RESUMO
RATIONALE: The ion-molecule chemistry in typical atmospheric pressure ion sources is essentially thermodynamically controlled. Methods relying on gas-phase protonation reactions, e.g. atmospheric pressure chemical ionization (APCI), thus suffer from the low reactivity of the equilibrated reagent ion population, which is mostly [H + (H2O)n](+). Reagent ion activation to yield reactive species such as H3O(+) is largely uncontrolled in commercial API mass spectrometers. METHODS: The ion activation stage (IAS) is realized as an ion 'tunnel' device. The 30-electrode geometry has an octagonal cross section and an inner diameter of 10 mm. The tunnel is mounted in a vacuum chamber, which directly attaches to the first pumping stage of API mass spectrometers. The effluent from a typical inlet capillary is expanding into the IAS. Reagent ions are generated at atmospheric pressure. Mass spectrometric analysis is performed with quadrupole and time-of-flight instruments. RESULTS: The performance of the IAS is demonstrated by the controlled activation of the initially equilibrated proton-bound water cluster system. It is shown that a gradual increase in the RF voltage amplitude applied to the electrode structure leads to a reproducible shift of the cluster distribution along with clearly discernible protonation thresholds of selected analytes. Increasing the radiofrequency (RF) voltage from zero to maximum values does not change the average ion residence time within the IAS. CONCLUSIONS: We have developed an IAS for operation in the intermediate (1-10 mbar) regime in the ion transfer region of API mass spectrometers. This stage is fully compatible with the recently introduced cAPCI method, which relies on the operation of a liquid point electrode generating very clean and stable thermal distributions of [H + (H2O)n] clusters. The IAS allows controlled ion activation by increasing the ion temperature, which is demonstrated by selective analyte protonation.
RESUMO
BACKGROUND: The causes underlying idiopathic intracranial hypertension (IIH) are poorly understood. METHODS: To identify disease-related biomarkers that could offer a new insight into IIH pathology, we analyzed the cerebrospinal fluid (CSF) of 18 patients with IIH and 18 controls using two-dimensional fluorescence differential in-gel electrophoresis (2-D DIGE). RESULTS: We found six proteins that were upregulated in IIH (sterol regulatory element-binding protein 1, zinc-alpha-2-glycoprotein, immunoglobulin heavy constant alpha 1 [IGHA1], alpha-1-antitrypsin [SERPINA1], serotransferrin, haptoglobin) and four proteins that were downregulated (hemopexin, angiotensinogen, vitamin-D-binding protein, transthyretin). The validity of our approach was confirmed for one candidate protein (angiotensinogen). To account for a dependency from blood-CSF barrier function, the ratio of angiotensinogen and albumin CSF-to-serum quotients (Qang/Qalb) was determined, which confirmed the downregulation of angiotensinogen in IIH (p = .04). CONCLUSION: Previous studies showed the intrinsic renin-angiotensin system (RAS) to regulate choroid plexus blood flow and CSF production. Altered levels of angiotensinogen could indicate an imbalance of the RAS in IIH that may provide new targets for therapeutic intervention.