The role of lactate besides the lactic acidosis

Lactic acidosis (LA) is the most common form of metabolic acidosis defined by values of lactate greater than 5 mmol / l and by a pH <7.34. The pathogenesis of LA involves hypoxic (type A) and non hypoxic (type B) causes which are often coexisting. Lactic acidosis is usual in hospitalized population especially in subjects in intensive care units, in which lactate levels on admission could be predictors of mortality even in the absence of organ dysfunction or shock. The outcome is mainly dependent on the cardiovascular effects of acidosis. In subjects with cardiogenic shock, the increased lactate/pyruvate ratio, detectable at onset, is correladed with mortality. An early assessment of blood and tissue lactate levels could play a role in the therapeutic management as well as in outcome. LA could be a unfavorable prognostic factor in cancer. The lactate would act also as "signal molecule" and as a promoting factor in angiogenesis and tumor progression. In the presence of risk factors for LA the role of metformin may be overrated. Despite the doctrinal progress to understand the pathogenesis and pathophysiology, there is not univocal consensus on the therapeutic treatment of LA. The identification and the attempt to remove the cause of acidosis are main aims; treatment with sodium bicarbonate is a matter of debate as the data on the cardiovascular effects and mortality are unclear. The therapy with carbicarb, dichloroacetate or THAM has shown no specific advantages in terms of mortality. In experimental models of LA and shock the use of sodium-hydrogen exchanger-1 (NHE1) selective inhibitors reduces cell damage and inflammatory cytokines synthesis; it also improves cardiac performance and decreases mortality

Giant phonon anomalies in the pseudo-gap phase of TiOCl

We report infrared and Raman spectroscopy results of the spin-1/2 quantum magnet TiOCl. Giant anomalies are found in the temperature dependence of the phonon spectrum, which hint to unusual coupling of the electronic degrees of freedom to the lattice. These anomalies develop over a broad temperature interval, suggesting the presence of an extended fluctuation regime. This defines a pseudo-gap phase, characterized by a local spin-gap. Below 100 K a dimensionality cross-over leads to a dimerized ground state with a global spin-gap of about 2$\Delta_{spin}\approx$~430 K.Comment: 4 pages, 3 figures, for further information see http://www.peter-lemmens.d

Pro-inflammatory genetic markers of atherosclerosis

Atherosclerosis (AS) is a chronic, progressive, multifactorial disease mostly affecting large and medium-sized elastic and muscular arteries. It has formerly been considered a bland lipid storage disease. Currently, multiple independent pathways of evidence suggest this pathological condition is a peculiar form of inflammation, triggered by cholesterol-rich lipoproteins and influenced both by environmental and genetic factors. The Human Genome Project opened up the opportunity to dissect complex human traits and to understand basic pathways of multifactorial diseases such as AS. Population-based association studies have emerged as powerful tools for examining genes with a role in common multifactorial diseases that have a strong environmental component. These association studies often estimate the risk of developing a certain disease in carriers and non-carriers of a particular genetic polymorphism. Dissecting out the influence of pro-inflammatory genes within the complex pathophysiology of AS and its complications will help to provide a more complete risk assessment and complement known classical cardiovascular risk factors. The detection of a risk profile will potentially allow both the early identification of individuals susceptible to disease and the possible discovery of potential targets for drug or lifestyle modification; i.e. it will open the door to personalized medicine

The antibody-drug conjugate loncastuximab tesirine for the treatment of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous subtype of non-Hodgkin lymphoma. Relapsed/refractory disease represents remains an unmet medical need, despite the introduction of novel cellular and targeted therapies. Loncastuximab tesirine is a cluster of differentiation19-targeting antibody-drug conjugate approved by the US Food and Drug Administration for relapsed DLBCL after 2 lines of systemic therapy based on a trial showing a 48.3% overall response rate. The spectrum of its clinical applications is expanding and is now being tested in other B-cell malignancies

Evaluation of carcass and meat traits of Muscovy duck fed with black soldier fly partially defatted meal

