Cetuximab-induced aseptic meningitis: case report and review of a rare adverse event.

BACKGROUND: Cetuximab is a commonly used antibody agent in the treatment of colorectal or head and neck cancer. Although it is generally well tolerated in most patients, cetuximab has been associated with some rare but serious adverse events. Aseptic meningitis is one such distinctly uncommon adverse drug reaction. CASE PRESENTATION: We present the case of a middle-aged Caucasian patient, who presented with fever and headache within a few hours of starting cetuximab therapy and was diagnosed with cetuximab-induced aseptic meningitis after a complete workup. CONCLUSION: To our knowledge, this is the ninth case of cetuximab-induced aseptic meningitis reported in literature. Because of a nonspecific clinical presentation, this adverse drug reaction can be easily misdiagnosed. It is important to increase awareness of this potentially severe reaction among oncologists

Everolimus (RAD001) sensitizes prostate cancer cells to docetaxel by down-regulation of HIF-1α and sphingosine kinase 1

Resistance to docetaxel is a key problem in current prostate cancer management. Sphingosine kinase 1 (SK1) and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathways have been implicated in prostate cancer chemoresistance. Here we investigated whether their combined targeting may re-sensitize prostate cancer cells to docetaxel. In hormone-insensitive PC-3 and DU145 prostate cancer cells the mTOR inhibitor everolimus (RAD001) alone did not lead to significant cell death, however, it strongly sensitized cells to low levels (5 nM) of docetaxel. We show that mTOR inhibition has led to a decrease in hypoxia-inducible factor-1α (HIF-1α) protein levels and SK1 mRNA. HIF-1α accumulation induced by CoCl2 has led to a partial chemoresistance to RAD001/docetaxel combination. SK1 overexpression has completely protected prostate cancer cells from RAD001/docetaxel effects. Using gene knockdown and CoCl2 treatment we showed that SK1 mRNA expression is downstream of HIF-1α. In a human xenograft model in nude mice single RAD001 and docetaxel therapies induced 23% and 15% reduction in prostate tumor volume, respectively, while their combination led to a 58% reduction. RAD001 alone or in combination with docetaxel has suppressed intratumoral mTOR and SK1 signaling, however as evidenced by tumor size, it required docetaxel for clinical efficacy. Combination therapy was well tolerated and had similar levels of toxicity to docetaxel alone. Overall, our data demonstrate a new mechanism of docetaxel sensitization in prostate cancer. This provides a mechanistic basis for further clinical application of RAD001/docetaxel combination in prostate cancer therapy

Kinetics of hydrogen evolution and absorption during electrochemical reactions as determined by monitoring the volume of hydrogen bubbles

The piezo electric technique (P.E.T) devised in this department is a highly sensitive method for measuring the total volume of gas bubbles suspended in a solution. This is achieved by simply performing a static compressibility test, causing small pressure fluctuations in the volume of a solution enclosed in a rigid vessel. Volume fluctuations may be produced by utilising the properties of piezo electric materials, which either change their shape in an applied electric field or generate electric fields when under pressure. Applying ac current to the piezo material positioned in this rigid vessel will cause a cyclic pressure fluctuation which can be measured by a second piezo crystal. On introducing a gas bubble into the system the coupling of both crystals is lessened, which can be measured as a decrease in the e.m.f. of the second crystal. This decrease in e.m.f. is a direct measure of the amount of gas present in the system. By cathodically producing H on an electrode which does not absorb hydrogen, and by using a hydrogen saturated solution, it is possible to calibrate the output e.m.f. These results are compared with those obtained using an electrode which does absorb hydrogen and this makes it possible to calculate the quantitative amount of gas absorbed by the metal. Experiments were carried out on a variety of metals with low and high hydrogen absorption capabilities. The metals under study included Fe, Au, Cu, Pt, Ti, Al, Al-3Mg, Al-5Mg and Duralumin. Comparative studies were performed between the P.E.T and the solid state vacuum extraction method for Ti, and between P.E.T. and the permeation method, as developed by Devanathan for Fe, and good agreement between these three methods was attained. The diffusion coefficient for Fe was found to be DH = 7 x 10- 6 cm2 s-1 , and for Al, DH = 1.87 x 10- 9 cm2 s-l, whilst its equilibrium solubility was found to be SH = 1 x 10- 4 gH/g Al. These results were compared with values found in the literature for Fe: no values were available for the results on Al. By introducing As into the electrolyte it was possible to show that at low concentration (2 ppm) As acts as a promoter for the h.a.r. on Ti, A1, A1-3Mg, A1-5Mg and as inhibitor in the case of Duralumin. At higher concentrations >5 ppm As acts as inhibitor for the same reaction. A mechanism for this effect is proposed. A detailed study was made on the growth mechanism of hydrides on Ti with and without As. It was shown that As acts as an inhibitor for the formation of y-hydrides on Ti. Proposals for extension of the work and uses in industry and research are made

