PubMed Health⌕ Search

Biomedical subjects

S Zanelli

Publications and source records attributed to S Zanelli.

9 recordsLinked to original sources

Effect of graded hypoxia on the high-affinity CPP binding site of the NMDA receptor in the cerebral cortex of newborn piglets.

Previous studies have shown that the N-methyl-D-aspartate (NMDA) receptor is modified during hypoxia in the cerebral cortex of newborn piglets. The present study tests the hypothesis that the NMDA receptor 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) high-affinity binding site is modified during hypoxia and that the degree of modification correlates with the progressive decrease in cerebral cellular energy metabolism and increase in lipid peroxidation induced by hypoxia. Studies were conducted in twelve anesthetized, ventilated newborn piglets, five normoxic and seven hypoxic which were exposed to decreased fraction of inspired oxygen (FiO2) to achieve varying phosphocreatine (PCr) levels. 3[H]-CPP binding was performed with CPP concentrations ranging from 0.5 to 1500 nM at 23 degrees C for 40 min in P2 membrane fractions. Brain tissue PCr levels were determined biochemically. Conjugated dienes (CDs) were measured as an index of lipid peroxidation. In the normoxic group, B(max) (receptor number) for the CPP binding site was 329+/-93 fmol/mg protein and Kd (dissociation constant) 137+/-44 nM, the mean PCr value was 2.5+/-0.4 micromol/g brain and the CD level was 0.0 nmol/g brain. As tissue hypoxia worsened, there was a gradual decline in tissue PCr as well as receptor B(max) and K(d) values, and there was an increase in conjugated dienes. Both the receptor B(max) (r=0.90) and Kd (r=0.72) decreased in a linear relationship as PCr decreased. As the levels of CDs increased both the receptor B(max) (r=0.88) and Kd (r=0.68) decreased in a linear fashion. The data show that there is not a critical hypoxic threshold for modification of the CPP binding site of the NMDA receptor, but that modification is coupled to a gradual decrease in brain cell energy metabolism and increase in lipid peroxidation. We speculate that hypoxia-induced modification of the NMDA receptor is mediated not only by changes in the receptor recognition site but also by an alteration of brain cell membrane structure secondary to conjugated diene formation.

Animals↗

[Bacterial meningitis in infants 1 to 8 weeks old].

Bacterial meningitis in the newborn and infant remains a serious problem, with a mortality rate of 24% and a morbidity rate ranging from 30 to 50%. This retrospective study conducted between January 1982 and December 1997, aims to characterize the epidemiology of bacterial meningitis in infants less than 60 days of age. Thirty-five infants between 6 and 60 days of age, hospitalized for bacterial meningitis in the pediatric units of Edouard-Herriot Hospital in Lyon, France, were included. The clinical presentation was not specific for most cases, hyperthermia being the most common symptom (97%). Neurological symptoms such as bulging fontanelle or nuchal rigidity were present in 30% and 8% of the cases, respectively. The four predominant meningeal pathogens were: group B streptococcus (36%), Escherichia coli (28%), meningogoccus (8.6%) and Staphylococcus aureus (8.6%). This study emphasizes the importance of prompt diagnosis, including CSF evaluation, and antimicrobial therapy in infants less than 2 months of age presenting an isolated fever.

Anti-Bacterial Agents↗

Hypoxia-induced generation of nitric oxide free radicals in cerebral cortex of newborn guinea pigs.

Previous studies have shown that brain tissue hypoxia results in increased N-methyl-D-aspartate (NMDA) receptor activation and receptor-mediated increase in intracellular calcium which may activate Ca++-dependent nitric oxide synthase (NOS). The present study tested the hypothesis that tissue hypoxia will induce generation of nitric oxide (NO) free radicals in cerebral cortex of newborn guinea pigs. Nitric oxide free radical generation was assayed by electron spin resonance (ESR) spectroscopy. Ten newborn guinea pigs were assigned to either normoxic (FiO2 = 21%, n = 5) or hypoxic (FiO2 = 7%, n = 5) groups. Prior to exposure, animals were injected subcutaneously with the spin trapping agents diethyldithiocarbamate (DETC, 400 mg/kg), FeSO4.7H2O (40 mg/kg) and sodium citrate (200mg/kg). Pretreated animals were exposed to either 21% or 7% oxygen for 60 min. Cortical tissue was obtained, homogenized and the spin adducts extracted. The difference of spectra between 2.047 and 2.027 gauss represents production of NO free radical. In hypoxic animals, there was a difference (16.75+/-1.70 mm/g dry brain tissue) between the spectra of NO spin adducts identifying a significant increase in NO free radical production. In the normoxic animals, however, there was no difference between the two spectra. We conclude that hypoxia results in Ca2+-dependent NOS mediated increase in NO free radical production in the cerebral cortex of newborn guinea pigs. Since NO free radicals produce peroxynitrite in presence of superoxide radicals that are abundant in the hypoxic tissue, we speculate that hypoxia-induced generation of NO free radical will lead to nitration of a number of cerebral proteins including the NMDA receptor, a potential mechanism of hypoxia-induced modification of the NMDA receptor resulting in neuronal injury.

Animals↗

Analysis of an accident at a solvent recovery plant.

