The immunological benefit of higher dose N-acetyl cysteine following mechanical ventilation in critically ill patients

Background

Sepsis complication is a major cause of death in multiple trauma critically ill patients. Defensin (cysteine rich anti-microbial peptides), as an important component of immune system, might play an important role in this process. There is also rising data on immunological effects of N-acetyl-cysteine (NAC), a commonly used anti-oxidant in oxidative stress conditions and glutathione (GSH) deficiencies. The aim of the present study was to evaluate the potential beneficial effects of NAC administration on multiple trauma patients with sepsis.

Methods

In a prospective, randomized controlled study, 44 multiple trauma critically ill patients who were mechanically ventilated and met the criteria of sepsis and admitted to the intensive care unit (ICU) were randomized into two groups . Control group received all standard ICU therapies and NAC group received intravenous NAC 3 gr every 6 hours for 72 hours in addition to standard therapies. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, length of ICU stay, ICU mortality were recorded. Levels of serum Immunoglobulin M (IgM), Human β-Defensin 2 (HβD2) and GSH were assessed at baseline and 24, 72, 120 hours after intervention.

Results

During a period of 13-month screening, 44 patients underwent randomization but 5 patients had to be excluded. 21 patients in NAC group and 18 patients in control group completed the study. For both groups the length of ICU stay, SOFA score and systemic oxygenation were similar. Mortality rate (40% vs. 22% respectively, p = 0.209) and ventilator days (Mean ± SD 19.82 ± 19.55 days vs. 13.82 ± 11.89 days respectively, p = 0.266) were slightly higher for NAC group. IgM and GSH levels were similar between two groups (p = 0.325, 0.125 respectively), HβD2 levels were higher for NAC group (at day 3).

Conclusion

High dose of NAC administration not only did not improve patients’ outcome, but also raised the risk of inflammation and was associated with increased serum creatinine.     

Impact of geophysical and meteorological conditions on the dispersion of NO2 in Canada

This study uses the CALPUFF modeling system to examine the impact of a region’s geophysical and meteorological conditions on the dispersion of nitrogen dioxide (NO₂) emitted from a new oil refinery proposed by the Newfoundland and Labrador Refining Corporation. The proposed construction site of the refinery in Placentia Bay in Newfoundland is compared to the three Canadian locations of Edmonton, Yarmouth, and Whitehorse due to the differences in their geophysical and meteorological conditions. NO₂ was selected as the modeled contaminant for this study due to the many severe ecosystem, health, and societal risks associated with its exposure to humans, animals, and the environment. Differences on the impact of each studied region’s geophysical and meteorological conditions led the proposed construction site in Newfoundland to be the only advisable construction site for this refinery out of the four regions examined. Although Yarmouth is also a coastal region, its geophysical and meteorological conditions cause NO₂ to disperse into the land, while in Newfoundland, NO₂ is dispersed over water. The maximum NO₂ concentrations simulated for Edmonton and Whitehorse are considerably high and exceed the NO₂ limit for at least one of the two standards proposed by the Newfoundland and Labrador Department of Environment and Conservation and the National Ambient Air Quality Standard. Results show that a region’s geophysical and meteorological conditions have large impacts on the dispersion of pollutants and require careful consideration when selecting a refinery site.     

Bamboo leaf-based carbon dots for efficient tumor imaging and therapy

In this study, carbon dots synthesized from bamboo leaf cellulose were used simultaneously as a staining agent and for doxorubicin delivery to target cancer cells. Owing to their nontoxic properties, the production of carbon dots from bamboo leaves is a green approach involving optimized application of bamboo tree waste. For multifunctional applications, the carbon dots were modified with 4-carboxybenzylboronic acid and doxorubicin to improve target specificity and drug delivery to HeLa tumor cells. The resulting modified carbon dots were characterized using different analytical techniques, which showed that they were biocompatible, nontoxic, and highly stable over a wide range of pH values and at high ionic strengths. Furthermore, in vitro confocal microscopy studies demonstrated their blue fluorescence and cellular pathway for entering HeLa cells via folate receptor-mediated endocytosis. Cell viability data and flow cytometry results also confirmed the selective uptake of the carbon dots by HeLa cells, which significantly enhanced cell cytotoxicity.

