Evaluation of mitochondrial respiratory function in highly glycolytic glioma cells reveals low ADP phosphorylation in relation to oxidative capacity

High-grade gliomas are aggressive and intensely glycolytic tumors. In the present study, we evaluated the mitochondrial respiratory function of glioma cells (T98G and U-87MG) and fresh human glioblastoma (GBM) tissue. To this end, measurements of oxygen consumption rate (OCR) were performed under various experimental conditions. The OCR of T98G and U-87MG cells was well coupled to ADP phosphorylation based on the ratio of ATP produced per oxygen consumed of ~2.5. In agreement, the basal OCR of GBM tissue was also partially associated with ADP phosphorylation. The basal respiration of intact T98G and U-87MG cells was not limited by the supply of endogenous substrates, as indicated by the increased OCR in response to a protonophore. These cells also displayed a high affinity for oxygen, as evidenced by the values of the partial pressure of oxygen when respiration is half maximal (p ₅₀). In permeabilized glioma cells, ADP-stimulated OCR was only approximately 50% of that obtained in the presence of protonophore, revealing a significant limitation in oxidative phosphorylation (OXPHOS) relative to the activity of the electron transport system (ETS). This characteristic was maintained when the cells were grown under low glucose conditions. Flux control coefficient analyses demonstrated that the impaired OXPHOS was associated with the function of both mitochondrial ATP synthase and the adenine nucleotide translocator, but not the phosphate carrier. Altogether, these data indicate that the availability and metabolism of respiratory substrates and mitochondrial ETS are preserved in T98G and U-87MG glioma cells even though these cells possess a relatively restrained OXPHOS capability.     

Oxidative stress biomarkers of exposure in the blood of cichlid species from a metal-contaminated river

The oxidative stress biomarkers of exposure, such as reduced glutathione (GSH), activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and the levels of lipid peroxidation (LPO), were measured in the blood of three cichlid fish (Oreochromis niloticus, Tilapia rendalli, and Geophagus brasiliensis) taken during two seasons from two sites, unpolluted and polluted by industrial effluents, to evaluate the effectiveness of these biomarkers in assessing the impact of water contamination. The LPO levels in the blood were higher in fish from the metal-contaminated site and the chronic exposure led to significant changes in GPx, CAT, and SOD activities in all three cichlid species. The considerable variation of responses in these cichlids to water contamination evidenced differences in sensitivity to the metal contamination and/or in the potential to respond to it highlighting the importance of using a set of related biomarkers to assess the impact of water contamination.     

Hydrating effects of moisturizer active compounds incorporated into hydrogels: in vivo assessment and comparison between devices

Background  Water is an important factor on the appearance and function of the skin and, when dehydrated, it becomes rough and flaky. The measurement of stratum corneum hydration is widely employed to verify the moisture effect of topical products.
Aims  This study has evaluated in vivo the stratum corneum hydration, by the electrical measurements of skin, after treatment with different moisturizers presented in gel base. MoistureMeter® and Corneometer were used as bio-instruments. Urea, the herbal extract ( Imperata cylindrical ), the NMF™ components and the carbohydrate derivate compound (xylityglucoside, anhydroxylitol, and xylitol) were used as the active substances.
Methods  The study protocol was carried out according to the three-factor factorial design. The gels were applied on both forearms of eight female volunteers. However, each volunteer had one untreated skin area as the skin moisture control. The electrical capacitance of the skin was measured by both instruments in different times: after application (0 time), 30, 60, 120, 240 and 360 min.
Results  Gel base, gel containing herbal extract, and gel containing NMF™ components statistically have equal moisture effect measurements, according to both bio-instruments. However, the values obtained for urea, carbohydrate derivate compound, and untreated skin (control) have statically different results in both devices.
Conclusion  The gel containing urea and the carbohydrate derivate compound gel have promoted the most intense moisture effect compared with the other formulations. The measurements of hydration between the devices generated different absolute values; however, the statistical analysis has shown similar precision among the measurements.     

Effect of cyclospasmol on early diabetic retinopathy

A randomized, double-blind, placebo controlled study to investigate the long-term effect of Cyclospasmol^R (cyclandelate) on the abnormal permeability of the blood-retinal barrier was performed in 26 patients with insulin-dependent diabetes mellitus for at least 1 year and minimal retinopathy. Cyclospasmol 400 mg or placebo capsules were taken 4 times daily for 12 months by equal numbers in both groups.Each patient underwent a routine ophthalmoscopic examination, retinal fluorescein angiography and quantitative vitreous fluorophotometry to assess the permeability of the blood-retinal barrier just before the trial and following 6 and 12 months of therapy. Laboratory tests for determining blood and urine glucose levels and blood HbA₁-levels were also carried out at these assessments.Statistically significant changes in diabetic control, in HbA₁-levels or in the frequency of retinal microaneurysms could not be shown in either treatment group during the trial, nor were there any significant differences in these parameters between the two groups. Analysis of fluorophotometric data on fluorescein penetration into the left posterior vitreous demonstrated significant reductions in this parameter during the trial compared to the pretreatment level in Cyclospasmol treated diabetics. These changes in the pretreatment level after 6 and 12 months also differed significantly between the two groups.However, this statistically significant beneficial reduction in fluorescein penetration into the left posterior vitreous did not occur in the right eye in the Cyclospasmol group.In placebo treated patients a consistently deleterious trend for this parameter was observed for both eyes during the one year study. The consistently beneficial trend in the right eye following Cyclospasmol and the consistently deleterious trend in both eyes following placebo with regard to the abnormal permeability of the blood-retinal barrier of diabetics with minimal retinopathy could probably be explained by the small number of patients in both groups. No side-effects were reported.     

Familial gigantiform cementoma with brittle bone disease, pathologic fractures, and osteosarcoma: a possible explanation of an ancient mystery

We describe four individuals of an African-American family with a predominantly diaphyseal bone disease associated with familial gigantiform cementoma (FGC), a disorder typically seen in Caucasians. The mother and her children presented with deformities of the jaws, abnormalities of the long bones, and pre-pubertal pathologic fractures. The index patient carried the diagnosis of osteosarcoma (OS). In addition, we provide a possible explanation for the jaw abnormalities of King Tutankhamen's father in the 18th dynasty in Egypt around 1350 BC.