1,721,625 research outputs found
A New Current for the Mitochondrial Permeability Transition
No full textMitochondrial F1/FO ATP synthase participation in the mitochondrial permeability transition pore complex (PTPC) remains controversial. Neginskaya et al. (Cell Rep. 2019;26:11–17) reported an unexpected current with PTPC-like properties in F1/FO ATP synthase C subunit knockout cells that could explain part of the conflictual literature
A randomized, double-blind trial comparing 5-aminolaevulinic acid nanoemulsion with methyl 5-aminolaevulinate in daylight photodynamic therapy for actinic keratosis
No full textEvaluation of the treatment costs and duration of topical treatments for multiple actinic keratosis based on the area of the cancerization field and not on the number of lesions
Full text linkBackground: The cost of topical treatments for actinic keratosis (AK) has historically been evaluated in relation to the number of lesions requiring treatment or simply by the price of a single tube/sachet of the drug used. Objective: To demonstrate a new method of costing topical treatments in AK, which takes into account the actual cancerization area treated. Methods: In order to evaluate the actual cost of each treatment, the official approval status of the drug was used to estimate the amount of cream needed per one cm 2 . This value was then applied to the hypothetical cancerization area sizes to demonstrate the impact of the size treated on the actual cost of treatment. The price considered was the ex-factory price in Italy. Results: Areas which could be treated with a single tube/sachet of Metvix ® , Picato ® , Aldara ® , Solaraze ® and Zyclara ® were 200, 25, 25, 33.3 and 200 cm 2 , respectively. For the treatment of smaller areas (<100 cm 2 ), treatment with Metvix ® was the most costly topical option in Italy. However, for the treatment of cancerization areas larger than 100 cm 2 , Metvix ® was the least expensive treatment option. Treatment with Metvix ® was least long, requiring a single day of treatment for an area of up to 200 cm 2 , compared with up to 224 days of treatment with Aldara ® for the treatment of a similar size. Conclusion: Changing treatment costing strategy in the management of multiple AKs towards costing per cancerization area instead of costing per lesion is a much more accurate representation of the ‘real world cost’ for AK
Molecular mechanisms and consequences of mitochondrial permeability transition
No full textMitochondrial permeability transition (mPT) is a phenomenon that abruptly causes the flux of low molecular weight solutes (molecular weight up to 1,500) across the generally impermeable inner mitochondrial membrane. The mPT is mediated by the so-called mitochondrial permeability transition pore (mPTP), a supramolecular entity assembled at the interface of the inner and outer mitochondrial membranes. In contrast to mitochondrial outer membrane permeabilization, which mostly activates apoptosis, mPT can trigger different cellular responses, from the physiological regulation of mitophagy to the activation of apoptosis or necrosis. Although there are several molecular candidates for the mPTP, its molecular nature remains contentious. This lack of molecular data was a significant setback that prevented mechanistic insight into the mPTP, pharmacological targeting and the generation of informative animal models. In recent years, experimental evidence has highlighted mitochondrial F1Fo ATP synthase as a participant in mPTP formation, although a molecular model for its transition to the mPTP is still lacking. Recently, the resolution of the F1Fo ATP synthase structure by cryogenic electron microscopy led to a model for mPTP gating. The elusive molecular nature of the mPTP is now being clarified, marking a turning point for understanding mitochondrial biology and its pathophysiological ramifications. This Review provides an up-to-date reference for the understanding of the mammalian mPTP and its cellular functions. We review current insights into the molecular mechanisms of mPT and validated observations — from studies in vivo or in artificial membranes — on mPTP activity and functions. We end with a discussion of the contribution of the mPTP to human disease. Throughout the Review, we highlight the multiple unanswered questions and, when applicable, we also provide alternative interpretations of the recent discoveries
The Golgi apparatus is an inositol 1,4,5-trisphosphate-sensitive Ca2+ store, with functional properties distinct from those of the endoplasmic reticulum.
No full textPREDOMINANZA DEL CEPPO AFIDE-ASPECIFICO DEL VIRUS DEL NANISMO GIALLO DELL'ORZO (BYDV) NELLE INFEZIONI RISCONTRATE NEL FRIULI-VENEZIA GIULIA
No full textPhotodynamic therapy for non-melanoma skin cancers.
No full textAbstract: Photodynamic therapy (PDT) consists of topical or systemic delivery of photosensitizing drugs followed by ir-
radiation with light. Topical PDT is currently carried out with 5-aminolaevulinic acid (ALA) or methylaminolaevulinate
(MAL) both metabolized in the cells to protoporphyrinIX (PpIX), a photosensitizing molecule absorbing visible light. As
the rate of ALA-induced PpIX synthesis and accumulation is higher in malignant cells than in normal ones, PDT is able to
exert a selective action on neoplastic tissues. PpIX transfers its energy to molecular oxygen generating reactive oxygen
species. The subsequent oxidation of lipids, amino acids and proteins together with transcription and release of inflamma-
tory mediators induces cell necrosis, apoptosis and immunemodulation.
ALA 20% or MAL 16% (solution or cream) are applied over the skin lesion and then irradiated with blue or red light, de-
pending on the thickness of the tumour. No anaesthesia is needed. Usually two-three treatments are sufficient for actinic
keratosis, basal cell carcinoma, Bowen’s disease, the main dermatologic indications for PDT. Topical PDT is well suited
for lesions that would otherwise require extensive surgical procedures and for patients with contraindications to surgery or
with multiple lesions.
We review action mechanism, procedures and indications of PDT for non-melanoma skin cancers
Lesioni vescicolo-bollose e prurito in paziente affetto da insufficienza renale terminale
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