Non-ionic Surfactant Based <Emphasis Type="Italic">In Situ</Emphasis> Forming Vesicles as Controlled Parenteral Delivery Systems

Non-ionic surfactant (NIS) based in situ forming vesicles (ISVs) present an affordable alternative to the traditional systems for the parenteral control of drug release. In this work, NIS based ISVs encapsulating tenoxicam were prepared using the emulsion method. Tenoxicam-loaded ISVs were prepared using a 2².3¹ full factorial experimental design, where three factors were evaluated as independent variables; type of NIS (A), molar ratio of NIS to Tween®80 (B), and phase ratio of the internal ethyl acetate to the external Captex® oil phase (C). Percentage drug released after 1 h, particle size of the obtained vesicles and mean dissolution time were chosen as the dependent variables. Selected formulation was subjected to morphological investigation, injectability, viscosity measurements, and solid state characterization. Optimum formulation showed spherical nano-vesicles in the size of 379.08 nm with an initial drug release of 37.32% in the first hour followed by a sustained drug release pattern for 6 days. DSC analysis of the optimized formulation confirmed the presence of the drug in an amorphous form with the nano-vesicles. Biological evaluation of the selected formulation was performed on New Zealand rabbits by IM injection. The prepared ISVs exhibited a 45- and 28-fold larger AUC and MRT values, respectively, compared to those of the drug suspension. The obtained findings boost the use of ISVs for the treatment of many chronic inflammatory conditions.     

Genetic Ablation of Butyrate Utilization Attenuates Gastrointestinal Salmonella Disease

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Root-favoured biomass allocation improves growth and yield of field-grown rice (<Emphasis Type="Italic">Oryza sativa</Emphasis> L.) plants only when the shoot sink is expandable

We tested the hypothesis that high root/shoot (R/S) in rice improves plant growth and yield when the shoot sink is expandable, and that in a genotype with exaggerated R/S ratio, the shoot growth is not limited by root resources. This study involved the three rice genotypes, Giza 178, PM12, and Moroberekan with a range of R/S ratios and shoot sink sizes. Root regrowth after trimming or high- and low-nitrogen treatments revealed that Moroberekan has consistently high root-favoured biomass partitioning than Giza 178 or PM12. Increasing the R/S ratios by detillering improved the culm growth in Giza 178 and PM12 (by 43.4 and 17.7% of control, respectively) but not Moroberekan, indicating that PM12 was closer to achieving its growth potential than Giza 178 but Moroberekan was operating at maximal shoot growth potential because of high R/S ratio and small sink size. Under drought, shoot growth, gas exchange, and grain yield correlated strongly with R/S ratio and root length density (RLD) in the droughted but not the well-watered plants. We further hypothesized that R/S ratio of Moroberekan was in excess of shoot requirement for optimum growth. Crossing Moroberekan to PM12 generated three F1 hybrids with intermediate R/S ratios but higher growth, gas exchange, and yield than either parent. We conclude that increasing the R/S ratio improved growth and yield in PM12 but not Moroberekan, because the shoot sink size was expandable in PM12. Moreover, lower R/S ratios than that of Moroberekan could support higher shoot growth if shoot sink is expandable.     

A Structural Model for the Escherichia coli DnaB Helicase Based on Electron Microscopy Data

The DnaB protein is the major replicative DNA helicase in Escherichia coli. It hydrolyzes ATP to promote its translocation in the 5′ to 3′ direction on single-stranded DNA templates, facilitating the separation of strands of duplex DNA in its path. This places it on the lagging strands at replication forks during chromosomal DNA replication. Electron microscopic images of negatively stained DnaB protein have been studied and processed to produce a three-dimensional reconstruction of the protein oligomer at 2.7 nm resolution. While it is known that the native protein is a complex of six identical 52kDa subunits, the specimen shows threefold rather than sixfold symmetry, with three outer stain-excluding regions surrounding another six, more massive, lobules. There is a channel through the particle that appears fully open on both sides. Based on these results, a structural model for the oligomer is presented, and functional implications are considered.     

A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies

Background

Fifty random genetically unstudied families (limb-girdle muscular dystrophy (LGMD)/myopathy) were screened with a gene panel incorporating 759 OMIM genes associated with neurological disorders. Average coverage of the CDS and 10 bp flanking regions of genes was 99 %. All families were referred to the Neurosciences Clinic of King Faisal Specialist Hospital and Research Centre, Saudi Arabia. Patients presented with muscle weakness affecting the pelvic and shoulder girdle. Muscle biopsy in all cases showed dystrophic or myopathic changes. Our main objective was to evaluate a neurological gene panel as a first-line diagnostic test for LGMD/myopathies.

Results

Our panel identified the mutation in 76 % of families (38/50; 11 novel). Thirty-four families had mutations in LGMD-related genes with four others having variants not typically associated with LGMD. The majority of cases had recessive inheritance with homoallelic pathogenic variants (97.4 %, 37/38), as expected considering the high rate of consanguinity in the study population. In one case, we detected a heterozygous mutation in DNAJB responsible for LGMD-1E. Our cohort included seven different subtypes of LGMD2. Mutations of DYSF were the most commonly identified cause of disease followed by that in CAPN3 and FKRP. Non-LGMD myopathies were due to mutations in genes associated with congenital disorder of glycosylation (ALG2), rigid spine muscular dystrophy 1 (SEPN1), inclusion body myopathy2/Nonaka myopathy (GNE), and neuropathy (WNK1). Whole exome sequencing (WES) of patients who remained undiagnosed with the neurological panel did not improve our diagnostic yield.

