Hybrid Gold Nanorod-Based Nanoplatform with Chemo and Photothermal Activities for Bimodal Cancer Therapy.

Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death.

Osteoporosis in children with severe congenital neutropenia: bone mineral density and treatment with bisphosphonates.

A high incidence of decreased bone mineral density (BMD) has been described in patients with severe congenital neutropenia (SCN). The objectives of the study are to describe changes in BMD in children with SCN treated with granulocyte colony-stimulating factor and evaluate the response to treatment with bisphosphonates in those who had osteoporosis. A prospective open-label study was performed evaluating BMD and metabolism in 9 Chilean patients with SCN, administrating bisphosphonates in those with osteoporosis. Follow-up ranged between 7 months and 3.5 years. Six out of 9 patients had reduced BMD on initial assessment: 3 had osteoporosis (z score <-2) and 3 had osteopenia (z score <-1). Four children presented vertebral fractures. Two presented osteopenia on follow-up without clinical symptoms. Five patients were treated with bisphosphonates, increasing their BMD z score (mean increase 1.2, range 0.27 to 2.62). z Score of hydroxyproline/creatinine ratios, which was elevated in 4 patients with osteoporosis, decreased during treatment (mean decrease 2.18, range 1.56 to 2.53). Four patients remodeled and reexpanded fractured vertebrae during treatment. No side effects of bisphosphonates were seen on follow-up. Osteoporosis is an important comorbidity in SCN patients probably due to increased bone resorption. Bisphosphonates seem to be an effective treatment for osteoporosis in these patients.

[Tracheobronchomalacia in pediatric patients: clinical experience]. / Traqueobroncomalacia en pacientes pediátricos: experiencia clínica.

BACKGROUND: Tracheobronchomalacia is characterized by a deficiency in the cartilaginous support of the trachea and bronchi and hypotony in the myoelastic elements, that lead to different levels of airway obstruction. AIM: To report our experience in the treatment of traqueobronchomalacia. MATERIAL AND METHODS: Retrospective review of 24 patients with tracheomalacia of different levels (3 tracheobronchomalacia, 3 laryngotracheomalacia) and 8 patients with bronchomalacia. RESULTS: The age at diagnosis ranged from 9 days to 9 years. Clinical presentation was recurrent wheezing in 19 patients, stridor in 6 and atelectasis in 4. The associated factors were neurological impairment in 8, congenital heart disease in 10 and prolonged mechanical ventilation in 4. The diagnosis was done by flexible bronchoscopy in all patients, using sedation and allowing spontaneous breathing. At the moment of diagnosis, treatment consisted in oxygen supply in 14 patients, physiotherapy in 21, beta 2 adrenergic agonists in 27, racemic epinephrine in 8, mechanical ventilation in 12, ipratropium bromide in 5 and inhaled steroids in 13. After diagnosis, 24 patients received bronchodilator therapy with ipratropium bromide, 15 received racemic epinephrine and 22 received inhaled steroids. In 21, beta 2 adrenergic agonists were discontinued. Thirteen patients required ventilation support and home oxygen. Twenty two patients showed a satisfactory clinical evolution and 6 patients died. CONCLUSIONS: The clinical presentation of tracheobronchomalacia is varied and diagnosis is done by flexible bronchoscopy. Treatment will depend on the severity of the disease, but beta 2 adrenergic agonists should be excluded.