Biological and physicochemical implications of the aging process on titanium and zirconia implant material surfaces

Statement of problemChanges in physicochemical properties because of implant material aging and natural deterioration in the oral environment can facilitate microbial colonization and disturb the soft-tissue seal between the implant surfaces.PurposeThe purpose of this in vitro study was to investigate the effect of aging time on the physicochemical profile of titanium (Ti) and zirconia (ZrO₂) implant materials. Further microbiology and cell analyses were used to provide insights into the physicochemical implications of biological behavior.Material and methodsDisk-shaped specimens of Ti and ZrO₂ were submitted to roughness, morphology, and surface free energy (SFE) analyses before nonaging (NA) and after the aging process (A). To simulate natural aging, disks were subjected to low-temperature degradation (LTD) by using an autoclave at 134 ºC and 0.2 MPa pressure for 20 hours. The biological activities of the Ti and ZrO₂ surfaces were determined by analyzing Candida albicans (C. albicans) biofilms and human gingival fibroblast (HGF) cell proliferation. For the microbiology assays, a variance analysis method (ANOVA) was used with the Tukey post hoc test. For the evaluation of cellular proliferation, the Kruskal-Wallis test followed by Dunn multiple comparisons were used.ResultsTi nonaging (TNA) and ZrO₂ nonaging (ZNA) disks displayed hydrophilic and lipophilic properties, and this effect was sustained after the aging process. Low-temperature degradation resulted in a modest change in intermolecular interaction, with 1.06-fold for TA and 1.10-fold for ZA. No difference in biofilm formation was observed between NA and A disks of the same material. After 48 hours, the viability of the attached HGF cells was very similar to that in the NA and A groups, regardless of the tested material.ConclusionThe changes in the physicochemical properties of Ti and ZrO₂ induced by the aging process do not interfere with C. albicans biofilm formation and HGF cell attachment, even after long-term exposure.     

rHuEpo administration in patients with low-risk myelodysplastic syndromes: evaluation of erythroid precursors' response by fluorescence in situ hybridization on May-Grunwald-Giemsa-stained bone marrow samples

The issue of whether, in patients affected by myelodysplastic syndromes (MDS), haematological response to cytokines, particularly to recombinant human erythropoietin (rHuEpo), is a phenomenon related to the stimulation of normal haemopoietic cells or to the differentiation of cells belonging to the abnormal clone remains an open question. To assess the pattern of response to rHuEpo treatment of bone marrow (BM) cells, we evaluated in 13 low-risk MDS patients with known cytogenetic abnormalities the number of cytogenetically normal and abnormal cells by conventional cytogenetic analysis (CCA) and by a fluorescence in situ hybridization (FISH) technique, enabling the simultaneous visualization of FISH chromosomal abnormalities in morphologically and immunophenotypically identifiable BM elements. Patients responding to rHuEpo presented a lower number of abnormal metaphases at diagnosis in comparison with patients who did not respond (22.74% vs 76.23%, P = < 0.001). This was confirmed by the combined morphological FISH analysis, showing that, before treatment, BM samples from patients responding to rHuEpo had a lower proportion of both FISH abnormal erythroid (36.48% vs 66.93%, P = 0.002) and myeloid (40.76% vs 67.70%, P = 0.014) elements than unresponsive patients. After rHuEpo treatment, responding patients presented a significantly lower proportion of FISH abnormal erythroid precursors than observed before treatment (16.93%vs 36.48%, P = 0.017). Likewise, in responding patients, a significantly lower proportion of FISH abnormal erythroid elements (16.93% vs 66.30%, P < 0.001) was detected in comparison with unresponsive patients. These findings provide evidence that, in low-risk MDS patients with known cytogenetic abnormalities, response to rHuEpo may be due to the proliferation of karyotypically normal erythroid precursors, possibly representing residual normal erythroid elements.     

Chromosome banding analysis and genomic microarrays are both useful but not equivalent methods for genomic complexity risk stratification in chronic lymphocytic leukemia patients

