Differential effects of antiepileptic drugs on human bone cells

Antiepileptic drugs (AED) have been associated to in vivo deleterious consequences in bone tissue. The present work aimed to characterize the cellular and molecular effects of five different AED on human osteoclastogenesis and osteblastogenesis. It was observed that the different drugs had the ability to differentially modulate both processes, in a way dependent on the identity and dose of the AED. Shortly, valproic acid stimulated either osteoclastogenesis and osteoblastogenesis, whereas carbamazepine, gabapentin, and lamotrigine revealed an opposite behavior; topiramate elicited a decrease of osteoclast development and an increase in osteoblast differentiation. This is the first report describing the direct effects of different AED on human primary bone cells, which is a very important issue, because these drugs are usually consumed in long-term therapeutics, with acknowledged in vivo effects in bone tissue.     

Effects of polymorphisms of LHR and FSHR genes on sexual precocity in a Bos taurus x Bos indicus beef composite population

The purpose of the present research was to investigate the effects of polymorphisms of luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR) genes, evaluated by polymerase chain reaction-restriction fragment length polymorphism in European-Zebu composite beef heifers from six different breed compositions. The polymorphism site analysis from digestion with HhaI and AluI restriction endonucleases allowed the genotype identification for LHR (TT, CT and CC) and FSHR (GG, CG and CC) genes. A high frequency of heterozygous animals was recorded in all breed compositions for both genes, except in two compositions for LHR. The probability of pregnancy (PP) at first breeding was used to evaluate the polymorphism effect on sexual precocity. The PP was analyzed as a binary trait, with a value of 1 (success) assigned to heifers that were diagnosed pregnant by rectal palpation and a value of 0 (failure) assigned to those that were not pregnant at that time. Heterozygous heifers showed a higher pregnancy rate (67 and 66% for LHR and FSHR genes, respectively), but no significant effects were observed for the genes studied (P = 0.9188 and 0.8831 for LHR and FSHR, respectively) on the PP. These results do not justify the inclusion of LHR and FSHR restriction fragment length polymorphism markers in selection programs for sexual precocity in beef heifers. Nevertheless, these markers make possible the genotype characterization and may be used in additional studies to evaluate the genetic structure in other bovine populations.     

Redescription of a rare deep-sea batfish, <Emphasis Type="Italic">Halieutopsis bathyoreos</Emphasis> (Lophiiformes: Ogcocephalidae)

Halieutopsis bathyoreos Bradbury, 1988 (Lophiiformes: Ogcocephalidae), previously described only on the basis of the holotype (62.6mm in standard length) from the central North Pacific, is redescribed on the basis of the holotype and six additional specimens (41.2–68.7mm in standard length) collected from the western South Pacific, off Papua New Guinea, and the western North Pacific, including the Japanese Archipelago. Halieutopsis bathyoreos is distinguished from its congeners by having a shelflike rostrum extending anteriorly well beyond the mouth, a dorsal escal lobe slightly bisected ventrally, an illicial cavity square in outline and completely visible in ventral view, and lacking tubercles on the ventral surface of the disk. The following characters are newly added to the diagnoses of this species: rostrum width 21–29% of head length, tubercles on the dorsal surface of the disk about half the diameter of those on the lateral margin, and 13–15 large lateral-line scales on the tail.     

Triamterene-β-cyclodextrin systems: Preparation,characterization and in vivo evaluation

The purpose of this research was to improve the solubility and therefore dissolution and bioavailability of triamterene, a poorly water soluble diuretic, by complexation with β-cyclodextrin. Triamterene has been reported to show low bioavailability after oral administration, with wide intersubject variation. This study presents the formulation of solid dispersions of triamterene with β-cyclodextrin—by cogrinding, kneading, and coevaporation, using low pH conditions—and their characterizations, evaluation of improvement in dissolution profiles, and in vivo advantage. Phase solubility studies indicated complex with possible stoichiometry of 1∶1 and a stability constant of 167.67M⁻¹. The solid dispersions were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, x-ray diffraction, and differential scanning calorimetry studies. The characterization studies confirmed inclusion of the phenyl ring of triamterene within the nonpolar cavity of β-cyclodextrin in the coevaporate. Remarkable improvement in in vitro drug release profiles in 0.1 N HCl and pH 6.8 phosphate buffer was observed with all dispersions, especially the coevaporate. The coevaporate, when administered orally in rats, also exhibited improved in vivo activity, as measured by net sodium ion excretion, as compared with triamterene powder. Thus, coevaporation of the drug and β-cyclodextrin from acidified alcohol provide the optimum condition for inclusion complexation to give a binary system with remarkable improvement in in vitro drug release profile and in vivo performance.     

