Advanced Glycation End-Products in Blood Serum-Novel Ischemic Stroke Risk Factors? Implication for Diabetic Patients.

New predictors of ischemic incidents are constantly sought since they raise the awareness of patients and their doctors of stroke occurrence. The goal was to verify whether Advanced Glycation End Products (AGEs), in particular AGE10, could be one of them. The AGE10 measurement was conducted using a non-commercial ELISA assay in the blood serum of neurological patients without cerebrovascular event (n = 24), those with transient brain attack (TIA) (n = 17), and severe ischemic stroke (n = 35).

Ceramides and sphingosine-1-phosphate as potential markers in diagnosis of ischaemic stroke.

Background: Brain imaging in stroke diagnostics is a powerful tool, but one that can fail in more challenging cases, and one that is not particularly useful in identifying transient ischaemic attacks (TIAs). Thus, new reliable blood biomarkers of cerebral ischaemia are constantly sought.

Objective: We studied the potential usefulness of sphingolipids (SFs) as biomarkers of acute ischaemic stroke and TIA.

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells.

An azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2',3'-e][1,4]thiazine (DQT), has recently been shown to exhibit immunosuppressive activities in mouse models. It also inhibited the expression of CXCL10 at the protein level, at non-toxic concentrations, in the culture of KERTr cells treated with double-stranded RNA, poly(I:C). In this report, we demonstrated that DQT inhibits the transcription of the CXCL10 gene.

Topically applied azaphenothiazines inhibit experimental psoriasis in mice.

The therapeutic efficacy of topically applied azaphenothiazine derivatives: 9-chloro-6-acetylaminobutylquinobenzo[3,2-b][1,4]thiazine (compound 4) and 6-chloroethylureidoethyldiquino[3,2-b;2';3'-e][1,4]thiazine (compound 5) in the amelioration of inflammatory symptoms of imiquimod-induced psoriasis in mice was investigated. Clobederm®, containing clobetasol propioniate, served as a reference drug. The application of the compounds led to thinning of the epidermis and reduction of the cell layers.

Long-lasting reduction in clonogenic potential of colorectal cancer cells by sequential treatments with 5-azanucleosides and topoisomerase inhibitors.

Background: The currently approved therapies fail in a substantial number of colorectal cancer (CRC) patients due to the molecular heterogeneity of CRC, hence new efficient drug combinations are urgently needed. Emerging data indicate that 5-azanucleosides are able to sensitize cancer cells to the standard chemotherapeutic agents and contribute to overcoming intrinsic or acquired chemoresistance.

Methods: CRC cells with different genetic backgrounds (HCT116, DLD-1, HT-29) were sequentially treated with 5-azanucleosides and topoisomerase inhibitors.

Regulation of sphingomyelin metabolism.

Sphingolipids (SFs) represent a large class of lipids playing diverse functions in a vast number of physiological and pathological processes. Sphingomyelin (SM) is the most abundant SF in the cell, with ubiquitous distribution within mammalian tissues, and particularly high levels in the Central Nervous System (CNS). SM is an essential element of plasma membrane (PM) and its levels are crucial for the cell function.

Propolis changes the anticancer activity of temozolomide in U87MG human glioblastoma cell line.

Background: Propolis is a honey bee product which contains many active compounds, such as CAPE or chrysin, and has many beneficial activities. Recently, its anti-tumor properties have been discussed. We have tested whether the ethanolic extract of propolis (EEP) interferes with temozolomide (TMZ) to inhibit U87MG cell line growth.

Increased concentration of metronidazole and its hydroxy metabolite in colon cancer in women.

Background: Metronidazole (MTZ) is indicated in the prevention of infections during surgical procedures. However, some data have shown that metronidazole has carcinogenic potential.

Methods: In the present work, we determined concentrations of metronidazole and its hydroxy metabolite (MTZOH) in colorectal cancer patients.

[The role of ceramides in selected brain pathologies: ischemia/hypoxia, Alzheimer disease].

 Ceramides, members of the sphingolipids, are produced in the central nervous system by de novo synthesis, sphingomyelin hydrolysis or the so-called salvage pathway. They are engaged in formation of lipid rafts that are essential in regulation and transduction of signals coming to the cell from the environment. Ceramides represent the major transmitters of the sphingomyelin pathway of signal transduction.

Ceramide profiles in the brain of rats with diabetes induced by streptozotocin.

Diabetes is associated with disturbances of brain activity and cognitive impairment. We hypothesize that ceramides may constitute an important contribution to diabetes-linked neuro-dysfunction. In our study we used rats injected with streptozotocin (STZ) as a model of severe hyperglycemia.

Trimethyltin-evoked apoptosis of murine hippocampal granule neurons is accompanied by the expression of interleukin-1beta and interleukin-1 receptor antagonist in cells of ameboid phenotype, the majority of which are NG2-positive.

Interleukin-1beta (IL-1beta) has been implicated in various neuropathologies, while IL-1 receptor antagonist (IL-1ra) has been shown to reduce neuronal injury. We investigated the pattern of expression of both cytokines in murine hippocampus after trimethyltin (TMT) intoxication. Using a ribonuclease protection assay, we demonstrated induction of transcription of IL-1beta and IL-1ra 3 days following TMT treatment which correlated with the peak of neuronal apoptosis.

The ameboid phenotype of NG2 (+) cells in the region of apoptotic dentate granule neurons in trimethyltin intoxicated mice shares antigen properties with microglia/macrophages.

NG2+, stellate cells present in the adult central nervous system (CNS) have been recently recognized as a distinct glial class, identified as multipotent progenitor cells. Antigenically, they are indistinguishable from oligodendroglia progenitor cells. In response to a variety of CNS insults, these cells become rapidly activated and undergo morphological changes accompanied by increased cellular proliferation.

Anti-myelin basic protein T cells protect hippocampal neurons against trimethyltin-induced damage.

We investigated the influence of administration of autoimmune T cells on trimethyltin-induced degeneration of hippocampal neurons. Female Lewis rats received 8 mg/kg trimethyltin intraperitoneally alone, or followed 24 h later by a second intravenous injection of anti-myelin basic protein T cells (green fluorescent protein-tagged). Neurodegeneration was assessed by NeuN and Nissl cell counts 21 days after trimethyltin injection.

Leukocyte acid phosphatase and metabolic efficiency of phagocytes in the first lactation trimester of cows from a leukaemic herd.

In Black-and-White cattle, polymorphism of acid phosphatase (AcP) of blood leukocytes is determined by a pair of autosomal alleles. The aim of the study was to determine the relationship between AcP polymorphism and the metabolic efficiency of phagocytes in the first months after calving of cows naturally infected with the bovine leukaemia virus. The studied population consisted of 91 Black-and-White cows aged 3-6 years, from one herd.

Trimethyltin-evoked neuronal apoptosis and glia response in mixed cultures of rat hippocampal dentate gyrus: a new model for the study of the cell type-specific influence of neurotoxins.

We investigated the effects of a potent neurotoxin, trimethyltin (TMT), on mixed neuronal/glial cultures derived from rat hippocampal dentate gyrus. We found that TMT induced neuronal cell death in a concentration dependent manner, which was estimated by microtubule degeneration, hematoxylin histological staining and the TUNEL method. This cell death is most probably of an apoptotic type as suggested by Hoechst staining.