Anti-tumor effect of honokiol alone and in combination with other anti-cancer agents in breast cancer

Honokiol, an active component isolated and purified from Chinese traditional herb magnolia, was demonstrated to inhibit growth and induce apoptosis of different cancer cell lines such as human leukaemia, colon, and lung cancer cell lines; to attenuate the angiogenic activities of human endothelial cells in vitro; and to efficiently suppress the growth of angiosarcoma in nude mice. In this study, we have demonstrated that treatment of different human breast cancer cell lines with honokiol resulted in a time- and concentration-dependent growth inhibition in both estrogen receptor-positive and -negative breast cancer cell lines, as well as in drug-resistant breast cancer cell lines such as adriamycin-resistant and tamoxifen-resistant cell lines. The inhibition of growth was associated with a G1-phase cell cycle arrest and induction of caspase-dependent apoptosis. The effects of honokiol might be reversely related to the expression level of human epidermal growth receptor 2, (HER-2, also known as erbB2, c-erbB2) since knockdown of her-2 expression by siRNA significantly enhanced the sensitivity of the her-2 over-expressed BT-474 cells to the honokiol-induced apoptosis. Furthermore, inhibition of HER-2 signalling by specific human epidermal growth receptor 1/HER-2 (EGFR/HER-2) kinase inhibitor lapatinib synergistically enhanced the anti-cancer effects of honokiol in her-2 over-expressed breast cancer cells. Finally, we showed that honokiol was able to attenuate the PI3K/Akt/mTOR (Phosphoinositide 3-kinases/Akt/mammalian target of rapamycin) signalling by down-regulation of Akt phosphorylation and upregulation of PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) expression. Combination of honokiol with the mTOR inhibitor rapamycin presented synergistic effects on induction of apoptosis of breast cancer cells. In conclusion, honokiol, either alone or in combination with other therapeutics, could serve as a new, promising approach for breast cancer treatment.     

Repairability of dental siloranes in vitro

Objectives

Aim of the study was the investigation of the repairability of a silorane (Filtek Silorane, 3M Espe, Seefeld, Germany) after different surface pretreatments in vitro.

Methods

54 silorane specimens (5 mm × 5 mm × 5 mm) were fabricated and stored in saline solution (24 h/37 °C). Their surface was polished with abrasive paper (600 grit), etched with phosphoric acid (10 s) and rinsed with water (30 s). Repair was performed with a silorane based on one of the 9 treatment protocols (each n = 6): no additional treatment (NAT), silorane primer (P) and silorane bond (B), B only, sandblasting (SB), SB plus P/B, SB plus B, CoJet and silane (CJ), CJ plus P/B, CJ plus B. Whole silorane specimens (5 mm × 5 mm × 10 mm) with no repair served as control. Specimens were sectioned and microtensile bond strength (μTBS) was measured (30 beams per group, surface area approx. 1.2 mm², crosshead-speed 1 mm/min) statistical analysis (ANOVA, Tukey HSD, p < 0.05) was performed.

Results

μTBS of the specimens was significantly influenced by the surface pretreatment (p < 0.001). The highest μTBS was determined for CJ/B and SB/B, which were not significantly different from the control. NAT, SB and CJ benefited from an additional treatment with B (p < 0.01). The additional use of P did not improve μTBS, but was detrimental for the SB and CJ groups (p < 0.05).

Significance

Siloranes can be repaired with either SB or CJ in combination with a silorane bond, the additional use of silorane primer is disadvantageous.     

发作和癫痫分类框架术语及概念的修订:国际抗癫痫联盟分类和术语委员会报告,2005-2009

癫痫分类的历史很大程度上都是取决于敏锐的临床观察和专家意见.首次对发作的分类始于1960年,随后官方做出的更新是1981年发作分类[1981年国际抗癫痫联盟(ILAE)分类和术语委员会]和1989年的癫痫分类(1989年ILAE分类和术语委员会).ILAE的分类在很大程度上是基于传统的概念,它早于现代神经影像学、基因技术和分子生物学的概念.当年的制定者也预见到,随着新信息的获得和科技发展,其分类必须随之变化.制定分类方案不是一项简单的任务.专家们曾尝试更新1981年和1989年分类方案,但是没有提出任何新建议.     

Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005–2009

The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy. Generalized and focal are redefined for seizures as occurring in and rapidly engaging bilaterally distributed networks (generalized) and within networks limited to one hemisphere and either discretely localized or more widely distributed (focal). Classification of generalized seizures is simplified. No natural classification for focal seizures exists; focal seizures should be described according to their manifestations (e.g., dyscognitive, focal motor). The concepts of generalized and focal do not apply to electroclinical syndromes. Genetic, structural–metabolic, and unknown represent modified concepts to replace idiopathic, symptomatic, and cryptogenic. Not all epilepsies are recognized as electroclinical syndromes. Organization of forms of epilepsy is first by specificity: electroclinical syndromes, nonsyndromic epilepsies with structural–metabolic causes, and epilepsies of unknown cause. Further organization within these divisions can be accomplished in a flexible manner depending on purpose. Natural classes (e.g., specific underlying cause, age at onset, associated seizure type), or pragmatic groupings (e.g., epileptic encephalopathies, self‐limited electroclinical syndromes) may serve as the basis for organizing knowledge about recognized forms of epilepsy and facilitate identification of new forms.     

Are absences truly generalized seizures or partial seizures originating from or predominantly involving the pre-motor areas? Some clinical and theoretical observations and their implications for seizure classification

In both the current (1981) ILAE Classification of Epileptic Seizures and the recently Proposed Diagnostic Scheme for People with Epilepsy and Epileptic Seizures, typical absence seizures are defined as generalized seizures, implying widespread subcortical and cortical neuronal involvement from onset with impairment of consciousness as the clinical hallmark. Clinical observations from three patients and clinical and experimental data from the literature suggest, however, that: (1) consciousness is retained in many typical absences; (2) the true hallmark of these seizures is arrest of motor initiation due to disturbance of pre-motor area frontal-lobe function; (3) typical absences and partial seizures from these areas may show similar clinical and EEG features and involve the same neuronal circuits. The neuronal system primarily involved in these seizures consists of a relatively limited cortico-thalamo-cortical circuit, including the reticular thalamic nucleus, the thalamocortical relay and the predominantly anterior and mesial frontal cerebral cortex, with the cortex probably acting as the primary driving site. Typical absences thus should not be classified or defined as generalized seizures, particularly since neuropathological and imaging studies increasingly argue for localized structural abnormalities, even in idiopathic or primary generalized epilepsy. These observations further highlight the intrinsic weaknesses of the current classification system for seizures and support further adaptations of the diagnostic system currently under development.     

An investigation of the allergenic constituents of Cladonia stellaris (Opiz) Pous & VeŽda ('silver moss', 'reindeer moss' or 'reindeer lichen')

The sensitizing potency of Cladonia stellaris ('reindeer lichen silver moss') extracts was determined in guinea pigs by a modified FCA (Freund's complete adjuvant) lest. The lichen showed a moderate sensitizing potency. Similar investigations with pure common lichen constituents revealed a moderate sensitizing potency for fumarprotocetraric acid and atranorin and a weak one for evernic acid, stictic acid and both forms of usnic acid. Although generallt weak, (–)-usnic acid was at least 2 × stronger than (+)-usnic acid. After separation of the Cladonia ether extract into 'usnic-acid-free' and 'usnic-acid-containing' fractions, perlatolic acid was identified as the main allergenic constituent of the 'usnic-acid-free fraction'. Stictic, evernic. fumarprotocetraric acid and atranorin were not detectable. Lichens and lichen products generally possess a weak to moderate sensitizing capacity. Compared with common sensitizers of occupational and environmental importance, these products play only a minor role.     

