Patients with ultrasound diagnosis of hepatic steatosis are at high metabolic risk.

Background and aims: Hepatic steatosis is the basis of non-alcoholic fatty liver disease (NALFD). Mere fat accumulation within hepatocytes is considered the mild form of NAFLD, but can progress in some patients to advanced steatohepatitis (NASH), which may lead to fibrosis, cirrhosis or hepatocellular carcinoma. However, even hepatic steatosis alone may be a risk factor for cardiovascular disease (CVD). Patients and methods: In the present real life study 106 patients from the outpatient clinic of the Department for Gastroenterology and Hepatology with either NAFLD (n = 60) or other typical diagnoses (n = 46) were included. Ultrasound examination identified 77 patients with hepatic steatosis. Liver enzymes, lipid profile, surrogate cell death markers, and adiponectin were determined. Transient elastography (Fibroscan®) and bioelectrical impedance analysis (BIA) were performed. Results: Mean patient age was 46 years (23 - 62) for non-NAFLD and 53 years (18 - 71) for the NAFLD group. ALT and AST did not differ significantly between the two groups. Adiponectin and HDL were significantly lower in NAFLD (p < 0.05) and BIA profiles showed higher fat and fat free mass. Non-NAFLD patients with steatosis also exhibited an adverse metabolic profile. Overall steatosis was associated with factors of metabolic syndrome (MS) and CVD. Prevalence of CVD and factors of MS hint to steatosis as an early event for these conditions. Conclusion: Patients with steatosis are at higher cardiovascular and metabolic risk without differences in transaminases levels compared to those without steatosis. Steatosis diagnosed by ultrasound needs to rise attention for further metabolic alterations including CVD.

Reporting standard for describing first responder systems, smartphone alerting systems, and AED networks.

Standardized reporting of data is crucial for out-of-hospital cardiac arrest (OHCA) research. While the implementation of first responder systems dispatching volunteers to OHCA is encouraged, there is currently no uniform reporting standard for describing these systems. A steering committee established a literature search to identify experts in smartphone alerting systems. These international experts were invited to a conference held in Hinterzarten, Germany, with 40 researchers from 13 countries in attendance. Prior to the conference, participants submitted proposals for parameters to be included in the reporting standard. The conference comprised five workshops covering different aspects of smartphone alerting systems. Proposed parameters were discussed, clarified, and consensus was achieved using the Nominal Group Technique. Participants voted in a modified Delphi approach on including each category as a core or supplementary element in the reporting standard. Results were presented, and a writing group developed definitions for all categories and items, which were sent to participants for revision and final voting using LimeSurvey web-based software. The resulting reporting standard consists of 68 core items and 21 supplementary items grouped into five topics (first responder system, first responder network, technology/algorithm/strategies, reporting data, and automated external defibrillators (AED)). This proposed reporting standard generated by an expert opinion group fills the gap in describing first responder systems. Its adoption in future research will facilitate comparison of systems and research outcomes, enhancing the transfer of scientific findings to clinical practice.

Hepatocyte apoptotic bodies encasing nonstructural HCV proteins amplify hepatic stellate cell activation: implications for chronic hepatitis C.

Chronic hepatitis C infection leads to increased hepatocyte apoptosis. Because engulfment of apoptotic bodies (ABs) by hepatic stellate cells (HSC) is profibrogenic, we compared the effects of ABs derived from hepatitis C virus (HCV)-negative vs HCV-infected (Con1+) Huh7 hepatoblastoma cells on fibrogenic and activation-related mRNA expression by a human HSC line (LX2). Uptake of Huh7(Con1+) ABs by LX2 cells dose dependently upregulated profibrotic genes (COL1A1, TGFB1; TIMP1; TIMP2). When normalized to the apoptotic cytokeratin-18 M30 neoepitope, HCV(+) ABs exhibited a more pronounced effect than HCV(-) ABs. In contrast, neither noningested ABs nor nucleic acids obtained from Huh7, Huh7(Con1+) or HepG2 cells triggered those AB-dependent effects. Both the engulfment of Huh7(Con1+) ABs and their effects were partially blocked by masking of phosphatidylserine with annexin V and completely inhibited by the class-A scavenger receptor ligand, polyinosinic acid. Our findings demonstrate that AB uptake stimulates HSCs and indicate that HCV infection leads to amplified fibrogenic mRNA expression and enhanced HSC activation.

