Administration of antibody to the lung protects mice against pneumonic plague

Intratracheal delivery of aerosolized monoclonal antibodies with specificity for Yersinia pestis LcrV and F1 antigens protected mice in a model of pneumonic plague. These data support the utility of inhaled antibodies as a fast-acting postexposure treatment for plague.     

Local release of dexamethasone from polymer millirods effectively prevents fibrosis after radiofrequency ablation

Recent studies show that after radiofrequency (RF) ablation, fibrosis occurs at the ablation boundary, hindering anticancer drug transport from a locally implanted polymer depot to the ablation margin, where tumors recur. The purpose of this study is to investigate strategies that can effectively deliver dexamethasone (DEX), an anti-inflammatory agent, to prevent fibrosis. Polymer millirods consisting of poly(D,L-lactide-co-glycolide) (PLGA) were loaded with either DEX complexed with hydroxypropyl beta-cyclodextrin (HPbeta-CD), or an NaCl and DEX mixture. In vitro release studies show that DEX complexed with HPbeta-CD released 95% of the drug after 4 days, compared to 14% from millirods containing NaCl and DEX. Rat livers underwent RF ablation and received either DEX-HPbeta-CD-loaded millirods, PLGA millirods with an intraperitoneal (i.p.) DEX injection, or control PLGA millirods alone. After 8 days in vivo, heightened inflammation and the appearance of a well-defined fibrous capsule can be observed in both the control experiments and those receiving a DEX injection (0.29 +/- 0.08 and 0.26 +/- 0.07 mm in thickness, respectively), with minimal inflammation and fibrosis present in livers receiving DEX millirods (0.04 +/- 0.01 mm). Results from this study show that local release of DEX prevents fibrosis more effectively than a systemic i.p. injection.     

Self-organization, interfacial interaction and photophysical properties of gold nanoparticle complexes derived from resilin-mimetic fluorescent protein rec1-resilin

In this investigation we report the synthesis of optically coupled hybrid architectures based on a new biomimetic fluorescent protein rec1-resilin and nanometer-scale gold nanoparticles (AuNPs) in a one-step method using a non-covalent mode of binding protocol. The presence of uniformly distributed fluorophore sequences, -Ser(Thr)-Tyr-Gly- along the molecular structure of rec1-resilin provides significant opportunity to synthesize fluorophore-modified AuNPs bioconjugates with unique photophysical properties. The detailed analyses of the AuNP-bioconjugates, synthesized under different experimental conditions using spectroscopic, microscopic and scattering techniques demonstrate the organizational pathways and the electronic and photophysical properties of the developed AuNP-rec1-resilin bioconjugates. The calculation of the bimolecular quenching constant using the Stern-Volmer equation confirms that the dominant mechanism involved in quenching of fluorescence of rec1-resilin in the presence of AuNP is static. Photoacoustic infrared spectroscopy was employed to understand the nature of the interfacial interaction between the AuNP and rec1-resilin and its evolution with pH. In such bioconjugates the quenched emission of fluorescence by AuNP on the fluorophore moiety of rec1-resilin in the immediate vicinity of the AuNP has significant potential for fluorescence-based detection schemes, sensors and also can be incorporated into nanoparticle-based devices.     

Immunoglobulin A anti‐phospholipid antibodies in Swedish cases of systemic lupus erythematosus: associations with disease phenotypes,vascular events and damage accrual

Immunoglobulin (Ig) G‐ and IgM‐class anti‐cardiolipin antibodies (aCL) and lupus anti‐coagulant (LA) are included in the 1997 update of the American College of Rheumatology (ACR‐97) systemic lupus erythematosus (SLE) criteria. Despite limited evidence, IgA‐aCL and IgA anti‐β₂‐glycoprotein‐I (anti‐β₂GPI) were included in the 2012 Systemic Lupus International Collaborating Clinics criteria. The present study aimed to evaluate IgG‐/IgA‐/IgM‐aCL and anti‐β₂GPI occurrence in relation to disease phenotype, smoking habits, pharmacotherapy, anti‐phospholipid syndrome (APS) and organ damage among 526 Swedish SLE patients meeting ACR‐97. Patients with rheumatoid arthritis (n = 100), primary Sjögren’s syndrome (n = 50) and blood donors (n = 507) served as controls. Anti‐phospholipid antibodies (aPL) were analysed by fluoroenzyme‐immunoassays detecting aCL/anti‐β₂GPI. Seventy‐six (14%) SLE cases fulfilled the Sydney APS‐criteria, and ≥ 1 aCL/anti‐β₂GPI isotype (IgG/IgA/IgM) occurred in 138 SLE patients (26%). Forty‐five (9%) of the SLE cases had IgA‐aCL, 20 of whom (4%) lacked IgG‐/IgM‐aCL. Seventy‐four (14%) tested positive for IgA anti‐β₂GPI, 34 (6%) being seronegative regarding IgG/IgM anti‐β₂GPI. Six (1%) had APS manifestations but were seropositive regarding IgA‐aCL and/or IgA anti‐β₂GPI in the absence of IgG/IgM‐aPL and LA. Positive LA and IgG‐aPL tests were associated with most APS‐related events and organ damage. Exclusive IgA anti‐β₂GPI occurrence associated inversely with Caucasian ethnicity [odds ratio (OR) = 0·21, 95% confidence interval (CI) = 0·06–0·72) and photosensitivity (OR = 0·19, 95% CI = 0·05–0·72). Nephritis, smoking, LA‐positivity and statin/corticosteroid‐medication associated strongly with organ damage, whereas hydroxychloroquine‐medication was protective. In conclusion, IgA‐aPL is not rare in SLE (16%) and IgA‐aPL analysis may have additional value among SLE cases with suspected APS testing negative for other isotypes of aPL and LA.     

