Cytotoxicity of ZnO Nanoparticles Can Be Tailored by Modifying Their Surface Structure: A Green Chemistry Approach for Safer Nanomaterials

ZnO nanoparticles (NP) are extensively used in numerous nanotechnology applications; however, they also happen to be one of the most toxic nanomaterials. This raises significant environmental and health concerns and calls for the need to develop new synthetic approaches to produce safer ZnO NP, while preserving their attractive optical, electronic, and structural properties. In this work, we demonstrate that the cytotoxicity of ZnO NP can be tailored by modifying their surface-bound chemical groups, while maintaining the core ZnO structure and related properties. Two equally sized (9.26 ± 0.11 nm) ZnO NP samples were synthesized from the same zinc acetate precursor using a forced hydrolysis process, and their surface chemical structures were modified by using different reaction solvents. X-ray diffraction and optical studies showed that the lattice parameters, optical properties, and band gap (3.44 eV) of the two ZnO NP samples were similar. However, FTIR spectroscopy showed significant differences in the surface structures and surface-bound chemical groups. This led to major differences in the zeta potential, hydrodynamic size, photocatalytic rate constant, and more importantly, their cytotoxic effects on Hut-78 cancer cells. The ZnO NP sample with the higher zeta potential and catalytic activity displayed a 1.5-fold stronger cytotoxic effect on cancer cells. These results suggest that by modifying the synthesis parameters/conditions and the surface chemical structures of the nanocrystals, their surface charge density, catalytic activity, and cytotoxicity can be tailored. This provides a green chemistry approach to produce safer ZnO NP

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi

Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: A pilot study

Background. We sought to assess the safety and efficacy of enzyme replacement therapy (ERT) with recombinant human-galactosidase A (rh-alpha-Gal A) in kidney transplant recipients with Fabry disease, a previously unstudied population. Methods. Three male kidney transplant recipients with biochemically, genetically, and histologically confirmed Fabry disease and documented Fabry myocardiopathy received the rh-alpha-Gal A, agalsidase beta, 1 mg/kg of body weight every 2 weeks by intravenous infusion and were monitored biochemically, clinically, and electrocardiographically and echocardiographically for 18 months. Results. Patients showed biochemical, clinical/functional, and morphologic response to ERT. Plasma globotriaosylceramide decreased 23% to 50%. Extremity pain resolved within 2 months in the patient with this manifestation. On echocardiography, left ventricular mass, end diastolic diameter (EDD), and cardiac contractility, shown by ejection fraction (EF), improved in 2 of the 3 patients receiving essentially all planned infusions. EDD and EF remained basically stable, but cardiac morphologic abnormalities progressed in the other patient, who had a 5-month interruption in ERT after the initial month. Mild mitral insufficiency persisted in all patients, as did atrial fibrillation in the affected individual. After a combined total of 116 infusions, no treatment-related adverse event, intolerance, or seroconversion was seen. Renal function remained stable and the immunosuppression regimen unchanged in all patients. Conclusion. Our pilot study provides preliminary evidence that ERT with agalsidase beta, 1 mg/kg every 2 weeks, is safe and often effective against extra-renal manifestations in kidney transplant patients with Fabry disease. Studies with longer courses of this and higher doses of ERT are merited in this population

Effects of 1,25(OH)(2)D-3 in experimental mesangial proliferative nephritis in rats

