Effects of miltefosine and other alkylphosphocholines on human intestinal parasite Entamoeba histolytica

The protozoan parasite Entamoeba histolytica is the cause of amoebic dysentery and liver abscess. It is therefore responsible for significant morbidity and mortality in a number of countries. Infections with E. histolytica are treated with nitroimidazoles, primarily with metronidazole. At this time, there is a lack of useful alternative classes of substances for the treatment of invasive amoebiasis. Alkylphosphocholines (alkyl-PCs) such as hexadecyl-PC (miltefosine) were originally developed as antitumor agents, but recently they have been successfully used for the treatment of visceral leishmaniasis in humans. We examined hexadecyl-PC and several other alkyl-PCs with longer alkyl chains, with and without double bond(s), for their activity against two strains of E. histolytica. The compounds with the highest activity were oleyl-PC, octadecyl-PC, and nonadecenyl-PC, with 50% effective concentrations for 48 h of treatment between 15 and 21 microM for strain SFL-3 and between 73 and 98 microM for strain HM-1:IMSS. We also tested liposomal formulations of these alkyl-PCs and miltefosine. The alkyl-PC liposomes showed slightly lower activity, but are expected to be well tolerated. Liposomal formulations of oleyl-PC or closely related alkyl-PCs could be promising candidates for testing as broad-spectrum antiprotozoal and antitumor agents in humans.     

Hyperthyroidism mimicking increased intracranial pressure

We report a 32-year-old woman presenting with progressive symptoms of increased intracranial pressure and slight enlargement of the ventricles on CT scan. The underlying cause was hyperthyroidism due to Graves' disease. With treatment to correct the hyperthyroid state, all symptoms rapidly disappeared. The rare onset of hyperthyroidism with symptoms indicating intracranial hypertension, and the possible pathophysiologic mechanisms are discussed.     

Subkutaner Tumor bei einem Jugendlichen

A 13-year-old adolescent presented with an enlarging subcutaneous mass beneath the right eyebrow. Clinically suspicious for dermoid cyst or pilomatrixoma, it was decided to remove the tumour completely. Based on histopathological examination the diagnosis of intravascular papillary endothelial hyperplasia (IPEH) was made. Histopathological features are discussed with regard to the possible pathogenesis.     

Chlamydophila abortus pelvic inflammatory disease

We report the first documented case of an extragestational infection with Chlamydophila abortus in humans. The pathogen was identified in a patient with severe pelvic inflammatory disease (PID) by sequence analysis of the ompA gene. Our findings raise the possibility that Chlamydiaceae other than Chlamydia trachomatis are involved in PID.     

Correlation between humoral and cellular immune responses and the expression of the hepatitis A receptor HAVcr-1 on T cells after hepatitis A re-vaccination in high and low-responder vaccinees

Introduction

We recently published a study on the persistence of seroprotection 10 years after primary hepatitis A vaccination in an unselected study population of 1014 vaccinees. The majority of these vaccinees still exhibited sufficient protective antibody levels, while 2% displayed antibody concentrations below detection level. In order to investigate whether the low antibody levels were due to decline after primary vaccination or due to an intrinsic inability to sufficiently respond to hepatitis A antigen, we sought to recruit these low/no responder vaccinees to characterize their immune responses in more detail after booster vaccination in comparison to high responder vaccinees.

Materials and methods

Prior to and one week after booster vaccination with a hepatitis A vaccine, antibody levels, cytokine levels (IL-2, IFN-γ and IL-10) and CD surface marker expression on peripheral blood mononuclear cells were determined in a study population comprised of 52 individuals. Additionally, the hepatitis A HAV cellular receptor 1 (HAVcr-1) TIM-1, being also expressed on CD4+ T cells and associated with immunomodulatory properties, was measured by RT-PCR before and after hepatitis A booster.

Results

Our data indicate that there is indeed a small group of hepatitis A vaccinees that can be classified as low/no responders as their antibody levels remain below the seroprotection level of 20 mIU/ml after booster vaccination. We further describe a good correlation between antibody concentrations and cellular responses, showing that low antibody production is associated with low antigen specific cytokine levels (IL-2, IFN-γ, IL-10) and vice versa. While there was no significant difference in the expression of the most common surface markers on T and B cells before and after booster vaccination in low and high responder vaccinees, the expression of HAVcr-1 on CD4 T cells correlated significantly with the antibody responses and cytokine levels, suggesting this receptor as cellular prediction marker of immune responsiveness to hepatitis A.

