Modelling crystal aggregation and deposition in the catheterised lower urinary tract

Urethral catheters often become encrusted with crystals of magnesium struvite and calcium phosphate. The encrustation can block the catheter, which can cause urine retention in the bladder and reflux into the kidneys. We develop a mathematical model to investigate crystal deposition on the catheter surface, modelling the bladder as a reservoir of fluid and the urethral catheter as a rigid channel. At a constant rate, fluid containing crystal particles of unit size enters the reservoir, and flows from the reservoir through the channel and out of the system. The crystal particles aggregate, which we model using Becker–Döring coagulation theory, and are advected through the channel, where they continue to aggregate and are deposited on the channel’s walls. Inhibitor particles also enter the reservoir, and can bind to the crystals, preventing further aggregation and deposition. The crystal concentrations are spatially homogeneous in the reservoir, whereas the channel concentrations vary spatially as a result of advection, diffusion and deposition. We investigate the effect of inhibitor particles on the amount of deposition. For all parameter values, we find that crystals deposit along the full length of the channel, with maximum deposition close to the channel’s entrance.     

Laxative-induced Diarrhoea: A Continuing Clinical Problem

Seven women spent an average of 127 days in hospital and were extensively investigated, including a laparotomy, before their complaints of abdominal pain, diarrhoea, and weight loss were shown to be due to excessive taking of laxatives. All denied taking laxatives and in none were the characteristic features of the effects of cathartics on the colon seen on sigmoidoscopy or radiological examination.Hypokalaemia and other electrolyte abnormalities were common and were thought to be due to a combination of severe diarrhoea and vomiting. The rectal mucosa was seen to be abnormal on biopsy only in the three patients who had taken senna preparations. The diagnosis was not easy and was finally established either by analysis of the urine and stools or by searching the patient''s ward locker.     

Localizing Brain Regions Associated with Female Mate Preference Behavior in a Swordtail

Female mate choice behavior is a critical component of sexual selection, yet identifying the neural basis of this behavior is largely unresolved. Previous studies have implicated sensory processing and hypothalamic brain regions during female mate choice and there is a conserved network of brain regions (Social Behavior Network, SBN) that underlies sexual behaviors. However, we are only beginning to understand the role this network has in pre-copulatory female mate choice. Using in situ hybridization, we identify brain regions associated with mate preference in female Xiphophorus nigrensis, a swordtail species with a female choice mating system. We measure gene expression in 10 brain regions (linked to sexual behavior, reward, sensory integration or other processes) and find significant correlations between female preference behavior and gene expression in two telencephalic areas associated with reward, learning and multi-sensory processing (medial and lateral zones of the dorsal telencephalon) as well as an SBN region traditionally associated with sexual response (preoptic area). Network analysis shows that these brain regions may also be important in mate preference and that correlated patterns of neuroserpin expression between regions co-vary with differential compositions of the mate choice environment. Our results expand the emerging network for female preference from one that focused on sensory processing and midbrain sexual response centers to a more complex coordination involving forebrain areas that integrate primary sensory processing and reward.     

Development of a gradient elution high-performance liquid chromatography assay with ultraviolet detection for the determination in plasma of the anticancer peptide [Arg, -Trp, mePhe]-substance P (6–11) (antagonist G), its major metabolites and a C-terminal pyrene-labelled conjugate

[Arg⁶, -Trp^7,9, mePhe⁸]-substance P (6–11), code-named antagonist G, is a novel peptide currently undergoing early clinical trials as an anticancer drug. A sensitive, high efficiency high-performance liquid chromatography (HPLC) method is described for the determination in human plasma of antagonist G and its three major metabolites, deamidated-G (M1), G-minus Met¹¹ (M2) and G[Met¹¹(O)] (M3). Gradient elution was employed using 40 mM ammonium acetate in 0.15% trifluoroacetic acid as buffer A and acetonitrile as solvent B, with a linear gradient increasing from 30 to 100% B over 15 min, together with a microbore analytical column (μBondapak C₁₈, 30 cm×2 mm I.D.). Detection was by UV at 280 nm and the column was maintained at 40°C. Retention times varied by <1% throughout the day and were as follows: G, 13.0 min; M1, 12.2 min; M2, 11.2 min; M3, 10.8 min, and 18.1 min for a pyrene conjugate of G (G–P). The limit of detection on column (LOD) was 2.5 ng for antagonist G, M1–3 and G–P and the limit of quantitation (LOQ) was 20 ng/ml for G and 100 ng/ml for M1–3. Sample clean-up by solid-phase extraction using C₂-bonded 40 μm silica particles (Bond Elut, 1 ml reservoirs) resulted in elimination of interference from plasma constituents. Within-day and between-day precision and accuracy over a broad range of concentrations (100 ng/ml–100 μg/ml) normally varied by <10%, although at the highest concentrations of M1 and M2 studied (50 μg/ml), increased variability and reduced recovery were observed. The new assay will aid in the clinical development of antagonist G.     

Curvature- and fluid-stress-driven tissue growth in a tissue-engineering scaffold pore

Cell proliferation within a fluid-filled porous tissue-engineering scaffold depends on a sensitive choice of pore geometry and flow rates: regions of high curvature encourage cell proliferation, while a critical flow rate is required to promote growth for certain cell types. When the flow rate is too slow, the nutrient supply is limited; when it is too fast, cells may be damaged by the high fluid shear stress. As a result, determining appropriate tissue-engineering-construct geometries and operating regimes poses a significant challenge that cannot be addressed by experimentation alone. In this paper, we present a mathematical theory for the fluid flow within a pore of a tissue-engineering scaffold, which is coupled to the growth of cells on the pore walls. We exploit the slenderness of a pore that is typical in such a scenario, to derive a reduced model that enables a comprehensive analysis of the system to be performed. We derive analytical solutions in a particular case of a nearly piecewise constant growth law and compare these with numerical solutions of the reduced model. Qualitative comparisons of tissue morphologies predicted by our model, with those observed experimentally, are also made. We demonstrate how the simplified system may be used to make predictions on the design of a tissue-engineering scaffold and the appropriate operating regime that ensures a desired level of tissue growth.