65 research outputs found
Dissection of the role of calpain in the regulation of autophagy
No full textLo scopo principale del progetto di dottorato è stato quello di studiare il ruolo delle calpaine ubiquitarie nella regolazione del processo autofagico. Differenti tecniche biochimiche, di microscopia confocale e elettronica, ci hanno portato all'identificazione di una proteina target della micro-calpaina: Bif-1. L'azione proteasica su Bif-1 sembra sia indispensabile per la fissione e il trasporto di porzioni del Golgi verso il sito di formazione dell'autofagosome
Integrated care of chronic degenerative non-communicable diseases and rehabilitation: the odd couple?
No full textChronic degenerative non-communicable diseases affecting different organs and systems are considered by the World Health Organization (WHO) as the emergent epidemic in the third millennium..
Analgesic effectiveness and tolerability of oral oxycodone/naloxone and pregabalin in patients with lung cancer and neuropathic pain. An observational analysis
No full textINTRODUCTION:
Cancer-related pain has a severe negative impact on quality of life. Combination analgesic therapy with oxycodone and pregabalin is effective for treating neuropathic cancer pain. We investigated the efficacy and tolerability of a dose-escalation combination therapy with prolonged-release oxycodone/naloxone (OXN-PR) and pregabalin in patients with non-small-cell lung cancer and severe neuropathic pain.
METHODS:
This was a 4-week, open-label, observational study. Patients were treated with OXN-PR and pregabalin. Average pain intensity ([API] measured on a 0-10 numerical rating scale) and neuropathic pain (Douleur Neuropathique 4) were assessed at study entry and at follow-up visits. The primary endpoint was response to treatment, defined as a reduction of API at T28 ≥30% from baseline. Secondary endpoints included other efficacy measures, as well as patient satisfaction and quality of life (Brief Pain Inventory Short Form), Hospital Anxiety and Depression Scale, and Symptom Distress Scale; bowel function was also assessed.
RESULTS:
A total of 56 patients were enrolled. API at baseline was 8.0±0.9, and decreased after 4 weeks by 48% (4.2±1.9; P<0.0001 vs baseline); 46 (82.1%) patients responded to treatment. Significant improvements were also reported in number/severity of breakthrough cancer pain episodes (P=0.001), Brief Pain Inventory Short Form (P=0.0002), Symptom Distress Scale (P<0.0001), Hospital Anxiety and Depression Scale depression (P=0.0006) and anxiety (P<0.0001) subscales, and bowel function (P=0.0003). At study end, 37 (66.0%) patients were satisfied/very satisfied with the new analgesic treatment. Combination therapy had a good safety profile.
CONCLUSION:
OXN-PR and pregabalin were safe and highly effective in a real-world setting of severe neuropathic cancer pain, with a high rate of satisfaction, without interference on bowel function
L'abitato di Cà Spadolino di Coccanile (Copparo- FE) e il popolamento lungo i rami meridionali del delta del Po nell'età del Bronzo
No full textI lavori di realizzazione del metanodotto tra Minerbio (BO) e Cavarzere (VE), condotti nel 2006-2007, hanno permesso di individuare nel comune di Copparo (FE) le tracce di un abitato dell'età del Bronzo recente. In questo lavoro si prende in esame la documentazione archeologica dello scavo e si presenta una prima valutazione dell'insediamento all'interno di un contesto paleoambientale di estremo interesse per la prossimità all'antico ambiente deltizio, ai margini dell’antica frangia lagunare. Il sito localizzato a Ca’ Spadolino ad alcuni Km a NE di Coccanile, infatti, rappresenta una delle rare testimonianze archeologiche associate al percorso di uno dei rami meridionali del Po nell'età del Bronzo, ben evidenziato dall'analisi geomorfologica e dalla valutazione geoarcheologica della stratigrafia. Le analisi dei dati archeozoologici e dei resti archeobotanici permettono di completare la ricostruzione paleoambientale del contesto e di valutare l'impatto antropico nell'area in prossimità del Delta. L'attribuzione cronologica al Bronzo recente è supportata dallo studio dei reperti, prevalentemente ceramici, che includono tipologie ben attribuibili alle facies padane adriatiche e parzialmente da due datazioni al C14, effettuate su carboni.Recent excavations for laying a pipeline at Coccanile, near Copparo (Ferrara) allowed to discover a Bronze Age settlement at a depth of -1,5 and -2,5/-3 m under the ground level, related to an ancient branch of Po river. The archaeological deposit included several anthropic layers alternated with alluvial sediments. An enlarged excavation of 20 x 6 m allowed to locate the oldest archaeological level (US 821) above natural sediments composed of silt and sand with convex surface (FIG. 4). This was covered by alluvial deposit that could have also weared the upper part of the earlier anthropic occupation. The sequence followed with another archaeological layer (US 896) with posts structure (USS 1049/1052/-1050) suggesting a wooden feature bounding the settled area (FIG. 6). A third layer linked to human activities (US 892), was very thick (up to 60 cm ca.) and excavated in two levels, the lower connected to several features (post holes and an hypothetical embankment, the higher corresponding to the phase of abandonment.
