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Biomedical subjects

F Montesanti

Publications and source records attributed to F Montesanti.

4 recordsLinked to original sources

Neutrophil migration, oxidative metabolism, and adhesion in elderly and young subjects.

OBJECTIVE: To evaluate neutrophil functions in the elderly. METHODS: We investigated the PMN migration in vivo and PMN superoxide production and adhesion in response to a variety of compounds; PMN have been isolated both from blood and from a skin experimental exudate (obtained by Senn's skin window technique) of 25 normal elderly and of 25 normal young control subjects. RESULTS: No difference was found in PMN migration in vivo (62.9 +/- 21.3 x 10(6) and 65.5 +/- 9.1 x 10(6) PMN/cm2/24 hours in elderly and young subjects respectively), neither were different the adhesion under basal condition and after some stimuli and the superoxide production in basal condition and in response to STZ and PMA in two groups. In elderly subjects superoxide production, in response to fMLP, markedly resulted lower than in young controls both by circulating PMNs (3.6 +/- 2.7 and 9.3 +/- 3.3 nMOLES O2-/10(6) PMN respectively, p < 0.0001) and by exudate PMNs (13.6 +/- 4.3 and 19.4 +/- 6 nMOLES O2-/10(6) PMNs respectively, p < 0.005). CONCLUSION: Many PMN functions in the elderly do not differ from young people, suggesting that the overall defense function of these cells is not affected by aging. The only parameter that we have found to be different between the two groups is the poor superoxide production after fMLP stimulus of PMNs. The stimulus- and function-specificity of this defect in PMNs from elderly subjects indicates the existence of a dysregulation of the signal transduction pathway distal to fMLP receptor and proximal to NADPH oxidase activation.

Adult↗

The acute-phase response after bisphosphonate administration.

In patients who have never previously received bisphosphonate therapy, the intravenous administration of 4-amino-1-hydroxybuthilidene-1,1-bisphosphonate (AHButBP), 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), or 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) induced an acute-phase response (APR) irrespective of the underlying disease, manifested by a fall in circulating lymphocyte number and serum zinc concentration and in a rise in C-reactive protein (CRP); a febrile reaction occurred in 30% of the patients. The APR was maximally expressed within 28-36 hours of i.v. administration of the bisphosphonates and disappeared 2-3 days later despite continuous treatment. These effects were dose dependent and the lowest doses necessary for an APR were 10 mg of AHButBP and AHPrBP and 75 mg of AHHexBP. Doses up to 1,000 mg/day i.v. of dichloromethanebisphosphonate (Cl2MBP) were devoid of these side effects. In patients treated with either a single i.v. dose of amino-bisphosphonates which resulted in an APR or with a suboptimal dose, a subsequent challenge 12-160 days later of the high dose failed to cause a rise in CRP or a fall in the lymphocyte count. The desensitization to AHButBP or AHPrBP was also seen following pretreatment with Cl2MBP. These findings suggest that bisphosphonates interact with macrophage-like cells resident in the skeleton and stimulate interleukin-1 release which is responsible for the appearance of the APR. At the same time, however, the bisphosphonates render these cells insensitive to further stimulation for several months.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗

Treatment of Paget's disease of bone with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate.

4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHButBP) was given intravenously (2.5-25 mg/day for 4 days) to 14 patients with Paget's disease of bone, five of whom had been treated with dichloromethylidene bisphosphonate (C12MBP) 32 months earlier. In the nine patients who had not been treated previously with bisphosphonates, the short course of AHButBP induced a suppression of serum alkaline phosphatase and urinary hydroxyproline values down to 30% of initial values. The biochemical suppression of the disease was sustained for 2-18 months and the time to relapse did correlate to the logarithm of the dose (P less than 0.001). In the five patients previously treated for Paget's disease, an apparent resistance to treatment with AHButBP was observed. However, in these patients both serum alkaline phosphatase and urinary hydroxyproline fell to or even below the nadir values which had previously been achieved with C12MBP, irrespective of the degree of relapse. Thus the degree of suppression of Paget's disease of bone, achievable after treatment with bisphosphonates, seems to be constant for each patient, such that normal levels of serum alkaline phosphatase and urinary hydroxyproline cannot usually be attained in patients with extremely active disease.

Alendronate↗