186,563 research outputs found
Economic evaluation of screening programs for hepatitis C virus infection: evidence from literature
No full textSilvia Coretti,1 Federica Romano,1 Valentina Orlando,2 Paola Codella,1 Sabrina Prete,1 Eugenio Di Brino,1 Matteo Ruggeri1 1Post-Graduate School of Economics and Management (ALTEMS), Università Cattolica del Sacro Cuore, Rome, Italy; 2Center of Pharmacoeconomics (CIRFF), Department of Pharmacy, Federico II University, Naples, Italy Background: Hepatitis C is a liver infection caused by hepatitis C virus. Its main complications are cirrhosis and liver cancer. According to the World Health Organization (WHO), more than 185 million people worldwide are infected with hepatitis C virus and, of these, 350,000 die every year. Due to the high disease prevalence and the existence of effective (and expensive) medical treatments able to dramatically change the prognosis, early detection programs can potentially prevent the development of serious chronic conditions, improve health, and save resources. Objective: To summarize the available evidence on the cost-effectiveness of screening programs for hepatitis C. Methods: A literature search was performed on PubMed and Scopus search engines. Trip database was queried to identify reports produced by the major Health Technology Assessment (HTA) agencies. Three reviewers dealt with study selection and data extraction blindly. Results: Ten papers eventually met the inclusion criteria. In studies focusing on asymptomatic cohorts of individuals at general risk the cost/quality adjusted life year of screening programs ranged between US 50,000/quality adjusted life year gained, while in those focusing on specific risk factors the incremental cost-effectiveness ratio ranged between 128,424/quality adjusted life year gained. Age of the target population and disease prevalence were the main cost-effectiveness drivers. Conclusion: Our results suggest that, especially in the long run, screening programs represent a cost-effective strategy for the management of hepatitis C. Keywords: hepatitis C, screening, early detection, cost-effectivenes
L-Carnitine attenuates fibrosis and inflammation in C57BL/6 mice with dietary-induced steatohepatitis
No full textNonalcoholic steatohepatitis (NASH) represents an advanced stage of fatty liver disease developed in the absence of alcohol abuse and its prevalence is increasing in western countries in parallel with Type 2 Diabetes and metabolic syndrome incidence.
NASH is a strong marker of cardiovascular risk and in the last few decades it has become evident that there is a mutual interaction between heart and liver influencing their individual functions.
In effect, NASH characterized by excess of intracellular fatty acids, severe inflammatory and fibrotic state, plays a critical role in two principal tissues: liver and heart.
Several studies have examined the effectiveness of L-Carnitine (LC) in liver function and have recognized LC as a nutritional supplementation in cardiovascular disease.
The present study was designed to investigate the effects of LC administration on liver and heart function and morphology in mice models of steatohepatitis, induced by a methionine-choline deficient diet (MCD).
C57BL/6 mice male (n=18, age:12 weeks) were divided in 3 different groups: control group (CONTR) were fed for 6 weeks with a normal diet while both MCD and LC groups received MCD diet. From the 4th week LC group received MCD diet enriched with 200mg/kg/die LC (drinking water). The results showed that there are no significant differences in body weight between MCD and LC mice groups, while, as expected, there is a significant weight loss in MCD and LC groups in respect with CONTR. Furthermore, insulin sensitivity (IPGTT test) and GLUT4 protein content showed no differences between groups.
Tissues fat deposition, inflammatory infiltration and fibrosis were, then, investigated. Different histopathology staining methods showed that LC significantly reduces fat accumulation. Immunofluorescence assay revealed an important downregulation of the two markers of tissue fibrosis: alpha smooth muscle actin protein level and Kruppel-like factor (KLF15). To clarify LC cellular mechanisms in counteracting inflammatory liver state, we evaluated NFκB pathway and PPARγ: our results indicated that NFkB increase, caused by MCD diet, was markedly attenuated by LC. In addition, LC significantly stimulates Ca2+/calmodulin-dependent kinases II activity, suggesting that LC could ameliorate mitochondrial function. Noteworthy, we observed LC actives ERKs pathway, which is correlated with a reduction of oxidative stress and hepatotoxicity.