The geomorphological analysis based on geomorphological data and on the stratigraphy led to recognize dynamics of alluvial aggradatio
Shortened conditioning and lighter stimulation regimen for Dynamic Cardiomyoplasty: Preliminary results.
No full textCalpain restrains the stem cells compartment in breast cancer
No full textCAPNS1 is essential for the stability and function of ubiquitous CAPN1 and CAPN2. Calpain modulates by proteolytic cleavage many cellular substrates and its activity is often deregulated in cancer cells, therefore calpain inhibition has been proposed as a therapeutical strategy for a number of malignancies. Here we show that CAPNS1 depletion is coupled to impairment of MCF7 and MCF10AT cell lines growth on plate and defective architecture of mammary acini derived from MCF10A cells. In soft agar CAPNS1 depletion leads to cell growth increase in MCF7, and decrease in MCF10AT cells. In both MCF7 and MCF10AT, CAPNS1 depletion leads to the enlargement of the stem cell compartment, as demonstrated by mammosphere formation assays and evaluation of stem cell markers by means of FACS and western blot analysis. Accordingly, activation of calpain by thapsigargin treatment leads to a decrease in the stem cell reservoir. The expansion of the cancer stem cell population in CAPNS1 depleted cells is coupled to a defective shift from symmetric to asymmetric division during mammosphere growth coupled to a decrease in NUMB protein level
The never-ending story of cardiac biomarkers: A further step toward a very early detection of ischemic patients?
No full text
Calpain mobilizes Atg9/Bif-1 vesicles from Golgi stacks Upon autophagy induction by thapsigargin
No full textCAPNS1 is essential for stability and function of the ubiquitous calcium-dependent proteases micro- and milli-calpain. Upon inhibition of the endoplasmic reticulum Ca2+ ATPase by 100 nM thapsigargin, both micro-calpain and autophagy are activated in human U2OS osteosarcoma cells in a CAPNS1-dependent manner. As reported for other autophagy triggers, thapsigargin treatment induces Golgi fragmentation and fusion of Atg9/Bif-1-containing vesicles with LC3 bodies in control cells. By contrast, CAPNS1 depletion is coupled with an accumulation of LC3 bodies and Rab5 early endosomes. Moreover, Atg9 and Bif-1 remain in the GM130-positive Golgi stacks and Atg9 fails to interact with the endocytic route marker transferrin receptor and with the core autophagic protein Vps34 in CAPNS1-depleted cells. Ectopic expression of a Bif-1 point mutant resistant to calpain processing is coupled to endogenous p62 and LC3-II accumulation. Altogether, these data indicate that calpain allows dynamic flux of Atg9/Bif-1 vesicles from the Golgi toward the budding autophagosome
Efficacy and tolerability of low-dose oral prolonged-release oxycodone/naloxone for chronic nononcological pain in older patients
No full textFabio Guerriero,1,2 Carmelo Sgarlata,2 Claudio Marcassa,3 Giovanni Ricevuti,1,2 Marco Rollone1 1Azienda di Servizi alla Persona of Pavia, Istituto di Cura Santa Margherita, Pavia, Italy; 2Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy; 3Fondazione Salvatore Maugeri IRCCS, Veruno, Novara, Italy Purpose: Chronic pain is highly prevalent in older adults. Increasing evidence indicates strong opioids as a valid option for chronic pain management in geriatrics. The aim of this study was to evaluate efficacy and safety of low-dose oral prolonged-release oxycodone–naloxone (OXN-PR) in patients aged ≥70 years.Methods: This open-label prospective study assessed older patients naïve to strong opioids presenting with moderate-to-severe chronic pain. Patients were prescribed OXN-PR at an initial dose of 10/5 mg/day for 28 days. In case of insufficient analgesia, the initial daily dose could be increased gradually. The primary efficacy measure was change in pain intensity from baseline, assessed by a ten-point Numeric Rating Scale (NRS) at day 28 (T28). Changes in cognitive state, daily functioning, quality of life, constipation, and other adverse events were assessed.Results: Of 53 patients enrolled (mean 81.7±6.2 years [range 70–92 years]), 52 (98.1%) completed the 28-day observation. At T28, the primary end point (≥30% reduction in mean pain from baseline in the absence of bowel function deterioration) was achieved in 38 patients (71.7%). OXN-PR significantly relieved pain (NRS score –3.26; P<0.0001), as well as daily need for rescue paracetamol (from 86.8% at baseline to 40.4% at T28; P<0.001), and reduced impact of pain on daily activities (Brief Pain Inventory Short Form from 6.2±1.5 to 3.4±2.1; P<0.0001). OXN-PR was also associated with significant improvement in daily functioning (Barthel Index from 53.3±14.1 to 61.3±14.3; P<0.01). No changes were observed in cognitive status and bowel function. OXN-PR was well tolerated; only one patient (1.9%) prematurely withdrew from treatment, due to drowsiness.Conclusion: Findings from this open-label prospective study suggest that low-dose OXN-PR may be effective and well tolerated for treatment of moderate-to-severe chronic pain in older patients. Besides its effectiveness, these data indicate that low-dose OXN-PR may be considered a safe analgesic option in this fragile population and warrants further investigation in randomized controlled studies. Keywords: chronic pain, elderly, opioid, oxycodone, constipatio
- …
