Synthesis, characterization, and biocompatibility of novel injectable, biodegradable, and in situ crosslinkable polycarbonate-based macromers

A series of novel self-crosslinkable and biodegradable polymers, poly(hexamethylene carbonate-fumarate) and poly(hexamethylene carbonate) diacrylate, and their amphiphilic copolymers with polyethylene glycol, poly(ethylene glycol fumarate-co-hexamethylene carbonate-fumarate) (PEGF-co-PHMCF), were developed for tissue engineering using propylene oxide as an acid scavenger. The synthesized polymers are white, which makes them more suitable for self-crosslinking via photopolymerization. These novel polymers were fully characterized using nuclear magnetic resonance spectroscopy, Fourier-transform infrared spectroscopy, gel permeation chromatography, differential scanning calorimetry, and rheometry. The cytocompatibility of the photocrosslinked networks were evaluated by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. These polymers can be used as precursors to prepare polymer networks and scaffolds with controlled hydrophilicity, biodegradability, and mechanical characteristics. Results obtained suggest that these polymers are potentially useful as injectable and photocrosslinkable materials for cell delivery, tissue engineering, and drug delivery applications.     

The effects of two-stage carotid occlusion on spatial memory and pro-inflammatory markers in the hippocampus of rats

The purpose of this study was to evaluate the effects of cerebral hypoperfusion on cognitive ability, TNFα, IL1β and PGE2 levels in both hippocampi in a modified two-vessel occlusion model. Both common carotid arteries of adult male Wistar rats were permanently occluded with an interval of 1 week between occlusions. Learning and memory were significantly decreased after 1 month. This reduction was not significant after 2 months, which may be attributed to blood flow compensation. The TNFα level was significantly increased after 3 h and 1 day. IL1β was significantly increased after 1 day. After a week there was no significant difference in pro-inflammatory levels. Furthermore, there was no difference between right and left hippocampi. It is possible that TNFα and IL1β elevation initiates pathologic processes that contribute to memory impairment.     

Neonatal Lupus erythematosus Following Rheumatoid Arthritis: Case Report and Literature Review

Background: Neonatal lupus erythematosus (NLE) is a transient autoimmune disease of developing fetus and neonate in mothers with systemic lupus erythematosus (SLE). In this report we introduce an infant with NLE whose mother had rheumatoid arthritis. Case Presentation: Our case was a 40 day old male infant with discoid-like and annular skin lesions over forehead and neck, irritability and low grade fever. There was a history of prematurity due to preeclampsia. There was no cytopenia or cardiac involvement but liver enzymes were more than 5-fold increased. FANA, Anti Ro and La were negative. The mother had a history of un-controlled rheumatoid arthritis for 12 years with deformity in metacarpal and PIP and ulnar deviation in hands. FANA=1/640 and anti-SSB/La was positive in the mother but there was no other clinical and paraclinical sign of SLE. Without any treatment and during months, the skin and mucosal lesions gradually disappeared without any scar and liver enzymes reached the normal level. After 6 months follow up, he was symptom free with normal growth and development. Conclusion: We recommend to check anti SSA/Ro and anti SSB/La antibodies in all pregnant women with connective tissue diseases to prevent life-threatening involvement of the infant.Key Words: Neonatal Lupus, Rheumatoid Arthritis, Anti SSA/Ro, Anti SSB/La     

Effects of intravenous administration of fentanyl and lidocaine on hemodynamic responses following endotracheal intubation

Objectives

To compare the effects of intravenous fentanyl and lidocaine on hemodynamic changes following endotracheal intubation in patients requiring Rapid Sequence Intubation (RSI) in the emergency department (ED).

Thrombolysis in acute nonmassive pulmonary embolism: potential role of multidetector-row spiral computed tomography in decision making

In the setting of suspected or confirmed nonmassive pulmonary embolism (PE), transthoracic echocardiography (TTE) is an important tool to identify patients who could benefit from thrombolytic therapy, because of right ventricle (RV) dysfunction, and to monitor the dynamic response of the RV to reperfusion therapy. Unfortunately, certain patient characteristics such as obesity, lung disease, postsurgical state, or respiratory distress often lead to inadequate ultrasonographic imaging quality. In such patients, multidetector-row spiral computed tomography (MSCT) may become even more important. We present a female obese patient with acute nonmassive PE in whom TTE did not allow a reliable evaluation of the RV. Conversely, MSCT, beyond a direct demonstration of intravascular thrombi, detected multiple signs suggesting RV dysfunction. According to these findings, thrombolysis was safely performed, obtaining a rapid clinical improvement and a regression of RV dysfunction.     

Recombinant human lipocalin 2 acts as an antibacterial agent to prevent platelet contamination

Background

Bacterial contamination of platelet products is the major infectious risk in blood transfusion medicine, which can result in life-threatening sepsis in recipient. Lipocalin 2 (Lcn2) is an iron-sequestering protein in the antibacterial innate immune response, which inhibit bacterial growth. This study was aimed to evaluate the antibacterial property of Lcn2 in preventing bacterial contamination of platelets.

