200 Groton Rd
Ayer MA 01432
Medical School: Other - 2002
Accepts Medicare: Yes
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: 225386
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Dendronized Anionic Gold Nanoparticles: Synthesis, Characterization, and Antiviral Activity. - Chemistry (Weinheim an der Bergstrasse, Germany)
Anionic carbosilane dendrons decorated with sulfonate functions and one thiol moiety at the focal point have been used to synthesize water-soluble gold nanoparticles (AuNPs) through the direct reaction of dendrons, gold precursor, and reducing agent in water, and also through a place-exchange reaction. These nanoparticles have been characterized by NMR spectroscopy, TEM, thermogravimetric analysis, X-ray photoelectron spectroscopy (XPS), UV/Vis spectroscopy, elemental analysis, and zeta-potential measurements. The interacting ability of the anionic sulfonate functions was investigated by EPR spectroscopy with copper(II) as a probe. Different structures and conformations of the AuNPs modulate the availability of sulfonate and thiol groups for complexation by copper(II). Toxicity assays of AuNPs showed that those produced through direct reaction were less toxic than those obtained by ligand exchange. Inhibition of HIV-1 infection was higher in the case of dendronized AuNPs than in dendrons.Â© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Different pattern of contamination by legacy POPs in two populations from the same geographical area but with completely different lifestyles: Canary Islands (Spain) vs. Morocco. - The Science of the total environment
The archipelago of the Canary Islands is one of the so-called ultra-peripheral territories of the European Union due to its geographical location away from the continent. Although the level of socioeconomic development and lifestyle of this region is comparable to that of any other of the European Union, it is just 100 km off the coast of Morocco, in the African continent. The population of the Canaries has been extensively studied with respect to their levels of POPs, and it has been described that their levels are relatively high compared to other European regions. It has been speculated with that the proximity to Africa may be associated with this level of contamination, but so far this theory has not been verified. This paper describes for the first time the levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in a sample of the population of Morocco (n = 131), which were compared with those of a similar sample of the population of permanent residents in the Canary Islands (n = 100) in order to check this hypothesis. Our results showed that Moroccans have higher median values of OCPs than the residents in the Canaries (âˆ‘ OCP = 150.2 ng/g lw vs. 83.4 ng/g lw, p = 0.0001). Regarding the PCBs, although recent studies have reported that new environmental sources of PCBs exist in several African countries (including Morocco), the plasma levels of most congeners were significantly higher in Canarians than in Moroccans, especially for the dioxin-like PCBs (median = 7.3 ng/g lw vs. 0.0 ng/g lw, p = 0.0001). The detailed analysis of our results suggests that the levels of these pollutants in the Canarian people are more influenced by their lifestyle and the previous use of these chemicals in the archipelago than by its geographical vicinity with Morocco.
Mesoporous Silica Nanoparticles Decorated with Carbosilane Dendrons as New Non-viral Oligonucleotide Delivery Carriers. - Chemistry (Weinheim an der Bergstrasse, Germany)
A novel nanosystem based on mesoporous silica nanoparticles covered with carbosilane dendrons grafted on the external surface of the nanoparticles is reported. This system is able to transport single-stranded oligonucleotide into cells, avoiding an electrostatic repulsion between the cell membrane and the negatively charged nucleic acids thanks to the cationic charge provided by the dendron coating under physiological conditions. Moreover, the presence of the highly ordered pore network inside the silica matrix would make possible to allocate other therapeutic agents within the mesopores with the aim of achieving a double delivery. First, carbosilane dendrons of second and third generation possessing ammonium or tertiary amine groups as peripheral functional groups were prepared. Hence, different strategies were tested in order to obtain their suitable grafting on the outer surface of the nanoparticles. As nucleic acid model, a single-stranded DNA oligonucleotide tagged with a fluorescent Cy3 moiety was used to evaluate the DNA adsorption capacity. The hybrid material functionalised with the third generation of a neutral dendron showed excellent DNA binding properties. Finally, the cytotoxicity as well as the capability to deliver DNA into cells, was tested in vitro by using a human osteoblast-like cell line, achieving good levels of internalisation of the vector DNA/carbosilane dendron-functionalised material without affecting the cellular viability.Â© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Impact of the systematic introduction of low-cost bubble nasal CPAP in a NICU of a developing country: a prospective pre- and post-intervention study. - BMC pediatrics
The use of Nasal Continuous Positive Airway Pressure Ventilation (NCPAP) has begun to increase and is progressively replacing conventional mechanical ventilation (MV), becoming the cornerstone treatment for newborn respiratory distress syndrome (RDS). However, NCPAP use in Lower-Middle Income Countries (LMICs) is poor. Moreover, bubble NCPAP (bNCPAP), for efficacy, cost effectiveness, and ease of use, should be the primary assistance technique employed in newborns with RDS.To measure the impact on in-hospital newborn mortality of using a bNCPAP device as the first intervention on newborns requiring ventilatory assistance.Prospective pre-intervention and post-intervention study.The largest Neonatal Intensive Care Unit (NICU) in Nicaragua.In all, 230 (2006) and 383 (2008) patients were included.In May 2006, a strategy was introduced to promote the systematic use of bNCPAP to avoid intubation and MV in newborns requiring ventilatory assistance. Data regarding gestation, delivery, postnatal course, mortality, length of hospitalisation, and duration of ventilatory assistance were collected for infants assisted between May and December 2006, before the project began, and between May and December 2008, two years afterwards.The pre- vs post-intervention proportion of newborns who died in-hospital was the primary end point. Secondary endpoints included rate of intubation and duration of NICU stay.Significant differences were found in the rate of intubation (72 vs 39%; p < 0.0001) and the proportion of patients treated exclusively with bNCPAP (27% vs 61%; p <0.0001). Mortality rate was significantly reduced (40 vs 23%; p < 0.0001); however, an increase in the mean duration of NICU stay was observed (14.6 days in 2006 and 17.5 days in 2008, p = 0.0481). The findings contribute to the evidence that NCPAP, particularly bNCPAP, is the first-line standard of care for efficacy, cost effectiveness, and ease of use in newborns with respiratory distress in LMICs.This is the first extensive survey performed in a large NICU from a LMICs, proving the efficacy of the systematic use of a bNCPAP device in reducing newborn mortality. These findings are an incentive for considering bNCPAP as an elective strategy to treat newborns with respiratory insufficiency in LMICs.
