1,721,111 research outputs found
The Dual Function of Reactive Oxygen/Nitrogen Species in Bioenergetics and Cell Death: The Role of ATP Synthase
Full text link: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) targeting mitochondria are major causative factors in disease pathogenesis. The mitochondrial permeability transition pore (PTP) is a mega-channel modulated by calcium and ROS/RNS modifications and it has been described to play a crucial role in many pathophysiological events since prolonged channel opening causes cell death. The recent identification that dimers of ATP synthase form the PTP and the fact that posttranslational modifications caused by ROS/RNS also affect cellular bioenergetics through the modulation of ATP synthase catalysis reveal a dual function of these modifications in the cells. Here, we describe mitochondria as a major site of production and as a target of ROS/RNS and discuss the pathophysiological conditions in which oxidative and nitrosative modifications modulate the catalytic and pore-forming activities of ATP synthase
Oral immunotherapy in food allergy: how difficult to weigh its risks and benefits?
No full textTo the Editor:
The editorial by Thyagarajan et al1 entitled ‘‘Peanut oral immunotherapy
is not ready for clinical use’’ and published in the July
2010 issue of the Journal argued for limiting the clinical practice
of oral immunotherapy (OIT) by underlining that several important
questions about OITare still unanswered. Quoting the Hippocratic
Oath, ‘‘never do harm to anyone,’’ they also underlined that
OIT seemed to be generally safe but not without risks.
Wasserman et al2 replied to this editorial, stating that OIT for
food allergy is safe and effective. Paradoxically, those same authors
also reported the death of a child that happened during an
OIT formal trial performed in a tertiary pediatric center, adding
that it was due to a dosing error. Unfortunately, Wasserman
et al did not report any bibliography for that clinical case. They
did not give further details about the tertiary center involved or
about the trial in which the child took part.
Until now, no OIT-related death has been reported in the
literature. Thyagarajan et al replied back, apparently denying the
occurrence of such a death, and stated that ‘‘it is correct that there
have been no fatalities in the studies of OIT up to the present
time.’’3
We have recently published a systematic review about OIT,4
and we also have not found any deaths among all the trials published
up to now. In fact, OIT in food allergy has been used in Italy
for many years,5-7 and several adverse events have been described,
8 but a death caused by OIT has never been signaled. Nevertheless,
the letters quoted above put us in doubt: Did the child
die, or did he not?We really think it is important to know whether
a life-threatening event has happened because of a dosing mistake
while performing OIT. Mistakes are common in medical clinical
practice, and to knowhow it happened and which type of food was
the trigger would be useful.
Indeed, if that death happened in a tertiary center, how many
errors could happen if OIT comes into routine practice and starts
to be performed also in less experienced centers? We agree with
Thyagarajan et al1 that OIT can begin to be recommended only
after demonstrating that it is ‘‘superior to nonaction (or the current
standard of care).’’ For this reason, we believe that it is necessary
to know whether any life-threatening event has happened while
performing OIT because we are certain that it will help in carefully
and safely weighing the risks and benefits of OIT
Specific oral tolerance induction for food. A systematic review.
No full textBACKGROUND: Specific oral tolerance induction (SOTI) is a new therapeutic approach in the treatment of persistent food allergy.
OBJECTIVE: The purpose of this article is to systematically review the literature in order to identify, appraise, and synthesize the evidence about SOTI efficacy and safety.
METHODS: A comprehensive search for citations was conducted on May 2, 2009 using MEDLINE via PubMed. Randomized controlled trials (RCTs) including subjects of any age were considered. All these studies were assessed, discussed in details and evaluatedfor quality by authors in a standardized independent way.
RESULTS: 15 clinical trials were found. Of these, six trials met the inclusion criteria: three were open label RCT, three were double blind placebo controlled RCT. Two were conducted using sublingual immunotherapy, four using oral desensitization. Overall, the methodological quality of the studies was sufficient. The mean Jadad score of the studies was 3.33 (range = 2-5). Main characteristics and results of the studies were showed and discussed.
CONCLUSIONS: SOTI seems to be a possible approach to accelerate the development of tolerance in children affected by food allergy. However, other studies are needed to clarify which is the best treatment and protocol to follow in order to reduce the adverse events and to increase the percentage of success, before thinking that SOTI might be part of the clinical practice
Is cooked whole egg really less allergenic than pasteurized raw whole egg powder?
No full textNo abstrac
Can contrast-enhanced ultrasound with perfluorobutane add value in detection of hepatocellular carcinoma in cirrhosis during surveillance?
No full textNot availabl
Editorial on "Role of thermal ablation in the management of colorectal liver metastasis"
Full text linkAbstract not availabl
The pro-oncogenic protein IF1 does not contribute to the Warburg effect and is not regulated by PKA in cancer cells
Full text linkThe endogenous inhibitor of mitochondrial F1Fo-ATPase (ATP synthase), IF1, has been shown to exert pro-oncogenic actions, including reprogramming of cellular energy metabolism (Warburg effect). The latter action of IF1 has been reported to be hampered by its PKA-dependent phosphorylation, but both reprogramming of metabolism and PKA-dependent phosphorylation are intensely debated. To clarify these critical issues, we prepared stably IF1-silenced clones and compared their bioenergetics with that of the three parental IF1-expressing cancer cell lines. All functional parameters: respiration rate, ATP synthesis rate (OXPHOS), and mitochondrial membrane potential were similar in IF1-silenced and control cells, clearly indicating that IF1 cannot inhibit the ATP synthase in cancer cells when the enzyme works physiologically. Furthermore, all cell types exposed to PKA modulators and energized with NAD+-dependent substrates or succinate showed similar OXPHOS rate regardless of the presence or absence of IF1. Therefore, our results rule out that IF1 action is modulated by its PKA-dependent phosphorylated/dephosphorylated state. Notably, cells exposed to a negative PKA modulator and energized with NAD+-dependent substrates showed a significant decrease of the OXPHOS rate matching previously reported inactivation of complex I. Overall, this study definitively demonstrates that IF1 inhibits neither mitochondrial ATP synthase nor OXPHOS in normoxic cancer cells and does not contribute to the Warburg effect. Thus, currently the protection of cancer cells from severe hypoxia/anoxia and apoptosis remain the only unquestionable actions of IF1 as pro-oncogenic factor that may be exploited to develop therapeutic approaches
Food-Dependent Exercise-Induced Urticaria/Angioedema Caused by Lipid Transfer Protein in Two Children
No full textN/
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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