In parallel, to investigate LC anti-inflammatory and fibrotic role in heart, we studied STAT-3 activation: LC significantly decreases STAT 3 activation observed in MCD heart. This data is in accordance with the reduction of Calcium signaling in LC heart compared to MCD.
In conclusion, LC appear to exert different beneficial actions on the liver-heart axis counteracting steatohepa¬titis. LC supplementation may be used in order to prevent disease progression in these analyzed tissues, inhibiting the inflammation and fibrotic pathways
In vivo magnetic resonance studies of muscle mitochondrial function in transgenic mice
No full textAlterations in muscle mitochondrial function have been implicated in the pathogenesis of numerous metabolic disorders, including insulin resistance, type 2 diabetes, obesity, and the deleterious effects of aging. However, the precise role for mitochondrial function in these processes remains to be established. In vivo 31P Magnetic Resonance Spectroscopy (31P-MRS) is an effective technique that permits the non-invasive investigation of skeletal muscle metabolism and transgenic mice are a novel tool for examining the effects of specific genes on mitochondrial function. Combining these two approaches would be a powerful methodology for studying mitochondrial function but its implementation has been limited due to the small volume of muscle from which the MR signal can be obtained and the requirement that the region of interest (ROI) must remain still for the entire duration of these lengthy studies.
A new MR-compatible experimental set-up was developed to perform these experiments under low-dose anesthesia to minimize movement with constant physiological monitoring to ensure that the animal remained viable throughout the study. The unidirectional flux of ATP synthesis (Pi → ATP) was measured using 31P saturation-transfer MRS in two different transgenic mouse models overexpressing PGC-1α or UCP3. While PGC-1α has been shown to be a potent promoter of mitochondrial biogenesis and fiber-type remodelling, UCP3 seems to play a critical role in regulating mitochondrial activity, but, whether this might be its primary role is still a matter of debate. The rates of ATP production (VATP) were 19% lower in UCP3 +/+ mice with respect to their wild-type (WT) littermates (P=0.02) accompanied by a significant increase in energy expenditure and food intake, confirming a contributing role played by this protein in regulating mitochondrial energy production. In PGC-1α +/+ mice, VATP was increased in mice fed a regular chow (by 50%, P<0.01) or a high fat diet (by 58%, P<0.001) with respect to wild-type littermate mice, with no significant difference in energy expenditure, food intake or locomotor activity. In the mouse model overexpressing PGC-1α, higher rates of VATP suggest enhanced efficiency in ATP production.
This thesis has demonstrated that 31P-MRS can successfully be applied to the investigation of muscle mitochondrial function in transgenic mice in vivo
data set from Mollica G, Senesi P, Codella R, Vacante F, Montesano A, Luzi L, Terruzzi I. L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet. Dig Liver Dis. 2020 Mar;52(3):314-323. doi: 10.1016/j.dld.2019.09.002. Epub 2019 Oct 10. PMID: 31607566.
