Engraftment and differentiation of neocortical progenitor cells transplanted to the embryonic brain in utero

Transplantation of neural progenitors or stem cells is a most useful tool to investigate the relative contribution of cell-autonomous mechanisms and environmental cues in the regulation of cell specification and differentiation during CNS development. To assess the capability of neocortical progenitor cells to integrate into foreign brain regions, here we examined the fate of precursor cells isolated from the dorsal telencephalon of E12 ss-actin-EGFP transgenic mouse embryos after heterotopic/heterochronic transplantation to the E16 rat brain in utero. Our observations show that donor cells were able to penetrate, survive and produce mature cell types into wide regions of the host CNS. Namely, EGFP-positive cells acquired site-specific neuronal identities in many telencephalic regions, including neocortex, hippocampus, olfactory bulb and corpus striatum. In contrast, incorporation into more caudal sites was much less efficient. A fraction of donor cells formed large aggregates that remained segregated from the host milieu. Such aggregates contained mature neurons and glia, including some EGFP-negative elements of host origin, and developed the complex organization of the mature nervous tissue. On the other hand, transplanted cells that engrafted in the parenchyma of extratelencephalic regions predominantly generated glial types. The few neurons failed to acquire obvious site-specific phenotypic traits and did not integrate into the local host architecture. Altogether, our observations indicate that E12 neocortical progenitors are already committed towards regional identities and are unable to modify their phenotypic choices when exposed to heterotopic environmental conditions along different rostro-caudal domains of the embryonic CNS.     

Inhibitory action of conventional food-grade natural antioxidants and of natural antioxidants of new development on the thermal-induced oxidation of cholesterol

Cholesterol is a molecule with an unsaturated bond; therefore, like polyunsaturated fatty acids, it is prone to oxidation. Cholesterol oxidation products (COPs) are found in many common foods and have been shown to be atherogenic, cytotoxic, mutagenic and possibly carcinogenic. Therefore, efforts to prevent or to avoid COPs formation during manufacture and/or processing of foods are of high priority. The effect of natural antioxidants on COPs formation has not been extensively studied. We assayed the effect of some widely applied natural antioxidants, such as tocopherol homologs (alpha-T, gamma-T, and delta-T) and rosemary extract, and of some natural products of newly developed as antioxidants, such as the flavonoids quercetin, catechin, morin, and rutin, and also of an alkaloid-derived product, boldine, to inhibit cholesterol oxidation of soybean oil, added of cholesterol, induced in the Rancimat test conditions (150 degrees C and air bubbling). Formation of six different COPs at the induction period and at the 100 microS conductivity value was monitored by gas chromatography. Under the experimental conditions gamma-T, quercetin, and rosemary extract prove effective to inhibit both soybean oil oxidation and COP formation. alpha-T, catechin, and morin are less efficient to prevent COP formation. delta-T, rutin and boldine are devoid of protective action against COP formation. gamma-T, quercetin and rosemary extract may inhibit COP formation from the nucleus and from the lateral chain of the cholesterol molecule.     

Outbreak of hantavirus pulmonary syndrome, Los Santos, Panama, 1999-2000

An outbreak of hantavirus pulmonary syndrome occurred in the province of Los Santos, Panama, in late 1999 and early 2000. Eleven cases were identified; 9 were confirmed by serology. Three cases were fatal; however, no confirmed case-patient died. Case-neighborhood serologic surveys resulted in an overall hantavirus antibody prevalence of 13% among household and neighborhood members from the outbreak foci. Epidemiologic investigations did not suggest person-to-person transmission of hantavirus infection. By use of Sin Nombre virus antigen, hantavirus antibodies were detected in Oligoryzomys fulvescens and Zygodontomys brevicauda cherriei. This outbreak resulted in the first documented cases of human hantavirus infections in Central America.     

