An alternative technique to shape scaffolds with hierarchical porosity at physiological temperature

The method described in this work, termed GELPOR3D, is characterised by its simplicity of use, low-cost equipment, compositional flexibility, and lack of aggressive or toxic solvents or other thermal treatment. This technique ensures the generation of a three-dimensional network of interconnected pores (300–900 μm); in addition, a random and not necessarily connected porosity is generated, yielding a hierarchical porous architecture from the macro to the molecular scale. The interconnected pores, large enough to ensure an adequate vascularization and new tissue ingrowth, can be obtained by pouring a slurry containing a biodegradable thermogel (such as agarose and gellan) and a ceramic into a mold consisting of a three-dimensional network of rigid filaments. Additional pore distributions in the macropore region can be tailored as a function of the drying/preservation technology (10–100 μm) or the interaction between the inorganic particles coated by the polymeric components (0.1–1 μm). Moreover, porosity in the mesopore range can be created by shaping ceramics such as mesoporous silica or nanocrystalline carbonatehydroxyapatite. In addition to the various bioceramics that have been successfully shaped, this method is flexible enough to allow the introduction of certain substances whose controlled release may help to avoid some negative effects that usually appear with the implantation of a material, i.e. infection, inflammation, etc., or to simplify some of the many steps required for the successful integration of a graft.     

Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology.

It seems well established that CpG oligonucleotide Th1-biased adjuvant activity can be improved when closely associated with a variety of antigens in, for example, microparticles. In this context, we prepared 1-mum near non-charged poly(lactic-co-glycolic) acid (PLGA) 502 and PLGA 756 microparticles that loaded with high-efficiency antigen (50% ovalbumin (OVA), approximately) into their matrix and CpG-chitosan complexes (near to 20%) onto their surface maintaining OVA and CpG integrity intact. In the intradermal immunization studies, whereas OVA microencapsulated into PLGA 756 alone induced a strong humoral immune response assisted by a very clear Th1 bias (IgG2a/IgG1=0.88) that was decreased by CpG co-delivery (IgG2a/IgG1=0.55), the co-encapsulation of CpG with OVA in PLGA 502 particles significantly improved the antibody response and isotype shifting (IgG2a/IgG1=0.73) in comparison with mice immunized with OVA-loaded PLGA 502 (IgG2a/IgG1=0). This improvement was not correlated with the cellular immune response where the effect of co-encapsulated CpG was rather negative (2030 and 335pg/mL IFN-gamma for OVA PLGA 502 and OVA CpG PLGA 502, respectively). These results underscore the critical role of polymer nature and microparticle characteristics to show the benefits of co-encapsulating CpG motifs in close proximity with an antigen.     

The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain.

PURPOSE: It is not clear that the published estimates of the breast and ovarian cancer penetrances of mutations in BRCA1 and BRCA2 can be used in genetic counseling in countries such as Spain, where the incidence of breast cancer in the general population is considerably lower, the prevalence of BRCA2 mutations seems to be higher, and a distinct spectrum of recurrent mutations exists for both genes. We aimed to estimate these penetrances for women attending genetic counseling units in Spain. EXPERIMENTAL DESIGN: We collected phenotype and genotype data on 155 BRCA1 and 164 BRCA2 mutation carrier families from 12 centers across the country. Average age-specific cumulative risks of breast cancer and ovarian cancer were estimated using a modified segregation analysis method. RESULTS: The estimated average cumulative risk of breast cancer to age 70 years was estimated to be 52% [95% confidence interval (95% CI), 26-69%] for BRCA1 mutation carriers and 47% (95% CI, 29-60%) for BRCA2 mutation carriers. The corresponding estimates for ovarian cancer were 22% (95% CI, 0-40%) and 18% (95% CI, 0-35%), respectively. There was some evidence (two-sided P = 0.09) that 330A>G (R71G) in BRCA1 may have lower breast cancer penetrance. CONCLUSIONS: These results are consistent with those from a recent meta-analysis of practically all previous penetrance studies, suggesting that women with BRCA1 and BRCA2 mutations attending genetic counseling services in Spain have similar risks of breast and ovarian cancer to those published for other Caucasian populations. Carriers should be fully informed of their mutation- and age-specific risks to make appropriate decisions regarding prophylactic interventions such as oophorectomy.     

Intra-articular Treatment with Hyaluronic Acid. Comparative Study of Hyalgan and Adant

Forty-nine patients diagnosed as having gonarthrosis were given intra-articular treatment with hyaluronic acid (Adant or Hyalgan) in a blind randomised study. We concluded that the efficacy with Adant at 3 months after treatment was greater than with Hyalgan (50% versus 21.1%). The maximum improvement with hyaluronic acid was seen at 5 weeks in 75.4% and the adverse effects consisted of pain in the infiltration side which was almost twice as great with Adant (16.3%). Received: 23 July 1999 / Accepted: 10 December 1999     

Elderly patients on chronic hemodialysis: Effect of the secondary hyperparathyroidism on the hemoglobin level

In patients on chronic hemodialysis (CHD)hyperparathyroidism (HPTH) is associated withanemia and resistance to erythropoietin (EPO). This study included 86 CHD elderly pts (meanage 74.8 y, mean time on CHD = 50.5 mos); theywere divided into two groups: I (n = 31) – PTH> 250 pg/mL and II (n = 55) – PTH < 250 pg/mL.All these patients had been on CHD for> 6 mos. No differences were found betweengroups in respect to age, sex distribution andtime on CHD. The levels of creatinine, BUN, Ca,Al, Fe, albumin and ferritin were similar.Group I had a higher P level (5.4 vs 4.3 mg/dL,p = 0.001) and Ca x P (53.5 vs 43.7, p =0.009). Also the Hct (31 vs 33.5%, p = 0.008)and the Hb (10.4 vs 11.2 g/dL, p = 0.009) values werelower in Group I. The EPO dose (88 vs 85 U/kg/week,p = ns) was similar in the two groups.Our data showed that elderly patients with HPTHhave lower Hct and Hb levels than do youngerpatients on a similar EPO dose. We believethese patients will need a more aggressivetherapy with calcitriol.