Background. 1,25-Dihydroxyvitamin D-3 [1,25(OH)(2)D-3], the active form of vitamin D,, is a potent immunomodulatory agent on several cell types such as monocytes and mesangial cells. Recruitment of inflammatory cells, as well as stimulation of resident cells and mesangial matrix accumulation are key features of various experimental and human glomerular diseases. Here we show that 1,25(OH)(2)D-3 attenuates the morphologic and functional alterations in anti-Thy-1,1. nephritis. an experimental model of mesangial proliferative glomerulonephritis. Methods. The anti-Thy-1,1 group (group I) comprised 24 rats that at day 0 received 0.5 mt of saline containing 400 mug of monoclonal antibodies (mAb) anti-Thy-1,1 IgG. The antiThy-1,1 treated with 1.25(OH)(2)D-3 group (group II) were 24 rats given 1,25(OH)(2)D-3 at the dose of 25 ng/100 g body wt/day. From day -3 to day 14. At day 0, the rats received 400 mug of anti-Thy-1,1 monoclonal IgG. The control group (group III) comprised 12 rats injected with vehicle alone; the control group treated with 1,25(OH)(2)D-3 (group IV)-12 rats were given 1,25(OH)(2)D-3 as in group II without mAb administration. Proteinuria and urinary interleukin-h excretion were measured daily. Blood urea nitrogen and creatinine, creatinine clearance. calcium, and phosphate were measured at days 0, 4, 7, and 14. In addition to conventional periodic acid-Schiff staining. binding of anti-Thy-1,1 IgG and C3b complement fraction. His48- and ED1-positive cells were studied by immunofluorescence. Mesangial proliferation was studied by the proliferating cell nuclear antigen (PCNA) technique. Apoptosis was evaluated by the TUNEL assay. Results. The anti-Thy-1,1 treated with 1.25(OH),D, group versus the anti-Thy-1,1 alone group showed a significant reduction in urinary protein (at day 7, 424 +/- 228 vs. 66 +/- 30 mg/mg urinary creatinine. P = 0.02) and interleukin-h excretion (at day 3, 537 +/- 360 pg/mL vs. 110 +/- 34 pg/mg urinary creatinine. P = 0.015), reduced glomerular diameters (at day 7. 283 +/- 38 vs. 261 +/- 48 mum. P < 0.01). decreased neutrophil (at day 4, 20 +/- 12 His48-positive cells/glomerulus vs. 3.7 +/- 1.3 His48-positive cells/glomerulus, P < 0.001). and monocyte accumulation (day 7, 4.9 +/- 2.9 ED1-positive cells/glomerulus vs. 2.8 +/- 2.9 ED1-positive cells/glomerulus, P < 0.05), and attenuated glomerular cells proliferation (day 7. 13 +/- 3.2 PCNA-positive cells/glomerulus vs. 9.4 +/- 3 PCNA-positive cells/glomerulus, P < 0.01). Apoptosis showed a biphasic behavior with an early peak at day 4 in the anti-Thy-1,1 group (2.3 +/- 2.2 TUNEL positive ceils/glom) related to cellular lysis and a late peak at day 14 related to the recovery phase. Conclusions. 1,25(OH)(2)D-3 can reduce glomerular hypercellularity, inflammatory infiltration in anti-Thy-1,1 nephritis, preserving the apoptotic response of the reparative phase

Effects of 1,25(OH)2D3 in experimental mesangial proliferative nephritis in rats.

