On the use of Europium (Eu) for designing new metal-based anticancer drugs.

Europium oxide (Eu2O3) was used to evaluate the affinity of this rare earth element for interacting with double-stranded (ds) DNA molecules. To perform the study, we used single molecule force spectroscopy with optical tweezers and gel electrophoresis assays. Force spectroscopy experiments show that Eu2O3 presents a strong interaction with dsDNA, and the binding is independent on the ionic strength used in the surrounding environment. Among the main characteristics of the interaction, Eu2O3 tends to bind in a cooperative way, forming bound clusters of ∼ 3 molecules, and presents a high equilibrium association binding constant on the order of 105 M-1. In addition, gel electrophoresis confirm the weak electrostatic character of the interaction and explicit show that Eu2O3 does not interfere on drug intercalation into the double-helix. Such results demonstrate the potential of europium for interacting with nucleic acids and strongly suggest that this rare earth element may be considered for the design of new metal-based anticancer drugs in the future.

Energy transfer between CdS nanocrystals and neodymium ions embedded in vitreous substrates.

Experimental evidence has been observed for energy transfer from CdS nanocrystals, synthesized by the fusion method, to Nd(3+) ions embedded in vitreous substrates. These dot samples doped with neodymium have been investigated by combined optical absorption (OA), photoluminescence (PL), and time-resolved photoluminescence (PLRT) techniques. Radiative and nonradiative energy transfers between CdS dot and Nd(3+) ion levels, to our knowledge not reported before, can be clearly observed in the PL spectra where the emission band valleys correspond exactly to the energy absorption peaks of the doping ion. The PLRT data reinforce these energy transfer mechanisms in which the increasing overlap between the CdS PL band and the OA to the Nd(3+) levels decreases stimulated emissions from the doping ions.

Excitatory amino acid concentrations in ventricular cerebrospinal fluid after severe traumatic brain injury in infants and children: the role of child abuse.

BACKGROUND: Excitotoxicity is an important mechanism in secondary neuronal injury after traumatic brain injury (TBI). Excitatory amino acids (EAAs) are increased in cerebrospinal fluid (CSF) in adults after TBI; however, studies in pediatric head trauma are lacking. We hypothesized that CSF glutamate, aspartate, and glycine would be increased after TBI in children and that these increases would be associated with age, child abuse, poor outcome, and cerebral ischemia. METHODS: EAAs were measured in 66 CSF samples from 18 children after severe TBI. Control samples were obtained from 19 children who received lumbar punctures to rule out meningitis. RESULTS: Peak and mean CSF glycine and peak CSF glutamate levels were increased versus control values. Subgroups of patients with TBI were compared by using univariate regression analysis. Massive increases in CSF glutamate were found in children <4 years old and in child abuse victims. Increased CSF glutamate and glycine were associated with poor outcome. A trend toward an association between high glutamate concentration and ischemic blood flow was observed. CONCLUSIONS: CSF EAAs are increased in infants and children with severe TBI. Young age and child abuse were associated with extremely high CSF glutamate concentrations after TBI. A possible role for excitotoxicity after pediatric TBI is supported.

Increases in bcl-2 protein in cerebrospinal fluid and evidence for programmed cell death in infants and children after severe traumatic brain injury.

OBJECTIVES: To determine whether bcl-2, a protein that inhibits apoptosis, would be increased in cerebrospinal fluid (CSF) in infants and children after traumatic brain injury (TBI) and to examine the association of bcl-2 concentration with clinical variables. STUDY DESIGN: Bcl-2 was measured in CSF from 23 children (aged 2 months-16 years) with severe TBI and from 19 children without TBI or meningitis (control subjects) by enzyme-linked immunosorbent assay. CSF oligonucleosome concentration was also determined as a marker of DNA degradation. Brain samples from 2 patients undergoing emergent decompressive craniectomies were analyzed for bcl-2 with Western blot and for DNA fragmentation with TUNEL (terminal deoxynucleotidyl-transferase mediated biotin-dUTP nick-end labeling). RESULTS: CSF bcl-2 concentrations were increased in patients with TBI versus control subjects (P =.01). Bcl-2 was increased in patients with TBI who survived versus those who died (P =.02). CSF oligonucleosome concentration tended to be increased after TBI (P =.07) and was not associated with bcl-2. Brain tissue samples showed an increase in bcl-2 in patients with TBI versus adult brain bank control samples and evidence of DNA fragmentation within cells with apoptotic morphology. CONCLUSIONS: Bcl-2 may participate in the regulation of cell death after TBI in infants and children. The increase in bcl-2 seen in patients who survived is consistent with a protective role for this anti-apoptotic protein after TBI.

