Superior outcomes following cervical fusion vs. multimodal rehabilitation in a subgroup of randomized Whiplash-Associated-Disorders (WAD) patients indicating somatic pain origin-Comparison of outcome assessments made by four examiners from different disciplines.

Background And Aims: Whiplash-Associated Disorders (WAD) are characterized by great variability in long-term symptoms. Patients with central neck and movement-induced stabbing pain participated in a randomized study comparing cervical fusion and multimodal rehabilitation. As reported in our previous paper, more patients treated by cervical fusion than by rehabilitation experienced pain relief.

Cytotoxic effects of tetracycline analogues (doxycycline, minocycline and COL-3) in acute myeloid leukemia HL-60 cells.

Tetracycline analogues (TCNAs) have been shown to inhibit matrix metalloproteinases and to induce apoptosis in several cancer cell types. In the present study, the cytotoxic effects of TCNAs doxycycline (DOXY), minocycline (MINO) and chemically modified tetracycline-3 (COL-3) were investigated in the human acute myeloid leukemia HL-60 cell line. Cells were incubated with TCNAs in final concentrations of 0.

Towards an age-dependent transmission model of acquired and sporadic Creutzfeldt-Jakob disease.

Introduction: Sporadic Creutzfeldt-Jakob disease (sCJD) might be transmitted by surgery. The purpose of this study was to investigate potential susceptibility to sCJD from surgery at juvenile age and in early adulthood.

Methods: From Danish and Swedish national registries we identified 167 definite and probable sCJD cases with onset from 1987 through 2003, and 835 age-, sex- and residence-matched controls along with their surgical histories.

Translational gap in glioma research.

During the last five decades, enormous advances in treatment modalities for cancer and a better understanding of cancer cell biology have been accomplished but the prognosis of patients carrying malignant gliomas still remains poor despite hundreds of clinical trials have been carried out. In this article we review phase II clinical trials that have been completed and published in PubMed during 2011 in order to investigate potential reasons of clinical failure. We suggest that a translational gap, defined as a failure to translate basic research into clinical trials design may explain the poor outcome of phase II clinical trials.

Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance.

Background: There is increasing epidemiological evidence of etiological links between general surgery and sporadic Creutzfeldt-Jakob disease (sCJD) with long incubation periods. The purpose of this study was to identify specific surgical procedures potentially associated with sCJD to be targeted for preventive presurgical-intervention guidance.

Results: We propose a three-step clinical guidance outline where surgical procedures associated with sCJD clinical onset - potentially more contaminant - are taken into account.

Menadione : sodium orthovanadate combination eliminates and inhibits migration of detached cancer cells.

Exposure of cancer cells to anticancer agents in cultures induces detachment of cells that are usually considered dead. These drug-induced detached cells (D-IDCs) may represent a clinical problem for chemotherapy since they may survive anoikis, enter the circulation, invade other tissues and resume proliferation, creating a metastasis, especially in tissues where the bioavailability of anticancer agents is not enough to eliminate all cancer cells. In this study we evaluated the antiproliferative effect of menadione : sodium orthovanadate (M : SO) combination on A549 lung cancer cells as well as the ability of M : SO to induce cell detachment.

The stemness phenotype model.

The identification of a fraction of cancer stem cells (CSCs) associated with resistance to chemotherapy in most solid tumors leads to the dogma that eliminating this fraction will cure cancer. Experimental data has challenged this simplistic and optimistic model. Opposite to the classical cancer stem cell model, we introduced the stemness phenotype model (SPM), which proposed that all glioma cells possess stem cell properties and that the stemness is modulated by the microenvironment.

In vitro inhibition of topoisomerase IIα by reduced glutathione.

In most cells, the major intracellular redox buffer is glutathione (GSH) and its disulfide-oxidized (GSSG) form. The GSH/GSSG system maintains the intracellular redox balance and the essential thiol status of proteins by thiol disulfide exchange. Topoisomerases are thiol proteins and are a target of thiol-reactive substances.

Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells.

Gliomas are the most common primary brain tumor, and their treatment is still a challenge. Here, we evaluated the antiproliferative effect of a novel combination of two potent oxidative stress enhancers: menadione (M) and sodium orthovanadate (SO). We observed both short-term and prolonged growth inhibitory effects of M or SO alone as well as in combination (M:SO) on DBTRG.

