Mitochondrial transcriptional study of the effect of aflatoxins, enniatins and carotenoids in vitro in a blood brain barrier model.

C. maxima (var. Delica), a variety of pumpkin, is well known for its high concentration on carotenoids, possessing dietary benefits and antioxidant properties. Aflatoxins and enniatins are common mycotoxins present in food and feed with an extended toxicity profile in humans and animals. Both types of substances reach a wide range of tissues and organs and have the capability to penetrate the blood brain barrier. Since carotenoids and mycotoxins have been reported to modify diverse mitochondrial processes individually, transcriptional in vitro studies on human epithelial cells ECV 304 were conducted to analyze the relative expression of 13 mitochondria related genes. ECV 304 cells were differentiated for 9 days and treated for 2 h with: a) pumpkin (500 nM); b) aflatoxins (100 nM); c) enniatins (100 nM); d) aflatoxins (100 nM) and pumpkin (500 nM); e) enniatins (100 nM) and pumpkin (500 nM). Even at low concentrations, dietary carotenoids activity on mitochondrial genes expression reported a beneficial effect and, for most of the genes studied across the Electron Transport Chain (ETC), developed a protective effect when mixed with aflatoxins (AFs) or enniatins (ENs).

Retrospective analysis of common scoring systems and outcome in patients older than 60 years treated with reduced-intensity conditioning regimen and alloSCT.

In this retrospective study, 63 patients >60 years with hematological malignancies and treated with allo-SCT and with reduced-intensity conditioning (RIC) were reviewed. A total of 51% of patients suffered from AML or myelodysplastic syndromes. Disease status before transplantation was CR or PR 71 with 29% transplanted with active disease. Patients were classified according to three published prognostic indexes: (1) hematopoietic cell transplantation comorbidity index (HCT-CI); (2) European BMT (EBMT) score; and (3) Pretransplantation Assessment of Mortality (PAM) score. The 100-day and 1-year treatment-related mortality (TRM) were 6 and 22%, respectively, for the entire group. The 2-year OS and PFS were 60 and 58%, respectively. The incidence of grade II-IV acute GVHD (aGVHD) and extensive chronic GVHD was 46 and 48%, respectively. In a univariate analysis, neither the HCT-CI nor the EBMT score, nor the PAM score were predictive of TRM and OS. Only the occurrence of aGVHD affected the TRM and OS. ALLO-RIC is feasible in elderly patients. Even if those prognostic scores were not adapted to elderly patients, they did not predict for TRM and OS. aGVHD is the main cause of TRM and more efforts should be made to reduce its incidence without sacrificing graft vs tumor effect.

Primary neurologic screening and motor coordination of Dstdt-J mutant mice (dystonia musculorum) with spinocerebellar atrophy.

The autosomal recessive dystonia musculorum (Dst(dt-J)) mutation causes degenerative lesions of peripheral and central sensory pathways. A test battery of motor, sensory, postural, and autonomic functions was used to compare young control and homozygous Dst(dt-J) mice. The Dst(dt-J) mutants were severely impaired for muscle strength, limb coordination, and postural reflexes. As a result of a loss in motor control, the mutants were hypoactive in the open-field and fell quickly from the stationary beam. In sensory tests, the acoustic startle response was impaired, but not tactile reflexes and contact righting, attesting to preserved labyrinthine function and non-lemniscal pathways. Dst(dt-J) mutants were also distinguishable from controls on the basis of tremor, a paler skin, piloerection, and half-open eyes, as well as low body weight and fecal boli. Grooming episodes were less frequent in the mutants but without any reduction in grooming time. The neurologic screening battery delineated the functional integrity of some sensorimotor pathways in a spinocerebellar mutant whose severe phenotype prevents a more elaborate evaluation.

Human 'testicular dysgenesis syndrome': a possible model using in-utero exposure of the rat to dibutyl phthalate.

