There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

https://www.journal-of-hepatology.eu/article/S0168-8278(15)00259-7/pdf

EASL-ALEH Clinical Practice Guidelines: Non-invasive tests for evaluation of liver disease severity and prognosis.

The etiology of alcoholism in women is no longer a question of nature or nurture. Most observers would agree that alcoholism, both male and female, is mediated by genetic factors. The question is how much of the variance is explained by genetic factors and to what degree is this genetically mediated disorder moderated by personal characteristics of the woman. Among the most salient personal characteristics moderating the genetic vulnerability may be factors such as age, ethnicity, and presence of psychiatric comorbidity. Cultural factors and familial environmental factors are most likely predictors as well. Therefore, the chapter will discuss the genetic epidemiology of alcoholism in women. Genetic heterogeneity will be discussed and evidence presented that suggests the existence of two forms of alcoholism in women: one more environmentally determined and one more influenced by genetic mediation. Evidence for the existence of a genetic diathesis in women will be presented, noting extant literature involving twin and adoption designs. Suggestions for what might be transmitted from generation to generation (e.g., neurobiological factors, temperament) with special reference to preadolescent and adolescent girls will also be discussed.

Recent Developments in Alcoholism

Sex and gender-related differences in alcohol use and its consequences: Contemporary knowledge and future research considerations.

Background
We present a computational pathway analysis of the human genome that assigns enzymes encoded therein to predicted metabolic pathways. Pathway assignments place genes in their larger biological context, and are a necessary first step toward quantitative modeling of metabolism.

/pdf/computational-prediction-of-human-metabolic-pathways-from-1vtjddue2d.pdf

Computational prediction of human metabolic pathways from the complete human genome

The effect of severity of liver cirrhosis, an alcoholic and non-alcoholic genesis, on the results of serum lipids and lipoproteins was evaluated. Serum cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-Ch), and low-density lipoprotein cholesterol (LDL-Ch) were measured in the sera of 59 patients suffering from alcoholic cirrhosis and 34 patients with non-alcoholic cirrhosis. The level of serum triglycerides depends on the severity of liver damage in alcoholic liver cirrhosis, being the highest in Child-Pugh score B. The severity of liver damage significantly affects the HDL-Ch and LDL-Ch levels in cirrhosis of non-alcoholic origin, reaching the highest value for LDL-Ch and the lowest for HDL-Ch in score C. It should not be generalized that the levels of lipids and lipoproteins in liver cirrhosis progressively diminished with the deterioration of liver function. The serum HDL-Ch and LDL-Ch may be considered as markers of severity of liver damage in non-alcoholic cirrhosis, but the triglycerides only in disease of alcoholic origin.

/pdf/the-effect-of-the-severity-of-liver-cirrhosis-on-the-level-3ajmcpw47h.pdf

The effect of the severity of liver cirrhosis on the level of lipids and lipoproteins

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are most abundant in the liver, are the main enzymes involved in ethanol metabolism in humans. Gender-related differences in total liver ADH and ALDH activity among different animal species have been observed in many studies. We measured total ADH and ALDH activity, and the activity of class I-IV ADH in the livers of male and female patients. Total ADH and class I and II ADH activities were significantly higher in males than in females (P=0.0052, P=0.0074, P=0.020, respectively). Class III and IV ADH and total ALDH activities were not significantly different between the genders (P=0.2917, P=0.0590, P=0.2940, respectively). The results of our study clearly show that there is a difference in enzymatic activity between male and female patients for those isoenzymes that actively participate in ethanol oxidation in the liver (class I and II ADH), although the main form of ADH in this organ is class III ADH.

Gender‐related differences in hepatic activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in humans

Glycosylation is the most common chemical process of protein modification and occurs in every living cell. Disturbances of this process may be either congenital or acquired. Congenital disorders of glycosylation (CDG) are a rapidly growing disease family, with about 50 disorders reported since its first clinical description in 1980. Most of the human diseases have been discovered recently. CDG result from defects in the synthesis of the N- and O-glycans moiety of glycoproteins, and in the attachment to the polypeptide chain of proteins. These defects have been found in the activation, presentation, and transport of sugar precursors, in the enzymes responsible for glycosylation, and in proteins that control the traffic of component. There are two main types of protein glycosylation: N-glycosylation and O-glycosylation. Most diseases are due to defects in the N-glycosylation pathway. For the sake of convenience, CDG were divided into 2 types, type I and II. CDG can affect nearly all organs and systems. The considerable variability of clinical features makes it difficult to recognize patients with CDG. Diagnosis can be made on the basis of abnormal glycosylation display. In this paper, an overview of CDG with a new nomenclature limited to the group of protein N-glycosylation disorders, clinical phenotype and diagnostic approach, have been presented. The location, reasons for defects, and the number of cases have been also described. This publication aims to draw attention to the possibility of occurrence of CDG in each multisystem disorder with an unknown origin.

/pdf/congenital-disorders-of-glycosylation-part-ii-defects-of-3gbenk8wuv.pdf

Congenital disorders of glycosylation. Part II. Defects of protein O-glycosylation

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

Lech Chrostek

Papers

The effect of the severity of liver cirrhosis on the level of lipids and lipoproteins

Gender‐related differences in hepatic activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in humans

Congenital disorders of glycosylation. Part II. Defects of protein O-glycosylation

Liver fibrosis markers in alcoholic liver disease.

Relationship between serum acute-phase proteins and high disease activity in patients with rheumatoid arthritis