Passage through the carotid sheath: An alternative path to the pre-spinal route for direct repair of contralateral C7 to the lower trunk in total brachial plexus root avulsion injury

Context:In surgical management of global brachial plexus injuries, direct repair of contralateral C7 (cC7) to the anterior division of the lower trunk, can produce good extrinsic finger flexion. The pitfalls associated with the pre-spinal passage have, perhaps, proved to be a deterrent for using this technique routinely.Aims:The aim of this study is to demonstrate an alternative to pre-spinal route for cC7 transfer in brachial plexus avulsion injuries.Methods:We noted that the mobilised lower trunk, which reaches the level of the scalenus anterior by passage deep to the clavicle, can be brought to the suprasternal notch when brought out from below the clavicle. This area was dissected in two cadavres, and safe passage was found through the carotid sheath with the common carotid artery medially and the internal jugular vein with the vagus nerve laterally. The cC7 root dissected medial to the scalenus anterior muscle can be directly transferred along this path to the subcutaneous plane at the suprasternal notch. This study allowed us to execute a direct repair in ten clinical cases of global brachial plexus injuries. In each case, the passage was prepared rapidly and uneventfully. The repair was technically simple and could be performed comfortably using suitable fine suture materials. In none of these cases, did we need to shorten the humerus.Results:The clinical outcome of this technique is awaited.Conclusions:We advocate carotid sheath route to approximate the cC7 to the injured lower trunk in global palsies, as the risks associated with the pre-spinal route can be readily avoided.KEY WORDS: Anterior division of lower trunk, brachial plexus injury, carotid sheath route, contralateral C7, direct repair, finger flexion     

Role of nuclear hormone receptors in butyrate-mediated up-regulation of the antimicrobial peptide cathelicidin in epithelial colorectal cells

BACKGROUND AND AIMS: The human cathelicidin (LL-37) is one of the major antimicrobial peptides of the non-specific innate immune system in the intestinal tract. Altered expression has been associated with gastrointestinal disease. Recent studies demonstrated that butyrate induces LL-37 mRNA in colonic epithelial cells, however the underlying molecular mechanisms have not been elucidated. The objective of this study was to investigate the regulatory pathways involved in butyrate-induced up-regulation of LL-37. METHODS AND RESULTS: Treatment of Caco-2 and HT-29 cells with butyrate led to a time-dependent up-regulation of LL-37 mRNA expression as determined by semi-quantitative RT-PCR. Up-regulation of LL-37 mRNA by butyrate was subsequently followed by an increase in LL-37 protein expression as observed by immunofluorescence. Co-incubation of butyrate with a VDR, p38 MAPK, ERK 1/2 and TGF-beta1 receptor kinase inhibitor all reduced butyrate-mediated LL-37 mRNA up-regulation. In contrast, transfection of Caco-2 cells with a dominant-negative PPARgamma mutant vector did not affect butyrate-mediated up-regulation of LL-37 mRNA. CONCLUSION: Our results clearly demonstrate that butyrate-mediated up-regulation of LL-37 is influenced by several signalling pathways and receptors including MAPKs as well as VDR and TGF-beta1, but not by PPARgamma. These data may provide new opportunities in the treatment of gastrointestinal diseases.     

Impact of Glycosylation on the Local Backbone Flexibility of Well-Defined IgG1-Fc Glycoforms Using Hydrogen Exchange-Mass Spectrometry

We have used hydrogen exchange–mass spectrometry to characterize local backbone flexibility of 4 well-defined IgG1-Fc glycoforms expressed and purified from Pichia pastoris, 2 of which were prepared using subsequent in vitro enzymatic treatments. Progressively decreasing the size of the N-linked N297 oligosaccharide from high mannose (Man8-Man12), to Man5, to GlcNAc, to nonglycosylated N297Q resulted in progressive increases in backbone flexibility. Comparison of these results with recently published physicochemical stability and Fcγ receptor binding data with the same set of glycoproteins provide improved insights into correlations between glycan structure and these pharmaceutical properties. Flexibility significantly increased upon glycan truncation in 2 potential aggregation-prone regions. In addition, a correlation was established between increased local backbone flexibility and increased deamidation at asparagine 315. Interestingly, the opposite trend was observed for oxidation of tryptophan 277 where faster oxidation correlated with decreased local backbone flexibility. Finally, a trend of increasing C'E glycopeptide loop flexibility with decreasing glycan size was observed that correlates with their FcγRIIIa receptor binding properties. These well-defined IgG1-Fc glycoforms serve as a useful model system to identify physicochemical stability and local backbone flexibility data sets potentially discriminating between various IgG glycoforms for potential applicability to future comparability or biosimilarity assessments.     

An efficient and environmentally sustainable domino protocol for the synthesis of structurally diverse spiroannulated pyrimidophenazines using erbium doped TiO2 nanoparticles as a recyclable and reusable heterogeneous acid catalyst

An efficient and environmentally sustainable domino protocol has been presented for the synthesis of structurally diverse spiroannulated pyrimidophenazines involving a four component reaction of 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamine, cyclic ketones and amino derivatives in the presence of erbium doped TiO₂ nanoparticles as a recyclable and reusable heterogeneous acid catalyst. The present synthetic protocol features mild reaction conditions with operational simplicity, excellent yield with high purity, short reaction time and high atom economy with the use of a recoverable and reusable environmentally sustainable heterogeneous catalyst.

An efficient and environmentally sustainable domino protocol has been presented for the synthesis of structurally diverse spiroannulated pyrimidophenazines using erbium doped TiO₂ nanoparticles as a recyclable and reusable heterogeneous acid catalyst.     

Hydroxyapatite nanorods loaded with parathyroid hormone (PTH) synergistically enhance the net formative effect of PTH anabolic therapy

Parathyroid hormone (PTH) has been a major contributor to the anabolic therapy for osteoporosis, but its delivery to bone without losing activity and avoiding adverse local effects remain a challenge. Being the natural component of bone, use of hydroxyapatite for this purpose brings a major breakthrough in synergistic anabolism. This study focuses on synthesis, characterization and evaluation of in vitro and in vivo efficacy of PTH (1-34) adsorbed hydroxyapatite nanocarrier for synergistic enhancement in the anabolic activity of PTH for bone regeneration. The negative zeta potential of this nanocarrier facilitated its affinity to the Ca²⁺ rich bone tissue and solubilization at low pH enhanced specific delivery of PTH to the resorption pits in osteoporotic bone. In this process, PTH retained its anabolic effect and at the same time an increase in bone mineral content indicated enhancement of the net formative effect of the PTH anabolic therapy.     

Plasmonic Ag decorated CdMoO4 as an efficient photocatalyst for solar hydrogen production

The synthesis of Ag-nanoparticle-decorated CdMoO₄ and its photocatalytic activity towards hydrogen generation under sunlight has been demonstrated. The CdMoO₄ samples were synthesized by a simple hydrothermal approach in which Ag nanoparticles were in situ decorated on the surface of CdMoO₄. A morphological study showed that 5 nm spherical Ag nanoparticles were homogeneously distributed on the surface of CdMoO₄ particles. The UV/DRS spectra show that the band gap of CdMoO₄ was narrowed by the incorporation of a small amount of Ag nanoparticles. The surface plasmonic effect of Ag shows broad absorption in the visible region. The enhanced photocatalytic hydrogen production activities of all the samples were evaluated by using methanol as a sacrificial reagent in water under natural sunlight conditions. The results suggest that the rate of photocatalytic hydrogen production using CdMoO₄ can be significantly improved by loading 2% Ag nanoparticles: i.e. 2465 μmol h⁻¹ g⁻¹ for a 15 mg catalyst. The strong excitation of surface plasmon resonance (SPR) absorption by the Ag nanoparticles was found in the Ag-loaded samples. In this system, the role of Ag nanoparticles on the surface of CdMoO₄ has been discussed. In particular, the SPR effect is responsible for higher hydrogen evolution under natural sunlight because of broad absorption in the visible region. The current study could provide new insights for designing metal/semiconductor interface systems to harvest solar light for solar fuel generation.

Plasmonic enhancement of photocatalytic hydrogen generation is demonstrated using hierarchical Ag decorated CdMoO₄ synthesized using a hydrothermal method.