Ketamine abuse and apoptosis in the cortex in monkeys and mice

International Journal of Neuropsychopharmacology, 2008, v. 11, suppl. 1, p. 236-237, abstract no. P-06.11published_or_final_versionThe 26th CINP Congress, Munich, Germany, 13-17 July 2008

Epidemiology of acute primary angle-closure glaucoma in the Hong Kong Chinese population: prospective study.

OBJECTIVES: To determine the incidence of acute primary angle-closure glaucoma in the Hong Kong Chinese population, and to identify risk factors for this condition. DESIGN: Prospective study. SETTING: University teaching hospital, Hong Kong. PARTICIPANTS: Patients with acute primary angle-closure glaucoma presenting between 1 March 1998 and 29 February 2000. MAIN OUTCOME MEASURES: Demographic data, presenting symptoms and signs, temporal details of the presentation, and precipitating factors. The crude regional incidence was calculated according to the Hong Kong population census of 1991 and the age-specific incidence was calculated. RESULTS: Seventy-two cases (72 eyes of 72 patients) of acute primary angle-closure glaucoma were recruited. The crude incidence was 10.4 per 100,000 per year in the population aged 30 years and older. Patients at higher risk of attacks were those aged 70 years or older (age-specific incidence, 58.7 per 100,000 per year) and females, who had a relative risk of 3.8 compared with males (95% confidence interval, 1.7-8.4). Only four (5.6%) patients had a positive family history of acute primary angle-closure glaucoma. Seventeen (23.6%) patients were noted to have an upper respiratory tract infection before the attack, and 25 (34.7%) patients had taken antitussive agents. There was a statistically significant inverse correlation between the monthly attack rate and the monthly rate of influenza (Spearman's rank correlation coefficient = -0.388; P=0.031). CONCLUSION: There is a high incidence of acute primary angle-closure glaucoma among Chinese residents of Hong Kong, with elderly females at highest risk. A significant proportion of patients reported upper respiratory tract infection or the use of antitussive medication prior to attacks.published_or_final_versio

Achieving highly efficient gene transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles

Short dwell-time and poor penetration of the bladder permeability barrier (BPB) are the main obstacles to intravesical treatments for bladder diseases, and is evidenced by the lack of such therapeutic options on the market. Herein, we demonstrate that by finely tuning the molecular weight of our cationic polymer mucoadhesive nanoparticles, we enhanced our gene transfer, leading to improved adherence and penetrance through the BPB in a safe and efficient manner. Specifically, increasing the polymer molecular weight from 45 kDa to 83 kDa enhanced luciferase plasmid transfer to the healthy murine bladder, leading to 1.35 ng/g luciferase protein expression in the urothelium and lamina propria regions. The relatively higher molecular weight polymer (83 kDa) did not induce morphologic changes or inflammatory responses in the bladder. This approach of altering polymer molecular weight for prolonging gene transfer residence time and deeper penetration through the BPB could be the basis for the design of future gene therapies for bladder diseases

An integrated particle sampler and lung radiation dosimeter

A lung dosimeter that can record the nonradiological hazard of aerosol particles to the lung as well as the radiological hazard of air borne radionuclides that are attached to aerosol particles has been developed. The dosimeter is capable of recording aerosol particles of diameters from 10-2 μm to 102 μ by electrostatic collection in a specially designed dosimeter body. The aerosol size distribution is recorded on a mylar strip and the activity size distribution of α, β, and γ radiation emitting aerosols recorded on another strip coated with α-Al2O3:C. Both strips can be read by a specially built reader, the output of which can be used to calculate the nonradiological hazard and radiological hazard, respectively, and to give an overall picture of the exposure.published_or_final_versio

Down-regulation of GP130 signaling sensitizes bladder cancer to cisplatin by impairing Ku70 DNA repair signaling and promoting apoptosis

Chemoresistance is one of the barriers for the development of bladder cancer treatments. Previously, we showed that glycoprotein-130 (GP130) is overexpressed in chemoresistant bladder cancer cells and that knocking down GP130 expression reduced cell viability. In our current work, we showed that down-regulation of GP130 sensitized bladder cancer cells to cisplatin-based chemotherapy by activating DNA repair signaling. We performed immunohistochemistry and demonstrated a positive correlation between the levels of Ku70, an initiator of canonical non-homologous end joining repair (c-NHEJ) and suppressor of apoptosis, and GP130 in human bladder cancer specimens. GP130 knockdown by SC144, a small molecule inhibitor, in combination with cisplatin, increased the number of DNA lesions, specifically DNA double-stranded breaks, with a subsequent increase in apoptosis and reduced cell viability. Furthermore, GP130 inhibition attenuated Ku70 expression in bladder and breast cancer cells as well as in transformed kidney cells. In addition, we fabricated a novel polymer-lipid hybrid delivery system to facilitate GP130 siRNA delivery that had a similar efficiency when compared with Lipofectamine, but induced less toxicity

