[Update on the epidemiology, diagnosis and therapy of tuberculosis in HIV-infected patients]. / Aktuelle Aspekte zur Epidemiologie, Diagnose und Therapie der Tuberkulose bei HIV-infizierten Patienten.

Globally, the diagnosis and treatment of tuberculosis (TB) in HIV-co-infection has improved dramatically over the last 10 years. Nonetheless, the mortality of co-infected patients remains elevated. In European countries, the proportion of HIV-infected patients amongst all TB cases varies greatly; in Germany it is about 4 - 5%. HIV-infection changes the molecular epidemiology of TB and the drug resistance situation. In endemic areas, HIV-infected patients are often re-infected after completion of treatment for active TB. HIV has a profound influence on the anti-TB-immune response and antiretroviral therapy (ART) cannot completely restore normal immune function. The clinical presentation in advanced HIV-infection is atypical and disseminated disease is common. New "Point-of-Care" test methods are poised to improve the diagnoses of TB in HIV-infection; however, further research is required. The treatment of co-infection is complicated by drug interactions and the immune reconstitution syndrome (IRIS). New concepts and treatment regimens for chemoprevention of TB are necessary, especially for HIV-infected persons.

Parameters of haematology, clinical chemistry and lipid metabolism in the common marmoset and alterations under stress conditions.

Common marmosets are suitable non-human primate models for many human diseases. Standard values for blood parameters are required to evaluate physiological and pathological situations. Two studies were conducted: study I to determine standard values and study II to examine these under changed housing conditions. In study I, all parameters for clinical chemistry were similar in range for both genders with these specifics: male marmosets had significantly higher total and LDL cholesterol levels than females, whereas the mean corpuscular volume and the mean corpuscular haemoglobin were significantly lower than in females. In study II, glucose, lymphocytes and salivary cortisol were significantly lower, and faecal cortisol was increased during the change of housing conditions. In conclusion, standard values for haematology and clinical chemistry for the common marmoset were determined. Further on, parameters that are influenced by relocation stress and its importance for experimental results are described.

The conclusiveness of less-invasive imaging techniques (computer tomography, X-ray) with regard to their identification of bone diseases in a primate model (Callithrix jacchus).

BACKGROUND: Although common marmosets seem to be appropriate animal models to examine bone diseases, no data about the conclusiveness of less-invasive techniques are available. Therefore, the aim was to combine different techniques to analyse changes in bone metabolism of common marmosets with bone diseases. METHODS: Five monkeys were examined by X-ray, computer tomography (CT), histology and immunohistochemistry (IHC). RESULTS: Monkeys with lowest bone mineral density (BMD) showed increased bone marrow, decreased cancellous bone and decreased contrast in X-ray. Highest alkaline phosphatase (AP)-levels were detected in bones with low elastic modulus. Expression of osteopontin (OPN), osteocalcin (OC) and runt-related transcriptions factor 2 (RUNX 2) was detected in bones with high modulus. No expression was present in bones with lower modulus. Collagen type I and V were found in every bone. CONCLUSIONS: In conclusion, CT, X-ray and AP are useful techniques to detect bone diseases in common marmosets. These observations could be confirmed by IHC.

Analysis of the bone metabolism by quantitative computer tomography and clinical chemistry in a primate model (Callithrix jacchus).

BACKGROUND: Common marmosets are widely used as experimental primates; however, little is still known about their bone physiology. Therefore, the aim of our study was to analyse body weight, age and bone-specific blood parameters in relation to morphological bone parameters. METHODS: Fifty-eight common marmosets were analysed for blood calcium (Ca), inorganic phosphor (P(i) ), alkaline phosphatase (AP) and 17-ß-estradiol (E2). The examination of bone parameters was undertaken in the lumbar spine by computer tomography. RESULTS: There was a correlation between bone mineral density (BMD) and body weight, trabecular area ratio and polar moment as well as between BMD and AP or Ca (only males), whereas there were no correlations between BMD and age, P(i) or E2 in all analysed genders. CONCLUSIONS: Our data support the assumption that the common marmoset is a reliable primate model to study changes in bone metabolism because of the similarity of our results to humans.

Immune therapy for infectious diseases at the dawn of the 21st century: the past, present and future role of antibody therapy, therapeutic vaccination and biological response modifiers.

