Hydrophobic sodium fluoride‐based nanocrystals doped with lanthanide ions: assessment of in vitro toxicity to human blood lymphocytes and phagocytes

In vitro immunotoxicity of hydrophobic sodium fluoride‐based nanocrystals (NCs) doped with lanthanide ions was examined in this study. Although there is already a significant amount of optical and structural data on NaYF₄ NCs, data on safety assessment are missing. Therefore, peripheral whole blood from human volunteers was used to evaluate the effect of 25 and 30 nm hydrophobic NaYF₄ NCs dissolved in cyclohexane (CH) on lymphocytes, and of 10 nm NaYF₄ NCs on phagocytes. In the concentration range 0.12–75 µg cm^?2 (0.17–106 µg ml^?1), both 25 and 30nm NaYF₄ NCs did not induce cytotoxicity when measured as incorporation of [³H]‐thymidine into DNA. Assessment of lymphocyte function showed significant suppression of the proliferative activity of T‐lymphocytes and T‐dependent B‐cell response in peripheral blood cultures (n = 7) stimulated in vitro with mitogens phytohemagglutinin (PHA) and pokeweed (PWM) (PHA > PWM). No clear dose–response effect was observed. Phagocytic activity and respiratory burst of leukocytes (n = 5–8) were generally less affected. A dose‐dependent suppression of phagocytic activity of granulocytes in cultures treated with 25 nm NCs was observed (vs. medium control). A decrease in phagocytic activity of monocytes was found in cells exposed to higher doses of 10 and 30 nm NCs. The respiratory burst of phagocytes was significantly decreased by exposure to the middle dose of 30 nm NCs only. In conclusion, our results demonstrate immunotoxic effects of hydrophobic NaYF₄ NCs doped with lanthanide ions to lymphocytes and to lesser extent to phagocytes. Further research needs to be done, particularly faze transfer of hydrophobic NCs to hydrophilic ones, to eliminate the solvent effect. Copyright © 2014 John Wiley & Sons, Ltd.     

The influence of hydromorphological modifications of the littoral zone in lakes on macrophytes

The study aimed at determining the influence of hydromorphological modifications of the littoral zone in lakes on the occurrence and quantitative diversity of macrophytes. The field research was carried out at the peak of the growing season (June – September) between 2006 and 2009. Altogether, 457 transects were studied, located in 5 lakes. Studies on the hydromorphology were performed with the method of Lake Habitat Survey (LHS), and on macrophytes — with the method of transects. The studied sites were divided into 3 groups of different intensity of morphological transformations. The identified groups constituted the starting point for the analysis of influence exerted by transformations on macrophytes. The obtained results indicate that hydromorphological modifications of lakes are an important ecological factor affecting the occurrence and quantitative diversity of macrophytes. The transformations recorded in the studied reservoirs resulted mostly from recreational exploitation. They were responsible for mechanical elimination of dominant species, which led to an increased number of taxa, synanthropization and an average level of hemeroby as well as a decrease in the total vegetation cover. Helophytes were the most negatively affected group by the transformations, which reduce their contribution in the vegetation cover, whereas macroscopic filamentous algae and elodeids were positively affected.     

Impact of Obesity on the Risk of Venous Thromboembolism in an Inpatient Pediatric Population

Introduction: The incidence of venous thromboembolism in children has increased significantly over the past 20 years. Over the same period of time, there was an increase in the prevalence of obesity in the pediatric population. Obesity is a known risk factor for VTE in adults, but little information is available in children. Methods: This study evaluates the relation between obesity and VTE using a retrospective, case–control design, comparing the body mass index (BMI) of patients admitted with a diagnosis of VTE versus patients admitted with other diagnoses, at a single institution, between 2007 and 2011. Results: We studied 48 inpatients diagnosed with deep venous thrombosis or pulmonary embolism and a control group of 274 age and gender matched patients admitted with other diagnoses. We found obese patients (BMI > 95th percentile) to have significantly higher risk of VTE (odds ratio 2.1, with 95% CI 1.1–4.2) than patients of normal weight (BMI < 85th percentile). Overweight patients (BMI 85th–95th percentile) did not demonstrate a significant change in risk. Most of the VTE patients were adolescents and the majority of them had other identifiable risk factors for thrombosis. Conclusion: This study establishes a correlation between obesity and VTE in a group of hospitalized children, showing a risk for VTE in obese children similar to the one described in much larger adult cohorts.     

Imaging the effective networks associated with cortical function through intracranial high‐frequency stimulation

Direct electrical stimulation (DES) is considered to be the gold standard for mapping cortical function. A careful mapping of the eloquent cortex is key to successful resective or ablative surgeries, with a minimal postoperative deficit, for treatment of drug‐resistant epilepsy. There is accumulating evidence suggesting that not only local, but also remote activations play an equally important role in evoking clinical effects. By introducing a new intracranial stimulation paradigm and signal analysis methodology allowing to disambiguate EEG responses from stimulation artifacts we highlight the spatial extent of the networks associated with clinical effects. Our study includes 26 patients that underwent stereoelectroencephalographic investigations for drug‐resistant epilepsy, having 337 depth electrodes with 4,351 contacts sampling most brain structures. The routine high‐frequency electrical stimulation protocol for eloquent cortex mapping was altered in a subtle way, by alternating the polarity of the biphasic pulses in a train, causing the splitting the spectral lines of the artifactual components, exposing the underlying tissue response. By performing a frequency‐domain analysis of the EEG responses during DES we were able to capture remote activations and highlight the effect''s network. By using standard intersubject averaging and a fine granularity HCP‐MMP parcellation, we were able to create local and distant connectivity maps for 614 stimulations evoking specific clinical effects. The clinical value of such maps is not only for a better understanding of the extent of the effects'' networks guiding the invasive exploration, but also for understanding the spatial patterns of seizure propagation given the timeline of the seizure semiology.     