Morbidity and mortality associated with renal insufficiency and endovascular repair of abdominal aortic aneurysms: a 5-year experience

To evaluate the outcome of patients with renal insufficiency undergoing endovascular repair of abdominal aortic aneurysm (AAA), data were prospectively collected between 1998 and 2003 on patients undergoing elective repair of their AAA with a stent graft. The patients were divided into 2 groups: those with serum creatinine (Crs) concentrations <1.2 (Group A) and those with Crs > or =1.2 mg/dL not requiring hemodialysis (Group B). The outcomes of the procedure for these 2 groups were compared. Different variables that existed between the 2 groups and contributed to mortality included estimated blood loss (EBL), volume of contrast used in the operating room, incidence of diabetes (DM), tobacco use, and history of myocardial infarction (MI). In total, 213 patients underwent elective repair of their AAA with use of a stent graft: 61% who had a Crs <1.2 mg/dL (Group A) and 39% who had a Crs > or =1.2 mg/dL not requiring dialysis (Group B). Among 129 patients with normal renal function there was an 18.6% complication rate and 1.6% mortality rate. Of 83 patients with renal insufficiency not on hemodialysis 30.1% (Fisher's Exact Test = 0.076) had 1 or more complications and there was a 6% (Fisher's Exact Test = 0.166) mortality rate. One patient in Group A (0.8%) progressed to hemodialysis and 5 (6%) patients in Group B progressed to end-stage renal disease requiring hemodialysis (p=0.068). A statistically significant higher proportion of the patients in Group B had a history of MI (p<0.001). There was no difference in the amount of EBL between the 2 groups, but a significantly lower amount of contrast (p<0.05) was used in patients with renal insufficiency.     

Basic sanitary conditions in Iporanga, São Paulo State, Brazil

OBJECTIVE: To assess the pollution of water bodies by domestic sewage and to evaluate the basic sanitation conditions of residences and the knowledge of the local population concerning intestinal parasitic diseases and the hazards they present to public health. METHODS: Thirteen water samples were collected from each of four sites in different water bodies of the Bairro da Serra region, in Iporanga, S?o Paulo State. Rates of total and fecal coliforms were measured and median values were presented so as to show domestic sewage contamination in the area. Questionnaires were administered to 50% of local households in order to obtain information on water supply and disposal of domestic sewage and solid waste, and to evaluate knowledge of the transmission, health hazards, and prevention of intestinal parasitic diseases among the local population. RESULTS: The Betari river showed microbiological indexes indicative of pollution by domestic sewage. Higher levels were verified both upstream and downstream from the Bairro da Serra. Median values were even higher in two of the river's tributary streams, indicating strong pollution by domestic sewage and lack of conformity with current legislation. In 91% of the households investigated, sewage disposal was done by means of septic tanks, most of which were rudimentary and contributed to the contamination of the environment. The knowledge of 62% of interviewed subjects concerning the transmission of helminthic diseases was considered as poor. CONCLUSIONS: Our results indicate a risk of proliferation of intestinal parasitoses and of other water-transmitted diseases, an issue which is aggravated by increases in population caused by the region's vocation for ecotourism.     

Menstrual pattern and lipid profiles during use of medroxyprogesterone acetate and estradiol cypionate and NET-EN (200 mg) as contraceptive injections

The objectives of this study were to compare effects of medroxyprogesterone acetate 25 mg + estradiol cypionate 5 mg (Cyclofem) and norethisterone enanthate (NET-EN) upon the menstrual pattern and determine changes in lipoprotein parameters after 12 months of use. One-hundred females were included and 87 (45 with Cyclofem and 42 with NET-EN) women completing 12 months were evaluated. Menstrual changes were the leading complaint among users. At the end of 12 months, 20/45 (44.4%) and 18/41 (43.9%) Cyclofem and NET-EN users, respectively, had normal menstrual pattern. Irregular and infrequent bleeding were the two most important changes that occurred. The discontinuation rate at 12 months due to menstrual disturbances did not show any significant differences between the two preparations, but showed lower incidence compared to other studies. Total cholesterol, high-density, low-density and very low-density lipoprotein cholesterol and triglyceride levels decreased at 12 months in both groups and these changes were statistically significant.     