Glutathione-S-transferase subtypes α and π as a tool to predict and monitor graft failure or regeneration in a pilot study of living donor liver transplantation.

OBJECTIVE: Glutathione-S-transferase (GST) subtype α and π are differentially expressed in adult liver tissue. Objective of the study was if GST α and π may serve as predictive markers for liver surgery, especially transplantations. METHODS: 13 patients receiving living donor liver transplantation (LDLT) and their corresponding donors were analyzed for standard serum parameters (ALT, AST, γGT, bilirubin) as well as GST-α and -π before LDLT and daily for 10 days after LDLT. Patients (R) and donors (D) were grouped according to graft loss (R1/D1) or positive outcome (R2/D2) and above named serum parameters were compared between the groups. RESULTS: R1 showed significantly increased GST-α and significantly lower GST-π levels than R2 patients or the donors. There was a positive correlation between GST-α and ALT, AST as well as bilirubin and a negative correlation to γGT. However, γGT correlated positively with GST-π. Graft failure was associated with combined low GST-π levels in donors and their recipients before living donor liver transplantation. CONCLUSION: Our data suggest that high GST-α serum levels reflect ongoing liver damage while GST-π indicates the capacity and process of liver regeneration. Additionally, GST-π may be useful as marker for optimizing donor and recipient pairs in living donor liver transplantation.

Physiology and Morphological Correlates of Excitatory Transmission are Preserved in Glutamine Transporter SN1-Depleted Mouse Frontal Cortex.

Glutamine is an astroglia-derived precursor of the neurotransmitter glutamate, and its astroglia-to-neuron transfer is controlled by distinct glutamine transporters on the astrocytic and neuronal sites. In this study, we focused on the role of astrocytic glutamine efflux-mediating system N transporter SN1 in the maintenance of glutamatergic neurotransmission by analyzing the electrophysiological parameters ex vivo in the brain slices from control mice and mice in which vivo-morpholino technique was used to diminish SN1 protein. The glutamatergic transmission was characterized by electrophysiological recordings, ultrastructure of neuron terminals, and determination of proteins related to glutamate synaptic transmission: synaptophysin, synaptotagmin, and vit1A. The space-restricted ∼51,5% reduction of SN1 protein did not affect the expression of the neuronal glutamine transporter SAT2. SN1 depletion resulted in a reduction of field potentials (FPs), unaltered frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs/mEPSCs), and presented a tendency towards a decrease of long-term potentiation (LTP). Ultrastructurally, preserved number of synaptic vesicles, primarily localized centrally of the cell body, correlates with unchanged levels of synaptic proteins. Collectively, the study indicates that glutamatergic transmission proceeds relatively independently of the SN1 - mediated glutamine transfer to the synapse.

Impaired effect of activation of rat hippocampal 5-HT7 receptors, induced by treatment with the 5-HT7 receptor antagonist SB 269970.

Effects of the 5-HT(7) receptor antagonist SB 269970, administered for 14 days (1.25 mg/kg), were studied in ex vivo slices of rat hippocampus. To activate the 5-HT(7) receptor, 5-carboxamidotryptamine (5-CT, 200 nM) was applied in the presence of WAY 100635 (2 µM), a 5-HT(1A) receptor antagonist. In contrast to control preparations, no 5-HT(7) receptor-mediated increase in excitability nor depolarization and an increase in the input resistance of CA1 and CA3 pyramidal neurons were present in slices prepared from rats treated with SB 269970. The treatment also abolished the stimulatory effect of 5-HT(7) receptor activation on spontaneous excitatory postsynaptic currents recorded from CA1 stratum radiatum/lacunosum-moleculare interneurons. These data demonstrate that repeated administration of SB 269970 impairs the reactivity of the CA1 hippocampal neuronal network to 5-HT(7) receptor activation.