Role of selective V2-receptor-antagonism in septic shock: a randomized, controlled, experimental study

Introduction

V₂-receptor (V₂R) stimulation potentially aggravates sepsis-induced vasodilation, fluid accumulation and microvascular thrombosis. Therefore, the present study was performed to determine the effects of a first-line therapy with the selective V₂R-antagonist (Propionyl₁-D-Tyr(Et)₂-Val₄-Abu₆-Arg_8,9)-Vasopressin on cardiopulmonary hemodynamics and organ function vs. the mixed V_1aR/V₂R-agonist arginine vasopressin (AVP) or placebo in an established ovine model of septic shock.

Methods

After the onset of septic shock, chronically instrumented sheep were randomly assigned to receive first-line treatment with the selective V₂R-antagonist (1 μg/kg per hour), AVP (0.05 μg/kg per hour), or normal saline (placebo, each n = 7). In all groups, open-label norepinephrine was additionally titrated up to 1 μg/kg per minute to maintain mean arterial pressure at 70 ± 5 mmHg, if necessary.

Results

Compared to AVP- and placebo-treated animals, the selective V₂R-antagonist stabilized cardiopulmonary hemodynamics (mean arterial and pulmonary artery pressure, cardiac index) as effectively and increased intravascular volume as suggested by higher cardiac filling pressures. Furthermore, left ventricular stroke work index was higher in the V₂R-antagonist group than in the AVP group. Notably, metabolic (pH, base excess, lactate concentrations), liver (transaminases, bilirubin) and renal (creatinine and blood urea nitrogen plasma levels, urinary output, creatinine clearance) dysfunctions were attenuated by the V₂R-antagonist when compared with AVP and placebo. The onset of septic shock was associated with an increase in AVP plasma levels as compared to baseline in all groups. Whereas AVP plasma levels remained constant in the placebo group, infusion of AVP increased AVP plasma levels up to 149 ± 21 pg/mL. Notably, treatment with the selective V₂R-antagonist led to a significant decrease of AVP plasma levels as compared to shock time (P < 0.001) and to both other groups (P < 0.05 vs. placebo; P < 0.001 vs. AVP). Immunohistochemical analyses of lung tissue revealed higher hemeoxygenase-1 (vs. placebo) and lower 3-nitrotyrosine concentrations (vs. AVP) in the V₂R-antagonist group. In addition, the selective V₂R-antagonist slightly prolonged survival (14 ± 1 hour) when compared to AVP (11 ± 1 hour, P = 0.007) and placebo (11 ± 1 hour, P = 0.025).

Conclusions

Selective V₂R-antagonism may represent an innovative therapeutic approach to attenuate multiple organ dysfunction in early septic shock.     

Patient Safety Through RFID: Vulnerabilities in Recently Proposed Grouping Protocols

As RFID-tagged systems become ubiquitous, acceptance of this technology by the general public necessitates addressing related security/privacy issues. The past eight years have seen an increasing number of publications in this direction, specifically using cryptographic approaches. Recently, the Journal of Medical Systems published two papers addressing security/privacy issues through cryptographic protocols. We consider the proposed protocols and identify some existing vulnerabilities.     

On-line detection of transient neuropsychological disturbances during EEG discharges in children with epilepsy

Short-term memory tasks (visual-spatial and verbal) were devised to identify the influence of transient EEG discharges, without clinically manifest disturbances, on neuropsychological performance. 53 children with subclinical focal and generalized EEG discharges were tested 72 times and 16-channel telemetered EEG and video-recordings were made. 36 per cent of test sessions showed a significant preponderance of errors when discharges were recorded. Children with right-sided discharges had impaired performance in 50 per cent of their test sessions, with performance on the visual-spatial task most affected: left-sided discharges appeared to exert greater influence on the verbal task. These tests can easily be used to monitor six- to 15-year-old children.     

"Semi-invasive" vs. invasive approaches for intracranial EEG and seizure monitoring in epilepsy

When non-invasive studies fail to provide sufficient localising data to permit resective epilepsy surgery, intracranial seizure monitoring may have to be performed. Various techniques are available with specific advantages as well as disadvantages. "Semi-invasive" techniques, despite their name, remain essentially "invasive". The choice for a specific approach therefore should depend on the clinical problem in each individual patient rather than on theoretical preference.