Prevention of Recurrent Thrombosis in Antiphospholipid Syndrome: Different from the General Population?

Antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis with or without pregnancy morbidity in the presence of autoantibodies targeting proteins that associate with membrane phospholipids, termed “antiphospholipid antibodies” (aPL). Management of arterial and venous thromboses shares some similarities with management of arterial and venous thromboses in the general population; however, there are key differences. The majority of studies addressing management of thrombotic APS focus on secondary prevention. Vitamin K antagonists (VKA) are typically used for secondary prevention of venous thromboembolism in APS. Optimal management of isolated arterial thrombosis, in particular ischemic stroke, in patients with APS is controversial, and proposed therapeutic options have included antiplatelet agents and VKA. Primary prophylaxis in aPL-positive patients should be an individualized decision taking into account patient-specific risks. There may be a role for adjuvant therapies such as hydroxychloroquine, vitamin D, statins, or novel therapeutics in specific patient populations.     

Effect of hospital on variation in visual acuity and vision‐specific quality of life after cataract surgery

Objective To evaluate the contribution of hospital‐to‐hospital variability in changes in clinical and health‐related quality of life outcomes among patients undergoing cataract extraction by phacoemulsification. Methods Prospective observational study of 14 public hospitals. We recruited consecutive patients on waiting lists for cataract extraction. Clinical data were collected prior to the intervention and 6 weeks afterward. Subjects completed the visual function index (VF‐14) prior to the procedure and 3 months afterward. Univariate and multivariate analysis were performed for visual acuity and VF‐14 scores. Results Substantial differences were observed across the 14 hospitals. At baseline, mean visual acuity ranged from 0.16 to 0.34, and mean VF‐14 scores ranged from 48.06 to 75.89. Following cataract extraction, the mean improvement in visual acuity ranged from 0.35 to 0.57 and in VF‐14 scores from 10.94 to 41.70. The ranges were even more pronounced among patients with low visual acuity or low VF‐14 scores prior to the intervention. Significant differences remained in multivariate analysis. Within the multivariate analysis, the variable ‘hospitals’ had an R² of 0.069 for the visual acuity model and of 0.073 for the VF‐14 model, 20% and 13%, respectively, of the total variability explained. Variation was also observed within geographic regions. Conclusions Outcomes of patients undergoing cataract extractions vary widely from hospital to hospital, even within the same geographic region, explaining an important part of the results. Quality improvement efforts should concentrate on patients with low pre‐intervention visual acuity or vision‐related disability to reduce this variability in outcomes.     

Peroxisome proliferation and antioxidant enzymes in transplanted mussels of four basque estuaries with different levels of polycyclic aromatic hydrocarbon and polychlorinated biphenyl pollution

We aimed to determine the effects of changes in polycyclic aromatic hydrocarbon (PAH) and polychlorinated biphenyl (PCB) bioavailability on peroxisome proliferation and antioxidant enzymes to assess their potential use as pollution biomarkers. For this, mussels (Mytilus galloprovincialis) were sampled in Txatxarramendi and transplanted to Arriluze, Muskiz, and Plentzia (northern Spain), and vice versa. Arriluze was the most heavily polluted site, followed by Plentzia, Txatxarramendi, and Muskiz. Animals transplanted from a polluted station to a cleaner station lost contaminant load in three to six weeks, and when transplanted to a more polluted station, they accumulated PAHs and PCBs accordingly. Peroxisomal acyl-A oxidase (AOX) activity was the highest in animals from Arriluze, and animals transplanted to Arriluze showed increased AOX activity, reaching the levels of native mussels. Mussels from Txatxarramendi showed the lowest peroxisomal volume density (Vvp). Among mussels from Txatxarramendi, only those transplanted to Plentzia showed increased Vvp, whereas animals from Arriluze and Muskiz transplanted to Txatxarramendi after 2 d and six weeks, respectively, had decreased Vvp. Two days after transplant, superoxide dismutase and glutathione peroxidase activities were significantly lower in mussels from Arriluze and Muskiz, respectively, than in those from Txatxarramendi and than in animals transplanted to Txatxarramendi from these stations. In conclusion, transplant experiments with mussels are useful to assess the effects of pollution. Peroxisome proliferation, measured as induction of AOX or increased Vvp, shows great potential as a biomarker of pollution to be included in pollution monitoring programs. In the present work, we have demonstrated that peroxisome proliferation is a reversible phenomenon in mussels.     

Ontogeny of soluble and particulate prolyl endopeptidase activity in several areas of the rat brain and in the pituitary gland

We have analyzed the activity of prolyl endopeptidase (PEP) in several areas of the rat brain (brain cortex, striatum, brain stem, cerebellum and hypothalamus) and in the pituitary gland during ontogeny. In all of these areas, we observed a reduction in PEP activity during development. However, the temporal profile of these alterations was found to be area specific and differences in the ontogeny of the soluble and particulate forms of PEP were observed. Thus, by postnatal day 20 (PD20), soluble PEP activity had began to decrease in the brain cortex and striatum, whereas decreased soluble PEP activity was observed earlier, at PD15, in the brain stem and cerebellum. Changes in the particulate fraction were even more pronounced. Senescence was associated with decreased soluble PEP activity in the striatum, but in contrast, particulate PEP activity was found to be increased in the senescent brain stem. The present results indicate that alterations in the levels of activity of PEP may represent an important event in the development and aging of the central nervous system.     