Effects of 1,25(OH)2D3 in experimental mesangial proliferative nephritis in rats.Background1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the active form of vitamin D3, is a potent immunomodulatory agent on several cell types such as monocytes and mesangial cells. Recruitment of inflammatory cells, as well as stimulation of resident cells and mesangial matrix accumulation are key features of various experimental and human glomerular diseases. Here we show that 1,25(OH)2D3 attenuates the morphologic and functional alterations in anti-Thy-1.1. nephritis, an experimental model of mesangial proliferative glomerulonephritis.MethodsThe anti-Thy-1.1 group (group I) comprised 24 rats that at day 0 received 0.5mL of saline containing 400 μg of monoclonal antibodies (mAb) anti-Thy-1.1 IgG. The anti-Thy-1.1 treated with 1,25(OH)2D3 group (group II) were 24 rats given 1,25(OH)2D3 at the dose of 25 ng/100g body wt/day, from day -3 to day 14. At day 0, the rats received 400 μg of anti-Thy-1.1 monoclonal IgG. The control group (group III) comprised 12 rats injected with vehicle alone; the control group treated with 1,25(OH)2D3 (group IV)—12 rats were given 1,25(OH)2D3 as in group II without mAb administration. Proteinuria and urinary interleukin-6 excretion were measured daily. Blood urea nitrogen and creatinine, creatinine clearance, calcium, and phosphate were measured at days 0, 4, 7, and 14. In addition to conventional periodic acid-Schiff staining, binding of anti-Thy-1.1 IgG and C3b complement fraction, His48- and ED1–positive cells were studied by immunofluorescence. Mesangial proliferation was studied by the proliferating cell nuclear antigen (PCNA) technique. Apoptosis was evaluated by the TUNEL assay.ResultsThe anti-Thy-1.1 treated with 1,25(OH)2D3 group versus the anti-Thy-1.1 alone group showed a significant reduction in urinary protein (at day 7, 424 ± 228 vs. 66 ± 30 mg/mg urinary creatinine, P = 0.02) and interleukin-6 excretion (at day 3, 537 ± 360 pg/mL vs. 110 ± 34 pg/mg urinary creatinine, P = 0.015), reduced glomerular diameters (at day 7, 283 ± 38 vs. 261 ± 48 μm, P < 0.01), decreased neutrophil (at day 4, 20 ± 12 His48-positive cells/glomerulus vs. 3.7 ± 1.3 His48-positive cells/glomerulus, P < 0.001), and monocyte accumulation (day 7, 4.9 ± 2.9 ED1-positive cells/glomerulus vs. 2.8 ± 2.9 ED1-positive cells/glomerulus, P < 0.05), and attenuated glomerular cells proliferation (day 7, 13 ± 3.2 PCNA-positive cells/glomerulus vs. 9.4 ± 3 PCNA-positive cells/glomerulus, P < 0.01). Apoptosis showed a biphasic behavior with an early peak at day 4 in the anti-Thy-1.1 group (2.3 ± 2.2 TUNEL-positive cells/glom) related to cellular lysis and a late peak at day 14 related to the recovery phase.Conclusions1,25(OH)2D3 can reduce glomerular hypercellularity, inflammatory infiltration in anti-Thy-1.1 nephritis, preserving the apoptotic response of the reparative phase

Calcitriol oral therapy for the prevention of secondary hyperparathyroidism in patients with predialytic renal failure

Secondary hyperparathyroidism is a common feature of chronic renal failure and vitamin D deficiency plays an important role in the development of this abnormality. Several therapeutical calcitriol schedules have been used in treating uremic hyperparathyroidism but recently oral boluses have been proposed as more effective. In this study we compare the efficacy of three different oral calcitriol regimens in suppressing iPTH secretion in predialytic chronic renal failure. Sixteen (16) patients (mean age 51 +/- 16 years; creatinine clearance 22.9 +/- 9.8 ml; range 8-32 ml/min) were treated in a cross-over randomized design with oral daily calcitriol 0.5 micrograms/die (Treatment A), three oral boluses of 2 micrograms of calcitriol a week (Treatment B) and a single oral bolus of 2 micrograms of calcitriol a week (Treatment C). All treatment periods lasted three months and were followed by a wash-out period of one month. Serum iPTH (Allegro Nichols), 1-25 vitamin D (IRMA-MAB), total and ionized calcium (Nova 8 Pabish), serum phosphate, alkaline phosphatase and creatinine clearance were measured every two weeks. Serum iPTH was also determined in a control group of fifteen (15) patients (mean age 47 +/- 12 years, creatinine clearances of 21 +/-12 ml/min) observed for three months without calcitriol treatment. Daily oral intake of 0.5 micrograms of calcitriol prevents an increase of iPTH without causing hypercalcemia, but only oral boluses (B and C) decreased iPTH: from 270 +/- 169 pg/ml to 135 +/- 76 pg/ml (p < 0.01; B) and to 165 +/- 121 pg/ml (p < 0.05; C). Serum iPTH increased from 293 +/- 121 to 323 +/- 129 pg/ml (p = n.s.). No significant differences in renal function were observed during the different study periods. Our results confirm the good efficacy of multiple calcitriol oral boluses but also suggest for the first time a single weekly bolus as a reliable approach to the treatment of secondary hyperparathyroidism in pre-dialytic renal failure

