A Glimpse into Milestones of Insulin Resistance and an Updated Review of Its Management.

Insulin is the main metabolic regulator of fuel molecules in the diet, such as carbohydrates, lipids, and proteins. It does so by facilitating glucose influx from the circulation into the liver, adipose tissue, and skeletal myocytes. The outcome of which is subjected to glycogenesis in skeletal muscle and lipogenesis in adipose tissue, as well as in the liver.

Neuroleptic malignant syndrome: an easily overlooked neurologic emergency.

Neuroleptic malignant syndrome is an unpredictable iatrogenic neurologic emergency condition, mainly arising as an idiosyncratic reaction to antipsychotic agent use. It is characterized by distinctive clinical features including a change in mental status, generalized rigidity, hyperpyrexia, and dysautonomia. It can be lethal if not diagnosed and treated properly.

Lithium: a review of pharmacology, clinical uses, and toxicity.

A radical drug treatment for bipolar affective disorder (BD) is currently unavailable. This is attributed to the fact that the precise pathophysiology of this ailment is unclear though a genetic factor is an essential element in etiology. Dissimilar to other serious psychiatric categories such as psychoses and major depression the forecast of this disease is unpredictable.

CUG binding protein 1 binds to a specific region within the human albumin 3' untranslated region.

3' Untranslated regions (3'UTRs) of messenger RNAs have important roles in post-transcriptional regulation of gene expression and this is partly achieved through binding of specific proteins to sequences or structures within these regions. Previously, replacement of a native luciferase 3'UTR with the human albumin 3'UTR has been found to lead to a 10-fold increase in luciferase reporter activity. In this work we investigated protein binding to the human albumin 3'UTR.

Albumin 3'untranslated region facilitates increased recombinant protein production from Chinese hamster ovary cells.

Chinese hamster ovary (CHO) cells are used for recombinant protein production in the pharmaceutical industry but there is a need to improve expression levels. In the present work experiments were carried out to test the effectiveness of different 3'untranslated regions (3'UTRs) in promoting production of a naturally secreted luciferase. Seamless cloning was used to produce expression vectors in which Gaussia princeps luciferase coding sequences were linked to the human albumin, immunoglobulin or chymotrypsinogen 3'UTR.

An intercalation mechanism as a mode of action exerted by psychotropic drugs: results of altered phospholipid substrate availabilities in membranes?

Patients respond differently to psychotropic drugs, and this is currently a controversial theme among psychiatrists. The effects of 16 psychotropics on cell membrane parameters have been reported. These drugs belong to three major groups used in therapeutic psychiatry: antipsychotics, antidepressants, and anxiolytic/hypnotics.

In thrombin stimulated human platelets Citalopram, Promethazine, Risperidone, and Ziprasidone, but not Diazepam, may exert their pharmacological effects also through intercalation in membrane phospholipids in a receptor-independent manner.

Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs' intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A(2) (PLA(2)) and polyphosphoinositide (PPI) metabolism in thrombin-stimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique.

Effects of psychotropic drugs on the thrombin-induced liberation of arachidonate in human platelets.

Objective: To compare the effects of chlorpromazine (CPZ), prochlorperazine (PCP), trifluoperazine (TFP), clozapine (CLO), haloperidol (HPD), quetiapine (QTP), pimozide (PMZ), and olanzapine (OLP) as well as the tricyclic antidepressants amitriptyline AMI, imipramine IMI, and nortriptyline NTP on thrombin-induced liberation of arachidonic acid AA in platelets.

Methods: This work was carried out at the Department of Biomedicine, University of Bergen, Norway in 2006-2007. Human platelets pre labelled with [3H] arachidonate were incubated with thrombin in the absence and presence of the drugs, and the amount of free [3H] arachidonate liberated was determined.

Psychotropic drugs interfere with the tight coupling of polyphosphoinositide cycle metabolites in human platelets: a result of receptor-independent drug intercalation in the plasma membrane?

