Markers for the involvement of endothelial cells and the coagulation system in chronic urticaria: A systematic review

Chronic urticaria (CU) is a chronic inflammatory mast cell-driven disorder. Endothelial cells (ECs) contribute importantly to key features of CU. Several markers of EC (dys)function in CU have been reported, but have not yet been systematically reviewed. In this study, we systematically reviewed and categorized all published markers of EC functions in CU through a comprehensive search in Pubmed, The Cochrane Library, Web of Science, and SCOPUS using the following Mesh terms: CU AND pathogenesis AND (vasculopathy OR microangiopathy OR ECs OR marker). In total, 79 articles were selected and the identified biomarkers were categorized according to EC (dys)function in CU. The most frequent and consistently reported upregulated biomarkers in CU skin were adhesion molecules, TF, and P-selectin. The most frequently reported upregulated and reliable biomarkers in sera of CU patients were F1+2 for coagulation cascade involvement, D-dimers for fibrinolysis, and MMP-9 for vascular permeability. Emerging biomarkers described in the selected articles were endostatin, heat shock proteins, cleaved high molecular weight kininogen, and adipokines. This systematic review contributes to the pool of growing evidence for vascular involvement in CU where EC dysfunction is present in different aspects of cell survival, maintenance of vascular structure, and coagulation/fibrinolysis balance.     

[6]-Gingerol inhibits de novo fatty acid synthesis and carnitine palmitoyltransferase-1 activity which triggers apoptosis in HepG2

The de novo fatty acid synthesis catalyzed by key lipogenic enzymes, including fatty acid synthase (FASN) has emerged as one of the novel targets of anti-cancer approaches. The present study explored the possible inhibitory efficacy of [6]-gingerol on de novo fatty acid synthesis associated with mitochondrial-dependent apoptotic induction in HepG2 cells. We observed a dissipation of mitochondrial membrane potential accompanied by a reduction of fatty acid levels. [6]-gingerol administration manifested inhibition of FASN expression, indicating FASN is a major target of [6]-gingerol inducing apoptosis in HepG2 cells. Indeed, we found that increased ROS generation could likely be a mediator of the anti-cancer effect of [6]-gingerol. A reduction of fatty acid levels and induction of apoptosis were restored by inhibition of acetyl-CoA carboxylase (ACC) activity, suggesting an accumulation of malonyl-CoA level could be the major cause of apoptotic induction of [6]-gingerol in HepG2 cells. The present study also showed that depletion of fatty acid following [6]-gingerol treatment caused an inhibitory effect on carnitine palmitoyltransferase-1 activity (CPT-1), whereas C75 augmented CPT-1 activity, indicating that [6]-gingerol exhibits the therapeutic benefit on suppression of fatty acid β-oxidation.     

Experimental models of acute and chronic liver failure in nude mice to study hepatocyte transplantation

Although hepatocyte transplantation is a promising therapy for acute liver failure in human, there is still a lack of animal models suffering from hepatic injury in which the benefits of hepatocyte transplantation could be evaluated solely, without the bias caused by immunosuppression. As a consequence, the aim of the study was first to develop reproducible models of partial hepatectomy and of thioacetamide (TA)- or Jo2-induced acute liver failure in nude mice. Chronic liver disease was also investigated by repeated injections of sublethal doses of thioacetamide. Survival rates, routine histologic observations, alanin aminotransferase sera content, Ki67, and caspase 3 immunodetection were investigated both after 40% partial hepatectomy and after toxic-induced damages. Liver injuries were more severe and/or precocious in nude mice than in Balb/c mice for a given treatment with a maximum of acute injury obtained 24 h after single toxic injection, and were found to be transitory and reversible within 10 days. Toxics induced apoptosis followed by necrosis, confirming recent published data. Onset of fibrosis leading to reproducible chronic cirrhosis in nude mice correlated with increasing number of Ki67-positive cells, indicating that high levels of cell proliferation occurred. Chronic cirrhosis progressively reversed to fibrosis when the treatment ceased. Preliminary results demonstrated that engrafted xenogeneic hepatocytes could be detected in the host liver by anti-MHC class I immunohistochemistry. Fractions enriched in 2n or 4n hepatocytes by cell sorting using a flow cytometer were equivalent to the unpurified fraction in terms of engraftment in control nude mice or in nude mice subjected to PH. However, in mice suffering from liver injury 24 h after Jo2 or TA treatment, the engraftment of 2n hepatocytes was about twice that of an unpurified hepatocyte population or of a population enriched in 4n hepatocytes.     

Perspectives of Microstructure Refinement of Aluminum and Its Alloys by the Reciprocating Extrusion (Cyclic Extrusion Compression—CEC)

This paper presents a study on the perspectives of structure refinement of aluminum and its alloys by reciprocating extrusion (cyclic extrusion compression—CEC). The study included Al99.5 and Al99.992 aluminum and AlMg5 and AlCu4Zr alloy. Aluminum and alloys were deformed by reciprocating extrusion (CEC) in the strain range ϕ = 0.42 (1 CEC cycle) to ϕ = 59.8 (67 CEC cycles). After deformation, the structure of the specimens was investigated by optical microscopy (OM) and transmission electron microscopy (TEM), which revealed that the primary mechanism of hardening, over the range of applied strains, was the result of the propagation of shear bands throughout the specimens. The intersection of shear bands was found to divide the volume of the specimens into nano and microvolumes with dimensions limited by the width of the microbands. Due to structure renewal processes such as polygonization and dynamic geometric recrystallization, the formed micro and nano volumes were transformed into nano and micrograins with large misorientation angles. In terms of the occurrence of grain microstructure, a sustained uniform level of hardening was found, which was defined as steady-state flow. The research has shown that the steady state of flow is a result of the competitive interaction between the processes of hardening and structure renewal. The higher the metal purity, the higher the intensity of the structure renewal processes was. The formation of new grains and their growth under dynamic and post-dynamic recrystallization was observed in Al99.992 aluminum, in which high purity of the metal and high strain accumulation caused the growth of new grains at room temperature.     

