Thiamine deficiency: an update of pathophysiologic mechanisms and future therapeutic considerations.

Thiamine is an essential vitamin that is necessary to maintain the functional integrity of cells in the brain. Its deficiency is the underlying cause of Wernicke's encephalopathy (WE), a disorder primarily associated with, but not limited to, chronic alcoholism. Thiamine deficiency leads to the development of impaired energy metabolism due to mitochondrial dysfunction in focal regions of the brain resulting in cerebral vulnerability. The consequences of this include oxidative stress, excitotoxicity, inflammatory responses, decreased neurogenesis, blood-brain barrier disruption, lactic acidosis and a reduction in astrocyte functional integrity involving a loss of glutamate transporters and other astrocyte-specific proteins which together contribute in a major way to the resulting neurodegeneration. Exactly how these factors acting in concert lead to the demise of neurons is unclear. In this review we reassess their relative importance in the light of more recent findings and discuss therapeutic possibilities that may provide hope for the future for individuals with WE.

Proteomic analysis of the transitional endoplasmic reticulum in hepatocellular carcinoma: an organelle perspective on cancer.

The transitional endoplasmic reticulum (tER) is composed of both rough and smooth ER membranes and thus participates in functions attributed to both these two subcellular compartments. In this paper we have compared the protein composition of tER isolated from dissected liver tumor nodules of aflatoxin B1-treated rats with that of tER from control liver. Tandem mass spectrometry (MS), peptide counts and immunoblot validation were used to identify and determine the relative expression level of proteins. Inhibitors of apoptosis (i.e. PGRMC1, tripeptidyl peptidase II), proteins involved in ribosome biogenesis (i.e. nucleophosmin, nucleolin), proteins involved in translation (i.e. eEF-2, and subunits of eIF-3), proteins involved in ubiquitin metabolism (i.e. proteasome subunits, USP10) and proteins involved in membrane traffic (i.e. SEC13-like 1, SEC23B, dynactin 1) were found overexpressed in tumor tER. Transcription factors (i.e. Pur-beta, BTF3) and molecular targets for C-Myc and NF-kappa B were observed overexpressed in tER from tumor nodules. Down-regulated proteins included cytochrome P450 proteins and enzymes involved in fatty acid metabolism and in steroid metabolism. Unexpectedly expression of the protein folding machinery (i.e. calreticulin) and proteins of the MHC class I peptide-loading complex did not change. Proteins of unknown function were detected in association with the tER and the novel proteins showing differential expression are potential new tumor markers. In many cases differential expression of proteins in tumor tER was comparable to that of corresponding genes reported in the Oncomine human database. Thus the molecular profile of tumor tER is different and this may confer survival advantage to tumor cells in cancer.

Amyloidosis in FDG-avid lymph nodes.

Amyloidosis in lymph node that is FDG-avid is an unusual diagnosis. FDG PET/CT showed the presence of multifocal lymphadenopathy mainly axillary with a mesenteric mass. Surgical lymph node biopsy with histological examination confirmed the diagnosis of amyloidosis in a 64-year-old woman with an initial left axillary pain. Amyloidosis should be considered on the differential diagnosis for a FDG-avid lymphadenopathy. Other differential diagnosis usually includes malignancy such as lymphoma or metastatic disease, infection, or sterile inflammation.

Baculovirus expression and diagnostic utility of the glycoprotein E of bovine herpesvirus-1.1 Egyptian strain "Abu-Hammad".

A recombinant baculovirus construct expressing glycoprotein E (gE) of the Egyptian BoHV-1.1 Abu-Hammad strain (rBac/gE-AbuH) was generated and characterized. The recombinant gE (rgE) secreting protein in culture medium of infected insect cells was used as a coating antigen in an indirect enzyme-linked immunosorbent assay (ELISA) to test its utility for detection of antibody against gE of BoHV-1. Indirect gE-ELISA was compared to standard virus neutralization test and commercial blocking gE-ELISA for detection of anti-gE antibody in a panel of bovine sera. Antibody titers estimated by both ELISAs were closely correlated with those determined by virus neutralization test. In conclusion, the developed indirect gE-ELISA was a reliable candidate for inexpensive detection of anti-gE antibody in control and experimental bovine sera with high specificity and sensitivity. Moreover, it emphasized the diagnostic utility of gE based ELISAs to distinguish cattle infected with BoHV-1 from those vaccinated with the gE negative mutants.

Construction, characterization and immunogenicity of a glycoprotein E negative bovine herpesvirus-1.1 Egyptian strain "Abu-Hammad".

A full glycoprotein E (gE) deletion was generated in genome of the Egyptian BoHV-1.1 Abu-Hammad strain. Integrity of the gE negative (gE(-)) mutant virus was proved by successful specific PCR amplifications of gB, gC, tk, gD, gI and gE genes along with definite immune reaction to polyclonal anti-BoHV-1 antibody in infected cell culture. BoHV-1 gE(-) mutant exhibited growth kinetics inferior to those of the parental virus manifested as lower virus titers with delayed and poorer cytopathic effect in infected cells. Adjuvanted vaccines were made of the gE(-) mutant, live and killed; besides a conventional killed vaccine made of the parental virus and were used to immunize separate groups of calves. After i.m. vaccinations, no virus shedding could be detected in nasal swabs collected from all vaccinates and all calves remained apparently healthy. They all seroconverted to BoHV-1 as was revealed by virus neutralization test and a gB enzyme-linked immunosorbent assay (ELISA). Calves vaccinated with live and killed gE(-) vaccines did not elicit any detectable anti-gE antibody as shown by a blocking gE-ELISA. In conclusion, the constructed BoHV-1.1 gE(-) mutant was proved as safe and immunogenic as a reliable candidate for inclusion in a local marker vaccine.