparing plasma glucose, immunoreactive insulin, C-peptide and proinsulin concentrations during a 100-g oral glucose load in six healthy older male volunteers [aged 69 (65.9-74.9) years; median (95% confidence limits)] and seven young male controls [aged 24.0 (21.9-26.3) years]. Fasting and integrated concentrations of glucose and C-peptide were similar in the elderly and young. Although fasting, insulin and proinsulin levels were similar, integrated insulin (P=0.05) and proinsulin (P<0.05) concentrations were higher in the elderly than in controls. Insulin resistance, measured as homeostasis model assessment, was greater (P<0.05) in the elderly than in controls. Elderly men had greater molar ratios of integrated insulin:C-peptide (P<0.05) and proinsulin:C-peptide (P<0.01) but their respective fasting molar ratios were similar when compared with controls. Pancreatic beta-cell secretion in older subjects, as assessed by C-peptide concentrations, was inappropriately low in the presence of insulin resistance. Their post-prandial 'hyperinsulinaemia' is probably due to a combination of hyperproinsulinaemia and reduced metabolic clearance of insulin. Older subjects had disproportionately high proinsulin to C-peptide levels, suggesting pancreatic beta-cell dysfunction. These results are consistent with the notion that decreased insulin sensitivity and pancreatic beta-cell dysfunction may predispose the elderly to glucose intolerance.

Adult↗

Proinsulin and insulin responses to a mixed meal in hypertriglyceridaemic men.

AIM: To investigate the contribution of proinsulin to the "hyperinsulinaemia" of hypertriglyceridaemia. METHODS: Plasma glucose, triglyceride, immunoreactive insulin, and intact proinsulin concentrations were measured before and after a mixed meal in 11 hypertriglyceridaemic men and six healthy normotriglyceridaemic male controls. RESULTS: Hypertriglyceridaemic subjects had greater fasting (101 v 50 pmol/l) and integrated (139 v 81 x 0(-3) pmol/l/h) insulin concentrations than controls. Fasting and integrated glucose and proinsulin concentrations were similar in the two groups. CONCLUSIONS: Proinsulin does not contribute to the hyperinsulinaemia observed in hypertriglyceridaemic subjects and is therefore unlikely to contribute to the increased cardiovascular risk associated with hypertriglyceridaemia.

Adult↗

Diurnal variations in peripheral insulin resistance and plasma non-esterified fatty acid concentrations: a possible link?

Glucose tolerance becomes impaired towards the evening. Increased peripheral insulin resistance may be responsible, at least in part, for this effect. The mechanism for the diurnal variation in insulin sensitivity is undefined. It is, however, possible that variations in non-esterified fatty acids (NEFA) could contribute to this variation because NEFA have been implicated in the pathogenesis of insulin resistance. Therefore, we have investigated insulin sensitivity and plasma NEFA responses to insulin at 0830 h and 2030 h in nine healthy men by measuring arterialized plasma glucose and venous plasma NEFA concentrations during a short insulin tolerance test. The studies were standardized for a period of fasting, pre-test meal and exercise. Insulin sensitivity measured KITT was greater (P < 0.05) in the morning [(20 +/- 7) x 10(-3) mmol/L/min] than in the evening [(11.6 +/- 2) x 10(-3) mmol/L/min]. Fasting NEFA levels were lower (P < 0.01) in the morning (373 +/- 84 mumol/L) than in the evening (913 +/- 122 mumol/L). Following insulin, NEFA fell more slowly (P < 0.01) in the morning (149 +/- 26 mumol/L/15 min) than in the evening (491 +/- 91 mumol/L/15 min). These results confirm diurnal variations in insulin sensitivity and plasma NEFA concentrations irrespective of feeding and exercise. We speculate that the relatively elevated plasma NEFA levels in the evening are the cause rather than the consequence of increased insulin resistance at this time.

Adult↗

Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung.

Human interleukin 13 (IL-13) is a cytokine that has a profound effect on primary immune cells by inducing immunoglobulin production, proliferation of B cells, and the differentiation of cells of the monocytic lineage. IL-13 can inhibit the production of inflammatory cytokines by both macrophages and monocytes. Previously, IL-13 expression has been reported only in cells of the T-cell lineage and the mast cell line HMC-1. We now report the presence of IL-13 mRNA and protein in human alveolar macrophages (AMs) analyzed by the reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunoabsorbent assay (ELISA), respectively, and IL-13 protein in bronchoalveolar lavage fluid (BALF) of subjects with pulmonary fibrosis. We have investigated 13 patients from 49 to 75 yr of age with forms of pulmonary fibrosis, and eight healthy volunteers from 24 to 61 yr of age. Their AMs were obtained by bronchoalveolar lavage (BAL) and purified by adherence. The proportion of BAL purified AMs expressing IL-13 mRNA was increased in those subjects with fibrotic lung disease, in comparison with those from control subjects (11 of 13 versus 2 of 8, P < 0.01). IL-13 protein was detectable in the BALF of 8 of 13 patients with pulmonary fibrosis, but in none of the control subjects. AMs of four subjects with systemic sclerosis were cultured and IL-13 protein was increased in the culture supernatants when compared to the control subjects, although this did not reach significance. These findings show that IL-13 mRNA is not only a product of T cells, but is also expressed in both normal AMs and those from subjects with pulmonary fibrosis, and that at least some of the IL-13 mRNA is translated into protein and secreted in subjects with pulmonary fibrosis. We hypothesize that IL-13 may be expressed by normal human AMs as part of the homeostatic control process but its production may be increased in the presence of inflammatory lung disease.

Adult↗