Growth of mouse embryos in bicarbonate media buffered by carbon dioxide,hepes, or phosphate

The purpose of this study was to determine if mouse embryos could be grown successfully in a culture medium devoid of the carbon dioxide phase (CO₂). Mouse embryos fertilized in vivo were collected and cultured in Hepes medium with and without bicarbonate (HCO₃ ^–) and a phosphate medium with and without HCO₃ ^–. In these experiments no CO₂ gas phase was used. Further embryos were cultured in Whittingham's modified Tyrode's (T6) medium with a CO₂ gas phase and served as controls. The degree of embryonic development was noted. Surviving blastocysts were transferred to the uteri of pseudopregnant mice and delivery at term was allowed to occur. There was no significant difference in the degree of embryonic development in those embryos cultured in T6 or Hepes medium (+HCO₃ ^–) or in the number of live offspring obtained when these blastocysts were placed within the mouse uterus. Although embryonic development apparently proceeded successfully in the phosphate (+HCO₃ ^–) medium, none of these blastocysts survived when transferred to mouse uteri. No embryonic growth occurred in either the Hepes or phosphate media which were devoid of HCO₃ ^–. It appears that a Hepes medium containing HCO₃ ^–, which uses no CO₂ gas phase, is as effective as T6 medium, which uses a gas phase, in supporting in vitro mouse embryonic growth.     

African trypanosomes activate human fetal brain cells to proliferation and IFN-gamma production

We addressed the host-parasite interplay and the immunopathogenetic events occurring in the central nervous system (CNS) during human African trypanosomiasis. Human first trimester forebrain cells were stimulated with a trypanosome lymphocyte-triggering factor (TLTF) and studied for their immune response as exemplified by cell proliferation and IFN-gamma production. TLTF induced proliferation of human first trimester forebrain cells and IFN-gamma production at the mRNA and protein levels. Astrocytes are the major producers of IFN-gamma in response toTLTE These data illustrated for the first time a direct effect of a parasite factor on human brain cells. TargetingTLTF during the course of the disease may be considered in preventing the deadly neurological complications of human African trypanosomiasis. NeuroReport     

Dissemination of IMP-1 metallo- beta -lactamase-producing Acinetobacter species in a Brazilian teaching hospital.

OBJECTIVE: To evaluate the emergence and dissemination of metallo- beta -lactamase (MBL)-producing Acinetobacter species. DESIGN: All carbapenem-resistant Acinetobacter strains (1 strain per patient) collected during the period 1993-2001 were evaluated. SETTING: A Brazilian tertiary care teaching hospital (Hospital Sao Paulo, Sao Paulo). METHODS: Seventy-three strains of carbapenem-resistant Acinetobacter species were recovered from the organism bank of the hospital. All isolates were tested for antimicrobial susceptibility by broth microdilution methods, and the production of MBL was initially assessed by phenotypic tests (MBL Etest strip and a disk approximation test). The MBL enzymes were identified by polymerase chain reaction using primers for bla(IMP), bla(VIM), and bla(SPM), followed by gene sequencing. Genetic similarity among the carbapenem-resistant strains was evaluated by automated ribotyping. RESULTS: Only colistin and ampicillin-sulbactam showed reasonable in vitro activity against carbapenem-resistant isolates (97% and 74% of isolates susceptible, respectively). More than half of the isolates (55%) had a positive MBL phenotypic test result and a positive polymerase chain reaction result for bla(IMP-1). The proportion of IMP-1-producing Acinetobacter isolates among carbapenem-resistant strains increased from 0% in the 1993-1997 period to 29% in 1998 and 100% in the 1999-2001 period. No carbapenem-resistant Acinetobacter isolates that harbored bla(VIM) or bla(SPM) were detected. Molecular typing results revealed 20 ribogroups among carbapenem-resistant isolates. During the study period of 1994-2001, we identified 2 major ribogroups, 52-1 (MBL-negative and MBL-positive strains) and 60-7 (MBL-positive strains), that had a coefficient of similarity of 0.85 or higher. CONCLUSIONS: Our results indicate that IMP-1-producing strains of Acinetobacter emerged in our institution in 1998. Since then, production of this MBL was detected not only in the major ribogroups of carbapenem-resistant Acinetobacter species but also among isolates that belonged to 17 distinct ribogroups, indicating that this important mechanism of antimicrobial resistance was disseminated among distinct clones.     

Clinical trials in metastatic prostate cancer – Has there been real progress in the past decade?

Hormone refractory prostate cancer remains a challenge. While only palliative treatment strategies were available for the past several decades, many promising agents have been investigated over the past decade. Of those the taxanes appeared with significant anti-tumor activity and recently, two large randomized controlled trials demonstrated for the first time, a survival and palliative benefit with docetaxel based chemotherapy. In the current era, recurrent disease after local treatment for localized disease is diagnosed long before evidence of systemic disease. With earlier institution of hormonal treatments, patients are becoming "hormone refractory" earlier in the course of their disease with considerable long life expectancy. Hence, there is a greater need than ever for more treatment options for this expanding group of patients. A number of new systemic therapies have recently emerged, based on a deeper understanding of prostate cancer biology. Novel chemotherapeutics such as the epothilones, molecularly targeted therapies against angiogenesis, the proteosome and endothelin receptor antagonists, as well as biological agents such as anti-sense oligonucleotides are being tested as part of the armamentarium. Key to progress in the therapy of this fatal disease is the commitment and timely enrolment of prostate cancer patients in clinical trials.