Anticonvulsant effects of N6-cyclohexyladenosine microinjected into the CA1 region of the hippocampus on entorhinal cortex-kindled seizures in rats.

In this study, the role of adenosine A1 receptors of the hippocampal CA1 region in entorhinal cortex-kindled seizures was investigated in rats. Animals were kindled by daily electrical stimulation of the entorhinal cortex. In fully kindled rats, N(6)-cyclohexyladenosine (CHA; a selective A1 receptor agonist) and 1, 3-dimethyl-8-cyclopenthylxanthine (CPT; a selective A1 receptor antagonist) were microinfused bilaterally into the hippocampal CA1 region. Rats were stimulated and seizure parameters were measured. Results obtained showed that CHA (10 and 50 micro moles) decreased the afterdischarge duration (ADD) in the hippocampal CA1 region and entorhinal cortex, stage 5 seizure duration (S5D) and seizure duration (SD) only at the dose of 50 micro moles, and significantly increased the latency to stage 4 (S4L). Intrahippocampal CPT increased ADD and S5D, and significantly reduced the latency to stage 4 (S4L) at the dose of 10 micromoles. Pretreatment of rats with CPT (5 micro moles) before CHA (50 micro moles), significantly reduced the effect of CHA on seizure parameters. The results suggest that the CA1 region of the hippocampus plays an important role in spreading seizure spikes from the entorhinal cortex to other brain regions and activation of adenosine A1 receptors in this region participates in the anticonvulsant effects of adenosine agonists.     

Atrial Fibrillation in Patients with Constrictive Pericarditis: The Significance of Pericardial Calcification

Background: Although atrial fibrillation (AF) is commonly encountered in patients with constrictive pericarditis (CP), little has been done to clarify its associated predisposing factors. Our aim was to evaluate the association of age, gender, disease duration, and pericardial calcification with AF in these patients. Methods: The medical records of 44 patients with CP were reviewed. There were 13 (29.5%) with AF and 31 (70.5%) with sinus rhythm. The two groups were compared for demographic variables, disease duration, and the presence of pericardial calcification. Results: The male‐to‐female ratio was 3.4:1. Calcification was seen in 11 (25%) of the entire group. AF was much more common in those with calcification than those with sinus rhythm (odds ratio, 7.87 [95% CI, 1.73–35.78], P = 0.008). There was no association between the presence of AF and the age (P = 0.156) or gender (P ≈ 1.00). Logistic regression, however, showed that the chance of developing AF increased by 27% by each year of increase in disease duration (P = 0.025). Conclusion: It seems that in patients with CP, the presence of pericardial calcification and the increasing disease duration are associated with a higher chance of developing AF.     

IGF system in children with congenital disorders of glycosylation

Objective  The function of IGF system components is affected by their glycosylation status in vitro . However, little is known about the role of glycosylation status of these components in vivo . In this study we determined the impact of glycosylation on the endocrine IGF system in children with the rare syndrome of congenital disorders of glycosylation (CDG).
Design  Analyses of serum samples from children with CDG and healthy controls.
Patients  Children with CDG ( N  = 12) were recruited as part of a separate clinical study of mannose therapy at the Mayo Clinic. Serum from control children ( N  = 11) were obtained as routine samples before discard.
Measurements  Levels and glycosylation state of components of the IGF system and ability to form physiologically relevant ternary complexes composed of IGF, IGFBP-3, and an acid-labile subunit (ALS).
Results  Serum levels of IGF-1, IGF-2, ALS, and IGFBP-3 were reduced ( P <  0·05) in children with CDG when compared to controls. Immunoblot analysis showed incomplete glycosylation of ALS and IGFBP-3 and impaired ternary complex formation in CDG. Partial normalization of ALS and IGFBP-3 glycosylation was associated with improvement in linear growth in a child with CDG-Ib during initiation of oral mannose therapy.
Conclusions  Inadequate glycosylation of IGFBP-3 and ALS has a negative effect on the function of these proteins in vivo . This study provides the first evidence in humans for the importance of glycosylation on components of the IGF system.     

Topographic Features Retained after Antibiotic Modification of Ti Alloy Surfaces: Retention of Topography with Attachment of Antibiotics