Previous Leisure-Time Physical Activity Dose Dependently Decreases Ischemic Stroke Severity

In the present subanalysis of a cross-sectional study showing the favorable effect of prior transient ischemia, leisure-time physical activity, and lipid-lowering drug therapy on stroke severity, we aimed to evaluate whether previous physical activity was dose dependently associated to minor stroke (NIHSS 0–3) and to identify possible underlying factors. Among 362 consecutive patients, less severe stroke was related to weekly exercise duration prior to stroke (no exercise: 36.1%; <2 hours: 49.3%; 2–5 hours: 58.8%; >5 hours: 64.0%; P = 0.003). Only weak and moderate exercise practices were protective (weak: 50.0%; moderate: 79.3%; heavy: 22.2%; P < 0.0001). Such a beneficial effect was observed independently of age and was associated with a trend to a lower frequency of arterial hypertension, alcohol abuse, and a better metabolic profile. Besides other therapeutic approaches, physical activity may be a simple way to decrease cerebral ischemia severity

Endocannabinoids modulate human blood-brain barrier permeabilityin vitro

Background and Purpose Endocannabinoids alter permeability at various epithelial barriers, and cannabinoid receptors and endocannabinoid levels are elevated by stroke, with potential neuroprotective effects. We therefore explored the role of endocannabinoids in modulating blood–brain barrier (BBB) permeability in normal conditions and in an ischaemia/reperfusion model. Experimental Approach Human brain microvascular endothelial cell and astrocyte co-cultures modelled the BBB. Ischaemia was modelled by oxygen-glucose deprivation (OGD) and permeability was measured by transepithelial electrical resistance. Endocannabinoids or endocannabinoid-like compounds were assessed for their ability to modulate baseline permeability or OGD-induced hyperpermeability. Target sites of action were investigated using receptor antagonists and subsequently identified with real-time PCR. Key Results Anandamide (10 μM) and oleoylethanolamide (OEA, 10 μM) decreased BBB permeability (i.e. increased resistance). This was mediated by cannabinoid CB2 receptors, transient receptor potential vanilloid 1 (TRPV1) channels, calcitonin gene-regulated peptide (CGRP) receptor (anandamide only) and PPARα (OEA only). Application of OEA, palmitoylethanolamide (both PPARα mediated) or virodhamine (all 10 μM) decreased the OGD-induced increase in permeability during reperfusion. 2-Arachidonoyl glycerol, noladin ether and oleamide did not affect BBB permeability in normal or OGD conditions. N-arachidonoyl-dopamine increased permeability through a cytotoxic mechanism. PPARα and γ, CB1 receptors, TRPV1 channels and CGRP receptors were expressed in both cell types, but mRNA for CB2 receptors was only present in astrocytes. Conclusion and Implication The endocannabinoids may play an important modulatory role in normal BBB physiology, and also afford protection to the BBB during ischaemic stroke, through a number of target sites

Past and present of FIZ CHEMIE Berlin: Interview with Dr. René Deplanque, Managing Director

Available also from http://acscinf.org/publications/interviews/deplanque2010.phpSvetla Baykoucheva interviews Dr. René Deplanque, Managing Director of FIZ CHEMIE Berlin. Dr. Deplanque discusses the development of cheminformatics in Germany, the role of librarians, and the atmosphere in Berlin today, after the reunification