In vivo delivery of siRNA to the brain by carbosilane dendrimer. - Journal of controlled release : official journal of the Controlled Release Society
Nanotechnology offers a new platform for therapeutic delivery of antiretrovirals to the central nervous system (CNS). Nanoformulated antiretroviral drugs offer multifunctionality, that is, the ability to package multiple diagnostic and therapeutic agents in the same nanocompose, along with the added provisions of site-directed delivery, delivery across the blood-brain-barrier (BBB), and controlled release of therapeutics. We studied the viability of dendrimers and dendriplexes in human primary astrocytes, as well as their uptake by these astrocytes. Functional validation was performed by using specific siRNA against HIV-1 Nef to interfere to HIV-1 infectivity. A high efficiency in Nef silencing, reducing HIV-1 infectivity was observed in astrocytes treated with dendriplexes compared with control or siRandom treated astrocytes. More interestingly, we studied the biodistribution of the second generation of carbosilane dendrimer loaded with FITC (2G-(SNMe3I)11-FITC) in vivo, in BALB/c mice. Dendriplexes were inoculated into BALB/c mice by the retro-orbital venous plexus, and their localization was determined after 1 and 24h post-injection. Dendriplexes were detected inside the brain by a sensitive imaging system of fluorescent imaging in vivo (IVIS Lumina), and by confocal microscopy analysis of sections of OCT-embedded tissues. The 2G-(SNMe3I)11-FITC dendrimer transported efficiently siRNA into the brain, crossing the BBB. Moreover, this dendrimer successfully delivered and transfected siRNA to HIV-infected human primary astrocytes and achieved gene silencing without causing cytotoxicity. These results highlight the potential of this nanoformulation in the treatment of neurological disorders.Copyright Â© 2015 Elsevier B.V. All rights reserved.
Amphiphilic cationic carbosilane-PEG dendrimers: synthesis and applications in gene therapy. - European journal of medicinal chemistry
Here we synthesized carbosilane, generation 1 to 3, and PEG-based dendrons functionalized at the periphery with NHBoc groups and at the focal point with azide and alkyne moieties, respectively. The coupling of these two types of dendrons via click chemistry led to the formation of new hybrid dendrimers with two distinct moieties, the hydrophobic carbosilane and the hydrophilic PEG-based dendron. The protected dendrimers were transformed into cationic ammonium dendrimers. These unique amphiphilic dendrimers were studied as vectors for gene therapy against HIV in peripheral blood mononuclear cells (PBMC) and their performance was compared with that of a PEG-free carbosilane dendrimer. The presence of the PEG moiety afforded lower toxicities and evidenced a weaker interaction between dendrimers and siRNA when compared to the homodendrimer analogous. Both features, lower toxicity and lower dendriplex strength, are key properties for use of these vectors as carriers of nucleic material.Copyright Â© 2014 Elsevier Masson SAS. All rights reserved.