Effects of long-term exposure to Cu2+ and Cd2+ on the pentose phosphate pathway dehydrogenase activities in the ovary of adult Bufo arenarum: possible role as biomarker for Cu2+ toxicity

The effects of copper and cadmium on metabolism through the pentose phosphate pathway were evaluated in Bufo arenarum toad ovary. The effects of the two metals on dehydrogenases from this pathway were evaluated by three experiments: (1) in samples obtained from control females with addition of the metals to the reaction mixture (in vitro), (2) in samples obtained from control females and after long-term exposure of females to 4 and 100 microg/L of Cu or Cd in the incubation media (in vitro after exposure to the metals in vivo), and (3) 14CO2 production through the pentose phosphate pathway was evaluated after [U-14C]glucose microinjection on ovulated oocytes (in vivo after microinjection of the metals). Results from (1) evidenced inhibition of both enzyme activities but only above 1.5 mM Cu and Cd added to the reaction mixture. In (2) both glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities decreased in samples from the ovaries of females exposed in vivo to Cu, in a concentration-dependent manner (up to 90% in females exposed to 100 microg/L Cu: 2.12 +/- 1.57 NADPH micromol/min microg protein x 10(-5) vs 19.97 +/- 8.54 in control females). Cd treatment of the toads only rendered an inhibitory effect on 6-phosphogluconate dehydrogenase activity after exposure to 4 microg/L of the bivalent cation. (3) In vivo 14CO2 evolution significantly decreased in oocytes coinjected with 6.3 x 10(-3) mM Cu (calculated intracellular final concentration of the metal injected) and radioactive glucose. Cu and Cd concentration in samples from exposed females were always under detection limit by particle-induced X-ray emission. The results presented here are in agreement with a role for both glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities determination as biomarkers of effect and exposure for Cu but not for Cd toxicity.     

Inhibiting human astrocytoma growth: structure-activity relationships in neurostatin related glycolipids

Neurostatin, a mammalian brain inhibitor of division of astroblast and astrocytoma cells, was characterized as the disialoganglioside GD1b, 9-O-acetylated on the outer sialic acid residue (Galbeta1-->3GalNAcbeta1-->4(9-O-Ac-NeuAcalpha2-->8NeuAcalpha2-->3)Galbeta1-->4Glcbeta1-->1'-ceramide). Using semisynthetic approaches, we prepared and tested different gangliosides O-acetylated in the sialic acid and compared them to non-O-acetylated partners as inhibitors of U-373 glioma cells. Athough the O-acetylation of the sialic acid was the most important molecular feature for the antiproliferative activity of O-acetylated gangliosides, monosaccharide links Galbeta1--> 3GalNAcbeta1 and NeuAcalpha2-->8NeuAcalpha2 enhanced the inhibitory activity.     

Non-small cell lung cancer: from cytotoxic systemic chemotherapy to molecularly targeted therapy

Surgery is the only method of cure in lung cancer. Seldom its application with radical intent is possible. Despite the efforts aimed at integrating all the therapeutic strategies, the overall outcome of the management of this disease remains disappointing. For this reason, in the last three decades, thousands of preclinical and clinical attempts have been realised in order to investigate any possible way to cure this disease and significant steps forward have been made on the basis of the increasing "molecular knowledge" in the so called "post-genomic era". Particularly the impressive step forward in the biological characterization of cancer as a result of genetic/epigenetic multistep process has brought in a multitude of variables with staggering classification potentialities. "Benchside" and "bedside" scientists have assembled in functional teams to move the common efforts "translationally" to bridge basic and clinical research for a mutual synergistic enhancement. This paper represents the effort of a lung cancer focused translational research team made up of molecular biologists, medical oncologists and thoracic surgeons to achieve a comprehensive, but simple, review of the current status of the shift from cytotoxic to molecularly targeted therapy in lung cancer treatment potentially useful in the planning of translational research trials.