Size, shape and surface chemistry of nano-gold dictate its cellular interactions, uptake and toxicity

Colloidal gold is undoubtedly one of the most extensively studied nanomaterials, with 1000s of different protocols currently available to synthesise gold nanoparticles (AuNPs). While developments in the synthesis of AuNPs have progressed rapidly in recent years, our understanding of their biological impact, with particular respect to the effect of shape, size, surface characteristics and aggregation states, has struggled to keep pace. It is generally agreed that when AuNPs are exposed to biological systems, these parameters directly influence their pharmacokinetic and pharmacodynamic properties by influencing AuNPs distribution, circulation time, metabolism and excretion in biological systems. However, the rules governing these properties, and the science behind them, are poorly understood. Therefore, a systematic understanding of the implications of these variables at the nano-bio interface has recently become a topic of major interest. This Review Article attempts to ignite a discussion around the influence of different physico-chemical parameters on biological activity of AuNPs, while focussing on critical aspects of cellular interactions, uptake and cytotoxicity. The review also discusses emerging trends in AuNP uptake and toxicity that are leading to technological advances through AuNP-based therapy, diagnostics and imaging

TAS2R38 is a novel modifer gene in patients with cystic fbrosis

The clinical manifestation of cystic fbrosis (CF) is heterogeneous also in patients with the same cystic fbrosis transmembrane regulator (CFTR) genotype and in afected sibling pairs. Other genes, inherited independently of CFTR, may modulate the clinical manifestation and complications of patients with CF, including the severity of chronic sinonasal disease and the occurrence of chronic Pseudomonas aeruginosa colonization. The T2R38 gene encodes a taste receptor and recently its functionality was related to the occurrence of sinonasal diseases and upper respiratory infections. We assessed the T2R38 genotype in 210 patients with CF and in 95 controls, relating the genotype to the severity of sinonasal disease and to the occurrence of P. aeruginosa pulmonary colonization. The frequency of the PAV allele i.e., the allele associated with the high functionality of the T2R38 protein, was signifcantly lower in i) CF patients with nasal polyposis requiring surgery, especially in patients who developed the complication before 14 years of age; and ii) in CF patients with chronic pulmonary colonization by P. aeruginosa, especially in patients who were colonized before 14 years of age, than in control subjects. These data suggest a role for T2R38 as a novel modifer gene of sinonasal disease severity and of pulmonary P. aeruginosa colonization in patients with CF

Salivary cytokines and airways disease severity in patients with cystic fibrosis

About 50% of patients with cystic fibrosis (CF) have sinonasal complications, which include inferior turbinate hypertrophy (NTH) and/or nasal polyposis (NP), and different degrees of lung disease, which represents the main cause of mortality. Monitoring of sinonasal disease requires complex instrumental procedures, while monitoring of lung inflammation requires invasive collection of bronchoalveolar lavage fluid. The aim of this study was to investigate the associations between salivary cytokines levels and CF-related airway diseases. Salivary biochemical parameters and cytokines, i.e., interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-α), were analyzed in resting saliva from healthy subjects and patients with CF. Patients with CF showed significantly higher levels of salivary chloride, IL-6, IL-8, and TNF-α and lower calcium levels than healthy subjects. Among patients with CF, IL-6 and IL-8 were significantly higher in patients with NTH, while TNF-α was significantly lower in patients with NP. A decreasing trend of TNF-α in patients with severe lung disease was also observed. On the other hand, we did not find significant correlation between cytokine levels and Pseudomonas aeruginosa or Stenotrophomonas maltophilia colonization. These preliminary results suggest that salivary IL-6 and IL-8 levels increase during the acute phase of sinonasal disease (i.e., NTH), while the end stages of pulmonary disease and sinonasal disease (i.e., NP) show decreased TNF-α level

Intramedullary nailing for pertrochanteric fractures of proximal femur: a consecutive series of 323 patients treated with two devices

