Psychiatric side effects and fluctuations in serotonergic parameters in the treatment of chronic hepatitis C infection.

INTRODUCTION: Treatment of hepatitis C with peginterferon induces psychiatric side effects. These might include changes in serotonergic function. METHODS: Twenty-two hepatitis C patients were treated with peginterferon. At different time points, psychometric assessment was performed using the profile of mood states. Plasma samples were taken to study serotonergic parameters. RESULTS: Anger and depression increased compared to baseline, starting with anger (from week 3 onwards), followed by depression (from week 7 onwards). Other scores did not show consistent changes. No consistent changes were observed in tryptophan, tryptophan/large neutral amino acids ratio, biopterin and 5-hydroxyindoleacetic acid. The tyrosine/large neutral amino acids ratio, neopterin, phenylalanine/tyrosine ratio, and prolactin concentrations increased compared to baseline. Prolactin levels were associated with the occurrence of depression and anger. DISCUSSION: Particularly anger and depression increased during treatment. Neither a decrease in tryptophan and tryptophan availability was seen, nor a relationship between these parameters and the development of psychopathology. Therefore, other mechanisms in the induction of psychopathology should be considered. The observed increases in neopterin and phenylalanine/tyrosine ratio are indicative of changes in tetrahydrobiopterin, which is involved in the metabolism of serotonin, noradrenaline and dopamine, and possibly mediating the increase in prolactin. The increase in prolactin levels and its relationship with depression and anger needs further exploration.

Direct evidence of water-assisted sintering of cobalt on carbon nanofiber catalysts during simulated Fischer-Tropsch conditions revealed with in situ mossbauer spectroscopy.

Cobalt on carbon nanofiber model catalysts with very small dispersed cobalt particles of 5 nm were subjected to H(2)O/H(2) treatments at 20 bar and 220 degrees C. Using in situ Mossbauer spectroscopy we could unambiguously prove that oxidation of the nanoparticles by water will not occur when hydrogen is present. Only in a water/argon atmosphere did oxidation take place. This rules out oxidation as the deactivation mechanism in Fischer-Tropsch synthesis. Even more important, we define the relative humidity (RH) as a key parameter to understanding deactivation by water. At a RH below 25% sintering was absent even when measuring for 4 weeks, whereas at a high RH of 62% as much as half of the small super paramagnetic cobalt particles (<5 nm) sintered into larger particles in 1 week. Activity loss as measured at Fischer-Tropsch conditions amounted to 73%, which could be directly related to the metal dispersion loss 77% due to sintering as evidenced by detailed TEM analysis of the spent sample.

On the origin of the cobalt particle size effects in Fischer-Tropsch catalysis.

The effects of metal particle size in catalysis are of prime scientific and industrial importance and call for a better understanding. In this paper the origin of the cobalt particle size effects in Fischer-Tropsch (FT) catalysis was studied. Steady-State Isotopic Transient Kinetic Analysis (SSITKA) was applied to provide surface residence times and coverages of reaction intermediates as a function of Co particle size (2.6-16 nm). For carbon nanofiber supported cobalt catalysts at 210 degrees C and H(2)/CO = 10 v/v, it appeared that the surface residence times of reversibly bonded CH(x) and OH(x) intermediates increased, whereas that of CO decreased for small (<6 nm) Co particles. A higher coverage of irreversibly bonded CO was found for small Co particles that was ascribed to a larger fraction of low-coordinated surface sites. The coverages and residence times obtained from SSITKA were used to describe the surface-specific activity (TOF) quantitatively and the CH(4) selectivity qualitatively as a function of Co particle size for the FT reaction (220 degrees C, H(2)/CO = 2). The lower TOF of Co particles <6 nm is caused by both blocking of edge/corner sites and a lower intrinsic activity at the small terraces. The higher methane selectivity of small Co particles is mainly brought about by their higher hydrogen coverages.

[Changes in the management of patients with side effects from the treatment of hepatitis C]. / Wijzigingen in het beleid bij patiënten met bijwerkingen van de behandeling van hepatitis C.

Since hepatitis C can be treated more and more successfully, treatment should be considered in every patient. In some of the patients infected by viral genotype I, the duration of treatment can be shortened: 24 weeks instead of 48 weeks. Maintaining the optimal dosage of ribavirin and peginterferon alpha is of great importance for successful treatment. For this purpose, new guidelines are proposed with reference to the haematological side effects, recommending more restraint with the reduction of the dosage and treatment in case of complaints. Treatment with peginterferon alpha frequently causes psychiatric problems, particularly depressive symptoms that are sometimes severe. Adequate treatment and support, including the use of antidepressants, are necessary in such cases and are often effective.

Cobalt on carbon nanofiber catalysts: auspicious system for study of manganese promotion in Fischer-Tropsch catalysis.

STEM-EELS and XPS investigation shows manganese oxide to be closely associated with cobalt nanoparticles supported on carbon nanofibers thereby improving selectivity in Fischer-Tropsch catalysis.

