Evidence that peroxynitrite affects human osteoblast proliferation and differentiation.

Peroxynitrite (PN), a nitric oxide (NO*)-derived anion, has been associated with NO* damage in various cell types. We examined the effects of adding PN to cultured human osteoblast-like (hOB) cells obtained after hip arthroplasty. Exposure to PN (0.1-0.4 mM) decreased both hOB proliferation and differentiation, measured by [3H]thymidine uptake and alkaline phosphatase production, respectively. Incubation with 3-morpholinosydnonimine (SIN-1; 0.25-1 mM), an NO* and O2- donor that leads to PN release, also reduced both hOB proliferation and differentiation. Coincubation with both superoxide dismutase (SOD; 100 U/ml) and catalase (CAT; 50 U/ml), rendering SIN-1 a pure NO* donor, reversed its effects on hOB proliferation and differentiation. However, SIN-1-induced NO* production, measured by nitrite release to the hOB medium, was not altered by cotreatment with SOD and CAT. Expression of nitrotyrosine by hOB, a marker of PN action, was significantly increased after SIN-1 addition, as compared with untreated cells, as revealed by Western blot analysis. Interleukin-1alpha (IL-1alpha) and interferon gamma (IFN-gamma) but not tumor necrosis factor alpha (TNF-alpha) also significantly increased nitrotyrosine expression in these cells. These data show that PN is at least partially responsible for osteoblast derangement by NO* and that cytokines released during inflammatory arthropathies can induce PN production in hOB cells.     

Changes in cognitive and Language functioning of Preschool children with autism

Preschool children with autism and their normally developing peers were compared on the Stanford-Binet IV and Preschool Language Scale before and after 1 school year. Both measures showed that although the children with autism functioned at a lower level than their normally developing peers, the children with autism had narrowed this gap after treatment, making a nearly 19-point increase in IQ and an 8-point gain in language quotient. The IQ measure remained stable for the normally developing peers while their language showed a 7.73-point increase. The data support the notion that young children with autism can make very significant developmental gains.Special thanks to the parents and the children who participated in this study. Thanks also to Michael Alessandri, Jean Burton, David Celiberti, Nancy Gera-Moglia, Anne Nathan, and Lisa Kamean who assisted in the data collection process. We appreciate the cooperation of Alicia MacWright and Leisa Tomchek who taught two of the classes from which participants were drawn.     

Structural analysis of poly(3-alkylthiophene)s

Poly(3-hexylthiophene) (PT6), poly(3-octylthiophene) (PT8), poly(3-decylthiophene) (PT10) and poly(3-dodecylthiophene) (PT12) were synthesized by electrochemical and chemical polymerization. Investigation of these polymers by means of gel permeation chromatography indicates that the polymers prepared from the different monomers under similar conditions do not differ substantially considering molecular weight and molecular weight distribution. Bimodal distributions were found for electropolymerized polymers, and with increasing polymerization time, the high-molecular-weight and probably highly branched fraction increased relatively to the low-molecular-weight fraction. The microstructure of the polymers was investigated by nuclear magnetic resonance, and it has been found that the polymers exhibit more types of structural units than expected from a simple coupling of adjacent thiophene moieties in 2,5′-positions. Chemical oxidation with iron trichloride in chloroform gave soluble, high-molecular-weight poly(3-alkyl-thiophene)s with a rather low amount of irregular couplings, and these more regular polymers exhibited a higher degree of crytallinity. Room temperature conductivities of the oxidized polymers were between 0,1 and 30 S/cm depending on the polymerization conditions, but these values were rather independent of the length of the alkyl substituent.     

Efficacy evaluation of gadoteridol for MR angiography of intracranial vascular lesions

A phase III multicenter study was conducted in 89 patients with known intracranial vascular lesions to evaluate an extracellular gadolinium contrast agent, gadoteridol, for intracranial magnetic resonance (MR) angiography. The pre- and postcontrast MR angiograms of 82 patients were evaluated by the unblinded investigators and by two blinded readers (A and B) for visualization of lesions; arterial and venous anatomy; extent, size, and number of lesions; and disease classification. The unblinded readers indicated that lesions were visualized better on postcontrast images in the following categories: venous anatomy, 87 (81%) of 107 lesions; arterial anatomy, 43 lesions (40%); and extent or size of lesions, 38 lesions (36%). In 29 (35%) of 82 patients, the unblinded readers determined that enhanced MR angiography provided more diagnostic information than unenhanced MR angiography. The blinded readers determined that enhanced MR angiography provided more information for visualization of vascular anatomy in more than 60% of cases. The additional information provided with gadoteridol would have changed the diagnosis in nine (8%) of 107 lesions seen by the unblinded readers, 11 (12%) of 90 lesions seen by reader A, and three (3%) of 93 lesions seen by reader B. The results confirm that the use of gadoteridol improves the visualization of intracranial vascular lesions with MR angiography. The authors conclude that development of new postprocessing algorithms will improve the utility of contrast-enhanced MR angiography.     

