Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati subjects classified with the metabolic syndrome

Background and aimsCarbohydrate restriction (CR) has been shown to improve dyslipidemias associated with metabolic syndrome (MetS). We evaluated the effects of CR on lipoprotein subfractions and apolipoproteins in Emirati adults classified with the MetS.Methods and results39 subjects (15 men/24 women) were randomly allocated to a CR diet [20–25% energy from carbohydrate (CHO)] for 12 wk (CRD group) or a combination treatment consisting of CRD for 6 wk followed by the American Heart Association diet (50–55% CHO, AHA group) for an additional 6 wk. All subjects reduced body weight, LDL cholesterol and triglycerides (P < 0.01). At baseline all subjects had low concentrations of medium VLDL and total HDL particles associated with the very low plasma triglycerides and HDL cholesterol in this population. After 12 wk, the large VLDL subfraction was decreased over time for subjects in the CRD group (P < 0.01) while these changes were not observed in those subjects who changed to the AHA diet. The number of medium and small LDL particles decreased for all subjects rendering a less atherogenic lipoprotein profile. In agreement with these results, a significant decrease in apolipoprotein (apo) B was observed (P < 0.01). The medium HDL subfraction and apo A-II, which can be considered pro-atherogenic, were also decreased over time in the CRD group only.ConclusionsThese results suggest that weight loss favorably affects lipoprotein metabolism and that the CRD had a better effect on atherogenic VLDL and HDL than the low fat diet recommended by AHA.     

Children as receptors of living donors

The most important factor in life expectancy for children on renal replacement therapy (RRT) is to have a functioning graft when they reach adulthood (63 years  on transplantation vs 37 years on dialysis). The pediatric recipient is very suitable for a living donor transplantation (LDT), with few contraindications. There are several reasons that make LDT the most recommended RRT in children: pre-emptive transplant avoiding dialysis, good renal mass, minimal cold ischemia time, better HLA-matching and the possibility to program the time of surgery. Long term graft survival in LDT is significantly better than in cadaveric donor transplantation (CDT) (81.3%  LDT vs 60.8 % CDT at 10 years follow-up). Calculated half-life graft survival for recipients aged 2-5 years reaches 27.5 years in some series, making LDT the ideal option for these children. Adolescent recipients (12-17 years) have an excellent early graft survival, but the worst long term outcome compared with the rest of pediatric population. However, preemptive LDT has a 70% of graft survival at 10 years. Late rejections episodes associated with non-adherence factors are found in all series. Unrelated LDT in pediatric recipients outcome remain unclear.     

Patient information: when and what

The living donor kidney transplant should be considered a priority option providing better quality of life and survival for those needing renal replacement therapy. To increase their number, both nephrologists and patients, should be informed more and better, offering this option compared with LDKT alternatives (dialysis or kidney transplant from a deceased donor). The clinical nephrology consultations or specific pre-dialysis are the space where in stages 3 and 4 of renal failure should be started on LDKT informational approaches. Later, when seeking more detailed information and/or evaluation of potential donors, this could be provided at times and spaces specifically reserved for awareness professionals with the use of brochures or Internet addresses. Information should focus especially on the additional benefits of pre-emptive LDKT, the risks of nephrectomy and long term controls for the donor. Finally, donor, recipient and family should know that the donation will only be justified and may be accepted if the studies of risk/benefit for the donor and recipient have been faithfully evaluated according to the highest ethical standards.     

Relationship Between Tobacco Consumption and Health-related Quality of Life in Adults Living in a Large Metropolitan Area

The aim of this study was to analyze the relationship between health-related quality of life (HRQOL) and tobacco consumption in adult individuals (over the age of 15). The study was based on individual data from the City of Madrid Health Survey (ESCM05). Subjects were divided into three groups according to tobacco consumption: smokers, nonsmokers, and ex-smokers. HRQOL was measured using the COOP/WONCA quality-of-life vignettes. A multivariate adjustment with multinomial logistic regression was made, including the following as covariables: sociodemographic characteristics, comorbidities, drug use, and lifestyles. A total of 7341 individuals were interviewed (53.7% women), with an average age of 46.7 (SD = 19.02) years. The percentage of smokers was 27%, that of ex-smokers was 16.5%, and that of nonsmokers was 56.5%. There were no significant differences between smokers, ex-smokers, and nonsmokers in the raw scores obtained as totals from the COOP/WONCA questionnaire. Multivariate analysis revealed that smokers consume more antidepressant drugs (OR = 1.54, 95% CI = 1.09–2.16) and tranquilizers (OR = 1.91, 95% CI = 1.45–2.51), drink more alcohol (OR = 2.55, 95% CI = 2.11–3.08), get less physical exercise (OR = 1.33, 95% CI = 1.11–1.60), and have a lower quality of life (OR = 1.02, 95% CI = 1.00–1.04) than nonsmokers. Following adjustment for a significant number of covariables, sociodemographic as well as health-related, smokers consume more antidepressant drugs and tranquilizers, drink more alcohol, get less physical exercise, and demonstrate a lower HRQOL than nonsmokers.     