The cost-savings of implementing kangaroo mother care in Nicaragua. - Revista panamericana de salud puÌblica = Pan American journal of public health
To examine the costs of implementing kangaroo mother care (KMC) in a referral hospital in Nicaragua, including training, implementation, and ongoing operating costs, and to estimate the economic impact on the Nicaraguan health system if KMC were implemented in other maternity hospitals in the country.After receiving clinical training in KMC, the implementation team trained their colleagues, wrote guidelines for clinicians and education material for parents, and ensured adherence to the new guidelines. The intervention began September 2010 The study compared data on infant weight, medication use, formula consumption, incubator use, and hospitalization for six months before and after implementation. Cost data were collected from accounting records of the implementers and health ministry formularies.A total of 46 randomly selected infants before implementation were compared to 52 after implementation. Controlling for confounders, neonates after implementation had lower lengths of hospitalization by 4.64 days (P = 0.017) and 71% were exclusively breastfed (P < 0.001). The intervention cost US$ 23 113 but the money saved with shorter hospitalization, elimination of incubator use, and lower antibiotic and infant formula costs made up for this expense in 1 - 2 months. Extending KMC to 12 other facilities in Nicaragua is projected to save approximately US$ 166 000 (based on the referral hospital incubator use estimate) or US$ 233 000 after one year (based on the more conservative incubator use estimate).Treating premature and low-birth-weight infants in Nicaragua with KMC implemented as a quality improvement program saves money within a short period even without considering the beneficial health effects of KMC. Implementation in more facilities is strongly recommended.
Biophysical characterization of glycodendrimers as nano-carriers for HIV peptides. - Current medicinal chemistry
This paper examines the formation and stability of nano-complexes that could provide a new therapeutic approach against HIV-1 infection. Poly(propylene imine) glycodendrimers decorated with 2(nd) generation cationic carbosilane dendrons were generated and their use in polyplex formation checked. Owing to their positively-charged terminal amino groups the hybrid glycodendrimers can bind anionic peptides. It was shown that they form nano-complexes with the HIV-derived peptides P24, Gp160 and Nef. Complexes 130-190 nm in size were formed in molar ratios (dendrimer/ peptide) of (3-4):1. These were sufficiently stable over time and at different pHs. The results obtained suggest that the hybrid dendrimers studied can be considered as alternative carriers for delivering HIV peptides to dendritic cells.
Novel 'Si-C' carbosilane dendrimers as carriers for anti-HIV nucleic acids: studies on complexation and interaction with blood cells. - Colloids and surfaces. B, Biointerfaces
Treatment of HIV infection by gene therapy is a promising tool for combating AIDS. One of the primary limitations of gene therapy is the effective delivery of nucleic acids to the target cells. Dendrimers are nanoparticles that are increasingly being used as nucleic acid vehicles. We have synthesized "Si-C" amino-terminated carbosilane dendrimers [GnO3(NMe3)m](m+) functionalized with quaternary ammonium (NMe3(+)) terminal groups via hydrosilylation of allyl dimethylamine with the corresponding GnO3(SiH)m dendrimers and further addition of MeI. These dendrimers are soluble in water. Initially, complexation between these "Si-C" dendrimers and anti-HIV nucleic acids (oligodeoxynucleotides ANTITAR and GEM91, siRNA siP24) was studied and molar ratios for complete complexation were determined. Then the charge and size of the dendriplexes (complexes of "Si-C" dendrimers with nucleic acids) were analyzed and it was found that they possessed charges of +5 to +40 mV and sizes of 60-600 nm (zeta-size) or 50-100 nm (atomic force microscopy) suitable for cell transfection. Stability studies showed that the dendriplexes were stable over time and were resistant to degradation by serum albumin. The effects of dendrimers and their dendriplexes on erythrocytes (isolated and in whole blood) revealed that the dendriplexes were significantly less cytotoxic than the pure dendrimers. The effects of dendrimers and their dendriplexes on peripheral blood mononuclear cells (the main target of HIV) were analyzed and it was found that the dendriplexes were 10 times less cytotoxic than the pure dendrimers. Finally, transfection experiments revealed that "Si-C"-carbosilane dendrimers had a restricted ability to deliver long-chain double-stranded nucleic acids. The results indicate that these cationic carbosilane dendrimers are good candidates for delivering short-chain siRNA and oligodeoxynucleotide to HIV-infected peripheral blood mononuclear cells or lymphocytes.Copyright Â© 2013 Elsevier B.V. All rights reserved.
Synthesis, structure and molecular modelling of anionic carbosilane dendrimers. - Dalton transactions (Cambridge, England : 2003)
Anionic carbosilane dendrimers of generations 1-3 have been synthesized containing carboxylate G(n)X(C(2)H(4)CO(2)Na)(m) and sulfonate G(n)X(C(2)H(4)SO(3)Na)(m) peripheral groups and derived from two different cores, 1,3,5-(HO)(3)C(6)H(3) (X = O(3)) and Si(C(3)H(5))(4) (X = Si). The peripheral anionic groups make these dendrimers water soluble, despite their highly hydrophobic framework. These dendrimers present a net negative charge in water, which was influenced by the pH of the medium. This characteristic was studied by pH titration. Also molecular modeling calculations have been performed to study differences in an aqueous medium between carboxylate and sulfonate dendrimers of different cores. The results obtained were also compared with those obtained from DOSY NMR experiments and zeta-potential measurements.
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200 Groton Rd Ayer, MA 01432
200 Groton Rd Radiology Department
200 Groton Rd Radiology Department