In this study, carbon dots synthesized from bamboo leaf cellulose were used simultaneously as a staining agent and for doxorubicin delivery to target cancer cells.     

Shared amino acid sequences between major histocompatibility complex class II glycoproteins, type XI collagen and Proteus mirabilis in rheumatoid arthritis.

OBJECTIVES--To show molecular similarity between two sequences of Proteus mirabilis (haemolysin--ESRRAL; urease--IRRET) with HLA-DR antigens (EQRRAA) which are associated with rheumatoid arthritis (RA) and type XI collagen (LRREI), respectively; and, in patients with RA, to measure levels of antibody against a 16-mer synthetic peptide containing the ESRRAL sequence, and the haemolysin and urease proteins of Proteus mirabilis. METHODS--The homologous sequences EQRRAA and ESRRAL were modelled with Alchemy III, using the crystalline structure of DRB1*0101 (HLA-DR1). Sera from 40 patients with RA, 30 with ankylosing spondylitis (AS), and 30 controls were tested against synthetic ESRRAL peptide and the haemolysin of Proteus mirabilis by enzyme linked immunosorbent assay. Similar tests were also carried out on sera from 20 patients with RA, 40 with AS, and 15 controls, against Proteus mirabilis urease. RESULTS--Molecular modelling of the homologous sequences ESRRAL/EQRRAA and IRRET/LRREI showed stereochemical similarities. Antibodies to the 16-mer synthetic peptide containing the ESRRAL sequence, the haemolysin, and urease proteins were significantly increased in RA patients compared with AS patients (p < 0.001) and healthy controls (p < 0.001). No such increases were observed with three control peptides including the EDERAA sequence of DRB1*0402 (HLA-DR4/Dw10), the haemolysin proteins of Streptococcus pyogenes and Vibrio parahaemolyticus, and the urease of Bacillus pasteurii. CONCLUSION--The additive effect of the immune responses to the two Proteus mirabilis antigens, haemolysin (ESRRAL) and urease (IRRET), could be relevant in the aetiopathogenesis of RA.     

Long-term results of systemic thrombolysis therapy in aorto-iliac occlusive disease

BACKGROUND: Long term results of systemic lysis therapy with ultrahigh-dose urokinase (UHUK) in reopening aorto-iliac occlusive disease have not yet been evaluated. This prospective trial investigates the long-term primary patency rate, the rate of complications and assesses the role of different expected influence parameters on the primary patency rate. PATIENTS AND METHODS: 72 patients with aorto-iliac occlusive disease received daily intravenous infusions of UHUK either until reperfusion or--after at least 3 cycles--no progress in recanalization could be stated on two consecutive days by duplex scanning. RESULTS: Systemic lysis therapy was morphological at least partially successful in 44 patients (61.1%). Concomitant percutaneous transluminal angioplasty was performed in 41 patients (56.9%), surgery in 7 patients (9.7%) and both in further 5 patients (6.9%). In patients without surgery hemodynamical success could be achieved in 39 patients (54.2%) and even more important clinical success in 51 patients (70.8%). Compared to baseline results patients improved significantly in ankle/brachial pressure index and in Fontaine stages (p < 0.001), the same results could be seen after a mean follow-up period of 62 months. Thrombolysis was complicated in 4 patients (5.6%) by macroembolizations but no major bleedings or deaths occurred. Primary patency was 76%, 64%, and 43% after 1, 5 and 10 years. Male sex and distal localization were significantly correlated with lower primary clinical patency. CONCLUSION: Systemic lysis therapy is an alternative to surgical intervention in acute and subacute aorto-iliac occlusive disease, because it offers acceptable long-term results with a low rate of complications.