BACKGROUND: The disorders comprising human 'testicular dysgenesis syndrome' (TDS) may be increasing in incidence. TDS originates in fetal life but the mechanisms are not known, and discerning them requires an animal model. METHODS AND RESULTS: The study investigated whether male rats exposed in utero to dibutyl phthalate [DBP; 500 mg/kg on gestational days (GD) 13-21] would provide a suitable model for human TDS. DBP induced a high rate (>60%) of cryptorchidism (mainly unilateral), hypospadias, infertility and testis abnormalities, similar to those in human TDS. Cell-specific immunohistochemistry and confocal microscopy were used to track development of Sertoli [anti-Müllerian hormone (AMH), Wilm's tumour (WT-1) protein, p27(kip)], Leydig [3beta-hydroxysteroid dehydrogenase (3beta-HSD)], germ (DAZL protein) and peritubular myoid (smooth muscle actin) cells from fetal life to adulthood. In scrotal and cryptorchid testes of DBP-exposed males, areas of focal dysgenesis were found that contained Sertoli and Leydig cells, and gonocytes and partially formed testicular cords; these dysgenetic areas were associated with Leydig cell hyperplasia at all ages. Suppression ( approximately 90%) of testicular testosterone levels on GD 19 in DBP-exposed males, coincident with delayed peritubular myoid cell differentiation, may have contributed to the dysgenesis. Double immunohistochemistry using WT-1 (expressed in all Sertoli cells) and p27(kip) (expressed only in mature Sertoli cells) revealed immature Sertoli cells in dysgenetic areas. DBP-exposed animals also exhibited Sertoli cell-only (SCO) tubules, sporadically in scrotal and predominantly in cryptorchid, testes, or foci of SCO within normal tubules in scrotal testes. In all SCO areas the Sertoli cells were immature. Intratubular Leydig cells were evident in DBP-exposed animals and, where these occurred, Sertoli cells were immature and spermatogenesis was absent. Abnormal Sertoli cell-gonocyte interaction was evident at GD 19 in DBP-exposed rats coincident with appearance of multinucleated gonocytes, although these disappeared by postnatal day 10 during widespread loss of germ cells. CONCLUSIONS: Abnormal development of Sertoli cells, leading to abnormalities in other cell types, is our hypothesized explanation for the abnormal changes in DBP-exposed animals. As the testicular and other changes in DBP-exposed rats have all been reported in human TDS, DBP exposure in utero may provide a useful model for defining the cellular pathways in TDS.

A comparison between cemented, press-fit, and HA-coated interfaces in Kinemax total knee replacement.

There are possible advantages of using uncemented fixation in total knee replacement. In this prospective randomised multi-centre study, a comparison was made between cemented and two types of uncemented fixation for the Kinemax design. There were 12-14 cases in each group. Beads were inserted in the bones from which component migration was measured at time intervals up to 2 years. The axial migrations were significantly less for cemented and HA-coating, compared with press-fit, at all time intervals. The clinical data showed no differences at 2 years except for more cases of pain in the uncemented groups. Radiographically, the cemented interfaces showed the least change, press-fit showed a radiolucent line and a radiodense line, and HA showed a diffuse radiodensity adjacent to the components. It was concluded that for the Kinemax design of tibial component, press-fit was inferior to cemented, but that there was the potential for designing a special component for uncemented fixation for which HA-coating would be an advantage.

[Chronic exposure to environmental lead in Chilean infants. II: Effects on the psychomotor development]. / Exposición crónica a plomo ambiental en lactantes chilenos. II: Efectos en el desarrollo psicomotor.

BACKGROUND: Lactating children are specially susceptible to lead toxicity due to their underdeveloped nervous system, lower body mass, higher intestinal absorption and lower elimination rates. AIM: To determine the effects of lead exposure, comparing Chilean lactating children residing in rural areas with low lead exposure, and in urban areas with high lead exposure. MATERIAL AND METHODS: Newborns from public maternity hospitals of the rural locality of San Felipe and from Metropolitan Santiago, were recruited for the study. On admission to the study, umbilical cord and maternal blood samples were obtained and an inquiry about perinatal, sociohereditary and lead exposure history was done. Children were followed every 6 months until 24 months of age, measuring blood parameters and neurobehavioral development using Bayley scales. RESULTS: Three hundred twelve children from Santiago and 113 from San Felipe were studied. Maternal and children blood lead levels were higher in Santiago, but lower than those reported in other international studies. At 24 months of age, 4.5% of children from Santiago and 0.7% of children from San Felipe had levels over 10 micrograms/dl. No differences in neurobehavioral development were observed between children of both cities. At 24 months, scores of MDI scales were 91 in Santiago and 97 in San Felipe. The figures for PDI scale were 93 in Santiago and 93 in San Felipe. Main risk factors for a retarded neurobehavioral development were socieconomic level with a mean Odds ratio of 3.5 (0.99-12.4), made sex with an Odds ratio of 2.3 (1.09-5.07) and stimulation at home with an Odds ratio of 0.7 (0.53-0.82). CONCLUSIONS: In this cohort of children, no effect of lead levels on neurobehavioral development was found.