Methods

Recombinant Lcn2 was expressed in a eukaryotic expression system and following purification and characterization of the recombinant Lcn2, its minimum inhibitory concentration was determined. Then, platelet concentrates were inoculated with various concentrations of Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Enterococcus faecalis, and the antibacterial effects of Lcn2 was evaluated at 20–24°C.

Results

Results revealed that Lcn2 effectively inhibited the growth of 1.5 × 10⁴ CFU/ml S. epidermidis, P. aeruginosa, K. pneumoniae, E. coli, and E. faecalis at 40 ng/ml. At this concentration, Lcn2 also inhibited the growth of 1.5 × 10³ CFU/ml Staphylococcus aureus and Proteus mirabilis.

Conclusion

Recombinant Lcn2 inhibited growth of a variety of platelet-contaminating bacteria. Therefore, supplementation of platelet concentrates with Lcn2 may reduce bacterial contamination.     

Isolation,functional characterization,and biological properties of MCh‐AMP1, a novel antifungal peptide from Matricaria chamomilla L.

The antimicrobial activities of natural products have attracted much attention due to the increasing incidence of pathogens that have become resistant to drugs. Thus, it has been attempted to promisingly manage infectious diseases via a new group of therapeutic agents called antimicrobial peptides. In this study, a novel antifungal peptide, MCh‐AMP1, was purified by reverse phase HPLC and sequenced by de novo sequencing and Edman degradation. The antifungal activity, safety, thermal, and pH stability of MCh‐AMP1 were determined. This peptide demonstrated an antifungal activity against the tested Candida and Aspergillus species with MIC values in the range of 3.33–6.66 μM and 6.66–13.32 μM, respectively. Further, physicochemical properties and molecular modeling of MCh‐AMP1 were evaluated. MCh‐AMP1 demonstrated 3.65% hemolytic activity at the concentration of 13.32 μM on human red blood cells and 10% toxicity after 48 hr at the same concentration on HEK293 cell lines. The antifungal activity of MCh‐AMP1 against Candida albicans was stable at a temperature range of 30–50°C and at the pH level of 7–11. The present study indicates that MCh‐AMP1 may be considered as a new antifungal agent with therapeutic potential against major human pathogenic fungi.     

Evaluation of the Cytotoxic Activity of Crocin and Safranal,Constituents of Saffron,in Oral Squamous Cell Carcinoma (KB Cell Line)

Crocin and safranal are active ingredients in the saffron. Some studies have demonstrated antitumor activities of saffron ingredients. The aim of this study was to evaluate cytotoxic effects of crocin and safranal in oral squamous cell carcinoma (KB cells) and NIH 3T3 cell line as nonmalignant cells. The cells were incubated with crocin and safranal at 37°C for 24, 48, and 72 h, and cell viability was quantitated by MTT assay. Apoptotic cells, cell cycle distribution, and sub-G1 fraction were determined using propidium iodide staining of DNA fragmentation by flow cytometry. Crocin (0.05–4 mM) and safranal (0.2–3.2 mM) significantly inhibited the growth of KB cells (the inhibitory growth effects of all concentrations for both were >50% after 72 h), while they had less inhibitory effects on NIH 3T3 cells viability. The IC₅₀ values of crocin and safranal against NIH 3T3 cells after 72 h were determined as 2.8 and 0.3 mM, respectively. Crocin and safranal induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in the toxicity of crocin and safranal. Apoptotic effects of crocin and safranal in tumor cells were more than normal cells. Neither crocin nor safranal affected the cell cycle progression. Crocin and safranal exerted apoptotic effects in KB cell line.     

Intravenous immunoglobulins neutralize blocking antibodies in Guillain-Barré syndrome

Intravenous immunoglobulin (IVIg) treatment ameliorates the course of Guillain-Barré syndrome (GBS), but its specific mode of action is unknown. We attempted to delineate the effect of IVIg on neuromuscular blocking antibodies in GBS. A total of seven GBS serum samples were examined for blocking antibodies and the effect of IVIg with a macro-patch-clamp technique in mouse hemidiaphragms. First, serum was tested before and after treatment with IVIg. Second, we investigated with coincubation experiments whether the IVIg was capable of neutralizing neuromuscular blocking antibodies in GBS serum or affinity-purified immunoglobulin G (IgG) fractions. Finally, the mechanism of the neutralizing effect was studied by the coincubation of active blocking GBS IgG with Fab and Fc fragments prepared from IVIg. All GBS sera (two adults and two children) and GBS IgG fractions (three adults) taken before treatment with IVIg blocked evoked quantal release by approximately 90%. Blocking activity was markedly reduced in sera obtained after treatment with IVIg. Coincubation of the pretreatment blocking serum with the posttreatment serum, or with the IVIg preparation used for treatment, reduced the blocking activity of the pretreatment GBS serum. When GBS IgG was coincubated with IVIg, the blocking activity of GBS IgG was diminished dose-dependently. Monovalent and divalent Fab fragments prepared from the IVIg were as effective as whole IVIg, but Fc fragments were ineffective. Therapeutic IVIg is capable of neutralizing neuromuscular blocking antibodies in GBS by a dose-dependent, antibody-mediated mechanism. This may, in part, explain its therapeutic efficacy.