The aim of this study was to evaluate the carcass characteristics and breast meat quality in Muscovy duck (Cairina moschata domestica) fed different inclusion levels of a partially defatted black soldier fly larva (BSF) meal. A total of 256 Muscovy ducklings (average live weight, LW: 71.32\ub12.70 g) were reared from day 3 to day 48 and randomly allotted in 32 pens (8 replicates/treatment). Four different diets were formulated with increasing substitution level of corn gluten meal with BSF larva meal (0, 3, 6 and 9%; BSF0, BSF3, BSF6 and BSF9, respectively) and divided in 3 feeding phases: starter (1-14 days), grower (14-35 days) and finisher (35-48 days). At day 48, 2 animals/replicate were slaughtered and dissected to determine their carcass yields. The weights of spleen, bursa of Fabricius, liver, heart and abdominal fat were recorded. Breast and thigh muscles were then excised from 16 ducks/treatment and weighted. Ultimate pH (pHu) and L*, a*, b* colour values were then measured on breast muscle. The collected data were tested by means of oneway ANOVA evaluating the effect of dietary BSF inclusion level by polynomial contrasts. Significance was declared at P<0.05. The inclusion of BSF did not affect final LW (2,515.68\ub192.42 g on average). Hot and cold carcass weights showed a quadratic response (P<0.05) to increasing BSF larva meal, with a minimum corresponding to BSF6; however, refrigeration losses were not affected by treatments. Weight of spleen, bursa of Fabricius, liver and heart did not differ among treatments. The weight of abdominal fat showed a quadratic response to increasing BSF meal with a minimum corresponding to BSF6 group (P<0.05). Breast and thigh yields, pHu and L*, a*, b* colour values did not differ among groups. With the exception of BSF6, the inclusion of BSF meal did not affect meat traits and carcass characteristics, confirming the potential use of BSF meal in Muscovy duck diets

Apparent digestibility of insect protein meals for rainbow trout

Insect meals are considered to be promising future ingredients for aquaculture feeds. In past feeding trials in rainbow trout, insect meals were included in diets only on the basis of their nutrients content and energy density without taking into account their biological availability due to the lack of their digestible values. Apparent digestibility (ADC) provides good indication of the bioavailability of nutrients and energy thus providing rational basis for the correct inclusion of feedstuffs. The aim of this research was to assess, in an in vivo trial on rainbow trout, the ADC of five full fat insect meals: one Tenebrio molitor (TM), two Hermetia illucens obtained through two different process (HI1 and HI2), one Musca domestica (MD), and one Alphitobius diaperinus (AD). Fish were fed a high-quality reference diet (R) and test diets obtained mixing the R diet with each of the test ingredients at a ratio of 70:30. Diets contained 1% celite as inert marker. Fish were fed to visual satiety twice a day and faecal samples collected using a continuous automatic device. Faeces were freeze dried and frozen (-20 \ub0C) until analyses. The ADC of dry matter, crude protein and ether extract of each insect meal diet were calculated. ADC for dry matter varied between 70.07 (HI1) and 80.85 (TM). ADC for protein was above 84% in all treatments and resulted the highest in MD, TM and AD treatments. Ether extract apparent digestibility significantly differed among diets with the highest value reported for TM treatment. All treatments reported values higher than 96%. Observed differences could be due to the insect species and meal treatment but in general, tested insect meals were highly digestible for rainbow trout. The results from this research could be useful to optimize the diet formulation

Lipid peroxidation and nitric oxide metabolites in a group of subjects with obstructive sleep apnea syndrome

It is known that in OSAS the plasma lipid peroxidation has an opposite behavior in comparison with nitric oxide metabolites. In the re-examination of our survey of OSAS infjects we calculated the ratio between thiobarbituric acid reactive infstances (TBARS) and nitric oxide metabolites (NOx) in relation to OSAS severity. The study has regarded 48 OSAS infjects infdivided in two infgroups according to the apnea/hypopnea index-AHI-(Low=21 infjects with AHI 30). From the obtained data it is evident that the TBARS/NOx ratio is significantly higher in the H infgroup compared to L infgroup as well as this ratio is reduced in L infgroup in comparison with the whole group of OSAS infjects. In the entire group of OSAS infjects the TBARS/NOx ratio results positively correlated with AHI and ODI and inversely correlated with mSO2

