Effects of L-histidine on hydrogen peroxide-induced DNA damage and cytotoxicity in cultured mammalian cells.

L-Histidine markedly increased the growth- and DNA synthesis-inhibitory effects elicited by hydrogen peroxide in cultured Chinese hamster ovary cells. DNA single-strand breakage was also higher in the presence of the amino acid and, in addition, these breaks were characterized by a slower rate of repair, compared with that of the breaks generated by the oxidant alone. In the presence of L-histidine, hydrogen peroxide also produced DNA double-strand breakage, a lesion that cannot be detected in cells treated with even exceedingly high concentrations of the oxidant alone. Data reported herein suggest that the L-histidine-mediated increase of the cytotoxic response of cultured Chinese hamster ovary cells to hydrogen peroxide may be at least partially dependent on the formation of DNA double-strand break

Effects of NSAIDs and paracetamol (acetaminophen) on protein kinase C epsilon translocation and on substance P synthesis and release in cultured sensory neurons.

Celecoxib, diclofenac, ibuprofen, and nimesulide are nonsteroidal anti-inflammatory drugs (NSAIDs) very commonly used for the treatment of moderate to mild pain, together with paracetamol (acetaminophen), a very widely used analgesic with a lesser anti-inflammatory effect. In the study reported here, we tested the efficacy of celecoxib, diclofenac, and ibuprofen on preprotachykinin mRNA synthesis, substance P (SP) release, prostaglandin E(2) (PGE(2)) release, and protein kinase C epsilon (PKC\u25b) translocation in rat cultured sensory neurons from dorsal root ganglia (DRGs). The efficacy of these NSAIDs was compared with the efficacy of paracetamol and nimesulide in in vitro models of hyperalgesia (investigated previously). While nimesulide and paracetamol, as in previous experiments, decreased the percentage of cultured DRG neurons showing translocation of PKC\u25b caused by 100 nM thrombin or 1 \u3bcM bradykinin in a dose-dependent manner, the other NSAIDs tested did not have a significant effect. The amount of SP released by peptidergic neurons and the expression level of preprotachykinin mRNA were assessed in basal conditions and after 70 minutes or 36 hours of stimulation with an inflammatory soup (IS) containing potassium chloride, thrombin, bradykinin, and endothelin-1. The release of SP at 70 minutes was inhibited only by nimesulide, while celecoxib and diclofenac were effective at 36 hours. The mRNA basal level of the SP precursor preprotachykinin expressed in DRG neurons was reduced only by nimesulide, while the increased levels expressed during treatment with the IS were significantly reduced by all drugs tested, with the exception of ibuprofen. All drugs were able to decrease basal and IS-stimulated PGE(2) release. Our study demonstrates novel mechanisms of action of commonly used NSAIDS

Prevalence of and risk factors for fatty liver in the general population of Northern Italy: The Bagnacavallo Study

Background: The estimation of the burden of disease attributable to fatty liver requires studies performed in the general population. Methods: The Bagnacavallo Study was performed between October 2005 and March 2009. All the citizens of Bagnacavallo (Ravenna, Italy) aged 30 to 60 years as of January 2005 were eligible. Altered liver enzymes were defined as alanine transaminase > 40 U/l and/or aspartate transaminase > 37 U/l. Results: Four thousand and thirty-three (58%) out of 6920 eligible citizens agreed to participate and 3933 (98%) had complete data. 393 (10%) of the latter had altered liver enzymes and 3540 had not. After exclusion of subjects with HBV or HCV infection, liver ultrasonography was available for 93% of subjects with altered liber enzymes and 52% of those with normal liver enzymes. The prevalence of fatty liver, non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) was 0.74 (95%CI 0.70 to 0.79) vs. 0.35 (0.33 to 0.37), 0.46 (0.41 to 0.51) vs. 0.22 (0.21 to 0.24) and 0.28 (0.24 to 0.33) vs. 0.13 (0.11 to 0.14) in citizens with than in those without altered liver enzymes. Ethanol intake was not associated and all the components of the metabolic syndrome (MS) were associated with fatty liver. All potential risk factors were associated with a lower odds of normal liver vs. NAFLD while they were unable to discriminate AFLD from NAFLD. Conclusions: Fatty liver as a whole was highly prevalent in Bagnacavallo in 2005/9 and was more common among citizens with altered liver enzymes

Significant changes in the magma dynamics of Stromboli steady-state volcano recorded by clinopyroxene crystals.