No full text<p>data set from Mollica G, Senesi P, Codella R, Vacante F, Montesano A, Luzi L, Terruzzi I. L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet. Dig Liver Dis. 2020 Mar;52(3):314-323. doi: 10.1016/j.dld.2019.09.002. Epub 2019 Oct 10. PMID: 31607566.</p>
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<p>Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disorder. NAFLD, associated lipotoxicity, fibrosis, oxidative stress, and altered mitochondrial metabolism, is responsible for systemic inflammation, which contributes to organ dysfunction in extrahepatic tissues, including the heart. We investigated the ability of L-carnitine (LC) to oppose the pathogenic mechanisms underlying NAFLD progression and associated heart dysfunction, in a mouse model of methionine-choline-deficient diet (MCDD). Mice were divided into three groups: namely, the control group (CONTR) fed with a regular diet and two groups fed with MCDD for 6 weeks. In the last 3 weeks, one of the MCDD groups received LC (200 mg/kg each day) through drinking water (MCDD + LC). The hepatic lipid accumulation and oxidative stress decreased after LC supplementation, which also reduced hepatic fibrosis via modulation of α-smooth muscle actin (αSMA), peroxisome-activated receptor gamma (PPARγ), and nuclear factor kappa B (NfƙB) expression. LC ameliorated systemic inflammation, mitigated cardiac reactive oxygen species (ROS) production, and prevented fibrosis progression by acting on signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase 1-2 (ERK1-2), and αSMA. This study confirms the existence of a relationship between fatty liver disease and cardiac abnormalities and highlights the role of LC in controlling liver oxidative stress, steatosis, fibrosis, and NAFLD-associated cardiac dysfunction.</p>
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Local cryostimulation acutely preserves maximum isometric handgrip strength following fatigue in young women
No full textSeveral types of cryostimulation have been recently proposed to rapidly lower skin temperature therefore gaining a possible neuro/muscular recovery after strenuous exercise or, more generally, in sports. Local cryostimulation may be a viable and relatively portable tool to obtain physiological benefits in previously-efforted muscular districts. However, cohesive and standardized cryo-exposure protocols are lacking as well as the righteous procedure to efficaciously combine duration, treatments and temperature in relation to desirable effects on muscular strength. In this randomized-controlled study, fifty young women were tested for maximum isometric handgrip strength, before and after exhausting contractions.
Following the fatiguing protocol, the intervention group (cryo, n = 25, 24.7 ± 2.5 years, BMI 21.7 ± 1.8 kg/m2) underwent a 6-min local cryostimulation (−160 °C) on the extensor-flexor muscles of the dominant arm, while control-matched peers sat rested in a thermo-neutral room (22 ± 0.5 °C). Handgrip tests were repeated at baseline (T0), after cryostimulation (T1), and 15 min after T1 (T2). Throughout the protocol, the AUC of the strength performance was significantly higher in the cryo- compared to control group (P = 0.006). In particular, following fatigue and cryostimulation, the cryo group preserved higher strength at T1 with respect to controls (26.8 ± 2.8 vs 23.9 ± 2.8 kg, Bonferroni's post-hoc, P < 0.01). Likewise, ventral and dorsal temperature, recorded with a thermal camera, were lower in cryo- than control group (P < 0.0001).
In conclusion, a brief session of local cryostimulation may acutely preserve maximal isometric force in young women following a fatiguing protocol. These findings may have implications in orchestrating strategies of district muscular recovery
Star formation in the bright rimmed globule IC 1396N
No full textWe report mm-wave multiline and continuum observations of IC 1396N, a conspicuous bright, rimmed globule excited by the O6.5 star HD 206267 in the Cep OB2 association. Single-dish high resolution observations in CO and CS lines reveal the cometary structure of the globule with unprecedented detail. The globule head contains a dense core of 0.2 pc, whereas the tail, pointing away from the exciting star, has a total length of 0.8 pc. Two high velocity bipolar outflows have been identified in the CO maps: the first one is located around the position of a strong IRAS source in the head of the globule, and the second one, which was previously unknown, is located in the northern region. The outflows emerge from high density clumps which exhibit strong line emission of CS, HCO+, and DCO+. Within these clumps, the sources driving the outflows have been identified thanks to mm-wave continuum observations. The globule head harbors two YSOs separated by about 104 AU. SiO line observations of the central outflow unveals a highly collimated structure with four clumps of sizes <=0.1 