Intronic CYP46 polymorphism along with ApoE genotype in sporadic Alzheimer Disease: from risk factors to disease modulators

Increasing biological and clinical findings argue for a link between brain cholesterol turnover and Alzheimer Disease (AD), high cerebral levels of the former increasing Abeta load. Cerebral cholesterol elimination involves two mechanisms dependent on Apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46). The aim of this study was to evaluate an intronic variation in CYP46 (intron 2, T --> C ) along with ApoE genotype as risk factors for AD and to establish the correlation between CYP46/ApoE polymorphism and disease progression. One-hundred and fifty-seven AD patients, who had been followed periodically through 1-year follow-up after enrollment, and 134 age- and gender-matched controls entered the study. The distribution of CYP46 genotypes was significantly different in AD compared to controls (P<0.004), being CYP*C allele higher in AD patients ( P<0.002). ApoE 4 genotype was more frequent in AD (41.4%) than in controls (15.9%, P<0.0001). The odds ratio (OR) for AD risk in CYP46*C carriers was 2.8, and in ApoE epsilon4 carriers was 4.05; the OR for having both CYP46*C and ApoE epsilon4 was 17.75, demonstrating the their synergic effect on AD risk. In AD patients, CYP46*C along with ApoE epsilon4 genotype were associated with a higher cognitive decline at 1-year follow-up (P<0.02). These findings provide direct evidence that CYP46 and ApoE polymorphisms synergically increase the risk for AD development, and influence on the rate of cognitive decline

Gelatinases and their tissue inhibitors in a group of subjects with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) is associated with an elevated risk of cardiovascular events and stroke. Matrix metalloproteinases (MMPs) are endopeptidases involved in extracellular matrix degradation and then in the development and progression of cardiovascular diseases. Our aim was to evaluate plasma levels of gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) in a group of subjects with OSAS. We enrolled 48 subjects (36 men and 12 women; mean age 49.7 \ub1 14.68 yrs) with OSAS diagnosed with a 1-night cardiorespiratory study and then we subdivided these subjects into two subgroups according to the apnea/hypopnea index (AHI): Low (L = 21 subjects with AHI &lt;30) and High (H = 27 subjects with AHI &gt;30). We measured plasma concentration of the gelatinases and their inhibitors using ELISA kits. We observed a significant increase in plasma concentration of MMP-9, MMP-2, TIMP-1 and TIMP-2 in the entire group of OSAS subjects and in the two subgroups, with higher levels in the H in comparison with the L subgroup. In the whole group of OSAS subjects we also noted a significant decrease in MMP-9/TIMP-1 ratio in comparison with normal controls. Only MMP-9 was significantly correlated with the severity of the disease, expressed as AHI, with the oxygen desaturation index and also with the mean oxygen saturation. MMPs pattern is altered in OSAS and significantly influenced by the severity of the disease; it probably contributes to the vascular remodeling that leads to the atherosclerotic disease and cardiovascular complications

Analysis of the Blood Viscosity Behavior in the Sicilian Study on Juvenile Myocardial Infarction

Considering the role of hemorheology in coronary circulation, we studied blood viscosity in patients with juvenile myocardial infarction. We examined whole blood viscosity at high shear rate using the cone-on-plate viscosimeter Wells-Brookfield \ubd LVT and at low shear rate employing a viscometer Contraves LS30 in 120 patients (aged <46 years) with myocardial infarction, at the initial stage and subsequently 3 and 12 months after. At the initial stage, patients had an increased whole blood viscosity in comparison to normal controls. This hemorheological profile was not influenced by the cardiovascular risk factors, nor by the extent of coronary lesions, even if some differences were evident between patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI). The blood viscosity pattern at the initial stage did not influence recurring ischemic events or the onset of heart failure during an 18 months\u2019 follow-up. The neutrophil to lymphocyte ratio did not affect the blood viscosity pattern. We reevaluated 83 patients 3 months after and 70 patients 12 months after the acute coronary syndrome, and we found that the hemorheological parameters were still altered in comparison to normal controls at both times. We observed an impairment of the hemorheological pattern in young patients with myocardial infarction, partially influenced by the infarction type (STEMI and NSTEMI) and persisting in the long term