Calcitriol oral therapy for the prevention of secondary hyperparathyroidism in patients with predialytic renal failure

Secondary hyperparathyroidism is a common feature of chronic renal failure and vitamin D deficiency plays an important role in the development of this abnormality. Several therapeutical calcitriol schedules have been used in treating uremic hyperparathyroidism but recently oral boluses have been proposed as more effective. In this study we compare the efficacy of three different oral calcitriol regimens in suppressing iPTH secretion in predialytic chronic renal failure. Sixteen (16) patients (mean age 51 +/- 16 years; creatinine clearance 22.9 +/- 9.8 mi; range 8-32 ml/min) were treated in a cross-over randomized design with oral daily calcitriol 0.5 mu g/die (Treatment A), three oral boluses of 2 mu g Of calcitriol a week (Treatment B) and a single oral bolus of 2 mu g of calcitriol a week (Treatment C). All treatment periods lasted three months and were followed by a wash-out period of one month. Serum iPTH (Allegro Nichols), 1-25 vitamin D (IRMA-MAB), total and ionized calcium (Nova 8 Pabish), serum phosphate, alkaline phosphatase and creatinine clearance were measured every two weeks. Serum iPTH was also determined in a control group of fifteen (15) patients (mean age 47 +/- 12 years, creatinine clearances of 21 +/- 12 mi/min) observed for three months without calcitriol treatment, Daily oral intake of 0.5 mu g of calcitriol prevents an increase of iPTH without causing hypercalcemia, but only oral boluses (B and C) decreased iPTH: from 270 +/- 169 pg/ml to 135 +/- 76 pg/ml (p <0.01; B) and to 165 +/- 121 pg/ml (p <0.05; C). Serum iPTH increased from 293 +/- 121 to 323 +/- 129 pg/ml (p = n. s.). No significant differences in renal function were observed during the different study periods. Our results confirm the good efficacy of multiple calcitriol oral boluses but also suggest for the first time a single weekly bolus as a reliable approach to the treatment of secondary hyperparathyroidism in pre-dialytic renal failure

Biocompatibility evaluation of polyamide hemofiltration

Introduction. Postdilution hemofiltration with a polyamide membrane is a renal replacement technique widely used, but very little information is available regarding the biocompatibility of this treatment In this paper we report the results of an acute study of the biocompatibility of polyamide hemofiltration. Patients and methods. Complement activation such as C3a and C5a Des Arg (RIA), granulocyte degranulation like alpha 1 elastase intradialytic increase (ELISA) and the expression of high affinity membrane receptors for IL-2 (anti-TAC) were determined Beta 2-microglobulin (RIA) intradialytic decrease, as well as its convective removal, was evaluated The nature of protein layer adsorbed onto the polyamide membrane, at the end of the dialytic session was investigated with a new immunohistochemical technique. Cell-associated cytokine concentration (like IL-1 beta and IL-1Ra - ELISA) was determined on mononuclear cell lysates. Results. A low degree of complement activation was detected with the polyamide membrane when data were adjusted for hemoconcentration and for 1 m(2) of membrane surface area. An important convective removal not only of Beta 2-microglobulin (258+/-20 mg/session), but also of the activated anaphylatoxins (225+/-76 ng/ml for C3a and 22.5+/-4 ng/ml for C5a) was revealed A marked deposition of all coagulation factors with no detectable amount of immunoglobulins and complement factors was revealed on the polyamide membrane at the end of the dialytic session. No intradialytic (for lL-1beta) (from 14.1+/-3.0 to 13.5+/-2.9 pg/2.5 x 10(6) cell) and interdialytic (for IL-1Ra) (from 4572+/-1076 to 5408+/-615 pg/2.5 x 10(6) cell) cell-associated cytokine expression was induced by hemofiltration. Discussion and Conclusion. Polyamide hemofiltration is a highly biocompatible technique due to the use of a synthetic membrane with a sterile reinfusion fluid and the convective removal of the activated anaphylatoxins and Beta 2-microglobulin