Avoiding the prenatal programming effects of glucocorticoids: are there alternative treatments for the induction of antenatal lung maturation?

BACKGROUND: The long-term outcomes of antenatal glucocorticoids (GCs) vary between reports, and have generated controversy in terms of repeated and single-course events, causing irreversible effects on endocrine set points. AIM: This study aimed to assess the effects of alternative therapeutic agents other than synthetic glucocorticoid GC administration for fetal lung maturation. METHODS: A review of literature from PubMed, EMBASE, Cochrane Library, and Google Scholar was conducted to assess the use of alternative therapies to synthetic GCs using recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). End points included the rates of respiratory distress syndrome (RDS), mRNA expression for pneumocyte type II, concentration of surfactant proteins in alveolar lavage, morphological differences, histological proof of lung maturation, and angiogenesis or quantification of the surfactant pool. RESULTS: In all 41 studies examined, we found that ambroxol showed positive effects on lung maturation, but it has yet to be analyzed with sufficient significance in humans. Interleukins and TNF-alpha produce accelerated lung maturation, but have only been evaluated in basic research/experimental studies. Growth factors promote structural and functional growth in all phases of lung maturation, but little is known about their reciprocal effects and exact mechanisms as therapeutics. Thyroid releasing hormone or vitamin A cause detrimental side effects or were less effective for lung maturation. CONCLUSIONS: The efficacy and safety of these alternative agents are differentiated and none up to now can be recommended as an alternative to GCs.

An update on angiogenesis therapy.

Angiogenesis is a novel approach for the therapy of various ischemia-related pathophysiologic conditions. Proangiogenic growth factors have shown promising results in preclinical studies using protein- and gene-based therapies. However, their success in clinical trials is hindered by the lack of an optimal delivery strategy that would provide sustained and localized levels of the growth factors in the diseased tissue. Targeted delivery of proangiogenic agents is expected to demonstrate therapeutic efficacy of growth factors at relatively lower doses, without the risk of systemic toxicity in terms of unwanted angiogenesis. To achieve the above objectives, various drug delivery systems are under investigation. This review describes the basic mechanism of action of growth factors, their current status in preclinical and clinical studies, and the issue of drug delivery.

[Differential therapy of osteoporosis--an overview based on recent findings regarding the pathogenesis]. / Die Differentialtherapie von Osteoporosen--ein Uberblick auf der Basis neuerer Erkenntnisse zur Pathogenese.

Osteoporosis had long been considered as an unavoidable consequence of aging for which no prevention was possible, whereas it has recently been recognized as a disease that can be prevented and treated. It is of outstanding importance to choose a therapy tailored to the individual patient based on new findings on the pathogenesis of the different types of osteoporosis and the differential diagnosis related to these. During phases of rapid bone loss, usually at the beginning of postmenopause, but sometimes also in older patients, it is useful to use therapeutic drugs to slow down the high bone turnover to a physiological level when osteoporosis is imminent or manifest. The ideal therapy of established osteoporosis should stimulate bone formation and increase bone mass as well as correct changes in the architecture so that the incidence of new fractures will be reduced or even prevented. In case of an increased fragility, it is especially advantageous to increase the cortical bone mass and to stimulate periosteal bone formation in particular. Therapies increasing cortical porosity such as the administration of fluoride in large doses weaken the bones. Therapies reducing bone remodeling in the long term can inhibit bone reparation and compensatory periosteal bone formation, however. Future prospects for the therapy of osteoporosis using drugs are, on the one hand, an improved exploitation of present strategies by means of new galenical types of application, changes in the daily dosage, the introduction of interval therapies, and synergistic effects due to suitable combinations. On the other hand, new developments achieved by varying chemical structures, e.g., the structures of bisphosphonates and vitamin D metabolites and, above all, new strategies leading to increased bone mass while maintaining or even improving bone structure are urgently required. In addition to the vitamin D metabolites, mainly the parathyroid hormone fragments and growth hormones seem to be promising to achieve this aim. The direct use of cytokines (IGF-1, IGF-2, TGF-beta, etc.) is not yet possible because there is no suitable "drug targeting". An increase in bone mass that has been clinically documented does not necessarily indicate an increased mechanical stability. Bone quality results from a complex relationship between bone mass, bone structure, and the strength of the individual structure elements. Its quantitative measurement and influencing by therapies will be a great challenge to future osteoporosis research.

Clinical role of granulocyte-macrophage colony-stimulating factor.

The activity of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for increasing leukocyte production and enhancing mature neutrophil function has been clearly demonstrated in phase I clinical trials in patients with a variety of hematologic and malignant diseases. The focus of current studies includes determination of optimal administration schedules and its use in combination with myelosuppressive chemotherapy, radiation therapy or antimicrobial agents. The utility of GM-CSF as a stimulant of host defense against infections and tumors is also under study.