Modulation of Brain Glutathione Reductase and Peroxiredoxin 2 by α-Tocopheryl Phosphate

α-Tocopheryl phosphate (αTP) is a phosphorylated form of α-tocopherol. Since it is phosphorylated in the hydroxyl group that is essential for the antioxidant property of α-tocopherol, we hypothesized that αTP would modulate the antioxidant system, rather than being an antioxidant agent per se. α-TP demonstrated antioxidant activity in vitro against iron-induced oxidative stress in a mitochondria-enriched fraction preparation treated with 30 or 100 µM α-TP. However, this effect was not observed ex vivo with mitochondrial-enriched fraction from mice treated with an intracerebroventricular injection of 0.1 or 1 nmol/site of αTP. Two days after treatment (1 nmol/site αTP), peroxiredoxin 2 (Prx2) and glutathione reductase (GR) expression and GR activity were decreased in cerebral cortex and hippocampus. Glutathione content, glutathione peroxidase, and thioredoxin reductase activities were not affected by αTP. In conclusion, the persistent decrease in GR and Prx2 protein content is the first report of an in vivo effect of αTP on protein expression in the mouse brain, potentially associated to a novel and biologically relevant function of this naturally occurring compound.     

Cover Image,Volume 120, Number 8, August 2019

Circular RNAs (circRNAs) are novel noncoding RNAs and play crucial roles in various biological processes. However, little is known about the functions of circRNAs in osteogenic differentiation. The current study aimed to investigate the differential expression of circRNAs in rat dental follicle cells (rDFCs) during osteogenic differentiation, identified by RNA high-throughput sequencing and quantitative real-time polymerase chain reaction. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to further explore the biofunctions of circRNA biofunctions. Two hundred sixty-six differentially-expressed circRNAs that are involved in several important signaling pathways, including mitogen-activated protein kinases (MAPK) and transforming growth factor-β (TGF-β) signaling pathways were revealed. Among these, circFgfr2 and its predicted downstream targets, miR-133 and BMP6 (bone morphogenetic protein-6), were identified both in vivo and in vitro. For further validation, circFgfr2 was overexpressed in rDFCs, the results showed that the expression of miR-133 was downregulated and the expression of BMP6 was upregulated. Taken together, the results revealed the circRNA expression profiles and indicated the importance of circRNAs of rDFCs. In addition, circFgfr2 might promote osteogenesis by controlling miR-133/BMP6, which is a potential new target for the manipulation of tooth regeneration and bone formation.     

Morphological Changes in the Midgut of Aedes aegypti L. (Diptera: Culicidae) Larvae Following Exposure to an Annona coriacea (Magnoliales: Annonaceae) Extract

Bioinsecticides are important in the control of disease vectors, but data regarding their physiological effects on target insects are incomplete. This study describes morphological changes that occur in the midgut of third instar Aedes aegypti L. (Diptera: Culicidae) following treatment with a methanolic extract of Annona coriacea (Magnoliales: Annonaceae). Dissected midguts were subdivided into anterior and posterior regions and analyzed by light and scanning electron microscopy. Insects exposed to the extract displayed intense, destructive cytoplasmic vacuolization in columnar and regenerative midgut cells. The apical surfaces of columnar cells exhibited cytoplasmic protrusions oriented toward the lumen, suggesting that these cells could be involved in apocrine secretory processes and/or apoptosis. We report that A. coriacea extracts induced morphological alterations in the midgut of A. aegypti midgut larvae, supporting the use of plant extracts for control of the dengue vector.     

Structural Stability of Myoglobin in Organic Media

The structural stability of metmyoglobin in organic solvents and cosolvents was investigated aiming the choice of a suitable medium to perform its dissolution with maintenance of the native folding. The spectroscopic behavior of metmyoglobin solution in UV–Visible and circular dichroism was used to evaluate the solubility and the secondary structure. The results were dependable of the chemical structure of the organic compounds, their polarity and content, in the case of cosolvents. Protic solvents showed better ability than the aprotic ones for the biomolecule dissolution, since they are able to establish hydrogen bonds. Solvents with high polarity usually damage the secondary structure of the protein. Myoglobin was dissolved in pure methanol, ethylene glycol and glycerol. The secondary structure was retained in some extent. The controlled addition of sodium dodecyl sulfate to myoglobin aqueous solution changed the surface moiety of the protein. The complex was extracted to hexane with efficiency of 77%.