Optimality in the developing vascular system: branching remodeling by means of intussusception as an efficient adaptation mechanism.

The theory of bifurcating vascular systems predicts vessel diameters that are related to optimality criteria like minimization of pumping energy or of building material. However, mechanisms for producing the postulated optimality have not been described so far, and quantitative data on bifurcation diameters during development are scarce. We used an embryonic vascular bed that rapidly grows and adapts to changing hemodynamic conditions, the chicken chorioallantoic membrane (CAM), and correlated vascular cast and tissue section morphology with in vivo time-lapse video monitoring. The bifurcation exponent delta and associated parameters were quantitatively assessed in arterial and venous microvessels ranging in diameter from 30 to 100 microm. We observed emergence of optimality by means of intussusception, i.e., formation of transvascular tissue pillars. In addition to intussusceptive microvascular growth (IMG = expansion of capillary networks) and intussusceptive arborization (IAR = formation of feeding vessels from capillaries) the observed intussusception at bifurcations represents a third variant of nonsprouting angiogenesis. We call it intussusceptive branching remodeling (IBR). IBR occurred in vessels of considerable diameter by means of two alternative mechanisms: either through pillars arising close to a bifurcation, which increased in girth until they merged with the connective tissue in the bifurcation angle; or through pillars arising at some distance from the bifurcation point, which then expanded by formation of ingrowing tissue folds until they became connected to the tissue of the bifurcation angle. Morphologic evidence suggests that IBR is a wide-spread phenomenon, taking place also in lung, intestinal, kidney, eye, etc., vasculature. Irrespective of the mode followed, IBR led to a branching pattern close to the predicted optimum, delta = 3.0. Significant differences were observed between delta at arterial bifurcations (2.70 to 2.90) and delta at venous bifurcations (2.93 to 3.75). IBR, by means of eccentric pillar formation and fusion, was also involved in vascular pruning. Experimental changes in CAM hemodynamics (by locally increasing blood flow) induced onset of IBR within less than 1 hr. Our study provides morphologic and quantitative evidence that a similar cellular machinery is used for all three variants of vascular intussusception, IMG, IAR, and IBR. It thus provides a mechanism of efficiently generating complex blood transport systems from limited genetic information. Differential quantitative outcome of IBR in arteries and veins, and the experimental induction of IBR strongly suggest that hemodynamic factors can instruct embryonic vascular remodeling toward optimality.     

Effects of laundry detergents on Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Euroglyphus maynei.

BACKGROUND: House-dust mites in clothing and bedding are the source of major allergens. Based on studies of Dermatophagoides pteronyssinus only, weekly washing in hot water is recommended to kill dust mites and remove allergens from clothing and bedding. However, in the United States, washing is most often done in warm or cold water, and other mite species are involved. OBJECTIVE: The purpose of this study was to investigate the lethal effects of various temperatures of hot water alone and hot, warm, and cold water containing detergents and chlorine bleach on Dermatophagoidesfarinae, D. pteronyssinus, and Euroglyphus maynei. METHODS: Mites were soaked in test solutions at various temperatures and for various lengths of time, allowed time to recover, and then analyzed for survival. RESULTS: D. farinae was the most temperature-sensitive and chlorine bleach-sensitive of the three species. In 50 degrees C water alone, 100% mortality for D. farinae was obtained in 10 minutes, whereas most D. pteronyssinus and E. maynei survived. However, 53 degrees C-soaks for 12 and 5 minutes were needed to kill all D. pteronyssinus and E. maynei, respectively. Laundry detergents at their recommended and doubled concentrations and chlorine bleach generally increased mite mortalities over water alone for the three species. Soaking for 4 hours in warm water containing various detergents alone induced mortalities of 19 to 50%, 2 to 35%, and 14 to 46% for D. farinae, D. pteronyssinus, and E. maynei, respectively. CONCLUSIONS: Washing bed linens weekly in warm water with a 4-hour presoak containing most detergents and bleach will kill most D. farinae and, depending on the detergent brand, moderate numbers of D. pteronyssinus. Four-hour soaks in warm water containing the recommended concentrations of various detergents alone also kills moderate numbers of D. farinae, D. pteronyssinus, and E. maynei. Therefore, the cumulative effect of weekly washing with long presoaks should significantly reduce mite levels over time in bed linens, particularly when mattresses and pillows are encased to prevent reinfestation.     

Polyploidization and centrosome hyperamplification in inflammatory bronchi

OBJECTIVE AND DESIGN: Inflammatory and tumorous bronchi were screened in order to obtain new tumor relevant cytogenetic parameters. MATERIAL OR SUBJECTS: Bronchial cells of 32 patients were cultivated by standard cell culture procedures. METHODS: Tetraploidy and aneuploidy was determined by enumeration of chromosome 7 and 8 versus the number of centrosomes. The resulting data were correlated with histopathological data. RESULTS: Tetra- and aneuploidy of epithelial cells were detectable in 76% of tumor cell cultures, 75% of high grade inflammatory tissues and 40% of non- and low grade-inflammatory tissues. Additionally, we observed centrosome hyper-amplification and multipolar mitoses not only in the tumor but also in the early stages of inflammation. CONCLUSION: Inflammatory bronchi already show tumor-specific features and may consequently represent the preliminary genetic stage of cancer development in bronchi.     