Ruthenium (II) nitrofurylsemicarbazone complexes: new DNA binding agents

Complexes of the type [Ru(II)Cl(2)(DMSO)(2)L], where L are 5-nitrofurylsemicarbazone derivatives, were prepared in an effort to combine the potential anti-tumor activity of the metal and the free ligands. The new complexes are excellent DNA binding agents for calf thymus DNA. So, their in vitro anti-tumor activity was tested in cellular models and the complexes were found to be non-cytotoxic on the tumor cell lines assayed, neither in aerobic conditions nor in the bio-reductive assay performed. Redox behavior, lipophilicity and stability were studied in order to explain the lack of cellular cytotoxic effects. The complexes resulted 10-100 times more hydrophilic than the parent ligands thus the bio-activity of these compounds would be compromised by their inadequate lipophilic properties.     

Explicit criteria for prioritization of cataract surgery

Background  

Consensus techniques have been used previously to create explicit criteria to prioritize cataract extraction; however, the appropriateness of the intervention was not included explicitly in previous studies. We developed a prioritization tool for cataract extraction according to the RAND method.     

Influence of following Green's criteria for urinary stress incontinence surgical procedures

A series of 161 patients with urinary stress incontinence and who underwent either Kelly urethral plication or Marshall-Marchetti procecures were reviewed in order to evaluate the usefulness of following Green's criteria in the selection of type of surgery for stress incontinence. One-year follow-up failure rate was higher in patients with type I stress incontinence (23%) than in type II stress incontinence (15.5%), and also when the choice of surgical approach did not follow Green's criteria; statistical analysis of these data showed that differences did not reach a significant level (P > 0.05).     

Antioxidant enzymes and peroxisome proliferation in relation to contaminant body burdens of PAHs and PCBs in bivalve molluscs,crabs and fish from the Urdaibai and Plentzia estuaries (Bay of Biscay)

With the aim of studying levels of antioxidant and peroxisomal enzymes and the structure of peroxisomes in relation to body burdens of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), mussels Mytilus galloprovincialis, oysters Crassostrea sp., crabs Carcinus maenas and mullets Mugil cephalus were sampled in two Basque estuaries (Bay of Biscay): Urdaibai (Laida, Txatxarramendi, Arteaga, and downstream a sewage treatment plant-STP) and Plentzia. In general, animals showed higher concentrations of contaminants in winter than in summer and no relevant differences were detected among locations. Conversely, antioxidant enzyme activities were higher in summer. Enzyme expression was studied in mullets using immunochemical methods. By immunoblotting season-dependent differences were detected for Mn-superoxide dismutase (Mn-SOD). As for the immunohistochemical staining, mullets sampled in summer in Plentzia showed significantly higher optical densities for acyl-CoA oxidase and lower for both Cu,Zn-SOD and Mn-SOD than those collected downstream a STP as well as higher catalase immunostaining than those collected in winter. Peroxisomal volume density (V(vp)) of mussels sampled in Laida and Txatxarramendi did not show seasonal variations, while for oysters collected in Laida and Arteaga V(vp) was higher in summer. Crab and mullet V(vp) were also higher in summer. In conclusion, the estuaries of Urdaibai and Plentzia can be considered as low to moderately polluted areas and levels of PAHs and PCBs do not show marked variations apart from seasonal variations. Animals can be adapted to low pollution conditions and, under these circumstances, seasonal factors might affect biomarker responses to a greater extent than pollution variations.     

Efficacy of ganciclovir-loaded nanoparticles in human cytomegalovirus (HCMV)-infected cells

The use of albumin nanoparticles to enhance the antiviral activity of ganciclovir (GCV) while decreasing its intrinsic toxicity was evaluated in human fibroblasts. GCV was adsorbed onto preformed protein nanoparticles (Np A) or incubated with the albumin solution prior to the formation of nanoparticles (Np B) by a coacervation method. The antiviral efficacies in MRC-5 and CHN cells were assayed by plaque reduction assay and early antigen detection, with several MOI and time of drug addition (T0 and T48). Whatever cell line or assay tested, Np A is the most active formulation whereas the efficacy of Np B is similar to the ganciclovir conventional therapy. Moreover, the profile of the dose-activity curve of the drug as a function of MOI is not altered by the use of nanoparticles and the efficacy of all formulations improves when added at T48. On the other hand, Np B produces a decrease on the cytotoxicity of the free drug in non-infected cells. Both activity and cytotoxicity seem to be straight correlated to the drug internalisation by cells. Thus, Np A highly improves the drug uptake, whereas Np B leads to a similar drug internalisation than the free drug.