[Ten years of cognitive control training for depression: an overview of findings and challenges]. / Tien jaar cognitieve controletraining voor depressie: een overzicht van verwezenlijkingen en uitdagingen.

BACKGROUND: 2007 marks a shift in scientific literature on the cognitive vulnerabilities of depression. Preceded by a vast amount of studies exploring neuroplasticity and cognitive transfer effects, Siegle e.a. (Cognit Ther Res 2007; 31: 235-62) published the findings of a proof-of-principle study in which cognitive control training (cct) was applied to treat depression. This denotes an evolution towards clinically oriented cct studies targeting reduction of the vulnerability mechanisms of depression. Following this publication, several studies tested the effects of cct on emotional vulnerability. These studies show great variability.
AIM: This article provides an overview summarizing the findings of cct for depression published in the last 10 years.
METHOD: The results of a recently conducted systematic review were reviewed, with a particular interest in clinical implications and challenges.
RESULTS: cct shows beneficial effects on indicators of depression vulnerability (e.g., stress reactivity, rumination, symptomatology). Associated literature underlines the importance of intensive training procedures, use of an affective task context and task motivation.
CONCLUSION: cct shows potential as a clinical intervention for depression. However, several questions still need to be addressed before implementation into clinical practice is warranted.

High throughput therapeutic drug monitoring of clozapine and metabolites in serum by on-line coupling of solid phase extraction with liquid chromatography-mass spectrometry.

The characteristics of automated on-line solid phase extraction with liquid chromatography-mass spectrometry (SPE-LC-MS) are very amenable for flexibility and throughput in therapeutic drug monitoring (TDM). We demonstrate this concept of automated, on-line SPE-LC-MS for the analysis of clozapine and metabolites (desmethylclozapine and clozapine-N-oxide) in serum. Method development, optimisation and validation are described and a comparison with previously published methods for the determination of clozapine and metabolites in serum and plasma is made. Optimisation of chromatographic and SPE conditions for increased throughput resulted in SPE-LC-MS cycle times of only about 2.2 min, demonstrating the great potential of automated on-line SPE-LC-MS for TDM. The new method is shown to be clearly favourable, in particular in terms of ease of sample handling, throughput and detection limits. Recovery is essentially quantitative. Detection limits are at about 0.15-0.3 ng ml(-1), depending on the ionisation source used. Calibration follows a quadratic model for clozapine and its N-oxide and a linear model for the desmethyl metabolite (all cases: R > 0.99). Accuracy, evaluated at three concentration levels spanning the whole therapeutic range, shows that bias is less than 10%. Precision (intra - and inter assay) ranges from about 5% R.S.D. at the high end of the therapeutic range (700-1,000 ng ml(-1)) to about 20% R.S.D. (OECD defined limit) at the lower limit of quantitation ( approximately 50 ng ml(-1)). The lower limit of quantitation is well below the low end of the therapeutic range at 350 ng ml(-1).

On-fiber derivatization for direct immersion solid-phase microextraction. Part II. Acylation of amphetamine with pentafluorobenzoyl chloride for urine analysis.

On-fiber derivatization was used for solid-phase microextraction (SPME) in order to increase the detectability and extractability of drugs in biological samples. Amphetamine, which was used as a model compound, was derivatized with pentafluorobenzoyl chloride (PFBCl) and subjected to gas chromatography with electron capture or mass spectrometric detection. Extraction was performed by direct immersion of a 100 microm polydimethylsiloxane-coated fiber into buffered human urine. On-fiber derivatization was performed either after or simultaneously with extraction. The former procedure gave cleaner chromatograms but the latter turned out to be superior with respect to linearity and repeatability. For the on-fiber derivatization of amphetamine an excess of reagent is required. Because a considerable part of the PFBCl loaded on to the fiber is used up by reaction with matrix compounds and water, a reagent loading time of 5 min was needed to obtain a linear range (r = 0.9756) from 250 pg mL(-1) to 15 ng mL(-1). Due to an interfering matrix compound, the limit of detection was also found to be dependent on the reagent loading time, i.e., the limit of detection for a PFBCl loading time of 5 min is 250 pg mL(-1) whereas that for a 1 min loading time it is 100 pg mL(-1). The relative standard deviation (n = 7) of the method was about 11% at an amphetamine concentration of 1 ng mL(-1). The applicability of the method for the determination of drugs in biological samples is shown.

Fibers coated with molecularly imprinted polymers for solid-phase microextraction.