Passive electrical properties of motoneurons in aged cats following axotomy

The objective of this study was to determine whether the aging process influences the changes in the electrophysiological properties of motoneurons that occur as a consequence of axotomy. Accordingly, using intracellular recording and stimulating techniques, the basic electrical properties of control (unaxotomized) and axotomized spinal cord motoneurons of aged cats were determined. Compared with control motoneurons, axotomized motoneurons exhibited increases in input resistance (R_in), membrane time constant (τ_b) and the equalizing time constant (τ_c). While the electrotonic length (L) remained unchanged, axotomy induced a decrease in the total cell capacitance (C_cell. The post-axotomy reduction of C_cell indicates that the motoneuron surface area was reduced and the increased membrane time constant indicates that there was an increase in membrane resistivity (R_m). The post-axotomy conservation of L accompanied by an increase in R_m suggests that aged axotomized motoneurons undergo geometrical changes. Furthermore, calculations based on cable theory suggest that the diameter of the equivalent cylinder (d) decreased following axotomy, whereas the equivalent cylinder length (l) remained unaffected. It is concluded that axotomy produces significant alterations in the soma-dendritic portion of aged spinal motoneurons, as indicated by the changes found in their passive electrophysiological properties, and that the pattern of the response that occurs in axotomized motoneurons of adult cats is also present in axotomized motoneurons of aged animals.     

Adolescent Immunization: Focus on Implementation

ABSTRACT: On March 11–12, 1996, a workshop on how to implement new adolescent immunization (AI) recommendations was held in Atlanta, Ga. Sponsored by the Centers for Disease Control and Prevention, it was a collaborative effort of the National Immunization Program, the Division of Adolescent and School Health/National Center for Chronic Disease Prevention and Health Promotion, and the Hepatitis Branch/National Center for Infectious Diseases. The workshop brought together organizations and individuals interested in adolescent health and immunizations so they could address how new Al recommendations can be implemented most effectively. This article offers an overview of their discussions and suggestions, including issues of cooperation, education, legislation, and Al program development among health provider organizations, health departments, schools, community groups and various other agencies relating to adolescent health services.     

High-dose infliximab prophylaxis in endotoxin-induced uveitis.

PURPOSE: The aim of this study to analyze the preventive effect of high-dose infliximab in endotoxin-induced uveitis (EIU) in rabbits. METHODS: An experimental study was conducted on 64 rabbits. Salmonella typhimurium lipopolysaccharide endotoxin was intravitreally injected. Infliximab was intravenously (i.v.) injected 24 h before the intravitreal injection (20 mg/kg). The animals were randomly assigned to five groups: group A, saline intravitreal injection; group B, Infliximab i.v. group C, infliximab + saline; group D, intravitreal endotoxin and group E, infliximab i.v. + intravitreal endotoxin. With two masked observers, a microscopic examination of aqueous humor (cells, tumor necrosis factor [TNF] alpha) and aqueous protein level were performed 24 h after an endotoxin injection and 48 h after an infliximab infusion. RESULTS: Infliximab treatment, at a dose of 20 mg/kg, significantly improved all the parameters. Inflammatory cell infiltration was significantly reduced in the iris, ciliary body, and anterior chamber (U Mann-Whitney test, P = 0.01). Associated with a lower level of TNF-alpha and protein exudate in aqueous humor (U Mann-Whitney test, P = 0.01). CONCLUSIONS: Infliximab, at a dose of 20 mg/kg, is effective in the prophylaxis of the EIU.     

Blood Flow Increase by Cervical Spinal Cord Stimulation in Middle Cerebral and Common Carotid Arteries

The effect of spinal cord stimulation (SCS) on cerebral blood flow (CBF) has, in the past, been evaluated by semiquantitative techniques, but has not been used to treat CBF diseases. The aim of this study was to assess the effect of cervical SCS on regional blood flow by both semiquantitative and quantitative methods. Thirty‐five patients with cervical SCS‐implanted devices were enrolled. The following parameters were measured before and after cervical SCS: systolic and diastolic velocity (cm/s) in the middle cerebral artery (MCA) by transcranial Doppler (TCD) and volume blood flow quantification (ml/min) in the common carotid artery (CCA) by color Doppler. During cervical SCS there was a significant and bilateral increase in systolic (21%) and diastolic (26%) velocity in the MCA and in CCA blood flow (50%). We conclude that cervical SCS increases blood flow in the middle cerebral artery and common carotid artery. The consistent increase supports the potential usefulness of cervical SCS as an adjuvant treatment for cerebral blood flow diseases.