An accident in a plant for solvent recovery from solvent-contaminated wastes was examined. An experimental investigation of the accident was carried out using calorimetric and thermogravimetric techniques. The immediate cause of the accident was an unforeseen exothermic decomposition reaction. The main underlying cause of the accident was the absence of safety culture in the plant management, that resulted in the lack of a testing procedure to evaluate the thermal stability of the process feed. A simplified screening procedure based on differential scanning calorimetry was used in order to test the thermal stability of the nonvolatile fraction of the solvent-contaminated wastes present on the plant in order to be processed. More than 75% of the samples examined showed exothermal decomposition phenomena starting at temperatures higher than 100 degrees C. These phenomena were common to solvent wastes that originated from a number of different industrial activities. Thus, the thermal instability of the process feed is one of the main problems in solvent recovery operations. Our analysis of the accident suggested that the safe operation of waste solvent recovery processes requires an accurate characterization of the thermal stability of the process feed. Process safety is also increased by an adequate emergency vent and an accurate control of operating temperature, that may be reduced operating under vacuum. Safety devices may also include a water supply for emergency quench.

Accidents, Occupational↗

Precursors of dangerous substances formed in the loss of control of chemical systems.

Article 2 of Directive 96/82/EC on the control of major accident hazards caused by dangerous substances requires to consider also the hazards due to the dangerous substances "which it is believed may be generated during loss of control of an industrial chemical process", although no generally accepted guidelines are available for the identification of these substances. In the present study, the accidents involving the unwanted formation of dangerous substances as a consequence of the loss of control of chemical systems were investigated. A specifically developed database was used, containing data on more than 400 of these accidents and on the substances involved. The hazardous substances formed in the accidents and the precursors of these substances were identified. The influence of accident characteristics on the substances formed was investigated. In the context of the application of Directive 96/82/EC, an accident severity index and a hazard rating of the precursors of dangerous substances formed in the accidents were proposed. A lumping approach was used in order to develop schemes for the preliminary identification of substances that may be formed in the loss of control of chemical system. The results of accident analysis were used to test the schemes developed.

Accidents, Occupational↗

Oxygen free radical generation during in-utero hypoxia in the fetal guinea pig brain: the effects of maturity and of magnesium sulfate administration.

Previous studies have shown, employing direct measurements with electron spin resonance (ESR) spectroscopy, that hypoxia induces an increased production of oxygen free radicals (OFR) in the brain of the guinea pig fetus. The present study using the same approach, investigated the effects of maturity and Mg2+-pretreatment on hypoxia-induced OFR formation in the guinea pig fetal brain. The normoxic and the hypoxic groups were exposed for 60 min to 21% or 7% oxygen, respectively. The control group consisted of term fetuses exposed to normoxia (n=7) and hypoxia (n=7). The experimental groups consisted of the following: (a) for the investigation on maturity effect, preterm fetuses (40 days) exposed to normoxia (n=6) or hypoxia (n=6); and (b) for the Mg2+-pretreatment investigation, term fetuses (60 days) exposed to normoxia (n=6) or hypoxia (n=6) following maternal pretreatment with Mg2+ which consisted of an initial bolus of MgSO4 (600 mg/kg, i.p.) 1 h prior to hypoxia followed by a second dose (300 mg/kg, i.p.). Oxygen free radicals were measured by ESR spectroscopy in the fetal cerebral cortical tissue utilizing phenyl-N-tert-butylnitrone (PBN) spin trapping. Fetal brain tissue hypoxia was documented biochemically by decreased tissue levels of ATP and phosphocreatine. In the control group of term fetuses, the cortical tissue from hypoxic fetuses showed a significant increase in spin adducts (71% increase, p<0.01). In the preterm group, the cortical tissue from hypoxic fetuses showed a 33% increase in spin adducts (p<0.001). The baseline free radical generation during normoxia was 22.5% higher at preterm than at term (41.4+/-3.5 units/g issue vs. 33.8+/-9.3 units/g tissue, p<0.05). In Mg2+-treated groups, spin adduct levels in cortical tissue from hypoxic fetuses did not significantly differ from those of the normoxic group (30.2+/-9.9 units/g tissue, normoxic-Mg2+ vs. 30. 6+/-8.1 units/g tissue, hypoxic-Mg2+). The results indicate that the fetal brain at term may be more susceptible to hypoxia-induced free radical damage than at preterm and that Mg2+ administration significantly decreased the hypoxia-induced increase in oxygen free radical generation in the term fetal guinea pig brain in comparison with non-treated hypoxic group.

Analysis of Variance↗

Role of uterine artery Doppler investigation in pregnant women with chronic hypertension.

OBJECTIVE: To evaluate the role of uterine artery Doppler investigation in predicting perinatal outcome of patients with chronic hypertension. STUDY DESIGN: Uterine artery velocimetry was investigated at 24 weeks gestation in 78 chronic hypertensive pregnant women by means of color Doppler. The resistance index (RI) and the presence of a diastolic notch were recorded and related to the development of superimposed preeclampsia (SPE), pregnancy aggravated hypertension (PAH). and intrauterine growth retardation (IUGR). RESULTS: There were more pregnancy complications in the 25 patients with abnormal RI, compared with the 53 women with normal RI (SPE 12% vs. 0%, PAH 36% vs. 7% and IUGR 52% vs. 2%; P<0.01), and more in women with a bilateral diastolic notch compared with those without (SPE 23% vs. 0, PAH 54% vs. 4%, IUGR 85% vs. 2%; P<0.0001), while no differences were detected in those with only a unilateral notch, except for PAH (27% vs. 4%; P<0.01). CONCLUSION: Uterine artery Doppler velocimetry identifies a subgroup of chronic hypertensive patients with a high frequency of pregnancy complications.

Chronic Disease↗