Ethical aspects of organ donation activities

Renal transplant remains the treatment of choice for patients with end-stage renal disease. Human organs can be harvested from 2 main sources: living and deceased donors. Preference should be given to deceased-donor transplants since they represent the only source of organs for several nonrenal solid-organ transplants and the only modality where there is no risk to the donor. Unfortunately, even the most well-developed deceased-donor program (eg, the Spanish program) can barely cover 50% of its waiting list because the demand for deceased-donor organs far exceeds supply. The success of transplant surgery has created a waiting list dilemma. Despite all efforts, deceased-donor donation cannot meet current needs and therefore, living donation demands serious consideration. This is supported by the fact that the risk to live donors is minimal, graft survival is significantly better than that of deceased-donor kidneys regardless of HLA matching, and professional ethical philosophers have fewer difficulties with voluntary living donations than with the removal of an organ from a cadaver. This is especially true in our region. Living-related donation has always been acceptable ethically. It is, however, limited by the number of willing and qualified donors, the high incidence of familial renal diseases, and donor coercion (especially in our area). Living-unrelated donation increases the availability of donors, decreases the chances of coercion, and eliminates the problem of consanguinity. It raises, however, the ethical issues of commercialism, transplant tourism, and organ trafficking. The arguments for and against living-unrelated donation are innumerable. They have been the subject of several international forums and have raised endless discussions. We have set long ago a series of rules and regulations that are in close agreement with the recent Amsterdam and Kuwait resolutions. We have been continually modifying them over the last 15 years to try to implement our ideal, which is to protect the interest of the living donor and avoid commercialism.     

Unusual variation of popliteal arterial branches: 4 axes by early division of the peroneal artery

Embryonic development of arteries of the lower limb results from the union of dorsal and ventral systems, explaining many variations at different levels. Some of these are important to recognize during the radiological exam because they can affect therapeutic management. These variations are most often bilateral and symmetrical predominating at the popliteal and subpopliteal levels. Lippert classified them into three types: normal level of popliteal arterial branching, high division of popliteal artery, hypoplastic or aplastic branching with altered distal supply. The length of the tibioperoneal trunk may also vary, rarely measuring more than 5 cm. We report a case combining three variations, two of them previously described in the literature and the third one not yet reported: our patient presented four arteries due to early bifurcation of the peroneal artery.     

Usefulness of Pulsed Wave Tissue Doppler Imaging in Assessment of Left Ventricular Functions in Children with Beta-Thalassemia Major

Objective

To evaluate the changes in the LV systolic and diastolic function in children with beta-thalassemia major (β-TM) using pulsed wave tissue doppler (TD) echocardiography.

Methods

Clinical, conventional echo doppler and pulsed wave tissue doppler imaging parameters were compared in 40 beta-thalassemia major patients (mean age, 6.52?±?3.5 y) and 25 age and sex matched normal subjects (mean age, 6.5?±?2.7 y).

Results

There were no significant statistical differences between mean fractional shortening (FS) and ejection fraction (EF) of left ventricle (LV) of the patients and control group. Children with beta-thalassemia had significantly lower E′ wave velocities measured at the left ventricular septal annulus (8.1?±?3.3 vs. 13?±?2.5, P?<?0.001), lateral margin of the mitral annulus (9.1?±?5.4 vs. 13.3?±?2.5, P?<?0.001) and lateral margin of the tricuspid annulus (9.3?±?3.9 vs. 13.3?±?2.5, P?<?0.001) when compared to the control group. Furthermore children with beta-thalassemia had significantly lower E′/A′ wave ratio at the left ventricular septal annulus (0.76?±?0.34 vs. 1.36?±?0.23), lateral margin of the mitral annulus (0.83?±?0.17 vs. 1.28?±?0.22), and lateral margin of the tricuspid annulus ((0.90?±?0.27 vs. 1.26?±?0.23, (P?<?0.05) when compared to the control group.

Conclusions

This study showed that patients with beta-thalassemia major and normal conventional echo doppler parameters had statistically significant changes detected by pulsed wave tissue doppler imaging.     

The effects of 2{5(4-chlorophenyl) pentyl}oxirane-2-carbonyl-CoA on mitochondrial oxidations

2{5(4-Chlorophenyl)pentyl}oxirane-2-carbonyl-CoA (POCA-CoA) was prepared from 2{5(4-chlorophenyl)pentyl}oxirane-2-carboxylate (POCA) and characterised chromatographically. POCA-CoA does not inhibit citrate cycle oxidations or effect oxidative phosphorylation by rat liver mitochondria. POCA-CoA at low (μM) concentrations, but not free POCA^?, specifically inhibits palmitoyl-CoA oxidation at the stage of carnitine palmitoyltransferase I (CPT I) situated on the outer face of the inner mitochondria membrane. Palmitoyl-carnitine oxidation was not inhibited by POCA-CoA. POCA-CoA inhibits palmitoyl-CoA oxidation in liver mitochondria from fed rats more strongly than it does in mitochondria from fasted rats, similarly to the inhibition by malonyl-CoA [E. D. Saggerson and C. A. Carpenter, FEBS Lett. 129, 225 (1981)]. Palmitoyl-CoA, by contrast with palmitoylcarnitine, is not quantitatively oxidised to acetoacetate by liver mitochondrial fractions, presumably due to competing palmitoyl-CoA hydrolase activity. In the presence of POCA-CoA the amount oxidised is decreased further because the slower rate of oxidation allows more palmitoyl-CoA to be hydrolysed to palmitate. The oxidation of palmitoyl-CoA, but not that of palmitoyl-carnitine, was strongly decreased in washed liver and muscle mitochondrial fractions from POCA-fed animals. POCA^? inhibited the oxidation of {U-¹⁴C}palmitate in cultured human fibroblasts, and caused small increases in ¹⁴CO₂ production from {1-¹⁴C}pyruvate and {U-¹⁴C}glucose. Inhibition of β-oxidation at the stage of CPT I by POCA-CoA can explain the powerful hypoketonaemic and hypoglycaemic effects of POCA in fasted normal and fasted diabetic animals [H. P. O. Wolf, K. Eistetter and G. Ludwig, Diabetologia22, 456 (1982)].     