Incubation of platelets with increasing concentrations of thrombin produced large amounts of phosphatidic acid (PA) and distinct changes in phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2), prominent metabolites in the polyphosphoinositide (PPI) cycle. The relation between normalized PA and PIP or PIP2 levels in such thrombin-treated platelets from 22 normal donors gave a very similar pattern, suggesting tight control of the metabolites in the polyphosphoinositide (PPI) cycle. Prochlorperazine (PCP), trifluoperazine (TFP), haloperidol (HPD), quetiapine (QTP), pimozide (PMZ) and clozapine (CLO) interfered with this tight coupling produced by treating platelets with increasing thrombin concentrations.

The level of synthesis and secretion of Gaussia princeps luciferase in transfected CHO cells is heavily dependent on the choice of signal peptide.

There is a great demand for the improvement of mammalian cell production systems such that they can compete economically with their prokaryotic counterparts. Of a number of parameters that need to be explored to accomplish this we have tested the effects of different signal peptides on the synthesis and secretion of Gaussia princeps luciferase in mammalian cells. A series of plasmids were transfected into CHO cells where the coding region for the marine luciferase was fused to the signal peptide coding regions derived from different sources.

Vectors encoding seven oikosin signal peptides transfected into CHO cells differ greatly in mediating Gaussia luciferase and human endostatin production although mRNA levels are largely unaffected.

The signal peptide of the luciferase secreted by the marine copepod Gaussia princeps has been shown to promote high-level protein synthesis/secretion of recombinant proteins, being far superior to mammalian counterparts. The main aim of the present study was to investigate the effects of seven selected signal peptides derived from oikosins, house proteins of the marine organism Oikopleura dioica, on synthesis/secretion of recombinant proteins. Vector constructs were made in which the coding regions of two naturally secreted proteins, Gaussia luciferase and human endostatin (hEndostatin), were "seamlessly" fused to the signal peptide coding sequences of interest.

A mistletoe lectin (ML-1)-containing diet reduces the viability of a murine non-Hodgkin lymphoma tumor.

In this study we show that the characteristics of non-Hodgkin lymphoma (NHL) tumors in female Naval Medical Research Institute (NMRI, USA) mice fed mistletoe lectin (ML)-containing diets were different from those in mice fed control diet. The non-Hodgkin lymphoma tumor was originally established from a spontaneous tumor which developed in the inguinal region of a male mouse. Mice (five animals per group) were fed a lactalbumin (LA)-based control diet or a diet which provided up to 10 mg lectin per day.

In vivo studies on possible health consequences of genetically modified food and feed--with particular regard to ingredients consisting of genetically modified plant materials.

This synopsis reviews published in vivo studies on possible health consequences of genetically modified food and feed where the ingredients in question have consisted of genetically modified plant materials. The following, however, have not been taken into consideration:--ingredients consisting of genetically modified microorganisms or parts of animals/fish--ingredients produced by/from genetically modified organisms but without any DNA present--studies on consequences for the environment or biodiversity--in vitro studies or computer simulations. According to a Norwegian report "Gen-mat" (NOU 2000:29), and a more recent search in Medline and Citations Index, to our knowledge a total of ten studies have been published on the health effects of GM-foods and feeds.

Sodium butyrate stimulates the synthesis of firefly luciferase in transfected CHO cells but levels of BiP chaperone are unaffected.

A stably transfected CHO cell line (LUCLEAD) was used where the coding region of native Firefly luciferase was linked to the 3'-UTR of the bovine growth hormone, and the 5'-nucleotides coding for the albumin signal peptide were linked to the N-terminal end of the luciferase coding region. Incubation of cells with 1 or 2 mM sodium butyrate (SB) for 72 h had no effect on cell growth since cultures reached confluency at the same time as control cells. Although cell cultures incubated with SB at a concentration of 4 mM were only about 60% confluent the luciferase content was about 5-fold higher than that in control cells.