Reduction of extracellular ferricyanide Fe(CN)
6
−3 to ferrocyanide by intact cells reflects the activity of a trans-plasma membrane oxidoreductase that, in human red blood cells, utilizes ascorbic ...acid as an electron donor. We herein report that the flavonoids quercetin and myricetin, while inhibiting dehydroascorbic acid uptake—and thus the erythrocyte ascorbic acid content—effectively stimulate the extracellular reduction of ferricyanide. Other flavonoids such as rutin, acacetin, apigenin, and genistein do not show the same effect. The notion that quercetin or myricetin may serve as an intracellular donor for a trans-plasma membrane oxidoreductase is supported by the following lines of evidence: (i) they afford direct reduction of ferricyanide; (ii) extracellular reduction of ferricyanide was not mediated by direct effects of the flavonoids released by the cells and was abolished by the sulphydryl reagent parachloromercuribenzenesulfonic acid (
pCMBS); (iii) the intracellular concentrations of quercetin or myricetin well correlate with increases in ferricyanide reduction; (iv) the intracellular concentration of the flavonoids dramatically declines after ferricyanide exposure. Taken together, the results presented in this study demonstrate that myricetin and quercetin, which accumulate in large amounts in red blood cells, act as intracellular substrates of a
pCMBS-sensitive trans-plasma membrane oxidoreductase. This may represent a novel mechanism whereby these flavonoids exert beneficial effects under oxidative stress conditions.
Dr De Sanctis, Efficacy of trabectedin in advanced soft tissue sarcoma: beyond lipo- and leiDe Sanctis R, Marrari A, Marchetti S, et al. Drug Des Devel Ther. 2015;9:5785-5791.The authors note that on ...page 5787, Figure 1, the bottom bar is missing the label "liposarcoma".Read the original article
The 6min walk test (6MWT) has been recently chosen as the primary outcome measure in several international multicenter clinical trials in Duchenne muscular dystrophy (DMD) patients. In the last few ...years there has been increasing attention to the assessment of upper limbs. The Performance of Upper Limb (PUL) has been specifically developed for the assessment of upper limbs in DMD providing information of three domains (shoulder, elbow and distal). The first published data have shown that involvement of upper limb is present not only in non ambulant patients and early signs of involvement can also be found in younger ambulant DMD boys. The aim of this longitudinal Italian multicentric study was to evaluate the correlation between the 6MWT and the PUL in ambulant DMD boys. As part of this study all boys are assessed using both measures. The preliminary results in over 100 DMD boys show that early signs of shoulder involvement can already be found after the age of 8 and become increasingly more marked with age. Boys with 6MWT results above 400m generally have full scores or one or two points below the full score. Their scores slightly decrease between 350 and 400m with a more obvious fall in scores below the cut off point of 350 that become increasingly more marked with the decrease in meters on the 6MWT. Our results suggest that upper limb involvement can already be found in DMD boys even in the ambulant phase and the scores on the PUL reflect to some extent the overall impairment observed on the 6MWT.
Micrometastases, (metastases smaller than 2 mm), had benn subject of several studies. In literature is documented a prognostic worsening due to their presence. Research of micrometastases in sentinel ...lymph node is of great interest and can allow a clinical application with profitable cost efficacy ratio. The Authors discuss about clinical, prognostical and therapeutical implicationes in case of micrometastases into sentinel lympho nodes.
Rhodiola rosea L. (Crassulaceae) is a plant living at high altitudes in Europe and Asia. Its roots have long been used in the traditional medical system of these geographical areas to increase the ...organism resistance to physical stress; today, it has become an important component of many dietary supplements. In this study we investigate the antioxidant capacity of the R. rosea aqueous extract evaluating its ability to counteract some of the main damages induced by hypochlorous acid (HOCl), a powerful oxidant generated by activated phagocytes, to human erythrocytes. Ascorbic acid was used as a reference substance because of its physiological HOCl‐scavenging ability. Our study demonstrates that R. rosea is able to significantly protect, in a dose‐dependent manner, human RBC from glutathione (GSH) depletion, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) inactivation and hemolysis induced by the oxidant. Furthermore, we demonstrate that R. rosea aqueous extract acts from the inside of the erythrocyte suggesting a probable involving of cell components. The protection on GSH afforded by the R. rosea extract with respect to ascorbic acid, occurred also if added 2 or 5 min. later than the oxidant, suggesting a more rapid or powerful effect.
The recent development of therapeutic approaches for Spinal Muscular Atrophy (SMA) has highlighted the need to identify clinical outcome measures for planned therapeutic clinical trials that could be ...used across spectrum of abilities. The Hammersmith Motor Function Scale (HMFS) is a functional scale already used in ongoing clinical trials. In order to assess functions related to everyday activities an add on module exploring upper limb (ULM) was developed in 2009 with the aim of better measuring weaker patients. This is also being used in an ongoing clinical trial in SMA. We report the results of a longitudinal study showing the changes on both the Hammersmith Functional Motor Scale and on the Upper Limb Module over a 12 month period exploring the correlation between the two measures. Longitudinal data, including at least one assessment at baseline and one performed 12 months later was obtained in 80 non ambulant SMA patients. Our results showed that the ULM widens the spectrum of functional aspects assessed, especially at the weaker end of the spectrum of non ambulant SMA. A proportion of the patients with very low scores on the HFMS were still able to achieve a few upper limb activities. Our findings suggest that the combined use of the two scales will help to improve the sensitivity of the HMFS in detecting changes over time.
