Multicentric study of Brazilian patients with 21-hydroxylase deficiency: a genotype-phenotype correlation

We analyzed the clinical and molecular data of 205 patients with the three different clinical forms of 21-hydroxylase deficiency, in whom the clinical and molecular diagnosis were already defined. The most frequent mutations were I2 splice in the salt wasting form, I172N in the simple virilizing and V281L in the nonclassical form, presenting similar frequencies as those observed in other populations. We found a lower frequency of 21-hydroxylase gene deletion, similar to that previously identified in Argentinean and Mexican populations. Five new mutations were described in our population: G424S, H28+C, Ins 1003 1004 A, R408C and IVS2-2A>G. The genotype was classified in three groups according to the impairment of enzymatic activity observed in vitro, Group A: 0-2%, Group B: 3-7% and Group C: >20%. Group A mutations correlated with the salt wasting form, the Group B with simple virilizing form and Group C with the non classical form. The severity of genotype showed a positive correlation with higher 17OH-progesterone and testosterone levels. The I2 splice mutation in homo or hemizygosis confers classical form phenotype with both salt wasting and simple virilizing forms, precluding the prediction of the clinical form through genotype in pre and neonatal diagnosis. The good genotype-phenotype correlation in patients with 21-hydroxylase deficiency shows the usefulness of genotype to predict the clinical form for genetic counseling, prenatal diagnosis and to confirm neonatal screening diagnosis, except in cases with I2 splice mutation.     

Radiation-Guided Targeting of Combretastatin Encapsulated Immunoliposomes to Mammary Tumors

Purpose  Radiation upregulates expression of endothelial cell adhesion molecules providing a potential avenue for targeting drugs to irradiated tissue. Induced upregulation of E-selectin can be used to target immunoliposomes to solid tumors. The effects of targeting immunoliposomes containing the antivascular drug combretastatin disodium phosphate (CA4P) to irradiated mammary tumors were investigated in this study. Methods  Mice bearing transplanted MCa-4 mouse mammary tumors were assigned to one of the factorial treatments permuting the administration of free CA4P, tumor irradiation, CA4P encapsulated liposomes, and CA4P encapsulated immunoliposomes (conjugated with anti-E-selectin). Single and fractionated dosing of radiation and/or CA4P was evaluated. Results  For single dose treatments the group that received a single dose of radiation plus a single dose of immunoliposomes showed a significant delay in tumor growth compared to all other treatment groups. Fractionated radiation plus fractionated doses of immunoliposomes resulted in further tumor growth delay; however, it was not significantly different from other fractionated dose treatment groups that combined radiation and CA4P. Conclusions  Targeting of antivascular drugs to irradiated tumors via ligand-bearing liposomes results in significant tumor growth delay. This effect can be further potentiated using a fractionated irradiation dosing schedule combined with fractionated immunoliposome treatments. CBP and BV made equal contribution to this work.     

The behavior of visceral proteins in digestive surgery patients undergoing total peripheral parenteral nutrition enriched with branched-chain amino acids (BCAA)]

The objective of this study, is to confirm a clear benefit of protein synthesis after administration of branched amino acids in parenteral nutrition solutions. Particularly, on a parenteral total hypocaloric nutrition including lipids. Eighty one digestive surgical patients, were included in this study. Fifty with neoplastic disease and thirty one without. Patients in both study groups received a similar peripheral vein nutritional support regimen one week after surgical treatment. To evaluate the effects of the branched chain amino acid enrichment on total parenteral nutrition, we observed the behavior of short middle life proteins such as transferrin, prealbumin, and retinol binding protein, for their reliability as indexes of protein synthesis.     

Analgesic activity of affinin, an alkamide from Heliopsis longipes (Compositae)

Heliopsis longipes (Compositae) is a Mexican plant used as analgesic in pain toothache. A solution of 10mug/ml of dichloromethane extract from this plant showed analgesic activity determined by means of GABA release in mice brain slices. Through a bioassay-directed separation, fractions G-1, G-2, G-4 and G-6 at the same concentration were active. Affinin was the unique and common active compound, and evoke the GABA release 0.5min after administration at 1x10(-4)M concentration. Inactive compound were undeca-2E-en-8,10-dyinoic acid isobutylamide, hinokinin, 2'-hydroxyhinokinin, 3beta-sn-glyceroyl-(1'-palmitoxy)urs-12-ene, 13(18)-ursen-3beta-ol, 13(18)-ursen-3beta-acetate, beta-sitosterol and stigmasterol. The analgesic activity of Heliopsis longipes could be associated to affinin.