The importance of “first-blood circulation stage”, a new insight into the pathogenesis of clinical manifestations of preeclampsia

The tested hypothesis points out that exposure to environmental toxic substances originating from coal or other fossil fuels burning is the most decisive for the impacts of the metabolic synergy of nitrogen oxides as oxidants that cause hemoglobin oxidation to methemoglobin, and sulphur dioxide metabolites as inhibitors of antioxidants, in the bloodstream throughout the period of pregnancy. The main difference between the present three-stage hypothesis and other hypotheses is the assertion that, in the pathogenesis of early and late complicated pregnancy, methemoglobin takes on an important role. Methemoglobin by itself and from heme, redox-active ferric iron as a product of methemoglobin catabolism, has prooxidant properties and causes important structural and functional changes in the vascular endothelium, such as growth arrest, senescence, morphological alterations and cell apoptosis. Our own prospective study of methemoglobin in pregnancy revealed a significant rise and correlation between the ground level of SO2 and the level of methemoglobin: >1.5 g/L (r = 0.72, p 2, NOx, NO, NO2 and others) and that is an early biomarker of the identification of women with a pregnancy risk, and having an significant role upon adverse effects on mother and fetus health.

Liver regeneration as treatment target for severe alcoholic hepatitis

Severe alcoholic hepatitis(AH)is a distinct entity in the spectrum of alcoholrelated liver disease,with limited treatment options and high mortality.Supportive medical care with corticosteroids in selected patients is the only currently available treatment option,often with poor outcomes.Based on the insights into the pathogenetic mechanisms of AH,which are mostly obtained from animal studies,several new treatment options are being explored.Studies have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic target.Acknowledging evidence for the beneficial effects of granulocyte colony-stimulating factor(G-CSF)on liver regeneration and immunomodulation in animal models,several human studies investigated its role in the treatment of advanced alcohol-related liver disease and AH.Contrary to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH,these effects were not confirmed by a recently published multicenter randomized trial,suggesting that other options should rather be pursued.Stem cell transplantation represents another option for improving liver regeneration,but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing,with established lack of efficacy in patients with compensated cirrhosis.In this review,we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver regeneration.The lack of high-quality studies and evidence is a major obstacle in further treatment development.New insights into the pathogenesis of not only liver injury,but also liver regeneration processes are mandatory for the development of new treatment options.A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing,and data obtained from animal studies are essential for future research.

Methemoglobinemia—A biomarker and a link to ferric iron accumulation in Alzheimer’s disease

Understanding the mechanism of oxidative stress is likely to yield new insights regarding the pathogenesis of Alzheimer’s disease (AD). Our earlier work focused on the difference between hemoglobin and methemoglobin degradation, respectively leading to ferrous (Fe2+) iron, or ferric (Fe3+) iron. Methemoglobin has the role of carrier, the donor of cytotoxic and redox-active ferric (Fe3+) iron, which can directly accumulate and increase the rate of capillary endothelial cell apoptosis, and may cross into the brain parenchyma, to the astrocytes, glia, neurons, and other neuronal cells (neurovascular unit). This supposition helps us to understand the transport and neuronal accumulation process of ferric iron, and determine how iron is transported and accumulated intracellularly, identifiable as “Brain rust”. Earlier research found that the incidences of neonatal jaundice (p = 0.034), heart murmur (p = 0.011) and disorders such as dyslalia and learning/memory impairments (p = 0.002) were significantly higher in those children born from mothers with methemoglobinemia. Our hypothesis suggests that prenatal iron abnormalities could lead to greater neuronal death, the disease ageing process, and neurodegenerative disorders such as AD and other neurodegenerative diseases.

Hypothyroidism and Nonalcoholic Fatty Liver Disease:Pathophysiological Associations andTherapeutic Implications

Nonalcoholic fatty liver disease(NAFLD)is a complex clinical entity which can be secondary to many other diseases including hypothyroidism,characterized by lowering of thyroid hormones and increased thyroid stimulating hormone(TSH).A lot of emerging data published recently advocates the hypothesis that hypothyroid induced NAFLD could be a separate clinical entity,even suggesting possible treatment options for NAFLD involving substitution therapy for hypothyroidism along with lifestyle modifications.In addition,a whole new field of research is focused on thyromimetics in NAFLD/NASH treatment,currently in phase 3 clinical trials.In this critical review we summarized epidemiological and pathophysiological evidence linking these two clinical entities and described specific treatment options with the accent on promising new agents in NAFLD treatment,specifically thyroid hormone receptor(THR)agonist and its metabolites.