pc, which are located along the outflow axis and suggest episodic events in the mass loss process from the central star. Kinetic temperatures of ~ 50-100 K and hydrogen densities of fews 106 cm-3 have been estimated in the shocked regions traced by the strong SiO emission. The jet is also exposed to view by the means of interferometric HCO+ observations that confirms that it is very narrow (<=0.02 pc wide). The detection of blue- and redshifted CO emission along the globule rim suggests that IC 1396N is in a transient phase, undergoing one of the expansions or compressions predicted by theoretical models describing the evolution of cometary globules. Moreover, the CO data, together with near IR observations reported elsewhere, indicate that the star forming process is occurring also in the northern part of IC 1396N, at 0.5 pc from the central CS peak. The present observations provide evidence that several star-forming sites can develop even in a moderately massive globule like IC 1396N
COST-EFFECTIVENESS ANALYSIS of HERPES ZOSTER VACCINATION in Italian ELDERLY PERSONS
No full textObjectives: Herpes zoster (HZ) is characterized by a painful skin rash. Its main complication is postherpetic neuralgia (PHN), pain persisting or occurring after the rash onset. HZ treatment aims to reduce acute pain, impede the onset complications, and disease progression. The aim of this study was to assess the cost-effectiveness of HZ vaccination compared with no vaccination strategy, within the Italian context. Methods: The natural history of HZ and PHN was mapped through a Markov model with lifetime horizon. A population of patients aged between 60 and 79 years was hypothesized. Third party payer (Italian National Health Service, I-NHS) and societal perspectives were adopted. Data were derived from literature. Results and Conclusions: The incremental cost-effectiveness ratio of the vaccination equaled EUR 11,943 per quality-adjusted life-year (QALY) under the I-NHS perspective and EUR 11,248 per QALY under the societal perspective. Considering a cost-effectiveness threshold of EUR 30,000/QALY, the multi-way sensitivity analysis showed that vaccination is cost-effective regardless of the perspective adopted, in 99 percent of simulations
L-carnitine supplementation attenuates NAFLD progression and complications in a methionine and choline deficient mouse model
No full textBackground and Aims
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in developed countries. Lipid droplets accumulation, subsequent generation of reactive oxygen species (ROS) and fibrosis deposition cause the progression to non-alcoholic steatohepatitis (NASH). L-Carnitine (LC) has been proposed to prevent liver damage of various etiologies.
The aim of the study was to investigate the effects of LC supplementation on liver fat deposition, oxidative stress and fibrosis development mechanism in a mouse model of steatohepatitis induced by a methionine-choline deficient diet (MCDD). In the same model we also analyzed the role of LC on cardiac tissue, considering the highest rates of mortality in NAFLD due to cardiovascular events.
Methods
The MCD diet model, best approximates the histological features of human NASH. Ten-week-old male C57BL/6 mice were divided into 3 experimental groups: one group (n=10) were fed with 120g/week of normal diet (CNT) and two groups (n=10 each group) with 120g/week of MCDD for nr. 6 weeks. After the first 3 weeks, one of the MCDD food group was enriched with 200mg/kg/die oral LC (MCDD+LC) until the end of the experiments.
Results
The LC supplementation delayed liver lipid accumulation (-28%, p=0.0005) and increased pCAMKII protein level (p=0.0308) in respect of MCDD group. LC supplementation also showed a role in controlling liver ROS generation (p=0.0386), restored pERK protein (p=0.005) and consequently delayed hepatotoxicity by the action of PPARγ (p=0.0088) on Nf-ƙB expression (p=0.0009) compared with the MCDD group. Finally, LC supplementation caused a sharp decrease of αSMA (p=0.04) compared to the MCDD group.
In parallel, we investigated the LC role to control cardiac stress and ROS production. LC decreased ROS production (p=0.01). To control fibrosis progression, LC significantly decreases pSTAT3/STAT3 (p=0.01) and pERK2/ERK2 expression (p=0.02) compared with MCDD group. As in liver, LC significantly decreased αSMA protein level (p=0.04) in relation to MCDD group.
Conclusions
We have demonstrated that LC decreased the severity of experimental NAFLD progression controlling lipid accumulation, oxidative stress imbalance and fibrosis progression in both liver and cardiac tissues analyzed. LC affected the shared oxidative stress mechanism pathway. Further studies are required to determine whether a long-term LC supplementation is able to control the pathophysiologic evolution of this disease and its related complications
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