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Biomedical subjects

J Bukar

Publications and source records attributed to J Bukar.

4 recordsLinked to original sources

Inhaled insulin.

Inhalation of regular insulin for meal time glucose control has been found to be safe, efficacious and reliable in Type I and Type II diabetics. The administration of regular insulin through the human lungs by inhalation has been conducted in at least 14 short studies in both normal and diabetic subjects beginning as early as 1925. In all studies, significant insulin absorption and lowering of blood glucose was observed in the absence of penetration enhancers. Although a concern of variable dosing was raised in early studies, the development of new reproducible delivery systems has ensured that the variability of aerosol insulin can be as good, if not better, than subcutaneous (SC) injection. In the longest controlled studies in humans to date, both Type I and Type II insulin-dependent diabetics used a novel inhaled dry powder insulin delivery system for 3 months for meal time glucose control. The study results indicate that inhaled insulin provides equivalent glucose control, measured by hemoglobin A1c, when directly compared to SC injection. Interim results from an additional study with Type II diabetics who were failing oral hypoglycemic agents suggest that adjunctive therapy with inhaled insulin markedly improved glycemic control with a low risk of hypoglycemia. In all the 3 month studies the system was efficacious, well tolerated, well liked, and resulted in reproducible results. A potential advantage of aerosol insulin is that it is more rapidly absorbed (serum peak at 5-60 min) and cleared than SC injection (peak at 60-150 min), which provides a more relevant and convenient therapy for meal time glucose control. The relative efficiency of insulin delivery by aerosol, compared to SC injection, has been estimated from the dose measured at the exit point of the aerosol device, and found to range between 8 and 25% of SC, depending on the study.

Journal Article↗

Effect of recombinant human insulin-like growth factor I and early total parenteral nutrition on immune depression following severe head injury.

OBJECTIVE: To determine the effects of insulin-like growth factor I (IGF-I) and aggressive nutrition on CD4/CD8 ratios following head injury. DESIGN: Randomized controlled trial. SETTING: An urban level 1 trauma center. PARTICIPANTS: Head-injured patients with a Glasgow Coma Scale score of 4 to 10 within 6 hours of hospital admission requiring no major extracranial surgery with the exception of isolated lower-extremity fracture fixation. Fourteen patients were recruited and 11 completed the study. INTERVENTIONS: Patients were randomized to a continuous infusion of saline or 0.01 mg/kg per hour of recombinant human (rh) IGF-I. Both groups received parenteral nutrition and rapidly advanced to a total protein intake of 2 g/kg per day and a maximum nonprotein calorie intake of 40 kcal/kg per day. The nonprotein prescription was 1.25 times the metabolic energy expenditure determined by metabolic cart not to exceed a nonprotein calorie intake of 40/kcal. MAIN OUTCOME MEASURES: The CD4/CD8 ratios and serum IGF-I levels on days 1, 7, and 14. RESULTS: Administration of early aggressive nutrition eliminated the depressed CD4/CD8 ratio usually seen after head injury; administration of IGF-I increased the CD4/CD8 ratio while IGF-I levels were elevated. CONCLUSIONS: Infusion of rhIGF-I and aggressive early intravenous nutrition affects the immunologic response of patients with severe head injury.

Adult↗

Effects of recombinant human insulin-like growth factor-I (rhIGF-I) on total and free IGF-I concentrations, IGF-binding proteins, and glycemic response in humans.

To examine the effects of repeated administration of recombinant human insulin-like growth factor-I (rhIGF-I) on IGF-I levels, free IGF-I pharmacokinetics, glycemic response, and IGF-binding proteins (IGFBP), we administered rhIGF-I (0.03 mg/kg iv bolus) to 12 healthy males each morning for 5 consecutive days. Serum was collected over 24 h on days 1 and 5 for measurement of total and free IGF-I, glucose, insulin, and IGFBP. Total IGF-I was measured by RIA after acid/ethanol extraction. Free IGF-I was separated from binding protein-complexed IGF-I using size exclusion high performance liquid chromatography before measurement by RIA. IGFBP were quantitated by optical densitometry of Western ligand blots. Total IGF-I increased significantly from 0-24 h after administration on day 1 (mean +/- SD, micrograms/L: 120 +/- 44 to 166 +/- 51, P = 0.0002) but did not increase significantly from 24 h on day 1 to 0 h on day 5 (166 +/- 51 to 178 +/- 62) or from 0-24 h on day 5 (178 +/- 62 to 209 +/- 89). The area under the total IGF-I concentration curve was greater on day 5 than day 1 (311 +/- 99 min.g/L vs. 249 +/- 77, P = 0.0001). There were no significant differences in free IGF-I concentration or pharmacokinetic parameters or in the degree or timing of hypoglycemia between days 1 and 5. Plasma insulin levels decreased significantly following rhIGF-I administration (day 1 baseline: 53 +/- 11 pmol/L, nadir: 18 +/- 6 pmol/L at 30 min, P = 0.003); day 5 baseline: 47 +/- 15 pmol/L, nadir: 16 +/- 8 pmol/L at 30 min, P = 0.0003. Western ligand blotting revealed the transient appearance of a 30-kilodalton band which migrates in a manner similar to IGFBP-1. This band was undetectable at baseline, peaked between 150 and 210 min after rhIGF-I administration, and diminished by 480-600 min. The response was similar on days 1 and 5. There were no substantial changes in the serum levels of any other IGFBP. In summary, repeated iv bolus administration of rhIGF-I increased the level of total circulating IGF-I without changing free IGF-I disposition or glycemic response. A 30-kilodalton IGFBP band, most likely IGFBP-1, appeared transiently following rhIGF-I administration, probably as a result of suppression of insulin levels. IGFBP-2, -3, and -4 were unaffected.

Adult↗

Frozen desserts and glycemic response in well-controlled NIDDM patients.

Fructose is known to elicit a lower glycemic response than sucrose, and high-fructose desserts have been recommended for a diabetic diet. We compared a cholesterol-free tofu-based frozen dessert (TFD) containing high-fructose corn syrups with a dairy-based sucrose-sweetened ice cream (IC). Six male and six female non-insulin-dependent diabetic patients (mean age 51 yr, mean ideal body weight 143%, fasting blood glucose less than 160 mg/dl) with well-controlled diabetes and managed on oral hypoglycemic agents were studied. Subjects underwent three trials. In the first trial they ingested 50 g glucose, and in the next two trials they ingested 50-g carbohydrate equivalents of either TFD or IC in random sequence. Venous blood was drawn at intervals during the 3-h trials for glucose and insulin determinations. Fasting plasma glucose was not statistically different between IC and TFD trials (130 vs. 121 mg/dl). Peak glucose responses were at 120 min in both trials (190 mg/dl for IC and 222 mg/dl for TFD), with those for TFD being significantly higher (P less than 0.01). Mean glucose area and glycemic index for TFD were significantly greater than for IC (P less than 0.01 and P less than 0.03, respectively). There was no significant difference between mean insulin areas. In summary, the TFD, which contains soybean curd and high-fructose corn syrup, might have been expected to produce more satisfactory postprandial blood glucose levels than IC, which contains sucrose, yet a higher glycemic response was elicited. This is related to the substantial amount of total glucose in this "fructose" dessert.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