Accumulation of beta-amyloid in the brain microvessels accompanies increased hyperphosphorylated tau proteins following microsphere embolism in aged rats

To define mechanisms underlying neurovascular injury following brain embolism-induced neurodegeneration, we investigated temporal and spatial pathological changes in brain microvessels up to 12 weeks after microsphere embolism (ME) induction in aged male rats. Mild ME upregulated endothelial nitric oxide synthase (eNOS) and protein tyrosine nitration in brain microvessels. Strong beta-amyloid immunoreactivity coincident with increased eNOS immunoreactivity was observed in microvessels. Immunoblotting of purified brain microvessels revealed that beta-amyloid accumulation significantly increased 1 week after ME induction and remained elevated for 12 weeks. Importantly, beta-amyloid accumulation in brain parenchyma was also observed in areas surrounding injured microvessels at 12 weeks. Levels of Alzheimer's-related hyperphosphorylated tau proteins also concomitantly increased in neurons surrounding regions of beta-amyloid accumulation 12 weeks after ME induction, as did glycogen synthase kinase (GSK3beta) (Tyr-216) phosphorylation. Taken together, ME-induced aberrant eNOS expression and subsequent protein tyrosine nitration in microvessels preceded beta-amyloid accumulation both in microvessels and brain parenchyma, leading to hyperphosphorylation of neuronal tau proteins through GSK3beta activation.     

Involvement of electrical coupling in the in vivo ictal epileptiform activity induced by 4-aminopyridine in the neocortex

In the present study we have investigated the possible role of gap junctions in the induction and manifestation of 4-aminopyridine-induced acute seizure activity both at the primary focus and at the mirror focus in anaesthetized rats by combining electrophysiological, pharmacological and molecular biological techniques. In the course of the intracellular recordings, unusual firing patterns that are assumed to be mediated by electrical coupling and appearing either randomly or in close time-locked manner with the ictal discharges were observed. In another series of experiments, a significant decrease in the intensity of seizure activity of the already active epileptic foci was detected when electrical synaptic transmission was blocked by carbenoxolone either at the primary focus or at the mirror focus. When electrical synaptic transmission was depressed relative to the initial baseline prior to the induction of epileptic focus, only a mild influence on the induction of seizure discharges occurred. The role of the gap junctional communication in the epileptiform activity was further investigated by following the expression pattern of two connexin genes. Both, connexin-32 and connexin-43 mRNA levels were significantly elevated at the primary focus as well as at the mirror focus, after 60 min of repeated ictal discharges.We conclude that gap junction communication probably became a part of the neuronal synchronization both in the primary and in the secondarily-induced acute epileptiform activity in the neocortex in vivo. These results, together with earlier observations, indicate a direction for the development of new drugs targeting gap junctions for therapeutic intervention.     

Medication-related osteonecrosis of the jaw: An institution’s experience

ABSTRACT

Objectives

This study aimed to evaluate and report the outcomes associated with the management of patients who were treated surgically for medication-related osteonecrosis of the jaw (MRONJ).Methods: Demographic and medical profiles of patients with a diagnosis of MRONJ were created. The type of surgical treatment, complications, and treatment outcomes were identified.Results: Twenty-one patients with an average age of 68.42 years (range 40–90 years) were included. Nineteen patients had only mandible involvement, one patient had only maxilla involvement, and one patient had both mandible and maxilla involvement. Thirteen patients underwent marginal resections. Eight patients underwent segmental resection of the mandible with immediate reconstruction. Nineteen patients healed without any complications. Two patients who had undergone segmental resection of the mandible experienced postoperative complications and needed a second surgery to achieve primary closure.Discussion: Advanced MRONJ can effectively be treated with resective surgery in combination with medical treatment.     

Osteotome Maxillary Sinus Lift Using Bovine Bone and Calcium Sulfate: A Case Series

Purpose: The purpose of this longitudinal study was to evaluate the success of bovine bone and calcium sulfate (CaSO₄) as sinus augmentation material with osteotome maxillary sinus lift. Materials and Methods: Thirty‐one osteotome sinus lift procedures were performed for 18 healthy patients (7 males and 11 females). A mixture of bovine bone and CaSO₄ (ratio, 4:1) was used as sinus augmentation material with simultaneous implant placement. Implants were loaded 4 to 5 months postimplant surgery. Cases were followed for an average of 23.4 months postloading (range, 12–60 months). Results: The mean age of the study group was 49.7 ± 10.66 years. The residual height of the alveolar ridge ranged from 5.5 to 11 mm (mean, 8.16 ± 1.52 mm). Four to 5 months after implant placement, the x‐ray showed a 1.5 to 5 mm apical shift of the sinus floor (mean, 3.47 ± 0.97 mm), which was maintained to the end of the evaluation period. At 12 months postloading, crestal bone loss ranged from 0.5 to 1.5 mm (mean, 0.87 ± 0.26 mm), and pocket depth ranged from 2 to 4 mm (mean, 2.9 ± 0.67 mm). No significant change in crestal bone loss or pocket depth was noticed afterward. Conclusion: Bovine bone plus CaSO₄ can be used successfully as a sinus augmentation material with osteotome sinus elevation. The use of CaSO₄ significantly improved the handling properties of bovine bone and helped to stabilize the bone graft particles during healing.     

Spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446/ST101) treatment rescues olfactory bulbectomy-induced memory impairment by activating Ca2+/calmodulin kinase II and protein kinase C in mouse hippocampus

Olfactory bulbectomy (OBX) in mice elicits impaired memory and cognitive functions. Here, we found that chronic oral administration of spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446/ST101) (0.1-1 mg/kg/day), a novel cognitive enhancer, significantly improved memory deficits as assessed by Y-maze and novel object recognition tasks in OBX mice. Immunostaining of cholinergic neurons in the medial septum by using an anti-choline acetyltransferase antibody indicated that chronic ZSET1446 treatment did not rescue cholinergic neurons. However, chronic treatment significantly restored OBX-induced decreases both in calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) phosphorylation without improving decreased extracellular signal-regulated kinase phosphorylation in the hippocampal CA1 region. Consistent with enhanced CaMKII and PKC phosphorylation, ZSET1446 treatment improved glutamate receptor 1 (Ser-831) phosphorylation in the hippocampal CA1 region. ZSET1446 treatment also significantly rescued impaired long-term potentiation (LTP) in the hippocampal CA1 region of OBX mice. Taken together, the cognition-enhancing effect of ZSET1446 is probably mediated in part by stimulation of CaMKII and PKC activities, which in turn rescue impaired hippocampal LTP in OBX mice.     

Dolichandroside A,a new α‐glucosidase inhibitor and DPPH free‐radical Scavenger from Dolichandrone falcata seem

A new phenylpropanoid glycoside, dolichandroside‐A, together with seven known compounds α‐lapachone, lapachol, aloesaponarin II, 8‐hydroxydehydroiso‐α‐lapachone, β‐sitosterol, 3,8‐dihydroxydehydroiso‐α‐lapachone and verbascoside were isolated from the active ethyl acetate soluble extract of heartwood of Dolichandrone falcata. All except for dolichandroside‐A are known compounds, but have been isolated for the first time from this plant. The structure of all these compounds was determined on the basis of 1D‐ and 2D‐NMR spectral data. All the isolates were tested for α‐glucosidase inhibitory and DPPH radical scavenging activity. This is the first report identifying DPPH scavenging activity and α‐glucosidase inhibitory activity in D. falcata. Furthermore, along with a new compound, dolichandroside‐A, this study also assigns for the first time α‐glucosidase inhibitory activity to verbascoside and aloe saponarin‐II. Copyright © 2008 John Wiley & Sons, Ltd.     

Pregnancy-related changes in tobacco, alcohol and cannabis use reported by antenatal patients at two public hospitals in South Australia

Background: Australian substance use data do not demonstrate pregnancy-related changes or distinguish between pregnant and lactating women.
Aims: To determine such changes by antenatal patients at two South Australian public hospitals accounting for 35% of the state's births.
Methods: In 2005–2006, all first visit antenatal women at the two hospitals were asked by clinic staff to complete an anonymous, self-administered questionnaire prompting details of substance use, current and previous (while not pregnant or lactating).
Results: Questionnaires were returned by 748 women, 34.4% of 2173 eligible in the study period. Women reported use at significantly lower rates than before pregnancy. Tobacco was most used in pregnancy (18.5%), followed by alcohol (11.8%) and cannabis (4.5%), with negligible use of other illicit substances. There was no significant difference in substance use related to trimester. Women with previous pregnancy losses were significantly more likely to use tobacco and alcohol. Younger women were more likely to use tobacco and cannabis, with no age-related differences in alcohol consumption. First pregnancy was the only factor independently associated with the likelihood of ceasing substance use when pregnant, but only in relation to alcohol.
Conclusions: Women were less likely to use all substances when pregnant, and health-care providers should reinforce and support these decisions. The use of cannabis and alcohol while pregnant was below expectations. Reported tobacco use was concordant with existing data and confirms that the risk of smoking in pregnancy remains a message difficult to communicate in the context of chronic nicotine dependence.     

Integration of Hot Tube Gas Forming and Die Quenching of Ultra-High Strength Steel Hollow Parts Using Low Pressure Sealed-Air

A low pressure sealed-air hot tube gas forming process of ultra-high strength steel tubes was developed not only to change the cross-section of the hollow products by bulging but also to increase the strength of components. Gas-formed components are typically formed by a controlled-gas pressure with extremely high internal pressure, which leads to affected production costs and safety. Moreover, compressing the gas with high pressure requires high energy during its preparation. Therefore, to simplify the internal pressure controlling system and improve the safety factor in gas forming processes, the sealed-air tubes are formed with a quite low initial pressure. The pressure of the sealed air increased with increasing temperature of the air inside the resistance-heated tube, and the bulging deformation was controlled only by axial feeding. The effects of the initial pressure and heating temperature on the bulging deformation and quenchability of the tubes, and the effect of the starting time of axial feeding on the bulging behavior were examined. Consequently, ultra-high strength steel bulged parts were produced even in low initial internal pressure and with the rapid heating of the tubes.