Impaired helix 12 dynamics due to proline 892 substitutions in the androgen receptor are associated with complete androgen insensitivity

Human Molecular Genetics (2006) 15, 921–931;     

Actitud expectante en el síndrome del cascanueces

Nutcracker syndrome is caused by compression of the left renal vein between the aorta and the superior mesenteric artery where it passes in the fork formed at the bifurcation of these arteries. The phenomenon results in left renal venous hypertension. The syndrome is manifested by left flank and abdominal pain, with or without unilateral haematuria. The nutcracker syndrome has been treated in various ways. We report one case of the syndrome and discuss the place of surveillance in its management.     

Synthese von 2-Carbazoylthio-essigsäuren und deren Cyclisierung zu 3-Amino-thiazolidin-2,4-dionen

Synthesis of 2-(Hydrazinocarbonylthio)-acetic Acids and Cyclization to 3-Aminothiazolidine-2,4-diones N-mono- or N,N-disubstituted hydrazines are reacted with carbonyl sulfide, triethylamine and halogenoacetic acids to yield the 2-(hydrazinocarbonylthio) acetic acids 1 , which are cyclizised to yield the 3-aminothiazolidine-2,4-diones 2 by dicyclohexylcarbodiimide.     

The prevalence and intensity of intestinal parasites in two Somalian communities

About 85% of the population of two Somali communities harboured soil-transmitted intestinal nematodes and/or protozoa. The commonest parasite (75% in the Lafoole institution and 59% in the Afgoye institution) was Trichuris trichiura. Mixed infections were common. The source of infection is contaminated fields around dwelling quarters, because of indiscriminate defaecation. One of the factors responsible for the higher incidence of hookworm in Lafoole (45%) compared with Afgoye (1.5%) may be the different soil character of the surrounding fields.     

Enantioselective metabolism and cytotoxicity of R-ifosfamide and S-ifosfamide by tumor cell-expressed cytochromes P450.

The anticancer prodrug ifosfamide (IFA) contains a chiral phosphorous atom and is administered in the clinic as a racemic mixture of R-IFA and S-IFA. Hepatic cytochrome P450 (P450) enzymes exhibit enantioselective preferences in the metabolism of R-IFA and S-IFA; however, the impact of this selectivity on P450-dependent anticancer activity is not known. Presently, the metabolism and cytotoxicity of R-IFA and S-IFA were determined in 9L gliosarcoma and Chinese hamster ovary tumor cells expressing an IFA-activating P450 enzyme and by in vitro steady-state kinetic analysis using cDNA-expressed P450 enzymes. Tumor cells expressing P450 enzyme CYP3A4 were the most sensitive to R-IFA cytotoxicity, whereas tumor cells expressing CYP2B1 or CYP2B6 were most sensitive to cyclophosphamide (CPA), an isomer of IFA. Correspondingly, CYP3A4-expressing cells and cDNA-expressed CYP3A4 metabolized R-IFA to yield the active, 4-hydroxylated metabolite at a 2- to 3-fold higher rate than they metabolized S-IFA or CPA. CYP2B cells and cDNA-expressed CYP2B enzymes metabolized CPA almost exclusively by 4-hydroxylation, whereas R-IFA and S-IFA were substantially converted to inactive, N-dechloroethylated metabolites. Further investigation revealed that CYP3A1, a rat enzyme, exhibited superior kinetic properties compared with the human enzyme CYP3A4, with R-IFA and S-IFA both metabolized with high catalytic efficiency by 4-hydroxylation and with a K(m) value of 200 microM, approximately 5-fold lower than CYP3A4. Based on these kinetic parameters and metabolic profiles, R-IFA is expected to exert greater anticancer activity than S-IFA or CPA against tumors that express CYP3A enzymes, whereas tumors expressing CYP2B enzymes may be more sensitive to CPA treatment.     

Paraganglioma of the cauda equina with associated intramedullary cyst: MR findings.

The MR imaging features of a paraganglioma of the cauda equina with associated spinal cord cysts are presented. MR imaging showed the tumor to be isointense with the spinal cord on all pulse sequences and to enhance homogeneously. The intramedullary cysts had increased signal intensity on proton density- and T2-weighted images, and involved the cervical and thoracic regions.