Genome complexity has been associated with poor outcome in patients with chronic lymphocytic leukemia (CLL). Previous cooperative studies established five abnormalities as the cut-off that best predicts an adverse evolution by chromosome banding analysis (CBA) and genomic microarrays (GM). However, data comparing risk stratification by both methods are scarce. Herein, we assessed a cohort of 340 untreated CLL patients highly enriched in cases with complex karyotype (CK) (46.5%) with parallel CBA and GM studies. Abnormalities found by both techniques were compared. Prognostic stratification in three risk groups based on genomic complexity (0-2, 3-4 and ≥5 abnormalities) was also analyzed. No significant differences in the percentage of patients in each group were detected, but only a moderate agreement was observed between methods when focusing on individual cases (κ=0.507; P<0.001). Discordant classification was obtained in 100 patients (29.4%), including 3% classified in opposite risk groups. Most discrepancies were technique-dependent and no greater correlation in the number of abnormalities was achieved when different filtering strategies were applied for GM. Nonetheless, both methods showed a similar concordance index for prediction of time to first treatment (TTFT) (CBA: 0.67 vs. GM: 0.65) and overall survival (CBA: 0.55 vs. GM: 0.57). High complexity maintained its significance in the multivariate analysis for TTFT including TP53 and IGHV status when defined by CBA (hazard ratio [HR] 3.23; P<0.001) and GM (HR 2.74; P<0.001). Our findings suggest that both methods are useful but not equivalent for risk stratification of CLL patients. Validation studies are needed to establish the prognostic value of genome complexity based on GM data in future prospective studies.     

Appetite suppressants and valvular heart disease

Appetite suppressants fenfluramine, dexfenfluramine, and phentermine have been used alone or in combination as an alternative to diet and surgery in the management of obesity. This therapy was halted in 1997 after reports of valvular lesions affecting almost one third of patients treated with these drugs. Fortunately, most cases of appetite suppressant-related valve disease are mild or moderate and rarely required valve repair or replacement. Follow-up studies have suggested improvement in valvulopathy after discontinuation of the treatment. The mechanism of valve disease induced by these drugs is speculative and may be related to their serotonergic effects. Echocardiographic features are similar to carcinoid heart disease and valvulopathy associated with ergot use. Most cases require only follow-up and endocarditis prophylaxis; surgery is rarely needed.     

Neoplastic circulating endothelial-like cells in patients with acute myeloid leukaemia

Accumulating evidence suggests that angiogenesis may play a key role in the pathogenesis of leukaemic disorders. Several studies have shown that bone marrow-derived endothelial cells (EC) may contribute to tumour angiogenesis and that in the peripheral blood of cancer patients there is an increased amount of circulating ECs (CECs) that may participate to new vessel formation. In this report, we showed that, in seven acute myeloid leukaemia (AML) patients with known cytogenetic abnormalities, CEC levels were significantly increased in comparison with controls and that a significant proportion of these CECs carried the same chromosomal aberration as blast cells (20-78%, mean value 42.1% of CECs). Most of CECs (mean value 74.4%) displayed immunophenotypic features of endothelial progenitor cells as they expressed CD133, a marker gradually lost during EC differentiation and absent on mature EC. These findings suggest a possible direct contribution of AML-related CECs to tumour vasculogenesis and possibly to the spreading and progression of the disease.     

Exercise capacity and circulating endothelial progenitor cells in hemodialysis patients

Mobilization of circulating endothelial progenitor cells (EPCs) is increased after acute exercise and training. This study aims to evaluate whether, in a low performance population, EPC levels may be related to exercise capacity in steady state conditions. Study population consisted of sixteen hemodialysis patients. The distance walked in the 6-minute walking test (6 MWD) and the maximal speed attained in an incremental treadmill test were used to assess the exercise capacity. Physical functioning was measured by the scale on the SF36 questionnaire. Quantification of peripheral blood CD34(+) cells and enumeration of EPCs, assessed as CD34(+) cells coexpressing AC 133 and vascular endothelial growth factor receptor-2, were performed. Hemoglobin concentration, white blood cells, high-sensitivity C-reactive protein, total cholesterol, and triglycerides were measured. Statistical analysis examined the relationship between blood progenitors cells versus performance parameters, laboratory parameters, age, body mass index, hemodialysis duration, and erythropoietin therapy. Univariate analysis revealed a significant association between percentage values of EPC and performance parameters only: 6 MWD (r=0.720; p=0.0017), maximal treadmill speed (r=0.721; p=0.0016), and physical functioning score (r=0.506; p=0.0453). A similar statistical association between EPC absolute values and performance parameters was found. No correlation between CD34 (+) and any parameter under study was observed. Multivariate analysis indicated 6 MWD as the most significant independent factor associated with EPC level. EPC percentage value was significantly lower (p=0.0087) in the worse (6 MWD < 300 m, n=8) than in the better performing group (6 MWD > 300 m, n=8). In a group of renal patients, mobilization of EPCs was related to the degree of exercise capacity, suggesting a possible connection with the cardiovascular risk in low performance populations limited by chronic diseases.