&amp;lt;p&amp;gt;Steady-state volcanic activity implies equilibrium between the rate of magma replenishment and eruption of compositionally homogeneous magmas, lasting for tens to thousands of years in an open conduit system. The Present-day activity of Stromboli volcano (Aeolian Islands, Southern Italy) has long been recognised as typical of a steady-state volcano, with a shallow magmatic reservoir (highly porphyritic or hp-magma) continuously refilled by more mafic magma (with low phenocryst content or lp-magma) at a constant rate and accompanied by mixing, crystallisation and eruption. The lp-magma is erupted only during more violent explosive events (paroxysms), which usually occur at intervals of a few years. However, the two most recent paroxysms occurred at very short timescales on 3 July and 28 August 2019 offering the unique opportunity of obtaining crucial information on the current magma dynamics of Stromboli.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Albeit the plumbing system shows such uniformity, clinopyroxene phenocrysts exhibit marked chemical heterogeneities and complex textures caused by continuous lp-hp magma mixing as well as antecryst recycling from different mush portions. The compositional zoning in clinopyroxene provides essential information on pre-eruptive magma dynamics, indicating multi-stage crystallization across the lp-hp-reservoirs, where diopsidic compositions are markers of more primitive, high-T magmas injecting into shallow, low-T domains of the plumbing system. By comparing clinopyroxene texture, chemistry and residence times from the Present-day eruptions with the previous Post-Pizzo activity, we conclude that a distinct phase in the life of Stromboli volcano commenced after the violent 2003 paroxysm. Our observations suggest there are more efficient mechanisms of mush disruption and cannibalization, in which old diopsidic antecrysts are continuously remobilized and transported by the lp-magmas permeating the mush. The disappearance of diopsidic recharge bands within augitic overgrowths indicates that over time, magmatic injections feeding the persistent Present-day activity are more intensively mixed and homogenized prior to eruption.&amp;lt;/p&amp;gt; </jats:p

External validation of surrogate indices of fatty liver in the general population: The Bagnacavallo study

We externally validated the fatty liver index (FLI), the lipid accumulation product (LAP), the hepatic steatosis index (HSI), and the Zhejiang University index (ZJU) for the diagnosis of fatty liver (FL) and non-alcoholic fatty liver disease (NAFLD) in the general population. The validation was performed on 2159 citizens of the town of Bagnacavallo (Ravenna, Italy). Calibration was evaluated by calculating the calibration slope and intercept and by inspecting calibration plots; discrimination was evaluated using the c-statistic. The average calibration slope was 1 and the average intercept was 0 for all combinations of outcomes and indices. For the diagnosis of FL, the c-statistic was 0.85 for FLI, 0.83 for ZJU, 0.82 for HSI, and 0.80 for LAP; for the diagnosis of NAFLD, the c-statistic was 0.77 for FLI, 0.76 for ZJU, 0.75 for HSI, and 0.74 for LAP. All indices were strongly correlated with each other. In conclusion, FLI, LAP, HSI, and ZJU perform similarly well to diagnose FL and NAFLD in the Bagnacavallo population, even if FLI has a small advantage as discrimination is concerned

Magma recharge and mush rejuvenation drive paroxysmal activity at Stromboli volcano

AbstractOpen-conduit basaltic volcanoes can be characterised by sudden large explosive events (paroxysms) that interrupt normal effusive and mild explosive activity. In June-August 2019, one major explosion and two paroxysms occurred at Stromboli volcano (Italy) within only 64 days. Here, via a multifaceted approach using clinopyroxene, we show arrival of mafic recharges up to a few days before the onset of these events and their effects on the eruption pattern at Stromboli, as a prime example of a persistently active, open-conduit basaltic volcano. Our data indicate a rejuvenated Stromboli plumbing system where the extant crystal mush is efficiently permeated by recharge magmas with minimum remobilisation promoting a direct linkage between the deeper and the shallow reservoirs that sustains the currently observed larger variability of eruptive behaviour. Our approach provides vital insights into magma dynamics and their effects on monitoring signals demonstrating the power of petrological studies in interpreting patterns of surficial activity.</jats:p