Sarcosine preconditioning induces ischemic tolerance against global cerebral ischemia.

Brain ischemic tolerance is an endogenous protective mechanism activated by a preconditioning stimulus that is closely related to N-methyl-d-aspartate receptor (NMDAR). Glycine transporter type 1 (GlyT-1) inhibitors potentiate NMDAR and suggest an alternative strategy for brain preconditioning. The aim of this work was to evaluate the effects of brain preconditioning induced by sarcosine, a GlyT-1 inhibitor, against global cerebral ischemia and its relation to NMDAR. Sarcosine was administered over 7 days (300 or 500 mg/kg/day, ip) before the induction of a global cerebral ischemia model in Wistar rats (male, 8-week-old). It was observed that sarcosine preconditioning reduced cell death in rat hippocampi submitted to cerebral ischemia. Hippocampal levels of glycine were decreased in sarcosine-treated animals, which was associated with a reduction of [(3)H] glycine uptake and a decrease in glycine transporter expression (GlyT-1 and GlyT-2). The expression of glycine receptors and the NR1 and NR2A subunits of NMDAR were not affected by sarcosine preconditioning. However, sarcosine preconditioning reduced the expression of the NR2B subunits of NMDAR. In conclusion, these data demonstrate that sarcosine preconditioning induces ischemic tolerance against global cerebral ischemia and this neuroprotective state is associated with changes in glycine transport and reduction of NR2B-containing NMDAR expression.

[The use of peripheral blood progenitor cells as an autologous hematopoietic support in high-dose chemotherapy. II. The experience of the Hematological Intensive Care Unit of the IPOFG. Franciso Gentil Portuguese Institute of Oncology]. / Utilização de células progenitoras do sangue periférico como suporte hematopoiético autólogo de quimioterapias de alta dose. II. Experiência da Unidade de Cuidados Hematológicos Intensivos do IPOFG.

We report the results of PBPC collection by large-volume leukaphereses and the hematologic recovery after high-dose chemotherapy supported by autologous PBPC reinfusion in a series of cancer patients treated at the Hematological Intensive Care Unit (UCHI) (Portuguese Institute of Oncology, Lisbon). Large volume leukaphereses were used to increase the efficacy of the PBPC collection. This modification of the standard apheresis technique allowed the harvesting, in only one session, of enough progenitors to proceed to transplantation in nearly 2/3 of patients and without significant toxicity. From December 1993 until September 1997, 95 autologous PBSC transplants were performed at the UCHI; 45% were performed in solid tumor patients and 55% in patients with hematologic malignancies. Hematologic recovery was similar to that published in the literature and related to the number of CD34+ cells infused. Patients supported with bone marrow in addition to PBPC showed delayed hematopoietic recovery, probably because the bone marrow harvest was only performed when an insufficient number of PBPC had been collected (2 x 10(6) CD34+ cells/Kg). The speed of hematological recovery differed per diagnosis, being higher in multiple myeloma and solid tumor patients and lower in Hodgkin's disease patients.

[The use of peripheral blood progenitor cells as an autologous hematopoietic support in high-dose chemotherapy. I. The rationale and results]. / Utilização de células progenitoras do sangue periférico como suporte hematopoiético autólogo de quimioterapias de alta dose. I. Racional e resultados.

We review the rationale for PBPC transplantation and the results reported in the literature. In order to prolong complete remissions and increase cure rates, high-dose chemotherapy is frequently used in the treatment of selected neoplasias. Hematological toxicity can be overcome by the infusion of autologous hemopoietic progenitors. Recently, peripheral blood is being used as the preferred source for hemopoietic progenitors, since it allows faster hematopoietic recoveries when compared to progenitors harvested from bone marrow. An adequate graft is defined by its content in clonogenic progenitors (mainly CFU-GM) and CD34 positive cells; these two parameters need to be accurately determined by specific laboratory methods. PBPC grafts are harvested using cell separators during leukaphereses; to increase efficiency, hemopoietic progenitors are first mobilized into the circulation with growth factors and or chemotherapy. PBSC transplantation may have procedure-associated toxicity related to the mobilization, harvest or reinfusion of the graft.

[Methods for preserving bone marrow for autologous transplantation]. / Métodos de conservação de medula óssea para transplantação autóloga.

For Autologous Bone Marrow Transplantation (ABMT) the patient's own marrow is harvested before myelotoxic high-dose radio-chemotherapy and later returned to promote hemopoietic reconstitution. Between harvest and return the bone marrow must be preserved. The time elapsed between harvest and return depends on the intended therapy. Although--bone marrow may keep its hematopoietic potential for a few days without freezing, preservation for longer periods imposes the need for cryopreservation. Some of the current methods for marrow preservation are reviewed, with special emphasis given to cryopreservation. Hospital de Santa Maria Bone Marrow Transplant Unit cryopreservation method is described.