While there have been considerable advances for outcome measures in ambulant children with Duchenne Muscular Dystrophy (DMD), no prospective longitudinal study has so far been devoted to the ...assessment of upper limbs. This information appears to be relevant for a better understanding of the disease progression in non ambulant patients. As a result of an international effort, a new tool, the Performance of Upper Limb (PUL) was specifically designed to assess upper limb function in DMD boys. The purpose of the PUL is to assess changes that occurs in motor performance of the upper limb over time both in ambulant and non-ambulant DMD boys and adults. A recent cross sectional study has demonstrated the ability of the PUL to assess a wide range of activities. The aim of the present study was to use the PUL in a cohort of DMD children and young adults to assess the range of findings at different ages and their changes over 12months. The results showed a progressive deterioration of scores with age, with early involvement of the proximal muscles that was more obvious after the age of 10years in the proximal domain and after the age of 15 in the more distal ones. The PUL Scale appears to be a useful tool for upper limb motor disease assessment in DMD ambulant and non-ambulant patients, that may be used in clinical trials and in clinical settings.
T.P.10 Pane, M; Palermo, C; Sivo, S ...
Neuromuscular disorders : NMD,
10/2014, Letnik:
24, Številka:
9
Journal Article
Recenzirano
The 6 min walk test (6MWT) has been recently chosen as the primary outcome measure in several international multicenter clinical trials in Duchenne muscular dystrophy (DMD) patients. In the last few ...years there has been increasing attention to the assessment of upper limbs. The Performance of Upper Limb (PUL) has been specifically developed for the assessment of upper limbs in DMD providing information of three domains (shoulder, elbow and distal). The first published data have shown that involvement of upper limb is present not only in non ambulant patients and early signs of involvement can also be found in younger ambulant DMD boys. The aim of this longitudinal Italian multicentric study was to evaluate the correlation between the 6MWT and the PUL in ambulant DMD boys. As part of this study all boys are assessed using both measures. The preliminary results in over 100 DMD boys show that early signs of shoulder involvement can already be found after the age of 8 and become increasingly more marked with age. Boys with 6MWT results above 400 m generally have full scores or one or two points below the full score. Their scores slightly decrease between 350 and 400 m with a more obvious fall in scores below the cut off point of 350 that become increasingly more marked with the decrease in meters on the 6MWT. Our results suggest that upper limb involvement can already be found in DMD boys even in the ambulant phase and the scores on the PUL reflect to some extent the overall impairment observed on the 6MWT.
Recent studies performed in our laboratory demonstrated that rabbit red blood cell hexokinase was remarkably inhibited by the cocktail ascorbic acid/Fe(II) (Stocchiet al.,1994,Arch. Biochem. ...Biophys.311, 160–167) and that the formation of dehydroascorbic acid was a key event in this process (Fioraniet al.,1996,Arch. Biochem. Biophys.334, 357–361). The present study was undertaken to determine the final hexokinase-inactivating species using cell-free extract as a model. Our results demonstrate superimposable kinetics of hexokinase decay promoted by either ascorbic acid/Fe(II) or dehydroascorbic acid in erythrocyte lysates in which the reduced glutathione (GSH) levels were variously manipulated. In particular, neither removal nor addition of this tripeptide was able to significantly alter the rate or extent of hexokinase inhibition. Thus, GSH-reductive processes are dispensable events in the process of hexokinase inhibition promoted by ascorbic acid/Fe(II) in red blood cells. As a consequence, dehydroascorbic acid appears to be the species which directly inhibits hexokinase. This inference is further supported by the observation that addition of dehydroascorbic acid to the purified enzyme leads to a remarkable inhibition in its activity.
T.P.11 Pane, M; Mazzone, E.S; Fanelli, L ...
Neuromuscular disorders : NMD,
10/2014, Letnik:
24, Številka:
9
Journal Article
Recenzirano
While there have been considerable advances for outcome measures in ambulant children with Duchenne Muscular Dystrophy (DMD), no prospective longitudinal study has so far been devoted to the ...assessment of upper limbs. This information appears to be relevant for a better understanding of the disease progression in non ambulant patients. As a result of an international effort, a new tool, the Performance of Upper Limb (PUL) was specifically designed to assess upper limb function in DMD boys. The purpose of the PUL is to assess changes that occurs in motor performance of the upper limb over time both in ambulant and non-ambulant DMD boys and adults. A recent cross sectional study has demonstrated the ability of the PUL to assess a wide range of activities. The aim of the present study was to use the PUL in a cohort of DMD children and young adults to assess the range of findings at different ages and their changes over 12 months. The results showed a progressive deterioration of scores with age, with early involvement of the proximal muscles that was more obvious after the age of 10 years in the proximal domain and after the age of 15 in the more distal ones. The PUL Scale appears to be a useful tool for upper limb motor disease assessment in DMD ambulant and non-ambulant patients, that may be used in clinical trials and in clinical settings.
PDF
