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Biomedical subjects

H Abboud

Publications and source records attributed to H Abboud.

8 recordsLinked to original sources
PubMed2003

PDGF BB and bFGF stimulate DNA synthesis and upregulate CSF-1 and MCP-1 gene expression in dental follicle cells.

CSF-1 and MCP-1, released by dental follicle cells, stimulate the influx of monocytes into the follicle sac and enhance the formation of osteoclasts that, in turn, resorb alveolar bone for the eruption pathway. PDGF and bFGF, released by cells adjacent to the follicle or by activated monocytes, are prime candidates that may regulate CSF-1 and MCP-1 gene expression. The present study demonstrates that PDGF and bFGF are mitogens for dental follicle cells and stimulate CSF-1 and MCP-1 mRNA, but with different time course kinetics. Peak induction of CSF-1 mRNA was observed at 6-8h, while maximal MCP-1 induction was observed at 2h. These findings suggest that MCP-1 is an early chemotactic signal for monocytes and that subsequent release of CSF-1 may act synergistically with MCP-1 to enhance monocyte influx. Further understanding of the molecular mechanisms by which cytokines regulate CSF-1 and MCP-1 may lead to more effective treatment regimens for disorders associated with abnormal tooth eruption.

Becaplermin↗
PubMed1999

Reduced intrapatient variability of cyclosporine pharmacokinetics in renal transplant recipients switched from oral Sandimmune to Neoral.

Sixty-six renal transplant patients maintained on Sandimmune, the traditional formulation of cyclosporine, participated in an open-label, sequential trial to compare intrapatient variability in drug exposure before and after a switch to Neoral. Three 12-hour cyclosporine pharmacokinetic profiles were obtained over approximately 6 weeks while patients were receiving Sandimmune. Patients were then switched to Neoral, with the dose adjusted as necessary to maintain target trough blood cyclosporine concentrations. At approximately 4 and 6 weeks postconversion, 2 additional pharmacokinetic profiles were obtained. Key pharmacokinetic variables analyzed were area under the concentration-time curve (AUC), maximum concentration (Cmax), and predose trough concentration (C0). Intrapatient variability in drug exposure for dose-normalized mean AUC, Cmax, and C0 was significantly reduced with Neoral, with 50 (76%), 57 (86%), and 45 (68%) patients experiencing reduced variability in AUC, Cmax, and C0, respectively (P < 0.001). Additionally, the total exposure to cyclosporine was more predictable from the trough level of cyclosporine with Neoral; the relationship between AUC and C0 was 0.81 for Neoral at both pharmacokinetic profiling time points but ranged from 0.49 to 0.69 for the 3 Sandimmune time points. The large reductions in intrapatient variability of pharmacokinetic variables for cyclosporine provided by Neoral indicate an improvement in the consistency of drug exposure, which may translate into important clinical benefits.

Adult↗
PubMed1998

Therapy of secondary hyperparathyroidism with 19-nor-1alpha,25-dihydroxyvitamin D2.

Secondary hyperparathyroidism contributes to significant morbidity in patients with chronic renal failure. The treatment of this disorder with vitamin D compounds, such as calcitriol, although effective at suppressing parathyroid hormone (PTH) secretion, may promote the development of hypercalcemia and hyperphosphatemia, thus increasing the risk for metastatic calcification. A new vitamin D analogue, 19-nor-1alpha,25-(OH)2D2 (paricalcitol; Zemplar, Abbott Laboratories, Inc, Chicago, IL) has recently been developed for the treatment of secondary hyperparathyroidism, and, in experimental animals, it was found to be less calcemic and phosphatemic than calcitriol. In double-blind clinical trials, paricalcitol effectively decreased the levels of PTH by 60%, yet the mean serum calcium values remained within the normal range. The few episodes of hypercalcemia that occurred in the paricalcitol-treated patients (8 of 400 determinations > or =11.0 mg/dL in 7 patients) were associated with marked decreases in PTH levels (87% +/- 2% less than baseline) and absolute values of PTH less than 100 pg/mL in four of the seven patients. PTH values less than 100 pg/mL, however, occurred in 15 patients, but were not invariably associated with frank hypercalcemia, although serum calcium levels increased to 10.63 +/- 0.3 mg/dL, slightly greater than the upper limits of normal. Additional studies to evaluate the conversion from calcitriol to paricalcitol therapy showed that a dose ratio of 1:4 (calcitriol:paricalcitol) could maintain control of high levels of PTH without significant alterations in serum calcium and phosphorus levels. These studies indicate that effective control of hyperparathyroidism can be achieved with paricalcitol therapy with minimal perturbation of serum calcium and phosphorus levels, and may have a therapeutic advantage over current treatment strategies.

Calcium↗
PubMed1998

19-Nor-1-alpha-25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis.

Paricalcitol (19-nor-1alpha-25-dihydroxyvitamin D2), a new vitamin D analog developed for the treatment of secondary hyperparathyroidism, was evaluated in three double-blind, placebo-controlled, dose-escalating, randomized multicenter trials. A total of 78 patients (40 Paricalcitol injection, 38 placebo) achieved treatment phase eligibility, which included intact parathyroid hormone (iPTH) > or = 400 pg/ml, normalized serum calcium levels between 8.0 and 10.0 mg/dl, and calcium x phosphorus product values less than 75. Study end points included a decrease in iPTH of at least 30% or a maximum of five dose escalations. After a 4-wk washout, paricalcitol or placebo was administered intravenously three times per week after dialysis for 12 wk. Study drug was started at a dose of 0.04 microg/kg and was increased by 0.04 microg/kg every 2 wk to a maximal allowable dose of 0.24 microg/kg or until at least a 30% decrease in serum iPTH was achieved. The dose of paricalcitol that decreased iPTH by at least 30% became the maintenance dose. Of 40 patients receiving paricalcitol, 27 (68%) had at least a 30% decrease in serum iPTH for 4 consecutive weeks, compared with three of 38 patients (8%) receiving placebo (P < 0.001). For patients who received 12 wk of treatment with paricalcitol, the levels of iPTH decreased significantly from 795+/-86 to 406+/-106 pg/ml (P < 0.001), whereas the values for PTH were 679+/-41 pg/ml before and 592+/-41 pg/ml after 12 wk of therapy in patients receiving placebo (P=NS). Also, there was a significant difference between treatment groups for the change from baseline PTH levels (P < 0.001). Paricalcitol treatment resulted in a significant reduction in serum alkaline phosphatase from 148+/-23 U/L to 101+/-14 U/L (P < 0.001) in patients treated for 12 wk compared with 120+/-9 U/L to 130+/-11 U/L (P=NS) in patients receiving placebo for 12 wk. Importantly, hypercalcemia did not occur before achieving target serum iPTH levels in any of the paricalcitol-treated patients. There was no significant difference for the change from baseline in serum phosphorus within or between treatment groups. There was no significant difference in adverse events between the paricalcitol and placebo-treated groups. These studies demonstrate that paricalcitol safely and effectively suppresses iPTH levels in hemodialysis patients. This second generation vitamin D analog may have a wider therapeutic window than current vitamin D preparations, and thus may allow reduction in PTH with less hypercalcemia.

Adult↗