Retention of radiotranslucent foreign bodies in the oesophagus as a cause of stridor

Two infants who presented with stridor were found to have radiotranslucent plastic objects impacted in the oesophagus at the level of the cricoid cartilage. From these 2 cases the lessons to be learnt are that oesophageal foreign bodies retained for even a short period may be a cause of stridor and that when these foreign bodies are not radiographically visible investigation must include the swallowing of contrast medium in which the foreign body should be visible as a translucency.S. Afr. Med. J., 48, 831 (1974)

Novel disulfide-bridged bioresponsive antisense oligonucleotide induces efficient splice modulation in muscle Myotubes in Vitro

Splice-modulating antisense therapy has shown tremendous potential in therapeutic development in recent years with four FDA-approved antisense drugs since 2016. However, an efficient and nontoxic antisense oligonucleotide (AO) delivery system still remains as a major obstacle in nucleic acid therapeutics field. Vitamin-E (α-tocopherol) is an essential dietary requirement for human body. This fat-soluble compound is one of the most important antioxidants which involves in numerous biological pathways. In this study, for the first time, we explored the scope of using α-tocopherol-conjugated bioresponsive AOs to induce splice modulation in mouse muscle myotubes in vitro. Our results showed that the bioresponsive construct efficiently internalized into the cell nucleus and induced exon 23 skipping in mdx mouse myotubes. Based on our exciting new results, we firmly believe that our findings could potentially benefit toward establishing a delivery approach to advance the field of splice-modulating AO therapy

Author Correction: Systematic evaluation of 2′-Fluoro modified chimeric antisense oligonucleotide-mediated exon skipping in vitro

Correction to: Scientific Reports https://doi.org/10.1038/s41598-019-42523-0, published online 15 April 201

Banding of the pulmonary artery

No Abstrac

Lymphomatoid granulomatosis A report of 4 cases

Only 1 case of lymphomatoid granulomatosis has previously been reported from South Africa. Experience with 4 such adult patients (2 blacks and 2 whites) is described. These patients were followed up for 15 - 48 months and none developed evidence of a lymphoma during this period. Fever, weight loss, cough and breathlessness were prominent symptoms in all patients. One patient, a black woman, with a diffuse interstitial paUern of lung involvement, had digital clubbing - a rare accompaniment that resolved after therapy. Dilated congestive cardiomyopathy was found in association with pulmonary nodules in a black male patient. All 4 patients were treated with cytotoxic regimens. The 2 patients treated with oral cyclophosphamide and prednisolone responded favourably. The possible explanation for paucity of reports of lymphomatoid granulomatosis from South Africa could be under-reporting, underdiagnosis or a true geographic/ethnic variation in the incidence of this condition

Thiomorpholino oligonucleotides as a robust class of next generation platforms for alternate mRNA splicing

Recent advances in drug development have seen numerous successful clinical translations using synthetic antisense oligonucleotides (ASOs). However, major obstacles, such as challenging large-scale production, toxicity, localization of oligonucleotides in specific cellular compartments or tissues, and the high cost of treatment, need to be addressed. Thiomorpholino oligonucleotides (TMOs) are a recently developed novel nucleic acid analog that may potentially address these issues. TMOs are composed of a morpholino nucleoside joined by thiophosphoramidate internucleotide linkages. Unlike phosphorodiamidate morpholino oligomers (PMOs) that are currently used in various splice-switching ASO drugs, TMOs can be synthesized using solid-phase oligonucleotide synthesis methodologies. In this study, we synthesized various TMOs and evaluated their efficacy to induce exon skipping in a Duchenne muscular dystrophy (DMD) in vitro model using H2K mdx mouse myotubes. Our experiments demonstrated that TMOs can efficiently internalize and induce excellent exon 23 skipping potency compared with a conventional PMO control and other widely used nucleotide analogs, such as 2′-O-methyl and 2′-O-methoxyethyl ASOs. Notably, TMOs performed well at low concentrations (5–20 nM). Therefore, the dosages can be minimized, which may improve the drug safety profile. Based on the present study, we propose that TMOs represent a new, promising class of nucleic acid analogs for future oligonucleotide therapeutic development

Antisense oligonucleotides targeting angiogenic factors as potential cancer therapeutics

Cancer is one of the leading causes of death worldwide and conventional cancer therapies such as surgery, chemotherapy and radiotherapy do not address the underlying molecular pathologies, leading to inadequate treatment and tumour recurrence. Angiogenic factors, such as EGF, PDGF, bFGF, TGF-β, TGF-α, VEGF, Endoglin and Angiopoietins play important roles in regulating tumour development and metastasis, and serve as potential targets for developing cancer therapeutics. Nucleic acid-based therapeutic strategies have received significant attention in the last two decades, and antisense oligonucleotide-mediated intervention is a prominent therapeutic approach for targeted manipulation of gene expression. Clinical benefits of antisense oligonucleotides have been recognised by the US Food and Drug Administration, with full or conditional approval of Vitravene, Kynamro, Exondys51 and Spinraza. Herein, we review the scope of antisense oligonucleotides that target angiogenic factors towards tackling solid cancers

Synthesis and electrochemical behavior of a model redox-active thiacalix[4]arene-tetrathiafulvalene assembly

Syntheses of the first bisthiacalix[4]arenes systems bridged by a tetrathiafulvalene (TTF) framework have been carried out through triethyl phosphite-mediated dechalcogenation dimerization of the corresponding 1,3-dithiole-2-ones. The cyclic voltammograms of the resulting bisthiacalix[4]arenes tethered by an electroactive TTF unit are provided, and exhibit an electrochemical response in the case of introduction of Ag+

Identification of coumarins in DCM bark, leaf and fruit extracts from Mammea neurophylla (Calophyllaceae) by LC-PDA-MSn

4-phenyl and 4-propylcoumarins display a wide variety of biological activities including anti-oxidant and anti-inflammatory effects, antiparasitical activities against Leishmania or Plasmodium as well as antibacterial, antiviral (HIV) and cytotoxic activities. Using LC-PDA-MSn we have developed a specific protocol allowing the simultaneous and qualitative detection of 4-phenyl and 4-propylcoumarins in DCM bark, fruit and leaf extracts obtained from Mammea neurophylla. By comparison of their retention times, MS and UV data with that of authentic samples, nine, seven and five 4-phenylcoumarins could be directly identified in bark, leaf and fruit extracts respectively. On the other hand, interlocking UV spectra and ESI-MSn data analysis allowed us to deduce plausible structures of five, eight and four other coumarins in bark, leaf and fruit respectively by comparison with their reported spectral data. During this study new Mammea A/AA 9-hydroxy-cyclo F and Mammea A/AB 9-hydroxy-cyclo F were identified. We believe that this protocol will be useful in case of dereplicative studies of Mammea and related species

Impact of stirring regime on piezocatalytic dye degradation using BaTiO3 nanoparticles

There is increasing demand to use readily accessible waste energy to drive environmentally friendly processes. Piezocatalysis, the process of converting mechanical energy such as vibration into a chemical process, is a breakthrough next generation approach to meet this challenge. However, these systems currently focus on using ultrasound to drive the chemical reaction and are therefore expensive to operate. We show that by using simple mechanical stirring and BaTiO3 particles we can remove Rhodamine B dye molecules from solution. After evaluating a range of stirring parameters, we demonstrate that there is an interplay between stirring speed, volume of liquid, catalyst structure and rate of dye removal. Our maximum degradation rate was 12.05 mg. g-1 catalyst after 1 hour of mechanical stirring at favourable conditions. This development provides a new insight into a low energy physical technique that can be used in environmental remediation processes