Boolean network model predicts cell cycle sequence of fission yeast

A Boolean network model of the cell-cycle regulatory network of fission yeast (Schizosaccharomyces Pombe) is constructed solely on the basis of the known biochemical interaction topology. Simulating the model in the computer, faithfully reproduces the known sequence of regulatory activity patterns along the cell cycle of the living cell. Contrary to existing differential equation models, no parameters enter the model except the structure of the regulatory circuitry. The dynamical properties of the model indicate that the biological dynamical sequence is robustly implemented in the regulatory network, with the biological stationary state G1 corresponding to the dominant attractor in state space, and with the biological regulatory sequence being a strongly attractive trajectory. Comparing the fission yeast cell-cycle model to a similar model of the corresponding network in S. cerevisiae, a remarkable difference in circuitry, as well as dynamics is observed. While the latter operates in a strongly damped mode, driven by external excitation, the S. pombe network represents an auto-excited system with external damping.Comment: 10 pages, 3 figure

Universal thermal and electrical conductivity from holography

It is known from earlier work of Iqbal, Liu (arXiv:0809.3808) that the boundary transport coefficients such as electrical conductivity (at vanishing chemical potential), shear viscosity etc. at low frequency and finite temperature can be expressed in terms of geometrical quantities evaluated at the horizon. In the case of electrical conductivity, at zero chemical potential gauge field fluctuation and metric fluctuation decouples, resulting in a trivial flow from horizon to boundary. In the presence of chemical potential, the story becomes complicated due to the fact that gauge field and metric fluctuation can no longer be decoupled. This results in a nontrivial flow from horizon to boundary. Though horizon conductivity can be expressed in terms of geometrical quantities evaluated at the horizon, there exist no such neat result for electrical conductivity at the boundary. In this paper we propose an expression for boundary conductivity expressed in terms of geometrical quantities evaluated at the horizon and thermodynamical quantities. We also consider the theory at finite cutoff outside the horizon (arXiv:1006.1902) and give an expression for cutoff dependent electrical conductivity, which interpolates smoothly between horizon conductivity and boundary conductivity . Using the results about the electrical conductivity we gain much insight into the universality of thermal conductivity to viscosity ratio proposed in arXiv:0912.2719.Comment: An appendix added discussing relation between boundary conductivity and universal conductivity of stretched horizon, version to be published in JHE

England SimSmoke: the impact of nicotine vaping on smoking prevalence and smoking‐attributable deaths in England

BACKGROUND AND AIMS: While the use of nicotine vaping products (NVPs) is widespread, their impact on smoking prevalence is controversial. This study considered the potential impact of NVPs on smoking prevalence in England. DESIGN: Indirect simulation model. The England SimSmoke model is validated through 2012, before NVP use became more widely used by smokers. Because information on NVP-related transitions is limited, an indirect method is used; the difference in observed smoking prevalence (reflecting NVPs) is compared with a 2012-2019 counterfactual No-NVP scenario (without NVPs) to estimate the impact of NVPs on smoking and smoking-attributable deaths. SETTING: England, 2000-2019. PARTICIPANTS: Nationally representative sample of population. MEASUREMENTS: England's population, mortality rates, and smoking prevalence estimates from three national surveys and tobacco control policies. FINDINGS: Between 2000 and 2012, SimSmoke projected a decline in age 18+ smoking prevalence of 23.5% in men and 27.0% in women. These projections, as well as those by specific age groups, were generally consistent with findings from the three national surveys. Comparing 2012-2019 relative reduction in age 18+ prevalence from the Annual Population Survey (males 27.5%) with the model-predicted No-NVP reduction (males 7.3%), the implied NVP-attributable relative reduction in adult smoking prevalence was 20.2% (95% CI, 18.8%-22.0%) for males and 20.4% (18.7%-22.2%) for females. The NVP-attributable reduction was 27.2% (22.8%-31.6%) for males and 31.7% (27.4%-36.5%) for females ages 18-24 and 18.6% (15.2%-21.8%) for males and 15.0% (11.1%-18.8%) for females ages 25-34, with similar reductions for ages 35 and above. The implied reduction in smoking prevalence between 2012 and 2019 equates to 165,660 (132,453-199,501) averted deaths by 2052. Other surveys yielded smaller, but relatively consistent results. CONCLUSIONS: An indirect method of simulation modeling indicates that substantial reductions in smoking prevalence occurred in England from 2012 to 2019 coinciding with the growth in nicotine vaping product use

Fluoxetine: a case history of its discovery and preclinical development

Introduction: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. Areas covered: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine’s effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. Expert opinion: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved