Nitrogen‐Rich Compounds of the Lanthanoids: The 5,5′‐Azobis[1H‐tetrazol‐1‐ides] of some Yttric Earths (Tb,Dy, Ho,Er, Tm,Yb, and Lu)

A set of N‐rich salts, 3 – 9 , of the heavy lanthanoids (terbium, 3 ; dysprosium, 4 ; holmium 5 ; erbium, 6 ; thulium, 7 ; ytterbium, 8 ; lutetium, 9 ) based on the energetic 5,5′‐azobis[1H‐tetrazole] (H₂ZT) was synthesized and characterized by elemental analysis, vibrational (IR and Raman) spectroscopy, and X‐ray structure determination. The synthesis of the lanthanoid salts 3 – 9 was performed by crystallization from concentrated aqueous solutions of disodium 5,5′‐azobis[1H‐tetrazol‐1‐ide] dihydrate (Na₂ZT?2 H₂O; 1 ) and the respective Ln(NO₃)₃?5 H₂O and yielded large rhombic crystals of the type [Ln(H₂O)₈]₂(ZT)₃?6 H₂O in ca. 70% of the theoretical yield. The compounds 3 – 9 are isostructural (triclinic space group P ) to the previously published yttrium salt 2 ; they show, however, a clear lanthanoid contraction of several crystallographic parameters, e.g., the cell volume or the Ln? O bond lengths of the Ln³⁺ ions and the coordinating H₂O molecules. The lanthanoid contraction influences the strengths of the H‐bonds, which can be observed as a red shift by 4 cm^?1 in the characteristic IR band, in particular from 3595 cm^?1 ( 3 ) to 3599 cm^?1 ( 9 ). In good agreement with previous works, 2 – 9 are purely salt‐like compounds without a coordinative bond between the tetrazolide anion and the Ln³⁺ cation.     

Thyroplasty revisions: frequency and predictive factors

Thyroplasty is the most commonly performed type of laryngeal framework surgery, and the surgical indications are gradually being expanded. Although many reports have described thyroplasty results and rates of success, no study has attempted to determine predictors of the need for revisions or other secondary surgical procedures. METHODS: Retrospective review of 118 primary thyroplasty procedures performed on 96 patients. Secondary surgical procedures were divided into planned second-stage procedures (all fat implantation due to scarring), touchup procedures (primarily fat or collagen injections to close localized glottic gaps), and thyroplasty revisions (for implant extrusion or slippage). Statistical analysis was performed via the chi-squared technique with p < 0.05 considered significant. RESULTS: 96 patients underwent thyroplasty, 58 for vocal fold paresis or paralysis and 38 for other indications. Thirty-two (33%) patients underwent secondary surgical procedures, including 4 planned second stage procedures, and 6 patients with progression of their underlying disease. Thirty-two secondary procedures were performed in the other 22 patients. Professional singers were found to be more likely to require touchup or planned second-stage procedures (p = 0.029). Patients with abnormal preoperative noise-toharmonic ratios were more likely to undergo secondary surgeries (p = 0.039). Maximum phonation time was not associated with need for secondary surgery. Implant material did not influence revision rates. CONCLUSIONS: Professional singers and those patients with severe voice disorders (as measured by more abnormal noise-to-harmonic ratios) are more likely to undergo secondary surgical procedures. The choice of implant material does not affect need for secondary surgical procedures.     

The frequency of hard glottal attacks in patients with muscle tension dysphonia, unilateral benign masses and bilateral benign masses

Hard or abrupt glottal attack (HGA) is one of the vocal behaviors often associated with benign lesion of the vocal folds. This study was designed to determine whether the frequency of HGA was different in hyperfunctional voice patients with and without vocal fold masses. One hundred and forty-seven subjects were studied. All subjects received a complete otolaryngological evaluation including strobovideolaryngoscopy, objective voice measures, and evaluation by a speech-language pathologist. Thirty-two patients were diagnosed with muscle tension dysphonia (19 male, 13 female) without vocal fold masses. Fifty-seven patients were diagnosed with unilateral vocal fold masses (29 male, 28 female), most of which were cysts. Fifty-eight patients were diagnosed with bilateral vocal fold masses (13 male, 45 female). Of the 45 females with bilateral vocal fold masses. 26 had a vocal cyst and reactive nodule and 19 had bilateral vocal fold nodules. The control group was balanced and matched based on sex and on percentage of singers and nonsingers. It consisted of 49 subjects with no vocal fold pathology (20 male, 29 female). The group was composed of professional speakers, singers, and nonprofessional speakers. All voice disordered groups demonstrated higher frequencies of HGA than the control group. Differences were found between the male and female subjects in this study. No differences were found between the various disorders. Differences were also found between the subgroups of bilateral masses, where the bilateral nodules group presented a higher frequency of HGA than the cyst and contralateral reactive nodule.     