Comparison of the effects of propylthiouracil, amiodarone, diphenylhydantoin, phenobarbital, and 3-methylcholanthrene on hepatic and renal T4 metabolism and thyroid gland function in rats

We studied the effects of propylthiouracil (PTU), amiodarone (AMIO), diphenylhydantoin (DPH), phenobarbital (PB), and 3-methylcholanthrene (MC) on thyroid histomorphology, on the hepatic and renal enzymes involved in endogenous and exogenous metabolism, and on the plasma levels and pharmacokinetics of thyroid hormones after 7 and 14 days of treatment. PTU and PB, by decreasing both serum tetraiodothyronine (T4) and triiodothyronine (T3), induced a massive increase in serum thyrotropin (TSH) and thus induced thyroid hypertrophy. AMIO and MC, by decreasing respectively serum T3 and T4, also induced an increase of TSH, but to a lesser extent, not sufficient to induce thyroid hypertrophy. Hepatic 5'-deiodinase activity was decreased in all treated rats. Inhibition of this enzyme by PTU was demonstrated in vitro; AMIO also decreased the enzyme activity by a still unelucidated mechanism, which probably requires intact cell plasma membranes, whereas in PB- and MC-treated rats the decrease in enzyme activity certainly resulted from decreased serum concentrations of T4. In PTU-treated rats, and probably in MC-treated rats, decreases in circulating thyroid hormones were primarily due to impairment of synthesis and/or of secretion by the thyroid. In contrast, in PB-treated rats, the decrease in serum thyroid hormone levels seems to be due to increased excretion of these hormones, as T4 serum clearance was significantly increased. PB, a microsomal enzyme inducer, increased the cytochrome b5 and P450 content as well as the cytochrome P450-dependent O-depentylation of pentoxyresorufin. The other type of enzyme inducer, MC, did not affect cytochrome b5 and P450 levels, but did increase the cytochrome P450 dependent O-deethylation of ethoxyresorufin. PB increased the glucuronidation of morphine, whereas MC increased the glucuronidation of 1-naphthol. However, serum T4 clearance, mainly determined by its hepatic conjugation rate, was increased only in PB-treated rats. It appears from this study that the close metabolic relationship between the liver/kidney and the thyroid should be taken into consideration when the findings of chronic toxicology and carcinogenicity studies are interpreted.     

Cloned measles virus-specific T lymphocytes from a twin with multiple sclerosis.

A measles virus-specific T lymphocyte clone derived from a measles-responder twin with multiple sclerosis has been produced. The cloned cells proliferate in response to measles virus but not mumps, vaccinia, or canine distemper viruses. The clone recognizes an antigen that is distributed in both the membrane and cytoplasmic fractions of cells infected with measles virus. Antigen is presented to the clone equally well by irradiated mononuclear cells obtained from the autologous subject and from her healthy, measles-nonresponder, HLA-identical twin. Studies with a panel of HLA-typed irradiated mononuclear cells indicate that antigen is presented to the clone in the context of a gene product linked to, but not identical with, HLA-DRw2. The clone produces interleukin 2 and has surface determinants recognized by OKT-3, OKT-4, and anti-HLA-DR monoclonal antibodies, but not by OKT-8. It thus appears to belong to the helper/inducer subpopulation of T lymphocytes.     

The action of valepotriates on the synthesis of DNA and proteins of cultured hepatoma cells.

Valtrate, didrovaltrate and deoxido-didrovaltrate were compared for toxicity on cultured rat hepatoma cells (HTC strain) and for their effects on the synthesis of DNA and proteins. Despite lacking the epoxide function in C (8)-C (11) position in its molecular structure, deoxido-didrovaltrate has a similar cytotoxicity to didrovaltrate. The toxicity of both these drugs is two times lower than that of valtrate. Incorporation tests with (3)H-thymidine and (3)H-leucine on cultured HTC cells revealed that a low dose of valtrate, rapidly and extensively inhibits the synthesis of both DNA and proteins. Didrovaltrate and deoxido-didrovaltrate have the same effect, but at double the dose.     

Stationäre Behandlungskosten von Hautkrankheiten

BACKGROUND AND OBJECTIVE: With the advent of the DRG system, German hospitals are being forced to improve cost transparency and to uncover inefficient structures. METHODS: Diagnosis-based costs were calculated in the Department of Dermatology in the University Hospital of Freiburg for ten samples, each containing 20 cases. By using in-patient files, cost and productivity information for the fiscal year 2000 was attributed to each single case in a bottom-up-approach. The resulting total costs per case were contrasted to their remuneration under the DRG system. RESULTS: Average case costs were determined between EUR 1,339.83 and EUR 5,714.73. With 19.3% to 28.4% of total costs, nursing costs were the biggest single cost factor. Prolonging the length of stay incurred average extra costs of EUR 144.26 to EUR 199.98 per case and day. The correlation of case costs and their corresponding DRG cost weights was modest with r=0,48. There was considerable cost variance within individual DRGs. CONCLUSIONS: The diagnosis-related cost calculation reveals striking cost differences relating to specific diagnoses. This method is more suitable for cost calculations in the hospital than more general approaches.