In the last decades of the 20th century, infectious diseases have re-emerged as a significant public health problem in the developed world. However, the available anti-infective armamentarium has proven to be alarmingly insufficient to combat many of the microbes that cause these diseases, such as drug resistant microbes, microbes for which therapy is not available or ineffective because of underlying host immune impairment, and microbes that only cause disease in the setting of impaired immunity but are not pathogens in normal individuals. Hence, there is an urgent need for new approaches to the treatment of infectious diseases that can increase the efficacy of anti-infective therapy and bolster the immune response to microbial agents in immunocompromised hosts, circumvent rising rates of antimicrobial drug resistance and be rapidly developed to fight emerging epidemics. Immune therapy, which encompasses pathogen-specific and non-pathogen specific modalities designed to augment or restore host immunity against disease causing microbes, are poised to play an important part in modern anti-infective therapy. Our growing understanding of host-microbe interaction and mechanisms of protective immunity have allowed for an increasingly rational approach to the design of immune based therapeutic modalities. As part of this effort, it is important to remember that the origin of modern anti-infective therapy was serum therapy, a pathogen-specific immune therapeutic modality. In this paper, we review the historical underpinnings and present and future applications of immune therapy for infectious diseases in light of current challenges to the field.

In vitro effects of interleukin-10, prednisolone, and GM-CSF on the non-specific immune function of human polymorphonuclear leucocytes and monocytes.

A wide range of immune-modulating effects make IL-10 a potential therapeutic option in the treatment of numerous diseases pathophysiological based on a dysregulation of cytokine production. The background of this study was to investigate, whether the beneficial effects of a therapeutic immunosuppression with IL-10 may be countered by an increased risk for infections due to impaired effector cell functions of unspecific immunity. We demonstrated the in vitro effects of IL-10 on phagocytosis (P), intracellular killing (K), and chemotactic activity (C) by human neutrophils (PMN) and monocytes (MON) using Candida albicans as test strain and compared the results to the effects of prednisolone and GM-CSF. IL-10 reduced significantly the intracellular killing rate of PMN compared to untreated phagocytes (60 +/- 16% versus 68 +/- 13%, mean +/- SD, p = 0.0002). High dose IL-10 (100 ng/ml) had a stimulating effect on the percentage of phagocytizing MON (70.2 +/- 12.7% vs. 66.9 +/- 14.2%, p = 0.0436), without impairing intracellular killing. Prednisolone reduced significantly the Candida uptake by MON (57 +/- 18.1% vs. 66. 9 +/- 14.2%, p = 0.0019). In contrast to prednisolone, neither MON nor PMN chemotaxis was suppressed by IL-10. In conclusion, IL-10 had only marginal immunosuppressive effects on the unspecific immunity compared to prednisolone.

Interleukin-10: effects on phagocytosis and adhesion molecule expression of granulocytes and monocytes in a comparison with prednisolone.

Interleukin-10 (IL-10) has potent anti-inflammatory and immunosuppressive properties. The potential therapeutic benefit may be compromised by the down-regulation of the non-specific immune system and an increased risk of infection. We studied the effects of IL-10 on important functions of native and granulocyte-macrophage colony-stimulating factor (GM-CSF) activated neutrophils and monocytes, namely phagocytosis and membrane expression of the beta superset2-integrins and of the intercellular adhesion molecule-1 (ICAM-1). In order to simulate the in vivo situation closely, we used whole blood flowcytometric assays. The effects of IL-10 (0.05, 1, 10, 100 ng/ml) were compared to those of prednisolone (10 superset-8-10 superset-5 Mol/l), an approved immunosuppressive drug which is known to impair phagocyte function. - Incubation with IL-10 for three hours significantly attenuated the ability of neutrophils to phagocytose E.coli, particularly in lower concentrations. On the other hand, high IL-10 concentrations (10, 100 ng/ml) slightly augmented monocyte phagocytosis. Similarly, expression of the beta subset2-integrins and of ICAM-1 on monocytes was markedly enhanced with IL-10 concentrations in the range from 1 to 100 ng/ml and IL-10 showed strong synergistic effects with GM-CSF in the enhancement of monocyte receptor expression. Neutrophil adhesion molecule expression was not affected. Prednisolone suppressed the phagocytosis of both cell types in a dose-dependent fashion but hardly altered the receptor numbers. Our study indicates that IL-10 can behave as a de-activator as well as an activator on the non-specific immune system, depending on the cell type and the concentration.