The simplicity and flexibility of solid-phase microextraction have been combined with the selectivity of molecularly imprinted polymers (MIPs). Silica fibers were coated reproducible with a 75-microm layer of methacrylate polymer either nonimprinted or imprinted with clenbuterol to compare their extraction characteristics under various conditions. Although the template molecule could be removed effectively from the imprinted polymer, structural analogues of clenbuterol were used for evaluation. The influence of pH on the extractability of brombuterol was investigated. Extraction yields up to approximately 80% were obtained when both types of fibers were used to extract brombuterol from phosphate buffer (pH 7.0). In contrast, yields of about 75 and <5% were obtained when extraction was performed from acetonitrile with imprinted and nonimprinted polymers, respectively, which demonstrates the selectivity of the MIP-coated fiber. Time sorption profiles were measured for the extraction of brombuterol from buffer and acetonitrile at the 10 and 100 ng/mL level with both types of fibers in order to compare extraction characteristics. Equilibrium times of about 30 and 90 min were found for the extraction of brombuterol from acetonitrile and buffer, respectively. The MIP-coated fibers were capable of extracting five structural analogues of clenbuterol from both buffer and acetonitrile, which suggests that the amine alcohol part of these molecules is responsible for interaction with the imprinted polymer. To achieve selective extraction of brombuterol from human urine, MIP-coated fibers were washed with acetonitrile after the extraction. Clean extracts and yields of approximately 45% were obtained, demonstrating the suitability of MIP-coated fibers for the analysis of biological samples.

Solid-phase microextraction for the analysis of biological samples.

Solid-phase microextraction (SPME) has been introduced for the extraction of organic compounds from environmental samples. This relatively new extraction technique has now also gained a lot of interest in a broad field of analysis including food, biological and pharmaceutical samples. SPME has a number of advantages such as simplicity, low cost, compatibility with analytical systems, automation and the solvent-free extraction. The last few years, SPME has been combined with liquid chromatography and capillary electrophoresis, besides the generally used coupling to gas chromatography, and has been applied to various biological samples such as, e.g., urine, plasma and hair. The objective of the present paper is a survey of the application of SPME for the analysis of biological samples. Papers about the analysis of biologically active compounds are categorised and reviewed. The impact of SPME on various analytical fields (toxicological, forensic, clinical, biochemical, pharmaceutical, and natural products) is illustrated. The main features of SPME and its modes are briefly described and important aspects about its application for the determination of pharmaceuticals, drugs of abuse and compounds of clinical and toxicological interest are discussed. SPME is compared with other sample pretreatment techniques. The potential of SPME and its main advantages are demonstrated. Special attention is paid to new trends in applications of SPME in bioanalysis.

Multiple solid-phase microextraction.

Theoretical aspects of multiple solid-phase microextraction are described and the principle is illustrated with the extraction of lidocaine from aqueous solutions. With multiple extraction under non-equilibrium conditions considerably less time is required in order to obtain an extraction yield that is equal to that of one extraction at equilibrium. On the other side, the extraction yield can be increased if multiple extraction is performed with the same total time as is needed for one extraction at equilibrium time. The effect of multiple extraction is strongly dependent on the value of the partition constant and for practical use the length of the desorption time is important. A good agreement between theoretical and experimental data has been obtained. Chromatograms are presented showing the potential of multiple solid-phase microextraction.

Determination of lidocaine in plasma by direct solid-phase microextraction combined with gas chromatography.

Direct-immersion solid-phase microextraction (SPME) has been used to extract the local anesthetic lidocaine from human plasma. A simplified model shows the relationship between the total amount of drug in plasma and the amount of drug extracted. The model takes into account that the drug participates between the fiber, sample and proteins. Therefore the model can also be used to obtain a good approximation of the drug-protein binding. Extraction yields of lidocaine in plasma are <1%, and the protein binding of lidocaine was found to be about 74% at pH 9.5. A SPME method has been developed for the determination of the total amount of lidocaine in plasma. The protein binding was reduced by acidification and, subsequently, the sample was deproteinized with trichloroacetic acid. With a 100-microm polydimethylsiloxane-coated fiber and addition of sodium chloride to the sample an extraction yield of about 12% at equilibrium (45 min) has been obtained. The relative standard deviation of this method is <10%. A linear range was found from 25 to 2000 ng ml(-1) lidocaine in plasma (r=0.998) with a detection limit of 5 ng ml(-1) in plasma. An extraction yield of about 80% could be obtained after an overnight extraction by use of a 65-microm polydimethylsiloxane-divinylbenzene-coated fiber. If an extraction time of 10 min is used with this fiber, the same yield is obtained as with the single-phase fiber in 45 min. However, the drawback of this mixed-phase fiber is its much shorter lifetime.

The safety and efficacy of ranitidine bismuth citrate in combination with antibiotics for the eradication of Helicobacter pylori.