The diagnosis and treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of metabolic syndrome and frequently accompanied with obesity, insulin resistance, hyperlipidemia and hypertension. NAFLD comprises a variety of clinical conditions ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH), with significant hepatic injury and possible progression to cirrhosis and hepatocellular carcinoma. The traditional "second hit" and the recent "multiple parallel hit" theories are the most popular explanations for the pathogenesis of NASH. NAFLD is usually diagnosed by ultrasonographic examination of the liver. For specific diagnosis of the extent and severity of NAFLD, in particular to determine NASH, the gold standard is still liver biopsy. Though, there are some promising non-invasive markers emerging for NAFLD diagnosis and assessment. Currently there is no specific therapy for NAFLD or NASH itself. Thus management of NAFLD mainly relies on initiating weight loss and on treatment of accompanying factors e.g. insulin resistance, hypertension or hyperlipidemia. In the present overview we aimed to summarize options for diagnosis and treatment of NAFLD and NASH based on the current literature.

Serum trypsin inhibitory activity and alpha-1-antitrypsin level in liver diseases.

Alpha-1-antitrypsin level and serum trypsin inhibitory activity were measured in patients with viral hepatitis, chronic hepatitis and liver cirrhosis. The most pronounced discrepancy between these two parameters were observed in patients with liver cirrhosis: the increase of alpha-1-At level was not accompanied by adequate increase of trypsin inhibitory activity. Some mechanisms potentially responsible for this discrepancy are discussed.

Conceptual analysis for knowledge-base design.

Knowledge-base design requires a thorough analysis of the concepts to be represented. If the analysis is incomplete or inaccurate, the resulting knowledge base may contain arbitrary restrictions, inconsistent data, or limitations that make future extensions impossible. Conceptual analysis is even more critical for sharing knowledge bases between heterogeneous systems. Analyses that are adequate for independent systems may cause incompatibilities when the systems share data. This paper discusses the kinds of problems that require a careful conceptual analysis and the difficulties caused by an incorrect or incomplete analysis. It also shows how independently developed knowledge bases can be related to one another by reanalyzing and redefining the basic concepts and relations. Such analysis is essential for sharing knowledge between systems developed for different purposes, such as relational and object-oriented databases or expert systems and natural language processors.

The first year as a neophyte RSO at a liberal arts college.

Union College is a small liberal arts college in the northeast with a good reputation in science. It is also one of the oldest schools in the nation, having been founded in 1795. Langmuir and Steinmetz taught here as did Chandler, the founder of the American Chemical Society and Ellery, one of the longest tenured Secretaries of Sigma Xi. Arthur and Carter became U.S. Presidents. We claim a Nobel Prize winner, the inventor of transistors, the person who developed the methods for producing quartz crystals and fiber optics. The presidents of du Pont and Kodak attended Union College. We are referred to as the "Mother of Fraternities," and we had the first radio station on a college campus (although not through the airways). Still, until recently, our reputation has been less than admirable among radiation safety experts. This article highlights some of the experiences of a new RSO at this well-acknowledged institution.

[Geography of lung cancer incidence among women and men of Upper Silesia in the years 1986-1990]. / Geografia zachorowalnosci na raka pluca wsród mezczyzn i kobiet na Górnym Slasku w latach 1986-1990.

During a five period (1986-1990) in Katowice province (Upper Silesia) there were 6,140 cases of lung cancer in males and 1,039 females recorded. The standardized (according to age structure of the world population) incidence of lung cancer in both groups, in 93 administrative units (45 cities, 48 communities) significantly vary and are geographically unevenly distributed. The incidence in selected areas in males can be compared with values characterizing regions of the world with highest indices (> 95 per 100,000); whereas in females the incidence of lung cancer is much lower. The prognosis for lung cancer incidence in the Upper Silesia, according to the regression analysis is pessimistic.

[The incidence of laryngeal cancer among males in the upper Silesia]. / Zachorowalnosc na raka krtani na Górnym Slasku.

In the years 1986-1990 within Upper Silesia Region (Katowice Voivodeship) 1240 larynx cancer cases were diagnosed. Larynx cancer standardized incidence rates there are: 12,5 cases per 100 thousand on the whole area, maximal--28.6 and minimal--2.2 per 100 thousand, taking into consideration 93 administrative units (45 towns and 48 community councils). Larynx cancer incidence rates were dynamically increasing every year by 3%. There has not been attained geographic correlation between highest larynx cancer incidence level and highest ambient air pollution.