Atención inicial de los traumatismos perineales graves / Primary treatment in complex perineal injuries

Se presentan los resultados de 29 pacientes con lesiones graves de periné, tratados en el Hospital de Emergencias en el período comprendido entre Enero de 1991 y Diciembre de 1997. En la serie predominó el sexo masculino (86.2 por ciento) y las causas fueron múltiples, destacándose los accidentes de tránsito (55.2 por ciento). Fueron evaluados clínicamente en la guardia y se efectuaron los exámenes complementarios de rutina. Se aplicó un esquema terapéutico ordenado con irrigación de los tejidos perineales, debridamiento quirúrgico y resección de las zonas desvitalizadas, dejando las heridas abiertas, colostomía cuando fue necesaria, antibioticoterapia, revisiones quirúrgicas repetidas cada 24 - 72 hs. y apoyo nutricional. La morbilidad fue del 24.1 por ciento y la mortalidad del 13.8 por ciento.

Atención inicial de los traumatismos perineales graves / Primary treatment in complex perineal injuries

Se presentan los resultados de 29 pacientes con lesiones graves de periné, tratados en el Hospital de Emergencias en el período comprendido entre Enero de 1991 y Diciembre de 1997. En la serie predominó el sexo masculino (86.2 por ciento) y las causas fueron múltiples, destacándose los accidentes de tránsito (55.2 por ciento). Fueron evaluados clínicamente en la guardia y se efectuaron los exámenes complementarios de rutina. Se aplicó un esquema terapéutico ordenado con irrigación de los tejidos perineales, debridamiento quirúrgico y resección de las zonas desvitalizadas, dejando las heridas abiertas, colostomía cuando fue necesaria, antibioticoterapia, revisiones quirúrgicas repetidas cada 24 - 72 hs. y apoyo nutricional. La morbilidad fue del 24.1 por ciento y la mortalidad del 13.8 por ciento. (AU)

[Chronic exposure to environmental lead in Chilean infants]. / Exposición crónica a plomo ambiental en lactantes chilenos.

BACKGROUND: In Chile, there are several sources of environmental lead exposure. However, the few studies about lead levels in Chilean infants, do not allow to establish the prevalence of high lead levels in this population. AIM: To measure blood lead levels in nursing infants, living in rural and urban areas, from birth until two years of age. SUBJECTS AND METHODS: Newborns from public maternity hospitals in Santiago and a rural area were selected for the study. An umbilical cord blood sample was obtained at birth and venous blood samples thereafter, every 6 months until the age of 24 months. Lead levels were measured by atomic absorption spectrophotometry. Atmospheric lead was measured simultaneously every week in Santiago and the rural area. RESULTS: Three hundred twelve children from Santiago and 113 from the rural area completed the 24 months follow-up. The mean lead exposure for infants living in Santiago and in the rural area was 1.23 +/- 0.66 and 0.19 +/- 0.15 micrograms/m3 respectively (p < 0.001). Mean blood levels were always higher in infants from Santiago, compared to those from the rural area. At 24 months, 4.5% of children from Santiago and 0.7% of children from the rural area had blood lead levels over 10 micrograms/dl. Significant risk factors for high lead levels were recent painting of the house where the infant lives, eating soil, biting banisters and familiar labor exposure to lead. CONCLUSIONS: Infants living in an urban area and exposed to increased atmospheric lead levels have higher blood lead levels than infants living in a rural area.

Regulation of oligodendrocyte development and central nervous system myelination by insulin-like growth factors.