Pankiller effect of prolonged exposure to menadione on glioma cells: potentiation by vitamin C.

Menadione (Vitamin K3) has anti-tumoral effects against a wide range of cancer cells. Its potential toxicity to normal cells and narrow therapeutic range limit its use as single agent but in combination with radiation or other anti-neoplastic agents can be of therapeutic use. In this paper, we first evaluated the early (within 3 h) effect of menadione on ongoing DNA replication.

Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions.

Objectives: Evidence of surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD) remains debatable in part due to misclassification of exposure levels. In a registry-based case-control study, the authors applied a risk-based classification of surgical interventions to determine the association between a history of surgery and sCJD.

Design: Case-control study, allowing for detailed analysis according to time since exposure.

Rapid inhibition of ongoing DNA synthesis in human glioma tissue by genistein.

The effect of genistein, a protein tyrosine kinase and topoisomerase II inhibitor, on the DNA synthesis rate was studied in 21 human glioma specimens obtained at routine craniotomies for tumor resection. Ongoing DNA synthesis rate was determined by using a method based on the generation of tissue mini-units immediately after tumor resection and short incubation time (0-120 min) with [methyl-3H]-thymidine. A 9-77% inhibition of DNA synthesis rate by 100 microM genistein was observed in 18/21 of the glioma specimens.

Strong inhibition of replicative DNA synthesis in the developing rat cerebral cortex and glioma cells by roscovitine.

The effects of the cyclin-dependent kinase inhibitors roscovitine and olomoucine on DNA synthesis rate during normal rat brain development were studied by using short time (90 min) incubation. Both purine analogues at 100 microM concentration decreased the DNA synthesis of rat cerebral cortex in an age-dependent manner. The maximum inhibitory effect (approximately 90% for roscovitine, approximately 60% for olomoucine) occurred in rats of 2-13 days postnatal age.

Ongoing DNA synthesis in the rat cerebral cortex is regulated by a proteolytic pathway independent of the proteasome and calpains.

By using mini-units of tissue and protease inhibitors in short term incubation (0-180 min), we studied the role of proteolysis for ongoing DNA replication in the developing rat cerebral cortex. The protease inhibitors TLCK, TPCK, PMSF, MG-132 and PSI markedly inhibited DNA synthesis. The inhibitory effects were concentration-dependent and of early onset (within 60 min).

Surgery and risk of sporadic Creutzfeldt-Jakob disease in Denmark and Sweden: registry-based case-control studies.

Background: Epidemiologic evidence of surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD) remains controversial.

Methods: From Danish and Swedish registries we selected 167 definite and probable sCJD cases (with onset between 1987 and 2003) and 3,059 controls (835 age-, sex-, and residence-matched, and 2,224 unmatched). Independent of case/control status, surgical histories were obtained from National Hospital Discharge Registries.

Effect of the Cdk-inhibitor roscovitine on mouse hematopoietic progenitors in vivo and in vitro.

Myelosuppression is one the most frequent side effects of chemotherapy. New agents that more selectively target cancer cells have been developed in attempt to improve the effects and to decrease the side effects of cancer treatment. Roscovitine is a purine analogue and cyclin-dependent kinase inhibitor.

Classification of surgical procedures for epidemiologic assessment of sporadic Creutzfeldt-Jakob disease transmission by surgery.

Background: In this preparatory phase of a case-control study, we propose and evaluate a new tool for classifying surgical procedures (SPs) in categories useful for epidemiologic research on surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD).

Methods: All SPs reported to the Swedish National Hospital Discharge Registry in the period 1974-2002, and undergone by 212 Swedish patients with registered diagnosis of CJD at death, hospital discharge or notification, in the period 1987-2002, 1060 age-, sex- and residence-matched controls and 1340 randomly chosen population controls, were reclassified into one of six categories of hypothetical transmission risk level. For that purpose the following two attributes were used: non-disposable instruments involved; and highest assigned ad-hoc risk level for four tissues or anatomical structures contacting such instruments.

Tissue distribution, pharmacokinetics and identification of roscovitine metabolites in rat.