Therapeutic concepts in mantle cell lymphoma

Mantle cell lymphoma has been considered an incurable disease with current chemotherapy regimens. Recent intense chemoimmunotherapy induction regimens with or without consolidation with autologous stem cell transplantation procedures are showing a potential for cure in a sizable fraction of patients. Similarly, in the salvage setting, preliminary experience with non‐myeloablative allogeneic transplant may cure some patients even after multiple therapeutic failures. However, the recent knowledge of the three basic biologic derangements that are integrated in the disease may change the therapeutic approach of the disease in the near future. In fact, new drugs that target more specifically the major molecular alterations of the disease are being progressively incorporated into the therapeutic armamentarium of the disease. In the near future, more individualized approaches that will take into account not only risk factors present at diagnosis but also biomarkers representative of the molecular alterations present in the disease are foreseen. In this review, we are going to discuss the current therapeutic approaches and the main new drugs that target more specifically the major molecular pathways alterations of the disease.     

Delivery systems for natural antioxidant compounds: Archaeosomes and archaeosomal hydrogels characterization and release study

The aim of this study was to use archaeosomes, a novel kind of liposomes made up by archaeal polar lipids, both multilamellars (MLVs) and unilamellars (SUVs), as a topical delivery system for natural antioxidant compounds recovered from olive mill waste. For comparative purpose an analogue formulation of phosphatidylcholine liposomes was prepared. SUVs were smaller than MLVs ones, showing size values smaller than 200nm, which was maintained during the stability study. Transmission electron microscopy showed spherical morphology for conventional liposomes while archaeosomes had more irregular membranes. Vesicle encapsulation efficiency was quite similar in both formulations and was enough to ensure a good antioxidant activity. Stability studies were performed one month after the preparation of formulations, which showed a high stability with no change in the initial characteristics of the suspensions. Furthermore, the possibility of incorporating the liposomal suspensions in different excipients (Carbopol-940(?) and Pluronic-127(?)) for topical administration was studied. In order to evaluate the release behaviour of the different systems prepared, in vitro diffusion studies were carried out using vertical diffusion Franz cells. In both cases the incorporation of the vesicles into the gels lead in a sustained release for 24h. Archaeosome gels released a similar amount of phenolic compounds regardless the excipient used, while in liposomal gels great release differences were found between carbopol and pluronic gel.     

A New Approach to Explore the Impact of Freeze-Thaw Cycling on Protein Structure: Hydrogen/Deuterium Exchange Mass Spectrometry (HX-MS)

Purpose

The impact of freeze-thaw (F/T) on structure integrity of protein therapeutics is poorly understood, partially due to lack of methods to detect protein structural perturbations during F/T processing in the frozen state.

Methods

A new approach of hydrogen/deuterium exchange was developed to separate and distinguish the specific impact of single freezing and F/T cycling on protein structure, using lactate dehydrogenase (LDH) as model system.

Results

In the freezing process, a fraction of LDH molecules that was inversely dependent on protein concentration was observed to partially denature its structure. Local structural perturbations were localized by peptide level HX analysis to the surface residues in segments 91–132, 170–237 and 288–331. In contrast, F/T cycling led to irreversible LDH aggregation with global structural unfolding. Residual solvent-protected structure was only detected in the aggregates for three segments, 13–31, 109–117 and 133–143, that were coincident with the consensus aggregation hotspots predicted by four different algorithms.

Conclusions

Results indicate freezing preferentially disturbs local structure at the surface residues, consistent with ice-solution interface-mediated denaturation mechanism. F/T-induced aggregation begins as partial denaturation during freezing, but is accompanied by more comprehensive structural rearrangement during F/T cycling.