Assessment of cellular responses after short- and long-term exposure to silver nanoparticles in human neuroblastoma (SH-SY5Y) and astrocytoma (D384) cells.

Silver nanoparticle (AgNP, 20 nm) neurotoxicity was evaluated by an integrated in vitro testing protocol employing human cerebral (SH-SY5Y and D384) cell lines. Cellular response after short-term (4-48 h, 1-100 µ g/ml) and prolonged exposure (up to 10 days, 0.5-50 µ g/ml) to AgNP was assessed by MTT, calcein-AM/PI, clonogenic tests. Pulmonary A549 cells were employed for data comparison along with silver nitrate as metal ionic form. Short-term data: (i) AgNP produced dose- and time-dependent mitochondrial metabolism changes and cell membrane damage (effects starting at 25 µ g/ml after 4 h: EC50s were 40.7 ± 2.0 and 49.5 ± 2.1 µ g/ml for SH-SY5Y and D384, respectively). A549 were less vulnerable; (ii) AgNP doses of ≤ 18 µ g/ml were noncytotoxic; (iii) AgNO3 induced more pronounced effects compared to AgNP on cerebral cells. Long-term data: (i) low AgNP doses (≤ 1 µ g/ml) compromised proliferative capacity of all cell types (cell sensibility: SHSY5Y > A549 > D384). Colony number decrease in SH-SY5Y and D384 was 50% and 25%, respectively, at 1 µ g/ml, and lower dose (0.5 µ g/ml) was significantly effective towards SH-SY5Y and pulmonary cells; (ii) cell proliferation activity was more affected by AgNO3 than AgNPs. In summary, AgNP-induced cytotoxic effects after short-term and prolonged exposure (even at low doses) were evidenced regardless of cell model types.

Assessment of gonadal function in boys and adolescents at the diagnosis of neoplastic disease.

OBJECTIVE: We assessed the gonadal function in boys with a newly diagnosed neoplastic disease prior to chemotherapy. Eighty-four boys (48 prepubertal and 36 pubertal) were evaluated, including 50 with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL), 10 with Hodgkin lymphoma (HL), and 24 with solid tumors. The control group consisted of 24 healthy prepubertal and 24 pubertal boys. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, and testosterone were determined, and testicular volumes were measured. RESULTS: Patients in prepuberty and early puberty (Tanner stages 1-3) diagnosed with ALL/NHL or solid tumor presented normal serum reproductive hormone levels, whereas in ALL/NHL patients in Tanner stages 4-5, the mean values of inhibin B were significantly lower (45.18 +/- 33.85 vs. 153.57 +/- 71.44 ng/L, p = 0.0027). In patients with HL in Tanner stages 4-5, a statistically significant lower mean inhibin B level (100.44 +/- 67.45 versus 153.57 +/-71.44 ng/L, p = 0.0027), higher mean FSH level (6.3 +/- 3.6 versus 4.6 +/- 2.2 mIU/mL, p = 0.05), and higher mean LH level (5.9 +/- 4.0 versus 3.6 +/- 1.8 mIU/mL, p = 0.05) were observed. No statistically significant differences were noted in assessed hormones in patients with solid tumors, independently of Tanner stage. CONCLUSION: Our analysis indicates that adolescents with ALL/NHL and HL prior to treatment, exhibit reduced levels of inhibin B, which indirectly suggests the possibility of spermatogenesis dysfunction.

Resting energy expenditure in children newly diagnosed with stage IV neuroblastoma.

Children with stage IV neuroblastoma (NBIV) are often malnourished at time of diagnosis, observed as high as 50%. The emphasis of this study was to determine whether an increased resting energy expenditure (REE) is a causative factor. Our hypothesis was that children diagnosed with NBIV have an increased REE, which normalizes with cancer treatment. Changes in nutritional status from time of diagnosis in response to nutritional support were examined. REE and nutritional evaluation were obtained three times: at diagnosis before starting treatment, where tumor burden is expected to be highest; after two courses of chemotherapy, where some response to treatment is expected; and after surgical excision of the primary tumor, where there was presumably minimal residual disease. Ten subjects completed the study. Results showed that REE was not increased, and there was no significant difference between phases (p = 0.29). Fifty percent of our subjects were malnourished at diagnosis. Because REE is not increased in NBIV, it is concluded that malnutrition seen in NBIV is not due to increased energy needs, but is likely due to decreased intake because of the intra-abdominal mass and malignant malaise.