The pharmacokinetics, biodistribution and the metabolic pathway of roscovitine were investigated in Sprague-Dawley rats after a single intravenous dose of 25 mg/kg. Blood, lungs, kidney, liver, testis, adipose tissue, spleen and brain were removed at different time-points. Plasma and tissue samples were analyzed using high performance liquid chromatography.

Tissue classification for the epidemiological assessment of surgical transmission of sporadic Creutzfeldt-Jakob disease. A proposal on hypothetical risk levels.

Background: Epidemiological studies on the potential role of surgery in Creutzfeldt-Jakob Disease transmission have disclosed associations with history of specific surgical interventions or reported negative results.

Methods: Within the context of a case-control study designed to address surgical risk of sporadic Creutzfeldt-Jakob Disease in Nordic European countries (EUROSURGYCJD Project), a strategy was adopted to categorise reported surgical procedures in terms of potential risk of Creutzfeldt-Jakob Disease acquisition. We took into account elements of biological plausibility, either clinically or experimentally demonstrated, such as tissue infectivity, PrP expression content or successful route of infection.

Analysis of roscovitine using novel high performance liquid chromatography and UV-detection method: pharmacokinetics of roscovitine in rat.

Roscovitine (2-(R)-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine, is a potent and selective inhibitor of cyclin-dependent kinases (CDKs). It inhibits cdc2, cdk2, cdk5 and erk 1 and 2 by competing for the ATP binding domain of the kinases. It inhibits cell proliferation; induces DNA fragmentation and causes cell cycle arrest in S phase.

The tolerability and efficacy of entacapone over 3 years in patients with Parkinson's disease.

The long-term safety and efficacy of the catechol-O-methyltransferase (COMT) inhibitor entacapone was investigated in a 3-year open-label extension of the 6-month double-blind placebo-controlled Nordic (NOMECOMT) study. After a wash-out following this study, 132 patients with Parkinson's disease (PD) experiencing motor fluctuations treated with levodopa/dopa decarboxylase (DDC) inhibitor received additional therapy with entacapone 200 mg, administered with each dose of levodopa. The most common adverse events (AEs) were insomnia (30%), dizziness (20%), nausea (20%), aggravated parkinsonism (17%) and hallucinations (14%).

Roscovitine inhibits ongoing DNA synthesis in human cervical cancer.

The effect of roscovitine, a purine analogue and cyclin dependent kinase inhibitor, on DNA synthesis rate in tissue mini-units obtained from human cervical cancers was investigated. Roscovitine (100 microM) gave a DNA synthesis rate inhibition by 61% (P<0.0001; range 23-93%) within 30 min of incubation.

Disulfiram is a potent in vitro inhibitor of DNA topoisomerases.

The drug disulfiram is a thiol-reacting drug that is relatively nontoxic when used alone and has been used in the therapy of alcohol abuse for more than 40 years. Several effects of this drug have been reported for DNA synthesis and cell proliferation. In this study, the inhibitory effect of disulfiram on topoisomerase I and II activity was investigated by measuring the relaxation of superhelical plasmid pBR322 DNA.

Plasma levels of 24S-hydroxycholesterol in patients with neurological diseases.

The brain is the exclusive or almost exclusive site of formation of 24S-hydroxycholesterol and we have shown that the circulating level of 24S-hydroxycholesterol is dependent upon the relation between cerebral production and hepatic clearance. In the present work we determined plasma levels of 24S-hydroxycholesterol in patients with various neurological diseases. Eleven subjects with brain death occurring 6-10 h before collection of the plasma samples had markedly reduced circulating levels of 24S-hydroxycholesterol (-43%, P<0.

Inhibition of DNA synthesis in human gliomas by roscovitine.

The early effect of 1-100 microM roscovitine, a purine analogue and cyclin-dependent kinase inhibitor, was studied on tissue specimens from eight human malignant gliomas. The tissue was incubated immediately after resection with DMEM containing [3H]methylthymidine plus vehicle alone or the proper concentration of roscovitine for 30-90 min. The DNA synthesis rate was assessed by measurement of [3H]methylthymidine incorporation into trichloroacetic acid insoluble material/mg protein/min.