Incidence and Predictors of Radial Artery Occlusion Associated Transradial Catheterization

In this study, we sought to assess the incidence and predictors of radial artery occlusion (RAO), which is a significant complication of transradial cardiac catheterization. We prospectively evaluated the results of 106 patients who underwent coronary angiography and percutaneous coronary intervention (PCI) via the transradial approach (TRA). At the 3^rd h of intervention, the radial artery was checked by palpation; color doppler ultrasonography was performed at the 24^th h. Fluoroscopy duration, procedure success, and complications of the radial artery were recorded. The procedure was successfully completed in all patients. RAO was detected in eight female and two male patients. In terms of RAO, there was a statistically significant difference between males and females (p=0.019). Other parameters did not show a significant correlation with RAO. Altough did not have any effect on procedural success, eight patients developed transient radial artery spasm. Gender was not associated with radial arterial spasms (p=0.19). TRA in the diagnosis and treatment of coronary artery disease has shown high procedural success and low complication rates; it addition, it presents a low economic burden. It should be used widely and be involved in the routine cardiology residency program.     

Molecular cloning and expression in Escherichia coli of an aquaporin-like gene from adult buffalo fly (Haematobia irritans exigua)

A gene fragment encoding a putative member of the aquaporin gene family was amplified using cDNA prepared from unfed adult buffalo fly poly(A)⁺ RNA and degenerate PCR primers designed from highly conserved regions of amino acids found in all members of the aquaporin gene family. This PCR product was labelled with digoxigenin-dUTP and used as a probe to screen a λgt-11 cDNA library constructed from unfed adult buffalo fly. One positively hybridizing clone (AqpBF1), contained an insert of 1878 bp, and DNA sequence analysis revealed an open reading frame of 753 bp encoding a polypeptide of predicted M _r = 26 163 Da. Comparison of the AqpBF1 deduced protein sequence with the GenBank database revealed significant homology to many aquaporin genes, including 72% identity with a partial DNA sequence encoding a member (drip) of the MIP protein family isolated from Drosophila melanogaster. The most closely related, full-length, GenBank sequence was an aquaporin gene isolated from the digestive tract of the sap-sucking insect Cicadella viridis , which was 53% identical to the buffalo fly AqpBF1 protein sequence. The full-length coding sequence of AqpBF1 was cloned into the (His)₆-fusion vector, pQE10, and the recombinant protein was expressed in Escherichia coli following induction by IPTG. The recombinant (His)₆-fusion protein was localized predominantly in the membrane fraction of E. coli . The protein was solubilized from E. coli membranes with n -octyl β-d-glucopyranoside and purified by affinity chromatography on a Ni⁺⁺–sepharose column in the presence of detergent.     

Müller Muscle-conjunctival Resection with or without Tarsectomy and Combined with Bandage Contact Lens Use in Ptosis Patients with Corneal Graft

PurposeTo examine the efficacy of ptosis correction with a Müller muscle-conjunctival resection with or without tarsectomy (MMCR±T), combined with bandage contact lens (BCL) use, in corneal graft patients.MethodsSeven patients with corneal grafts who underwent MMCR±T for treatment of ptosis were evaluated retrospectively. A BCL was applied to the grafts at the end of the surgery. The collected data included preoperative and postoperative visual acuity, marginal reflex distance 1 (MRD-1), presence of Hering’s dependency by the phenylephrine test, symmetry outcomes, and complications after MMCR±T.ResultsThe average duration between the penetrating keratoplasty and MMCR±T was 14 months, with a follow-up time of 10.4 months after MMCR±T. Hering’s dependency was observed in four (57.2%) patients before MMCR±T, and MRD-1 was increased in all patients based on preoperative phenylephrine tests. The mean preoperative MRD-1 was −0.14 ± 0.55 mm, and the mean postoperative MRD-1 was 2.35 ± 0.89 mm (p < 0.0001). Symmetry outcomes of perfect (<0.5 mm), good (0.5–1 mm), and fair (≥1 mm) were noted after MMCR±T in three, three, and one patients, respectively. During the follow-up, no obvious corneal epitheliopathy, keratitis, or corneal graft rejection/failure were noted in any cases. BCL use was well tolerated by all patients.ConclusionsMost patients achieved good surgical outcomes with the application of the BCL to protect the graft and with the use of the phenylephrine test and Hering’s dependency to predict the final eyelid position and symmetry. MMCR±T combined with BCL may therefore represent an alternative approach for correction of ptosis in patients with corneal graft.