Randomised clinical trial: escitalopram for the prevention of psychiatric adverse events during treatment with peginterferon-alfa-2a and ribavirin for chronic hepatitis C.

BACKGROUND Treatment of hepatitis C with peginterferon and ribavirin is associated with psychiatric side-effects, frequently necessitating dose reduction or therapy cessation. AIM To assess the efficacy of prophylactic escitalopram to prevent psychiatric side-effects during peginterferon and ribavirin treatment in a randomised, double-blind, placebo-controlled trial. METHODS Seventy-nine hepatitis C patients were treated with peginterferon and ribavirin. Patients received escitalopram (n = 40, 10 mg) or placebo (n = 39), which was initiated together with peginterferon and ribavirin. Primary outcomes were an increase of two points or more on the items reported sadness, inner tension and impaired concentration of the Montgomery-Asberg Depression Rating Scale, and hostile feelings of the Brief Anxiety Scale. Secondary outcome was the development of depression diagnosed by the Mini-International Neuropsychiatric Interview. Measurements were performed at baseline, week 4, 12 and 24 during anti-viral treatment, and 24 weeks thereafter. RESULTS The incidence of psychiatric side-effects was significantly lower in patients treated with escitalopram compared with placebo for all primary and secondary outcomes, except for impaired concentration: reported sadness 27.5 vs. 48.7% (P = 0.052), inner tension 17.5 vs. 38.5% (P = 0.038), impaired concentration 55.0 vs. 66.7% (P = 0.288) and hostile feelings 22.5 vs. 43.6% (P = 0.046) (escitalopram vs. placebo, Chi-squared test). The sum scores of all four endpoints showed an overall beneficial effect of escitalopram (P = 0.009, Mann-Whitney U-test). Depression occurred in 12.5% of the patients in the escitalopram-group vs. 35.9% in the placebo-group (P = 0.015, Chi-squared test). CONCLUSIONS Prophylactic treatment with escitalopram is effective in the prevention of psychiatric side-effects during interferon-based treatment of hepatitis C.

Cobalt particle size effects in the Fischer-Tropsch reaction studied with carbon nanofiber supported catalysts.

The influence of cobalt particle size in the range of 2.6-27 nm on the performance in Fischer-Tropsch synthesis has been investigated for the first time using well-defined catalysts based on an inert carbon nanofibers support material. X-ray absorption spectroscopy revealed that cobalt was metallic, even for small particle sizes, after the in situ reduction treatment, which is a prerequisite for catalytic operation and is difficult to achieve using traditional oxidic supports. The turnover frequency (TOF) for CO hydrogenation was independent of cobalt particle size for catalysts with sizes larger than 6 nm (1 bar) or 8 nm (35 bar), while both the selectivity and the activity changed for catalysts with smaller particles. At 35 bar, the TOF decreased from 23 x 10(-3) to 1.4 x 10(-3) s(-1), while the C5+ selectivity decreased from 85 to 51 wt % when the cobalt particle size was reduced from 16 to 2.6 nm. This demonstrates that the minimal required cobalt particle size for Fischer-Tropsch catalysis is larger (6-8 nm) than can be explained by classical structure sensitivity. Other explanations raised in the literature, such as formation of CoO or Co carbide species on small particles during catalytic testing, were not substantiated by experimental evidence from X-ray absorption spectroscopy. Interestingly, we found with EXAFS a decrease of the cobalt coordination number under reaction conditions, which points to reconstruction of the cobalt particles. It is argued that the cobalt particle size effects can be attributed to nonclassical structure sensitivity in combination with CO-induced surface reconstruction. The profound influences of particle size may be important for the design of new Fischer-Tropsch catalysts.

Human hepatic lymph nodes contain normal numbers of mature myeloid dendritic cells but few plasmacytoid dendritic cells.

We investigated whether the hyporesponsiveness of the adaptive arm of the liver immune system is related to the composition of the dendritic cell (DC) population in hepatic lymph nodes. Noninflamed human hepatic lymph nodes (LN) were obtained from multiorgan donors, inflamed hepatic LN from liver transplant recipients with autoimmune cholestatic liver diseases, and inguinal LN from kidney transplant recipients. Quantitative immunohistochemistry showed that all three types of LN contained comparable numbers of mature and immature myeloid DC, but that noninflamed and inflamed hepatic LN contained significantly fewer plasmacytoid DC as compared to inguinal LN. Likewise, DC-enriched cell preparations from hepatic LN contained relatively few plasmacytoid DC. The difference in numbers of plasmacytoid DC was confirmed in comparisons of hepatic LN and ileacal LN from the same organ-donors. Myeloid DC from hepatic LN showed similar expressions of HLA-DR, CD83, and CD86, and higher expression of CD80 compared to myeloid DC from inguinal LN. In conclusion, hepatic LN contain similar numbers of myeloid DC as muscle/skin lymph-draining LN, with no signs of immaturity, but relatively few plasmacytoid DC.