In summary, our studies show that IGFs are potent regulators of oligodendrocyte development and myelination in vitro and in vivo. IGFs act at several levels: by promoting proliferation of oligodendrocytes and oligodendrocyte precursors, by inducing immature oligodendrocyte precursors to develop into oligodendrocytes, and by regulating myelin gene expression and the amount of myelin produced per oligodendrocyte. Our findings indicate that IGFs play a crucial role in normal oligodendrocyte development and myelination, and suggest that IGFs may have applications for the promotion of remyelination in myelin disorders such as MS.

Action patterns of amylolytic enzymes as determined by the [1-14C]malto-oligosaccharide mapping method.

A valuable technique for oligosaccharide mapping, utilizing radioactive malto-oligosaccharides, multiple-ascent p.c., and radioautography, has been developed for identifying the action patterns of the glucoamylase isozymes, alpha-amylases, beta-amylase, glucosyltransferase, and glucanosyltransferase. The glucoamylase isozymes act by multi-chain mechanisms on malto-oligosaccharides and most likely on starch and glycogen. The alpha-amylases act endo-wise and randomly hydrolyze alpha-(1----4)- but not alpha-(1----6)-glucosidic bonds. These amylases may act by single-chain and/or multi-chain mechanisms, depending on the number of hydrolytic attacks per single encounter of the enzyme and the substrate. The beta-amylases hydrolyze malto-oligosaccharides by a multi-chain mechanism. A fungal glucosyltransferase from Aspergillus niger transfers glucose units by a single-chain mechanism from maltose to glucosyl acceptors to yield new gluco-oligosaccharides with alpha-(1----4) and alpha-(1----6) linkages. A novel type of transferase isolated from Bacillus subtilis acts by a multi-chain mechanism and transfers segments of 2 to 5 glucose residues from malto-oligosaccharides to acceptor co-substrates. An alpha-amylase from the same organism removes maltotriose units from the non-reducing ends of oligosaccharides by a multi-chain mechanism.

Affinity chromatography of two sets of isomeric antibodies having specificity for different oligosaccharide units of gum arabic.

Two sets of antibodies directed against different carbohydrate units of gum arabic were isolated from the sera of rabbits immunized intramuscularly with gum arabic and Freund's complete adjuvant. The isolation was effected by affinity chromatography on two columns attached in series and containing an absorbent of AH-Sepharose 4B with ligands of partially hydrolyzed gun arabic in the first column and an adsorbent of AH-Sepharose 4B with ligands of native gum arabic in the second column. The two populations of anti-gum arabic antibodies were obtained and have been designated as Set 1 and Set 2 on the basis of their mobilities on agar diffusion. The antibodies of Set 1 consisted of 4 isomeric antibodies and those of Set 2 consisted of 11 isomeric antibodies. Native gum arabic samples were oxidized with periodate or reduced with sodium borohydride and carbodiimide under standard conditions and the modified samples were totally inactive in the precipitin test. On the basis of methylation data and immunological results it was concluded that terminal disaccharide moieties of the gum having the structure beta-D-glucosyluronic acid-(1----6)-D-galactose and alpha-L-arabinofuranosyl-(1----4)-D-glucuronic acid were the immunodeterminant groups for Set 1 and Set 2 antibodies, respectively.

[Lead exposure and its effects on child health]. / Exposición al plomo y sus efectos en la salud infantil.

Childhood lead poisoning is a man-made disease whose magnitude has not yet been measured in Chile. In the U.S.A. it has been estimated that 4 percent of children have elevated blood lead levels and that among poor black children, this rate is as high as 18 percent. The main sources of symptomatic lead poisoning are lead-based paint used in interior and exterior house surfaces, airborne lead from leaded gasoline and industrial emissions. Lead can be transferred from any source to soil and dust. Other sources of lead are contaminated food and water, occupational sources, and lead glazed pottery. Neurological symptoms (hyperactivity, distractibility, lower intellectual development), psychological difficulties (behavioral deficits), hematologic abnormalities (reduction in the biosynthesis of heme, anemia), and metabolic changes (reduction in concentration of 1-25 dihydroxy vitamin D and in the metabolism of erythrocyte pyrimidine) have been shown to occur in lead poisoning. Recent data suggests that prenatal exposure to lead my be related to minor congenital abnormalities, tumors of the kidney, and growth abnormalities.