Periprosthetic infection is increasingly prevalent in orthopaedics with infection rates of 2% to 15% after total hip arthroplasty. To effectively decrease bacterial attachment, colonization, and subsequent development of periprosthetic infection, we previously described a method to covalently bond vancomycin to smooth Ti alloy surfaces. To attach vancomycin, the Ti surface is first passivated to create a fresh oxide layer. Previously, passivation has been achieved with an H₂SO₄/H₂O₂ etch that can destroy the topography of the underlying implant. Passivation by hydrothermal aging as well as by H₂SO₄/H₂O₂ incubation produced a robust oxide layer, but only hydrothermal aging left the geometry unaltered. These hydrothermally passivated Kirschner wires and smooth or beaded Ti surfaces were chemically coupled with vancomycin. Antibiotic-coupled samples representing all three geometries were uniformly covered with antibiotic, resisted colonization by Staphylococcus aureus for longer than 8 hours, and retained their biocompatibility as assessed by normal attachment and morphology of preosteocytic MLO-A5 cells. Using this technique, we believe it is possible to passivate many complex implant designs/geometries as a first step toward covalent bonding of antibiotics or other bioactive factors. One or more of the authors (JP, NJH) owns shares in SmartTech that could benefit from this technology; SmartTech did not fund any of this work. One or more of the authors have received grants from the National Institutes of Health (grants DE-13319 [IMS, CSA], DE-10875 [IMS, CSA], and AR-051303 [CSA, NJH, JP, IMS]), and the Department of Defense (grant DAMD17-03-1-0713 [CSA, NJH, JP, IMS]) for this study. Results presented are not the statement or policy of the funding agencies.     

Sex Differences and Laterality of Insulin Receptor Distribution in Developing Rat Hippocampus: an Immunohistochemical Study

This study aimed to compare the regional distribution of insulin receptor in various portions of newborn rat hippocampus on postnatal days 0 (P0), 7 (P7), and 14 (P14) between male/female and right/left hippocampi. We found that the number of insulin receptor (InsR)-immunoreactive-positive (InsR+) cells in CA1 continued to increase until P7 and remained unchanged thereafter. A marked increase in distribution of InsR+ cells in CA3 from P0 to P14 was observed, although there was a significant decline in the number of InsR+ cells in dentate gyrus (DG) at the same time. No differences between the right/left and male/female hippocampi were detected at P0 (P?>?0.05). Seven-day-old female rats showed a higher number of labeled cells in the left than in the right hippocampus. Moreover, the differences between the number of InsR+ cells in area CA1 and CA3 were statistically significant between males and females (P?P?相似文献   

“Marden-Walker Syndrome”: Neuropathologic Findings in Two Siblings

Neuropathologic examination of two siblings with phenotypic features consistent with Marden-Walker syndrome revealed central nervous system abnormalities which include reduction in the number of spinal anterior horn cells. The occurrence of these changes in a sibling pair provides strong evidence for a genetic etiology. The relationship between the neuropathologic changes and other phenotypic manifestations in this syndrome and in the closely related syndrome of Pena-Shokeir are discussed.     

Effect of transient hippocampal inhibition on amygdaloid kindled seizures and amygdaloid kindling rate

In this study the effect of transient inhibition of the CA1 region of the dorsal hippocampus by lidocaine on amygdala kindling rate and amygdaloid kindled seizures was investigated. In experiment 1, rats were divided into four groups. In group 1, animals were implanted only with a tripolar electrode into the amygdala but in groups 2-4, two guide cannulae were also implanted into the CA1 regions of the dorsal hippocampi. Animals were stimulated daily to be kindled. In groups 3 and 4, saline or 2% lidocaine (1 microl/2 min) was also injected respectively into the hippocampus, 5 min before each stimulation. Results obtained showed that amygdala kindling rate and the number of stimulations to receive from stage 4 to stage 5 seizure were significantly increased in group 4. In experiment 2, lidocaine (1% and 2%) was infused (1 microl/2 min) into the hippocampus of amygdala kindled rats bilaterally and animals were stimulated at 5, 15 and 30 min after drug injection. Twenty four h before lidocaine injection, saline was also infused (1 microl/2 min) into the hippocampus as control. Obtained results showed that afterdischarge duration was reduced 5 min after lidocaine (1% and 2%) injection. Stage 5 seizure duration was also decreased 5 and 15 min after 2% lidocaine. Thus, it may be suggested that in amygdala kindling, activation of the hippocampal CA1 region has a role in seizure acquisition and seizure severity so that inhibition of this region results in decreasing of seizure severity and retards amygdala kindling rate.     

Individual Characteristics and Peer Relations of Psychiatrically Hospitalized Aggressive Youths: Implications for Treatment

Objective: This study identified individual and peer-relations problems of inpatient youths who are aggressive, and whether youths who are aggressive in two settings have greater treatment needs than youths who are aggressive in one setting only. Method: 85 youths aged 10 to 16 years who were consecutively admitted to a psychiatric facility served as participants. Based on ratings by parents and hospital staff, youths were identified as aggressive in the community only, aggressive in the hospital only, aggressive in both settings, or nonaggressive. Dependent measures consisted of youth self-reports and ratings by parents and hospital staff. Results: Youths who demonstrate aggressive behavior in two settings have more nonaggressive behavior problems, more disturbed peer relations, and more hostile thinking than do nonaggressive youths, and some youths, although they may behave aggressively during hospitalization, have similar treatment needs as nonaggressive youths. Conclusions: Mental health professionals who work with youths in psychiatric settings need to develop treatment plans that directly address the more severe externalizing problems, hostile thinking, and peer problems of aggressive youths over and above that of nonaggressive youths, and should be aware that youths who behave aggressively during hospitalization may not have problems more severe than those of nonaggressive youths.