Hendrik Moorlag

Site-Specific Inhibition of Glomerulonephritis Progression by Targeted Delivery of Dexamethasone to Glomerular Endothelium

Glomerulonephritis represents a group of renal diseases with glomerular inflammation as a common pathologic finding. Because of the underlying immunologic character of these disorders, they are frequently treated with glucocorticoids and cytotoxic immunosuppressive agents. Although effective, use of these compounds has limitations as a result of toxicity and systemic side effects. In the current study, we tested the hypothesis that targeted delivery of dexamethasone (dexa) by immunoliposomes to activated glomerular endothelium decreases renal injury but prevents its systemic side effects. E-selectin was chosen as a target molecule based on its disease-specific expression on activated glomerular endothelium in a mouse anti-glomerular basement membrane glomerulonephritis. Site-selective delivery of AbEsel liposome-encapsulated dexamethasone strongly reduced glomerular proinflammatory gene expression without affecting blood glucose levels, a severe side effect of administration of free dexamethasone. Dexa-AbEsel liposomes reduced renal injury as shown by a reduction of blood urea nitrogen levels, decreased glomerular crescent formation, and down-regulation of disease-associated genes. Immunoliposomal drug delivery to glomerular endothelium presents a powerful new strategy for treatment of glomerulonephritis to sustain efficacy and prevent side effects of potent anti-inflammatory drugs.

Formaldehyde fixation and microwave irradiation

SummaryFormaldehyde is the most commonly used fixative in pathology laboratories. However, due to time pressures, this fixative is often not optimally exploited. the majority of biopsies are only partly fixed when histoprocessing is started, with adverse effects. This paper reports how formaldehyde fixation is improved, by using 1.5 min of microwave irradiation of tissue previously soaked for four hours in the fixation solution. It is argued that this beneficial effect of microwave irradiation can be attributed to the acceleration of the reaction of formaldehyde to the tissue. Formation of free formaldehyde, by the dehydration of methylene glycol present in the tissue when the irradiation starts, is also enhanced. Five different formaldehyde-containing fixatives were evaluated, using five different working protocols. Spleen was taken as a suitable tissue for these tests. The technique described leads to uniform microscopical results. It is a simple method and is suitable for use in routine laboratories.

MICROWAVE-STIMULATED STAINING OF PLASTIC EMBEDDED BONE-MARROW SECTIONS WITH THE ROMANOWSKY-GIEMSA STAIN - IMPROVED STAINING PATTERNS

Staining plastic sections with the Romanowsky-Giemsa method is both time-consuming and difficult. This paper reports how the staining time can be reduced to 25 min using microwave irradiation of the staining solution. It is shown that staining results depend on the fixative used, staining temperature, dye concentration and pH of the staining solution as well as on several parameters of the microwave irradiation technique. The staining patterns are improved when compared with those obtained by conventional staining of plastic sections. The colors are more brilliant and greater contrasts are observed. Basophilia, polychromasia, and orthochromasia accompanying red cell maturation are more pronounced. For white cell maturation the initial appearance of specific granules (neutrophil, basophil, and eosinophil) is more evident. Thus, cell classification is easily accomplished using the described technique. It is suggested that microwave-stimulated staining be considered for routine use.

Positive thinking in anxiety disordered children reconsidered

Negatively valenced thoughts are assumed to play a central role in the development and maintenance of anxiety. However, the role of positive thoughts in anxiety is rather unclear. In the current study we examined the role of negative and positive self-statements in the anxiety level of anxious and non-anxious children. Participants were 139 anxiety disordered children and 293 non-anxious children (8-18 years). Compared to non-anxious children, anxious children reported more negative thoughts, less positive thoughts and lower State of Mind (SOM) ratios (ratio of positive to negative thoughts). Negative thoughts and SOM ratios were the strongest predictors of anxiety level in anxious children; whereas both negative and positive thoughts were the strongest predictors of anxiety level in non-anxious children. To conclude, a lack of positive thoughts might be more than just an epiphenomenon of anxiety level and might deserve a place in the cognitive model of anxiety.