History, epidemiology and regional diversities of urolithiasis

Archeological findings give profound evidence that humans have suffered from kidney and bladder stones for centuries. Bladder stones were more prevalent during older ages, but kidney stones became more prevalent during the past 100 years, at least in the more developed countries. Also, treatment options and conservative measures, as well as ‘surgical’ interventions have also been known for a long time. Our current preventive measures are definitively comparable to those of our predecessors. Stone removal, first lithotomy for bladder stones, followed by transurethral methods, was definitively painful and had severe side effects. Then, as now, the incidence of urolithiasis in a given population was dependent on the geographic area, racial distribution, socio-economic status and dietary habits. Changes in the latter factors during the past decades have affected the incidence and also the site and chemical composition of calculi, with calcium oxalate stones being now the most prevalent. Major differences in frequency of other constituents, particularly uric acid and struvite, reflect eating habits and infection risk factors specific to certain populations. Extensive epidemiological observations have emphasized the importance of nutritional factors in the pathogenesis of urolithiasis, and specific dietary advice is, nowadays, often the most appropriate for prevention and treatment of urolithiasis

Organotypic modelling as a means of investigating epithelial-stromal interactions during tumourigenesis

The advent of co-culture approaches has allowed researchers to more accurately model the behaviour of epithelial cells in cell culture studies. The initial work on epidermal modelling allowed the development of reconstituted epidermis, growing keratinocytes on top of fibroblasts seeded in a collagen gel at an air-liquid interface to generate terminally differentiated 'skin equivalents'. In addition to developing ex vivo skin sheets for the treatment of burns victims, such cultures have also been used as a means of investigating both the development and repair of the epidermis, in more relevant conditions than simple two-dimensional culture, but without the use of animals. More recently, by varying the cell types used and adjusting the composition of the matrix components, this physiological system can be adapted to allow the study of interactions between tumour cells and their surrounding stroma, particularly with regards to how such interactions regulate invasion. Here we provide a summary of the major themes involved in tumour progression and consider the evolution of the approaches used to study cancer cell behaviour. Finally, we review how organotypic models have facilitated the study of several key pathways in cancer development and invasion, and speculate on the exciting future roles for these models in cancer research

Assessing metabolic flux in plants with radiorespirometry

Carbohydrates are the dominant respiratory substrate in many plant cells. However, the route of carbohydrate oxidation varies depending on the relative cellular demands for energy, reductant and precursors for biosynthesis. During these processes individual substrate carbon atoms are differentially released as carbon dioxide by specific reactions in the network, and this can be measured by monitoring the release of 14CO2 from a range of positionally labelled forms of [14C]glucose. Although the relative amounts of carbon dioxide produced from different carbon positions do not allow precise determination of fluxes, they are indicative of the route of carbohydrate utilisation. Such information can be used to determine whether comprehensive metabolic flux analysis is merited, and also to facilitate independent verification of flux maps generated by other techniques. This chapter describes an approach to determine and interpret the pattern of oxidation of carbohydrates by monitoring 14CO2 release during metabolism of exogenously supplied [1-14C]-, [2-14C]-, [3,4-14C]- and [6-14C]glucose. The method is exemplified by studies on Arabidopsis cell suspension cultures, but the protocol can be easily adapted for investigation of other plant materials

Energy, substrate and protein metabolism in morbid obesity before, during and after massive weight loss

OBJECTIVE: To investigate the effect of surgically induced weight loss on energy, substrate and protein metabolism of morbidly obese patients. DESIGN: A prospective, clinical intervention study of morbidly obese patients before and after surgical treatment. SUBJECTS: Eight morbidly obese patients (BMI 47.88 +/- 7.03). METHODS: Total energy expenditure (TEE; doubly labeled water method), sleeping metabolic: rate (SMR; respiration chamber), body composition (deuterium oxide component of doubly labeled water), substrate metabolism (48 h dietary records, 48 h urine collection and gaseous exchange in the respiration chamber) and whole body protein turnover (primed-continuous infusion of L-[1-C-13]-leucine) were measured before, 3 and 12 months after vertical banded gastroplasty (VBG). RESULTS: The TEE decreased as a result of a decreased SMR (64%) and non-SMR (36%; P = 0.0011, SMR as a function of fat-free mass (FFM) decreased after weight loss (P <0.05). The physical activity index (PAI), defined as TEE/SMR, was low and was not influenced by weight loss. Protein and carbohydrate oxidation decreased significantly after VBG (P <0.05), although 3 months after VBG protein oxidation did not decrease enough to prevent loss of FFM. The energy used for protein turnover was approximately 24% of SMR and did not change after weight loss. CONCLUSIONS: Compensatory processes that oppose weight loss of morbidly obese patients exist, as demonstrated by the disproportional reduction of SMR, and a low PAI, Protein turnover is not a major contributor to the disproportional reduction of SMR