Cell extracts from spleen and adipose tissues restore function to irradiation‐injured salivary glands

A cell extract from whole bone marrow (BM), which we named “BM Soup,” has the property to restore saliva secretion to irradiation (IR)‐injured salivary glands (SGs). However, BM cell harvesting remains an invasive procedure for the donor. The main objective of this study was to test the therapeutic effect of “Cell Soups” obtained from alternate tissues, such as adipose‐derived stromal cells (ADSCs) and spleen cells to repair SGs. BM Soup, Spleen Soup, ADSC Soup, or saline (vehicle control) was injected intravenously into mice with IR‐injured SGs (13Gy). Results demonstrated that all three cell soups restored 65–70% of saliva secretion, protected acinar cells, blood vessels, and parasympathetic nerves, and increased cell proliferation. Although protein array assays identified more angiogenesis‐related growth factors in ADSC Soup, the length of its therapeutic efficiency on saliva flow was less than that of the BM Soup and Spleen Soup. Another objective of this study was to compare “Fresh” versus “Cryopreserved (?80 °C)” BM Soup. It was found that the therapeutic effect of 12‐month “Cryopreserved BM Soup” was comparable to that of “Fresh BM Soup” on the functional restoration of IR‐injured SGs. In conclusion, both Spleen Soup and ADSC Soup can be used to mitigate IR‐damaged SGs.     

Effect of sodium alginate on the stability of natural soybean oil body emulsions

In this work, the influence of an anionic polysaccharide, sodium alginate (ALG), on the stability of soybean oil body (OB) emulsions under different environmental conditions, including NaCl, pH and freeze–thaw cycling, was studied by analyzing the particle electric charge, particle size and distribution, and using optical and fluorescence microscopy. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that the proteins on the surface of oil bodies were mainly oleosins. It was found that ALG can be adsorbed to the surface of oil bodies by strong electrostatic interactions at pH 4.5 and the optimal concentration of ALG was 0.35 wt% for 1 wt% OB emulsions. At pH 4–8, ALG-coated OB emulsions were more stable than uncoated OB emulsions with smaller particle size and more uniform size distribution due to the interaction between OB and ALG. The ALG-coated OB emulsions were also all stable against NaCl within the concentration range of 0–250 mM at pH 7 while uncoated OB emulsions aggregated gradually with the increase of NaCl concentration. For OB emulsions with higher concentration of 10–40 wt% which are frequently used in the food industry, the minimal concentration of ALG required to make stable emulsions was found to be 0.5–1 wt%, correspondingly. Coating oil bodies with ALG also significantly improved the stability of natural oil body emulsions against freeze–thaw cycling, which is of great significance to the further development of natural oil body-based products in food industry.

For the first time sodium alginate is used to improve the stability of oil body emulsions against salt, pH and freeze–thaw cycling.     

Lentivirus-mediated Gene Transfer in Hematopoietic Stem Cells Is Impaired in SHIV-infected,ART-treated Nonhuman Primates

Recent studies have demonstrated that genetically modified hematopoietic stem cells (HSCs) can reduce HIV viremia. We have developed an HIV/AIDS-patient model in Simian/human immunodeficiency virus (SHIV)-infected pigtailed macaques that are stably suppressed on antiretroviral therapy (ART: raltegravir, emtricitabine and tenofovir). Following SHIV infection and ART, animals undergo autologous HSC transplantation (HSCT) with lentivirally transduced cluster of differentiation (CD)34⁺ cells expressing the mC46 anti-HIV fusion protein. We show that SHIV⁺, ART-treated animals had very low gene marking levels after HSCT. Pretransduction CD34⁺ cells contained detectable levels of all three ART drugs, likely contributing to the low gene transfer efficiency. Following HSCT recovery and the cessation of ART, plasma viremia rebounded, indicating that myeloablative total body irradiation cannot completely eliminate viral reservoirs after autologous HSCT. The kinetics of recovery following autologous HSCT in SHIV⁺, ART-treated macaques paralleled those observed following transplantation of control animals. However, T-cell subset analyses demonstrated a high percentage of C-C chemokine receptor 5 (CCR5)-expressing CD4⁺ T-cells after HSCT. These data suggest that an extended ART interruption time may be required for more efficient lentiviral transduction. To avoid complications associated with ART interruption in the context of high percentages of CD4⁺CCR5⁺T-cells after HSCT, the use of vector systems not impaired by the presence of residual ART may also be beneficial.