Anti-inflammatory sesquiterpene lactones from Lourteigia ballotaefolia

Three sesquiterpene lactones were isolated from Lourteigia ballotaefolia (H. B. K.). 9beta-hydroxy-atripliciolide-8- O-tiglate ( 1) was isolated for the first time from this plant and was previously reported in Conocliniopsis prasiifolia (DC) K. et R., 9beta-hydroxy-atripliciolide-8- O-(5'-acetoxytiglate) ( 2) had been already reported in this species. The minor component, 9beta-(tigloyloxy)-atripliciolide, is a new compound. The anti-inflammatory activity of compounds 1 and 2 was evaluated using the croton oil ear test in mice.     

The role of endogenous heme oxygenase in the initiation of liver injury following limb ischemia/reperfusion

BACKGROUND/AIMS: Heme oxygenase (HO) derived liver protection was tested in mice following 1 h bilateral hindlimb ischemia and either 1.5 or 3 h reperfusion. METHODS: Groups consisted of limb ischemia/reperfusion (I/R), sham (no I/R), I/R+chromium mesoporphyrin (I/R+CrMP;40 micromol/kg, i.p.), or I/R+hemin (10 mg/kg, i.p.). The vital dye propidium iodide (PI), was used to measure hepatocellular death (#/0.1 mm(3)), while the number of sinusoids perfused by red blood cells (SP(RBC)) were measured from the periportal (Pp) and pericentral (Pc) zones of liver acini using intravital microscopy. Whole organ injury was estimated from serum alanine aminotransferase (ALT). RESULTS: SP(RBC) reduced within 1.5 h with no further decline following 3 h. CrMP resulted in a dramatic loss of SP(RBC) following 3 h only. Hemin restored perfusion in both zones. Hepatocellular death and organ injury increased at 1.5 and 3 h. At 1.5 h, CrMP further increased cell death in the Pc zone, as well as whole organ injury, while hemin restored cell viability. Increased HO mRNA, protein and activity suggested induction within 3 h. CONCLUSIONS: HO does not protect perfusion during the early stage (1.5 h), but becomes increasingly important in preserving liver perfusion and cell viability during the later stage (3 h) of liver injury.     

A Phase I trial of protracted oral fixed-dose temozolomide

BACKGROUND: The current Phase I trial was conducted to determine the dose-limiting toxicity (DLT), maximum tolerated dose, and recommended Phase II dose of oral fixed-dose temozolomide when administered for 5 of every 7 days on a continuous basis. METHODS: Patients received a fixed dose of temozolomide daily for 5 of every 7 days continuously. Four weeks of treatment were considered 1 treatment cycle. Patients were accrued at 7 different dose levels ranging from 100 mg/day to 360 mg/day. RESULTS: Forty-six patients received 111 cycles of therapy. DLT consisted of myelosuppression, particularly thrombocytopenia. The primary nonhematologic toxicities were nausea and emesis, which were easily controlled with antiemetics. CONCLUSIONS: Protracted administration of temozolomide at a fixed dose of 300 mg/day for 5 of every 7 days continuously was well tolerated and allowed greater dose intensity compared with various other schedules. This regimen could potentially increase antitumor activity as protracted temozolomide schedules inhibit DNA repair by depletion of the repair protein O6-methylguanine-DNA methyltransferase.     

Combined genital prolapse repair reinforced with a polypropylene mesh and tension-free vaginal tape in women with genital prolapse and stress urinary incontinence: a retrospective case-control study with short-term follow-up

BACKGROUND: To evaluate the tension-free vaginal tape (TVT) in both stress urinary incontinence (SUI) and occult SUI as an associated procedure at the time of tension-free polypropylene mesh repair for the treatment of genitourinary prolapse. METHODS: Forty-eight consecutive women undergoing surgery for genital prolapse and concurrent SUI from November 1999 to September 2002. Preoperatively, SUI was symptomatic in 29 women and occult in 19, with a positive stress test during repositioning of the prolapse. All patients had urethral hypermobility and none had intrinsic sphincter deficiency. The cystocele repair was performed in all patients according to the technique of tension-free polypropylene mesh. Twenty-six women had an associated TVT and 22 had no associated procedure for SUI (control group). The main outcome measures were postoperative SUI, voiding dysfunction, and recurrence of prolapse. RESULTS: The median follow-up was 20 +/- 10.1 months (range 7-41). Patient characteristics and preoperative urodynamic evaluation were similar in the two groups. In patients with preoperative SUI, postoperative SUI occurred in 1/15 of the TVT group (6.7%) vs. 5/14 (35.7%) in the control group (p < 0.05), and voiding dysfunction occurred in 2/15 patients of the TVT group (13.3%) vs. 0/14 in the control group (p > 0.05). In patients with preoperative occult SUI, postoperative SUI occurred in 0/11 of the TVT group vs. 1/8 (12.5%) in the control group (p > 0.05), and voiding dysfunction occurred in 3/11 patients of the TVT group (27.3%) vs. 0/8 in the control group (p < 0.05). Anatomic success on prolapse was 88.5% (23/26) and 86.4% (19/22) in the TVT and the control group, respectively (p > 0.05). CONCLUSION: In patients with preoperative SUI, TVT is more efficient than prosthetic cystocele repair alone to prevent postoperative SUI, without differences in voiding dysfunction. In patients with preoperative occult SUI, prosthetic cystocele repair is as efficient as TVT, with a decreased risk of voiding dysfunction.