Pharmacokinetics of clindamycin phosphate in the first year of life.

The pharmacokinetics of intravenously administered clindamycin phosphate was studied in 40 children less than 1 year of age. Mean peak serum concentrations were 10.92 micrograms/ml in premature infants less than 4 weeks of age, 10.45 micrograms/ml in term infants greater than 4 weeks, and 12.69 micrograms/ml in term infants less than 4 weeks of age. Mean trough concentrations were 5.52, 2.8, and 3.03 micrograms/ml, respectively, in the same groups. Serum half-life was significantly longer (8.68 vs 3.60 hours) in premature compared with term infants less than 4 weeks of age. Both premature and term infants less than 4 weeks had significantly decreased clearance when compared with infants greater than 4 weeks (0.294 and 0.678, respectively, vs 1.58 L/hr). Clearance was significantly greater (1.919 vs 0.310 L/hr) and serum half-life less (1.75 vs 7.57 hours) in infants with body weight greater than 3.5 kg. On the basis of these data it is recommended that in infants greater than 4 weeks or greater than 3.5 kg, intravenous clindamycin dosage be 20 mg/kg/day in four divided doses. In premature neonates less than 4 weeks, the dose should be reduced to 15 mg/kg/day in three divided doses. Term infants greater than 1 week of age may also receive 20 mg/kg/day in four doses.

Sodium needs of infants and children with ileostomy.

We studied gastrointestinal tract excretion of sodium and water in seven infants with an abdominal ileostomy (group 1) and three children with a Soave ileoendorectal pull-through (group 2). When the daily sodium intake of the patients was 5 to 7 mEq/kg (twice usual maintenance), average daily ileal sodium losses were 2.4 mEq/kg body weight in group 1 and 3.3 mEq/kg in group 2. Ten days after ileostomy closure in group 1, when the infants' daily sodium intake averaged 2 to 3 mEq/kg/day, gastrointestinal tract sodium losses were reduced to 0.3 mEq/kg body weight/day. The mean daily fecal weight and water also decreased after closure. Mean serum aldosterone concentration before closure was 84 ng/ml, and declined to 58 ng/100 ml after closure; and mean plasma renin values fell from 8.8 to 2.9 ng/ml/hr. In the children with an ileoendorectal pull-through, daily sodium intake was restricted to 0.3 to 0.5 mEq/kg/day, an amount that would maintain balance in a child of similar age with normal sodium conservation. Mean serum aldosterone concentration increased to 501 ng/ml (normal 1 to 22.7). Although renal conservation of sodium occurred promptly, gastrointestinal losses of sodium and water continued and the patients' sodium balance became negative. The diet of a patient with an ileostomy should include increased amounts of sodium until bowel continuity is restored.

Antral diaphragm--a cause of gastric outlet obstruction in infants and children.

Gastric outlet obstruction in infants and children may be due to a partial, prepyloric antral diaphragm. Twelve new patients are added to the 32 described previously. Onset of symptoms varied from shortly after birth to five years. Nonbilious vomiting was the most common presenting symptom. Radiographic evaluation requires specific technique for demonstration of the web and to differentiate this from pylorospasm and pyloric stenosis. Gastroscopy was employed in three patients. Repair usually consisted of incision of the web and construction of a patulous gastric outlet. All patients remained asymptomatic after operation. The etiology of the webs remains unknown, but they may result from an excessive local endodermal proliferation early in gastric development.