Conclusion

Whether hepatitis A low/non-responders deserve particular attention as a risk group or might display certain resistance to hepatitis A infection due to a lack of the hepatitis A receptor needs further investigations. At this stage we suggest that persons at high exposure risk should be carefully observed.     

Safety and immunogenicity of concomitant vaccination with the cell-culture based Japanese Encephalitis vaccine IC51 and the hepatitis A vaccine HAVRIX1440 in healthy subjects: A single-blind,randomized, controlled Phase 3 study

In travellers often several pre-departure immunizations are indicated, thus data are needed about possible interactions between vaccines. This Phase 3 study investigated the immunogenicity and safety of IC51 (JE vaccine) and HAVRIX^®1440 (hepatitis A vaccine) when administered alone or concomitantly to healthy subjects. The immune response was compared between single and concomitant vaccination in terms of geometric mean titre (GMT) and seroconversion rate (SCR) on Days 28 and 56. Immunogenicity was comparable for the 2 vaccines whether given together or separately which suggests that travellers to such regions could receive the vaccinations concomitantly.     

Agomelatine for Depression in Schizophrenia: A Case-Series

Objectives

Agomelatine, a melatonin (MT1/MT2) receptor agonist and 5-HT2C receptor antagonist, is a new antidepressant and a potential therapeutic option for major depressive episodes and negative symptoms in persons with schizophrenia. We investigated such treatment outcomes with respect to antidepressant efficacy, safety, and tolerability.

Methods

We report a consecutive case series of seven patients with schizophrenia and comorbid major depressive symptoms who received agomelatine for a period of at least six weeks in addition to stable doses of antipsychotic agents. General psychopathology, positive, negative and depressive symptoms were assessed with standardized interviews. Relevant blood parameters were assessed.

Results

Depressive symptoms improved significantly. Positive symptoms remained stable, while negative symptoms and global psychopathology improved significantly. Agomelatine was well tolerated in most patients.

Conclusions

Our findings provide initial evidence that agomelatine is safe and efficacious in treating depressive symptoms in patients with schizophrenia. Furthermore, agomelatine seems to be effective for the treatment of negative symptoms. Randomized controlled trials are necessary to confirm these first observations.     

Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine

Background

Immune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains.

Methods

An open-label, randomized, phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1 A/California/07/2009 vaccine. 408 subjects were stratified by age (18–59 and >60 years) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5 μg hemagglutinin antigen 21 days apart. Safety, immunogenicity and the influence of seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1 strain was assessed.

Results

A single vaccination with either dose induced substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition (HI) and neutralizing (MN) antibody titers in both adult and elderly subjects. A single 7.5 μg dose induced seroprotection rates of 86.9% in adults and 75.2% in elderly subjects. Two 7.5 μg vaccinations induced seroprotection rates in adult and elderly subjects of 90.9% and 89.1%, respectively. The robust immune response to vaccination was confirmed by analyses of neutralizing antibody titers. Both HI and MN antibodies persisted for ≥6 months post-vaccination. Between 34% and 49% of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at baseline. Higher baseline HI titers were associated with receipt of the 2008–09 or 2009–10 seasonal influenza vaccine. High baseline A/California/07/2009 neutralizing antibody titers were also associated with high baseline titers against A/New Caledonia/20/99, a seasonal H1N1 strain which circulated and was included in the seasonal vaccine from 2000–01 to 2006–07. Pre-adsorption with A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline titers in 55% of tested sera. The vaccine was well tolerated with low rates of fever.

Conclusions

A whole-virus H1N1 A/California/07/2009 vaccine was safe and well tolerated and a single dose induced substantial immune responses similar to seasonal influenza vaccines, probably due to immunological priming by previous seasonal influenza vaccines or infections.     

HEALTH CARE FOR WOMEN WITH CHILDREN IN GERMANY—PREVENTIVE AND REHABILITATIVE MEASURES FOR MOTHER AND CHILD

In Germany, the social health system tries to take into account the divergent expectations and needs of women with children. One of the available services for mentally ill women, the so called mother–child rehabilitation, is a special inpatient service for exhausted and depressed women. Mothers may bring their children along and children receive medical and psychological treatment as well if they need it. In the following, we describe and compare this service with other available services for women in Germany and draw some conclusions in regard to the future of these measures, taking funding problems into account.