L-glutamic acid-g-poly hydroxyethyl methacrylate nanoparticles: acute and sub-acute toxicity and biodistribution potential in mice

The aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD₅₀ was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS^® spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.KEY WORDS: biocompatibility, blood biochemistry, genotoxicity, histology, in vivo toxicity, micronucleus test, polymers     

Babesiosis as a cause of acute respiratory distress syndrome: a series of eight cases

Objectives: The characteristics of patients with Acute Respiratory Distress Syndrome (ARDS) as a complication of Babesia microti infection have not been systematically described.

Methods: Adult patients admitted to the medical intensive care unit (MICU) of a tertiary care hospital in the Lower Hudson Valley of New York from 1/1/2008 to 8/1/2016 were evaluated for ARDS complicating babesiosis.

Results: Of 22 patients with babesiosis in the MICU, eight (36.4%; 95% CI: 19.7–57.0%) had ARDS. Six patients (75%) developed ARDS following initiation of anti-babesia drug therapy; however, the mean duration of symptoms in these patients exceeded that of patients who developed ARDS prior to initiation of treatment (7.50 ± 3.83d vs. 4.50 ± 0.71d, p = 0.34). Three patients (37.5%; 95% CI: 13.7–69.4%) expired without recovery from ARDS. In comparison, the mortality rate for the 14 MICU babesiosis patients without ARDS was 14.3% (p = 0.31). There was a trend toward younger age in survivors relative to non-survivors (mean age 54.6 ± 13.8y vs. 74.0 ± 6.24y, p = 0.07). Three of the five survivors did not require mechanical ventilation. The mean sequential organ failure assessment score of non-survivors was significantly higher than that of survivors (12.3 ± 1.15 vs. 6.0 ± 1.4, p = 0.0006).

Conclusion: Among 22 critically ill adult patients with B. microti infection, ARDS developed in eight (35.4%), and three (37.5%) expired without resolution of the ARDS. ARDS often followed the initiation of anti-babesia drug therapy, raising the question of whether the death of the parasite per se contributed to its development. However, this observation was confounded by the longer duration of symptoms preceding initiation of drug therapy.     

Health-related quality of life in glomerular disease

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Antibody-based immunotherapies for Parkinsonian syndromes

<正>what is the rationale for immunotherapies in Parkinsonian syndromes(PS)? PS are neurodegenerative diseases which are clinically characterized by a hypokinetic phenotype in combination with additional motor and non-motor symptoms. One major patholog-     

Oral-lung microbiome interactions in lung diseases

The proximity and continuity of the oral cavity and the lower respiratory tract allows the oropharyngeal microbiome to be a major determinant of the lung microbiome. In addition, host-pathogen interactions related to the oropharyngeal microbiome or its metabolites could propagate systemic inflammation or modulate host defense mechanisms that could affect other organs, including the lung. There is increasing appreciation of the pathophysiologic significance of the lung microbiome, not only in the classical infection-related diseases, pneumonia, bronchiectasis, and cystic fibrosis, but also in chronic noninfectious lung diseases, such as chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis. In this review, we will explore the relationship of the oral microbiome with lung diseases, such as pneumonia, chronic obstructive pulmonary disease, asthma, and cystic fibrosis.