Exploring post-translational arginine modification using chemically synthesized methylglyoxal hydroimidazolones

The methylglyoxal-derived hydroimidazolones (MG-Hs) comprise the most prevalent class of non-enzymatic, post-translational modifications of protein arginine residues found in nature. These adducts form spontaneously in the human body, and are also present at high levels in the human diet. Despite numerous lines of evidence suggesting that MG-H-arginine adducts play critical roles in both healthy and disease physiology in humans, detailed studies of these molecules have been hindered by a lack of general synthetic strategies for their preparation in chemically homogeneous form, and on scales sufficient to enable detailed biochemical and cellular investigations. To address this limitation, we have developed efficient, multigram-scale syntheses of all MG-H-amino acid building blocks, suitably protected for solid-phase peptide synthesis, in 2-3 steps starting from inexpensive, readily available starting materials. Thus, MG-H derivatives were readily incorporated into oligopeptides site-specifically using standard solid-phase peptide synthesis. Access to synthetic MG-H-peptide adducts has enabled detailed investigations, which have revealed a series of novel and unexpected findings. First, one of the three MG-H isomers, MG-H3, was found to possess potent, pH-dependent antioxidant properties in biochemical and cellular assays intended to replicate redox processes that occur in vivo. Computational and mechanistic studies suggest that MG-H3-containing constructs are capable of participating in mechanistically distinct H-atom-transfer and single-electron-transfer oxidation processes. Notably, the product of MG-H3 oxidation was unexpectedly observed to disassemble into the fully unmodified arginine residue and pyruvate in aqueous solution. We believe these observations provide insight into the role(s) of MG-H-protein adducts in human physiology, and expect the synthetic reagents reported herein to enable investigations into non-enzymatic protein regulation at an unprecedented level of detail.     

Synthesis and preliminary investigations of the siRNA delivery potential of novel, single-chain rigid cationic carotenoid lipids

The success of nucleic acid delivery requires the development of safe and efficient delivery vectors that overcome cellular barriers for effective transport. Herein we describe the synthesis of a series of novel, single-chain rigid cationic carotenoid lipids and a study of their preliminary in vitro siRNA delivery effectiveness and cellular toxicity. The efficiency of siRNA delivery by the single-chain lipid series was compared with that of known cationic lipid vectors, 3β-[N-(N',N'-dimethylaminoethane)carbamoyl]-cholesterol (DC-Chol) and 1,2-dimyristoyl-sn-glyceryl-3-phosphoethanolamine (EPC) as positive controls. All cationic lipids (controls and single-chain lipids) were co-formulated into liposomes with the neutral co-lipid, 1,2-dioleolyl-sn-glycerol-3-phosphoethanolamine (DOPE). Cationic lipid-siRNA complexes of varying (+/-) molar charge ratios were formulated for delivery into HR5-CL11 cells. Of the five single-chain carotenoid lipids investigated, lipids 1, 2, 3 and 5 displayed significant knockdown efficiency with HR5-CL11 cells. In addition, lipid 1 exhibited the lowest levels of cytotoxicity with cell viability greater than 80% at all (+/-) molar charge ratios studied. This novel, single-chain rigid carotenoid-based cationic lipid represents a new class of transfection vector with excellent cell tolerance, accompanied with encouraging siRNA delivery efficiency.     

Laryngeal Myasthenia Gravis: Report of 40 Cases

Myasthenia gravis, an autoimmune disorder of the neuromuscular junction, is usually recognized because of ocular complaints or generalized weakness. We report a series of 40 patients who presented with dysphonia as their initial and primary complaint. Diagnostic testing included strobovideolaryngoscopy, electromyography (EMG) with repetitive stimulation and Tensilon testing, and laboratory and radiographic evaluation. Strobovideolaryngoscopy most commonly revealed fluctuating impairment of vocal fold mobility, either unilateral or bilateral. EMG detected evidence of neuromuscular junction abnormalities in all patients. Only one patient had evidence of antiacetylcholine receptor (ACh-R) antibodies, but many other abnormalities suggestive of autoimmune dysfunction were present. Pyridostigmine therapy was initiated in 34 patients but was not tolerated in 4. Of the remaining 30 patients, 23 reported improvement of symptoms. We conclude that myasthenia gravis can present with symptoms confined primarily to the larynx and should be included in the differential diagnosis of dysphonia.     

Paul Adrien Maurice Dirac (1902–1984)

Foundations of Physics -