Engineering kidneys from simple cell suspensions: an exercise in self-organization

Increasing numbers of people approaching and living with end-stage renal disease and failure of the supply of transplantable kidneys to keep pace has created an urgent need for alternative sources of new organs. One possibility is tissue engineering of new organs from stem cells. Adult kidneys are arguably too large and anatomically complex for direct construction, but engineering immature kidneys, transplanting them, and allowing them to mature within the host may be more feasible. In this review, we describe a technique that begins with a suspension of renogenic stem cells and promotes these cells’ self-organization into organ rudiments very similar to foetal kidneys, with a collecting duct tree, nephrons, corticomedullary zonation and extended loops of Henle. The engineered rudiments vascularize when transplanted to appropriate vessel-rich sites in bird eggs or adult animals, and show preliminary evidence for physiological function. We hope that this approach might one day be the basis of a clinically useful technique for renal replacement therapy.     

Involved field radiation for Hodgkin's lymphoma: The actual dose to breasts in close proximity

To decrease the risk of late toxicities in Hodgkin's lymphoma (HL) patients treated with radiation therapy (RT) (HL), involved field radiation therapy (IFRT) has largely replaced the extended fields. To determine the out-of-field dose delivered from a typical IFRT to surrounding critical structures, we measured the dose at various points in an anthropomorphic phantom. The phantom is divided into 1-inch-thick slices with the ability to insert TLDs at 3-cm intervals grid spacing. Two treatment fields were designed, and a total of 45 TLDs were placed (equally spaced) at the margin of the each of the 2 radiation fields. After performing a computed tomography simulation, 2 treatment plans targeting the mediastinum, a typical treatment field in patients with early stage HL, were generated. A total dose of 3060 cGy was delivered to the gross tumor volume for each field consecutively. The highest measured dose detected at 1 cm from the field edge in the planning target volume was 496 cGy, equivalent to 16% of the isocentric dose. The dose dropped significantly with increasing distance from the field edge. It ranged from 1.1–3.9% of the isocentric dose at a distance of 3.2–4 cm to <1.6% at a distance of >6 cm. Although the computer treatment planning system (CTPS) frequently underestimated the dose delivered, the difference in dose between measured and generated by CTPS was <2.5% in 90 positions measured. The collateral dose of radiation to breasts from IFRT is minimal. The out-of-field dose, although mildly underestimated by CTPS, becomes insignificant at >3 cm from the field edge of the radiation field.     

Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition

Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell–mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR–HLA-B*4405^EENLLDFVRF complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.     

Recent Developments in the Role of Coenzyme Q10 for Coronary Heart Disease: a Systematic Review

Purpose of Review

This review examines recent randomized clinical trials evaluating the role of coenzyme Q10 (CoQ10) in the management of coronary heart disease.

Recent Findings

CoQ10 is one of the most commonly used dietary supplements in the USA. Due to its antioxidant and anti-inflammatory effects, CoQ10 has been studied extensively for possible use in managing coronary heart disease. One of the most common applications of CoQ10 is to mitigate statin-associated muscle symptoms (SAMS) based on the theory that SAMS are caused by statin depletion of CoQ10 in the muscle. Although previous studies of CoQ10 for SAMS have produced mixed results, CoQ10 appears to be safe. Because CoQ10 is a cofactor in the generation of adenosine triphosphate, supplementation has also recently been studied in patients with heart failure, which is inherently an energy deprived state. The Q-SYMBIO trial found that CoQ10 supplementation in patients with heart failure not only improved functional capacity, but also significantly reduced cardiovascular events and mortality. Despite these positive findings, a larger prospective trial is warranted to support routine use of CoQ10. Less impressive are the effects of CoQ10 on specific cardiovascular risk factors such as blood pressure, dyslipidemia, and glycemic control.

Summary

Current evidence does not support routine use of CoQ10 in patients with coronary heart disease. Additional studies are warranted to fully determine the benefit of CoQ10 in patients with heart failure before including it in guideline-directed medical therapy.

     

Inconsistencies Between Actual and Estimated Blood Alcohol Concentrations in a Field Study of College Students: Do Students Really Know How Much They Drink?

BACKGROUND: Alcohol use by college students is commonly measured through the use of surveys. The validity of such data hinge on the assumption that students are aware of how much alcohol they actually consume. Recent studies call this assumption into question. Students tend to overestimate the appropriate sizes of standard drinks, suggesting that they might underestimate how much alcohol they consume. If this is true, then students' actual blood alcohol concentrations (BACs) should be higher than BACs estimated based on self-report data. The present study examined this issue METHODS: Breathalyzer readings and self-reported drinking data were collected from 152 college students during the fall of 2004. Estimated BACs were calculated by means of a standard formula, and the relation between actual and estimated BACs was examined. Factors contributing to discrepancies between the two values were identified RESULTS: Estimated BAC levels were significantly higher, not lower, than breath BAC measures. The accuracy of estimated BACs decreased as the number of drinks and amount of time spent drinking increased. Being male and drinking only beer predicted greater accuracy of estimated BACs CONCLUSIONS: Although laboratory data suggest that students underestimate how much they drink, the hypothesis was not supported by data collected in the field. It appears that students might actually overestimate rather than underestimate their levels of consumption when surveyed in the midst of a night of drinking. The findings corroborate observations made by other researchers and suggest that the findings of laboratory studies on college drinking do not necessarily extend to real-world settings.