Antiseptic Compounds Still Active Against Bacterial Strains Isolated from Surgical Wound Infections Despite Increasing Antibiotic Resistance

The in vitro activities of povidone iodine, potassium peroxymonosulfate, and dimethyldidecylammonium chloride were investigated against 379 nosocomial isolates of Staphylococcus aureus and Pseudomonas aeruginosa responsible for surgical wound infections in patients operated on between July 1995 and June 2001. Overall, the isolates were inhibited by the antiseptics at concentrations below those used routinely. In spite of increasing resistance to the various antibiotics used to treat surgical wound infections, no significant variation in the susceptibility to antiseptics was demonstrated during this 6-year study. Electronic Publication     

CNS access of selected H3-antagonists: ex vivo binding study in rats

Inflammation Research -     

Ein Fragebogen zur infertilitätsbedingten Belastung andrologischer Patienten

The infertility distress scale (IBS) has been designed to assess the stress perceived by andrological patients resulting from infertility. This review presents findings from different studies with a total of 769 patients. The scale consists of eight items. The stability of scores is very high even for a mean follow-up of 2 years. The scale correlates highly with an already validated measure of infertility distress. Correlations with measures of depressiveness are in the low to medium range. All in all, the psychometric results indicate that the IBS is a factor-stable, reliable and valid instrument for assessing chronic infertility distress in andrological patients. After the presentation of normative data, the usefulness of the IBS as a screening instrument for identifying highly distressed patients is discussed. Findings supporting the scale's sensitivity to change are also presented. The scale is a useful tool in clinical practice as well as in research.     

Modelling debonded stem-cement interface for hip implants: effect of residual stresses.

OBJECTIVE: To assess the effect of the residual stresses due to cement curing on the load transfer of cemented hip implants. DESIGN: The load transfer at the stem-cement interface of an idealized hip stem surrounded by cortical bone was investigated using a three-dimensional finite element analysis. A debonded stem-cement interface was considered to simulate a highly polished stem in contact with cement; Coulomb friction at the stem-cement interface was considered. BACKGROUND: Numerical analyses on the load transfer of cemented hip implants do not include residual stresses due to cement curing at the stem-cement interface. METHODS: The magnitude of the residual stresses was determined experimentally. In the finite element model, non-linear contact elements modelled the debonded stem-cement interface. In particular, the compressive radial residual stresses that are generated at the interface, due to the cement expansion during curing, were treated similar to a press-fit problem. RESULTS: The cement stress distributions were affected by the magnitude of the residual stresses. Failing to include residual stresses underestimated the cement stresses at the interface, mainly affecting the radial and hoop stresses. The load was transferred from the stem to the cement more uniformly along the interface once residual stresses were included. CONCLUSIONS: Because there is no chemical bond at the interface between the stem and cement, the interface resistance depends on friction thus radial residual compressive stresses developed by the cement curing play a direct role. RELEVANCE: Implant loosening of cemented hip implants is one of the major causes of late failure of the arthroplasty. The load is transferred from the stem to the bone primarily across the interfaces, consequently modelling accurately the interface is essential in predicting the load transfer.     

Stimulatory and inhibitory epitopes in the T cell responses of mice to Der p 1

BACKGROUND: The responses of mice to the mite allergen Der p 1 have been used to study the mechanisms of allergic sensitization and the development of new types of immunotherapy. Many of the studies require a knowledge of the T cell epitopes, and because Der p 1 is polymorphic, the effect of natural amino acid substitution in the allergen. The intranasal administration of peptides containing T cell epitopes can induce a mucosal tolerance but it is not known if the major activity is limited to stimulatory peptides and if, as found for autoimmunity, some epitopes are not inhibitory. OBJECTIVE: To determine and compare the sequences of Der p 1 which contain stimulatory epitopes for the high responding H-2(b) and H-2(q) mice and the sequences which induce tolerance by intranasal administration of peptides. METHODS: T cell responses of mice immunized with Der p 1 were measured by in vitro T cell stimulation assays so an extensive study of epitope recognition and intranasal tolerance could be made. Synthetic peptides were used to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to map the major H-2(b) epitope in detail. This included the effect of the common polymorphic amino acid 124 substitution found within this epitope. RESULTS: Three and two regions, respectively, were found to contain stimulatory T cell epitopes for H-2(b) and H-2(q) mice. The peptides in these regions were also the most active at inducing intranasal tolerance for the responding haplotype. The correspondence between inhibitory and stimulatory peptides was maintained for the fine mapping of the major H-2(b) epitope. This was found about a core region of 118-126 which was overlapping but separate to a consensus sequence for the binding of endogeneous peptides. Peptides with alanine at the naturally polymorphic residue 124 stimulated and inhibited responses to Der p 1 more effectively, while peptides with the valine 124 variant were immunogenic but poorly cross-reactive. CONCLUSIONS: The intranasal administration of peptides representing each of five epitopes recognized by two strains of mice were able to induce mucosal tolerance and the major tolerizing activity was limited to these epitopes. The position of the core major epitope for C57 mice, which differs from a previously predicted epitope, and its specificity for the natural alanine 124 variant is described.