Introduction: Pertrochanteric fractures (PFs) frequently affect the lower limb of osteoporotic patients and represent an important cause of morbidity and mortality in the elderly. In this prospective randomized controlled trial, we have compared functional and radiological results and complications of patients affected by PFs treated with two intramedullary proximal femoral nails. Materials: We enrolled 323 subjects with PFs, classified according to AO/OTA system as 31.A1 (pertrochanteric simple) and 31.A2 (pertrochanteric multifragmentary). Patients were divided into two groups according to the osteosynthesis devices: group A, Elos-Intrauma® nail (155 cases) and group B, Gamma 3-Stryker® nail (168 cases). Pre-operatively, the baseline characteristics of each patient (gender, age, weight and BMI) were collected. Intraoperative blood loss, subjective pain by visual analogue scale (VAS), esthetic satisfaction, functional scores of the hip by Harris Hip Score (HHS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were noted. The post-operative degree of fracture reduction was assessed. Each patient had a minimum follow-up of 12 months. Results: The study group was composed of 106 male and 217 female with an average age of 85.4 (range, 65-90, standard deviation (SD) 5.95) years. No statistical differences about sex and age distribution were noted between the two groups. Group A reported lower intraoperative blood loss, 45 ml vs 51 ml, respectively (p < 0.001). There was not any statistical difference about operative time. Group A had a better reduction of fracture (p = 0.0347). The greatest difference was detectable comparing subgroups 31.A2 (p = 0.032). There were no statistical differences about complication frequency and the overall rate was 25% (80 cases). Finally, there was no difference in terms of VAS, HHS, and WOMAC score between the two groups on each follow-up. Patients of group A showed a higher subjective satisfaction index at 1 post-operative year, 7.42 (SD 1.19) vs 6.45 (SD 1.35) of group B (p < 0.001). Conclusion: Elos® nail is a reliable device on a short-term follow-up and represents an alternative choice to the Gamma 3® nail, a well-known and appreciated system for over 25 years

Physical activity regulates tnfα and il-6 expression to counteract inflammation in cystic fibrosis patients

Background: Cystic fibrosis (CF) is one of the most common inherited diseases. It is characterised by a severe decline in pulmonary function associated with metabolic perturbations and an increased production of inflammatory cytokines. The key role of physical activity (PA) in improving the health status of CF patients and reducing lung function decline has recently been demonstrated. This study evaluated interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) expression in two subgroups of CF patients classified based on PA. Methods: We selected 85 CF patients; half of them regularly undertook supervised PA in the three years leading up to the study and half of them were not physically active. Patients were analysed for serum IL-6 and TNFα levels using enzyme-linked immunosorbent assays. Results: We found that the expression levels of IL-6 and TNFα differed in terms of their regulation by PA. In particular, TNFα levels negatively correlated with FEV1% decrease/year and FEV1% decrease (p = 0.023 and p = 0.02, respectively), and positively correlated with serum fasting glucose (p = 0.019) in PA CF patients. In contrast, in the NPA subgroup, TNFα levels were positively correlated with IL-6 (p = 0.001) and negatively correlated with adiponectin (p = 0.000). In addition, multiple logistic regression analysis confirmed that PA is an independent modulator of the inflammatory state. Conclusions: PA modulates inflammatory processes in CF patients by regulating the secretion of pro-inflammatory cytokines and thus ameliorating lung function. Our data show that PA is a useful complementary strategy in the management of CF and that TNFα may be a marker of these effects of PA

Acute disseminated encephalomyelitis onset : evaluation based on vaccine adverse events reporting systems

OBJECTIVE: To evaluate epidemiological features of post vaccine acute disseminated encephalomyelitis (ADEM) by considering data from different pharmacovigilance surveillance systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS) database and the EudraVigilance post-authorisation module (EVPM) were searched to identify post vaccine ADEM cases. Epidemiological features including sex and related vaccines were analysed. RESULTS: We retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40\ub121.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines. CONCLUSIONS: This study has a high epidemiological power as it is based on information on adverse events having occurred in over one billion people. It suffers from lack of rigorous case verification due to the weakness intrinsic to the surveillance databases used. At variance with previous reports on a prevalence of ADEM in childhood we demonstrate that it may occur at any age when post vaccination. This study also shows that the diminishing trend in post vaccine ADEM reporting related to Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B and human papilloma virus vaccine groups is most likely due to a decline in vaccine coverage indicative of a reduced attention to this adverse drug reactio

Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles

Background The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. Objectives To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator (CFTR) complex alleles. Methods We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p. [Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr; Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p. [Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p. Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. Results The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p. Asp1270Asn have scarce functional effects, while p. [Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans, or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met; Asp1270Asn] causes significantly (pT] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). Conclusions The effect of complex alleles partially depends on the mutation in trans. Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction

Clinical expression of cystic fibrosis in a large cohort of Italian siblings

Background: A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF. Methods: We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis. Results: Severe lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV1% at 12 years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15 years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5 years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance > 50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the "whole" CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency. Conclusions: Physicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain

Dietary intakes in infertile women a pilot study

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