BACKGROUND: Ranitidine bismuth citrate is a novel salt of ranitidine and a bismuth citrate complex. It has intrinsic antisecretory and anti-Helicobacter pylori activity, but monotherapy rarely eradicates H. pylori infection in man. AIM: A pilot study to investigate rates of H. pylori eradication achieved by co-prescription of ranitidine bismuth citrate with antibiotics, and to identify several regimens which would merit further investigation. METHOD: One hundred dyspeptic patients infected with H. pylori were randomly allocated to treatment with ranitidine bismuth citrate 800 mg b.d. plus either amoxycillin, metronidazole, clarithromycin, cefuroxime axetil, tetracycline, tetracycline plus metronidazole or clarithromycin plus tetracycline for 14 days. Eradication of infection was assessed using the 13C-urea breath test 4 weeks after the end of treatment. RESULTS: In a per protocol analysis eradication of H. pylori ranged between 22 and 100%; the intention-to-treat eradication rates ranged between 15 and 92%. No adverse events were specifically attributed to ranitidine bismuth citrate. CONCLUSION: Co-prescription therapy, using ranitidine bismuth citrate and one or more antibiotics, is suitable for further investigation in large-scale clinical trials in patients infected with H. pylori.

Degradation kinetics of antagonist [Arg6, D-Trp7,9, MePhe8]-substance P [6-11] in aqueous solutions.

Antagonist [Arg6, D-Trp7,9, MePhe8]-substance P {6-11} was subjected to a systematic stability study in which kinetic parameters were obtained for the degradation of this hexapeptide under several well-defined conditions. The influences of pH, temperature, ionic strength, buffer concentration, and initial concentration of the peptide on the reaction rate constant, kobs, were investigated with a stability-indicating reversed-phase high-performance liquid chromatographic system. From the pH-log kobs degradation profile, obtained at 63 degrees C, it appears that antagonist [Arg6, D-Trp7,9, MePhe8]-substance P {6-11} shows its maximum stability around pH 4.2. The half-life at this pH and temperature is 150 days. In both the hydroxyl- and proton-catalyzed parts of the pH-log kobs degradation profile, the influence of temperature was investigated and Arrhenius plots were constructed. The activation energies in both parts were comparable; however, the frequency factor in the hydroxyl-catalyzed part was 3.3 x 10(4) times higher than in the proton-catalyzed part. Eyring analysis of the data reveals that in both acidic and alkaline media the overall degradation was endotherm (delta H++ as well as delta G++ positive between 273 and 373 degrees K) and the entropy was negative. Increasing ionic strengths in acidic media causes an increase in kobs, while in alkaline media the kobs decreases with increasing ionic strength. Increasing buffer concentrations of acetate, phosphate, and carbonate led to an increase of kobs values. Drug concentrations up to 1 mg/ml at pH 10.8 and constant temperature and ionic strength have no influence on the overall degradation rate. At higher concentrations, above 1 mg/ml, kobs decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversed-phase high-performance liquid chromatography and capillary electrophoresis in the stability study of the neuropeptide growth factor antagonist [Arg6,D-Trp7,9,MePhe8]-substance P (6-11): a comparative study.

Reversed-phase high-performance liquid chromatography and capillary zone electrophoresis are widely used in protein and peptide analysis. Degradation of the basic peptide [Arg6,D-Trp7,9,MePhe8]-substance P (6-11) (antagonist G) was monitored with reversed-phase high-performance liquid chromatography, free capillary zone electrophoresis, and capillary zone electrophoresis with a capillary cationic coating. Capillary zone electrophoresis with a dynamically coated capillary provided better separation between antagonist G and its degradation products (formed at pH/Hv 13) than high-performance liquid chromatography and free zone capillary electrophoresis. Rate constants of the alkaline degradation of antagonist G measured with reversed-phase high-performance liquid chromatography and capillary zone electrophoresis with a dynamic coated capillary wall are similar whereas the values measured with free zone capillary electrophoresis are lower. Rate constants for the degradation of antagonist G in acidic media are comparable for the three techniques. It is concluded that capillary zone electrophoresis using a dynamic coating with Fluorad is the most suited of the above-mentioned techniques in analyzing antagonist G and its degradation products.

Campylobacter pylori. Diagnosis and treatment.

There is now a plethora of methods to diagnose colonization of the human stomach with Campylobacter pylori, such as microbiological culture on various media, identification of C. pylori in biopsies or biopsy smears using various stains or neurological methods, serological demonstration of specific anti-C. pylori antibodies, measuring urease activity with one of the many urease tests or using the 13C- or 14C-urea breath test. Therapy should be directed at permanent eradication of the organism. Eradication should only be diagnosed when no C. pylori organisms are demonstrable several weeks after the end of any therapy. The eradication rate with monotherapy is rather low. Combining colloidal bismuth subcitrate with an antibiotic improves the results. At present, triple therapy with colloidal bismuth subcitrate, amoxycillin or tetracycline, and metronidazole or tinidazole results in an eradication rate of over 80%. Bismuth seems to be essential in preventing antibiotic resistance formation.