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Biomedical subjects

P Kalsi

Publications and source records attributed to P Kalsi.

5 recordsLinked to original sources

Will mesenchymal stem cells differentiate into osteoblasts on allograft?

Tissue engineering approaches for bone blocks previously have used synthetic scaffolds. Bone graft (allograft) is used to fill bone defects, but standard processing can lessen this scaffold's osteoinductive potential. We wanted to test if allografts could be used to produce a viable bone block using mesenchymal stem cells. We hypothesized that mesenchymal stem cells differentiate into osteoblasts producing extracellular matrix when cultured on allografts. We also hypothesized that the addition of osteogenic supplements would increase the rate of differentiation. To test these hypotheses, mesenchymal stem cells were isolated from bone marrow aspirated from 10 patients and cultured on allografts from five donors (Group 2), producing 50 samples. This was repeated on allografts heat-treated to denature bioactive proteins (Group 1), and repeated again on allografts to which osteogenic supplements (Group 3) were added. Group 2 mesenchymal stem cells differentiated into osteoblasts producing higher levels of alkaline phosphatase, osteopontin, and Type I collagen matrix protein than Group 1. The rate of differentiation of Group 3 mesenchymal stem cells increased with the supplements. Overall, it was established that the bioactive proteins in the allograft stimulated mesenchymal stem cell differentiation into osteoblasts, with production of extracellular matrix, and that this differentiation increased with the addition of osteogenic supplements.

Alkaline Phosphatase↗

The relevance of persistent C-peptide secretion in type 1 (insulin-dependent) diabetes mellitus to glycaemic control and diabetic complications.

The effect of residual C-peptide secretion in longer standing IDDM on glycaemic control and the prevalence and evolution of complications over 2 years was evaluated. Thirty-one subjects with IDDM of 15.4 (1.5) years duration (mean SEM)) and residual C-peptide secretion, were matched for age, duration of diabetes and body mass index with 31 subjects without detectable C-peptide secretion. At trial entry and over 2 years, levels of HbA1, fructosamine and mean blood glucose were essentially similar in both groups. Levels of glycated albumin (GSA) were significantly higher in the C-peptide negative group after 3 and 9 months (P less than 0.05). An increased prevalence of proliferative retinopathy in the C-peptide negative group and of peripheral vascular disease in the C-peptide secretor group was apparent at entry to the study (both P less than 0.05), although no significant differences were observed after 1 or 2 years. There was no difference in the prevalence of peripheral or autonomic neuropathy, hypertension, nephropathy or ischaemic heart disease. Subjects with C-peptide concentrations greater than 0.100 pmol/ml at entry to this study had lower daily insulin requirements after 1 and 2 years, but behaved like the larger group with any detectable C-peptide secretion in all other respects. Residual C-peptide secretion was lost after 1 year in 7 patients, in whom glycaemic control during the year had been particularly poor. Insulin antibody titres were no different in the 2 groups at any time point. This study suggests that residual C-peptide secretion in longer standing IDDM confers the potential for limited improvements in glycaemic control. This effect appears to be insufficient to prevent the evolution of microvascular complications over a 2-year period. Residual C-peptide secretion and relative hyperinsulinaemia may be associated with an excess of peripheral vascular disease.

Adult↗

A comparison of direct measures of glycaemia and glycated blood proteins in insulin-dependent diabetes mellitus.

We have studied associations between various direct measures of glycaemia and glycated blood proteins in 113 subjects with insulin-dependent diabetes mellitus (IDDM), and examined whether or not the 'fructosamine' assay results were affected by differing patient serum concentrations of lipids, albumin or C peptide. Serum fructosamine correlated less closely with HbA1 (r = 0.44) than did HbA1 with glycated serum albumin (GSA) (r = 0.68). Serum fructosamine and GSA also were poorly correlated (r = 0.48). Although fructosamine, HbA1 and GSA correlated to a similar degree with fasting blood glucose (r range 0.34 to 0.37), GSA was most closely related to mean blood glucose (r = 0.39 vs. 0.30-0.35) and the M value (a marker of diurnal glycaemic instability) (r = 0.42 vs. 0.33-0.35). The serum concentration of fructosamine was not significantly affected by a variation in serum cholesterol, but tended to be lower in subjects with moderate hypertriglyceridaemia (p = 0.05). The fructosamine assay may be altered by moderately lipaemic serum but is not affected by serum albumin concentration in normoalbuminaemic patients with IDDM. Our study indicates, however, that GSA is a more reliable marker of short-term glycaemic control in IDDM than fructosamine.

Adolescent↗

An analysis of glycosylated blood proteins and blood glucose profiles over one year in patients with type 1 diabetes.

The clinical value of prospective measurement of several direct and indirect measures of blood glucose control in the management of Type 1 diabetes has been investigated. Ninety-eight Type 1 diabetic patients were followed over a period of 1 year after a 6-week period of intensification of management, with monthly measurements of blood glucose profiles and 3-monthly HbA1, glycosylated serum albumin, and fructosamine measurements. All measures improved markedly after the initial 6-week period (p less than 0.001), and all except glycosylated serum albumin and fructosamine then remained relatively stable. Of fourteen serial comparisons, glycosylated blood proteins were significantly correlated more often with levels of mean blood glucose and M value (on 4-7 occasions, rs 0.30-0.58) than with fasting blood glucose levels (on only 2-3 occasions, rs 0.34-0.44). Serum fructosamine levels correlated significantly with mean blood glucose on four occasion (rs 0.30-0.50), whilst glycosylated serum albumin and HbA1 correlated with mean blood glucose on six occasions (rs 0.36-0.54). Glycosylated serum albumin correlated with HbA1 and fructosamine levels throughout the year (rs 0.47-0.68 and 0.48-0.76, respectively), but HbA1 and fructosamine were less clearly correlated with each other (rs 0.38-0.44), with no significant association immediately after the period of intensive management or 3 months later.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relative clinical usefulness of glycosylated serum albumin and fructosamine during short-term changes in glycemic control in IDDM.

Serial changes in glycosylated blood proteins and direct measures of glycemia were studied in 100 subjects with insulin-dependent diabetes mellitus (IDDM) over a 6-wk period while attempts were made to improve glycemic control. All measures of glycemic control improved significantly (P less than .001). Mean +/- SE glycosylated hemoglobin (HbA1) fell from 9.1 +/- 0.2 to 8.0 +/- 0.1%, glycosylated serum albumin (GSA) from 9.8 +/- 0.4 to 7.3 +/- 0.3%, and fructosamine from 3.92 +/- 0.08 to 3.42 +/- 0.07 mM. Fasting blood glucose levels fell from 11.1 +/- 0.6 to 8.1 +/- 0.7 mM mean blood glucose levels from 12.5 +/- 0.3 to 8.8 +/- 0.03 mM, and the M value from 118 +/- 7 to 40 +/- 3 U. Mean percentage changes in direct measures of glycemia (32-66%) and GSA (29%) were greater than for fructosamine (11%) or HbA, (12%) levels (P less than .001). Furthermore, the correlation between the change in GSA and changes in direct measures of glycemia over the initial 2-wk period was significantly different from the corresponding correlations between direct measures of glycemia and fructosamine over this period (P less than .05-.01). Changes in GSA also correlated more closely than HbA1 or fructosamine did with direct measures of glycemia after 4 and 6 wk. The Spearman rank-correlation coefficient (rs) of absolute changes in GSA, fructosamine, and HbA1 after 2-6 wk ranged from 0.27 to 0.57, confirming that the three measures responded differently to changing glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