Conclusions

Our neurological panel achieved a high clinical sensitivity (76 %) and is an effective first-line laboratory test in patients with LGMD and other myopathies. This sensitive, cost-effective, and rapid assay significantly assists clinical practice especially in these phenotypically and genetically heterogeneous disorders. Moreover, the application of the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) guidelines applied in the classification of variant pathogenecity provides a clear interpretation for physicians on the relevance of such findings.

     

A monoamine in the gustatory cell of the frog's taste organ

Summary Fluorescence histochemistry reveals that in the frog's taste organ a yellow fluorescence is regularly observed at the most basal region of the sensory epithelium. The fluorescence has a strong intensity, but it fades rapidly upon the UV-irradiation. The peak of the emission spectrum is at 520 m. Following reserpine treatment the yellow fluorescence is markedly reduced, but not depleted completely. From these characteristics the monoamine fluorescence is regarded as representing 5-HT (serotonin).The ultrastructural study on sensory epithelia shows that the terminal portions of gustatory cell processes are localized at the basal region. These portions are filled with dense cored vesicles (700–1000 Å in diameter) and frequently opposed with nerve fibers penetrating into the epithelium. The gustatory cell processes are also interposed between the terminal portions or nerve fibers. The cytoplasm of the gustatory cell process is characterized by many mitochondria, fine filaments and glycogen particles, but contains few cored vesicles. The distribution of terminal portions of gustatory cell processes seems to correspond fairly well to that of the monoamine fluorescence observed discontinuously along the basal lamina. Accordingly it is concluded that the fluorigenic monoamine is localized in the cored vesicles of the gustatory cell.These results were reported in a preliminary form to the October, 1974 meeting of the Japan Society of Histochemistry and Cytochemistry.The authors gratefully acknowledge the support and helpful advice of Prof. Dr. T. Kanaseki.     

Elektronenmikroskopische Untersuchungen des verhornten Epithels im Vormagen der embryonalen und jungen adulten Maus

Zusammenfassung Die Zellen des Stratum granulosum in dem verhornten Epithel des Vormagens von 16–19 Tage alten Mäuseembryonen und von 1, 2, 7, 13 und 17 Tage alten Tieren wurden elektronenmikroskopisch analysiert. Die für diese Zellen spezifischen Keratohyalingranula kommen gleichzeitig im Kern und Cytoplasma vor. Intracristale Einschlüsse in den Mitochondrien werden ebenfalls als Keratohyalingranula gedeutet. Sie sind bisher nur in der hyperplastischen Haut der Maus gefunden worden. Es scheint, daß die Keratohyalingranula in allen genannten Zellteilen entstehen können. Im Cytoplasma stehen sie im Kontakt mit den Ribosomen. Keratohyalingranula im Kern und in den Mitochondrien haben auch manchmal einen Körnchensaum von unbekanntem chemischem Aufbau. Intracytoplasmatische Körperchen, die wahrscheinlich von der Plasmamembran abgeschnürt werden, treten oft zusammen mit den Keratohyalingranula auf. Keratohyalingranula in verschiedenen Entwicklungsstadien unterscheiden sich im Feinbau. Die Bedeutung des gleichzeitigen Vorkommens von Keratohyalingranula in verschiedenen Zellteilen wird diskutiert.

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Summary The cells of keratinized epithelia in the anterior part of the stomach of the mouse were investigated with the electron microscope in embryos of 16–19 days and in 1, 2, 7, 13 and 17 days old animals. Keratohyalin granules were found in the cytoplasm and the nucleus. Intracristal dense bodies in the mitochondria are also considered to be keratohyalin granules. These bodies have been observed so far only in the hyperplastic epidermis of the mouse. It appears likely that keratohyalin granules can originate in the above mentioned parts of the cell. In the cytoplasm keratohyalin granules are surrounded by ribosomes. The keratohyalin granules in the nucleus and the mitochondria are studded with frequently small particles of unknown chemical composition. Intracellular bodies probably originating from the plasma membrane often were found in the neighbourhood of the keratohyalin granules. The ultrastructure of the keratohyalin granules undergoes changes during development. The occurrence of keratohyalin granules in different parts of the same cell is discussed.

     

Development of silica-coated rare-earth doped strontium aluminate toward superhydrophobic,anti-corrosive and long-persistent photoluminescent epoxy coating

Long-persistent phosphorescent smart paints have the ability to continue glowing in the dark for a prolonged time period to function as energy-saving products. Herein, new epoxy/silica nanocomposite paints were prepared with different concentrations of lanthanide-doped aluminate nanoparticles (LAN; SrAl₂O₄:Eu²⁺,Dy³⁺). The LAN pigment was firstly coated with silicon dioxide (SiO₂) utilizing the heterogeneous precipitation technique to provide LAN-encapsulated between SiO₂ nanoparticles (LAN@SiO₂). The epoxy/silica/lanthanide-doped aluminate nanoparticles (ESLAN) nanocomposite paints were coated on steel. The prepared ESLAN paints were studied by transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X-ray fluorescence (XRF) analysis, and energy-dispersive X-ray spectroscopy (EDS). The transparency and coloration properties of the nanocomposite coated films were explored by CIE Lab parameters and photoluminescence spectra. The ultraviolet-induced luminescence properties of the transparent coated films demonstrated greenish phosphorescence at 518 nm upon excitation at 368 nm. Both hardness and hydrophobic activities were investigated. The anticorrosion activity of the nanocomposite films coated onto mild steel substrates immersed in aqueous sodium chloride (NaCl_(aq)) (3.5%) was studied by electrochemical impedance spectroscopy (EIS). The silica-containing coatings were monitored to exhibit anticorrosion properties. Additionally, the nanocomposite films with LAN@SiO₂ (25%) exhibited the optimized long-lasting luminescence properties in the dark for 90 min. The nanocomposite films showed highly reversible and durable long-lived phosphorescence.