Withdrawing Antihypertensive Treatment

Howes, L.G.,Krum, H. Medical Publications Korea 1989 Medical Progress Vol.11 No.3

ACE Inhibitors : Are There Any Clinical Differences?

Howes, Laurence G. Medical Publications Korea 1995 Medical Progress Vol.17 No.2

THE PERCUTANEOUS ABSORTION OF SOME ANIONIC SURFACTANTS

( D. Howes ) 대한화장품학회 1974 대한화장품학회지 Vol.4 No.1

Presented at the IFSCC Ⅷth International Congress on 'Cosmetics--Quality and Safety' organized by the Society of Cosmetic Chemists of Great Britain at London on 26-30th August 1974. SYNOPSIS. The irritant action of a surfactant to skin may be related to the ability of that surfactant to penetrate the stratum corneum and act upon the underlying viable tissues. The percutaneous absorption of some [¹⁴C-] labelled anionic surfactants has been measured in vivo in rats, after both consumertype applications and applications of longer duration, and the results have been compared with those from in vitro studies using isolated rat skin and human epidermis. The methodology for both the in vivo and in vitro studies will be outlined and results will be presented from experiments with a series of sodium soaps of normal fatty acids, sodium lauryl sulphate, sodium lauryl isethionate and sodium dodecy1benzene sulphonate. The in vivo techniques can also provide information as to the metabolic fate of topically applied surfactants under user type conditions. The usefulness of the in vitro techniques and their shortcomings will be discussed.

Duplex-Specific Nuclease-Amplified Detection of MicroRNA Using Compact Quantum Dot-DNA Conjugates

Wang, Ye,Howes, Philip D.,Kim, Eunjung,Spicer, Christopher D.,Thomas, Michael R.,Lin, Yiyang,Crowder, Spencer W.,Pence, Isaac J.,Stevens, Molly M. American Chemical Society 2018 ACS APPLIED MATERIALS & INTERFACES Vol.10 No.34

<P>Advances in nanotechnology have provided new opportunities for the design of next-generation nucleic acid biosensors and diagnostics. Indeed, combining advances in functional nanoparticles, DNA nanotechnology, and nuclease-enzyme-based amplification can give rise to new assays with advantageous properties. In this work, we developed a microRNA (miRNA) assay using bright fluorescent quantum dots (QDs), simple DNA probes, and the enzyme duplex-specific nuclease. We employed an isothermal target-recycling mechanism, where a single miRNA target triggers the cleavage of many DNA signal probes. The incorporation of DNA-functionalized QDs enabled a quantitative fluorescent readout, mediated by Förster resonance energy transfer (FRET)-based interaction with the DNA signal probes. Our approach splits the reaction in two, performing the enzyme-mediated amplification and QD-based detection steps separately such that each reaction could be optimized for performance of the active components. Target recycling gave ca. 3 orders of magnitude amplification, yielding highly sensitive detection with a limit of 42 fM (or 1.2 amol) of miR-148, with excellent selectivity versus mismatched sequences and other miRNAs. Furthermore, we used an alternative target (miR-21) and FRET pair for direct and absolute quantification of miR-21 in RNA extracts from human cancer and normal cell lines.</P> [FIG OMISSION]</BR>

Calculating Occupancy when One does not have Baseline: A Comparison of Different Options

Kim, Euitae,Howes, Oliver D,Yu, Kyung-Sang,Jeong, Jae Min,Lee, Jae Sung,Jang, In-Jin,Shin, Sang-Goo,Kapur, Shitij,Kwon, Jun Soo SAGE Publications 2011 Journal of cerebral blood flow and metabolism Vol.31 No.8

<P> Dopamine D2 receptor occupancy of antipsychotic drugs is calculated relative to the subject's D2 receptor binding potential (BP) in the drug-free state (baseline BP). Because baseline BP is seldom known in patients with schizophrenia, population means from unrelated control samples are often used to estimate it. However, this is likely to introduce bias and error into the occupancy measure. There is thus a need for a method to reliably estimate baseline BP for patient populations in whom it may be impractical or unethical to get baseline measurements. It has been previously found that the relationship between plasma concentration and dopamine receptor occupancy by antipsychotic drugs follows a sigmoid Emax model. Based on this, we developed a method for calculating dopamine D2 receptor occupancy by antipsychotic drugs using an inhibitory Emax model ( Imax method) that estimates individual baseline BPs. To validate this, we compared the result from the Imax method with actual occupancy and estimated occupancy calculated from the average baseline BP (substitution method). The data for validation were obtained from two different receptor occupancy studies with the antipsychotic medications YKP1358 and aripiprazole. We estimated the reliability between the true measured occupancy and the predicted occupancy using the intraclass correlation coefficient (ICC), and the variability of occupancy was also compared between the Imax and substitution methods. In YKP1358 study, all the ICCs of the Imax method were above 0.8, but those of the substitution method showed values lower than 0.8. In aripiprazole study, the ICCs of the Imax method were higher than those of the substitution method, but all the ICCs showed higher values than 0.8. The variability of Imax method was significantly smaller than that of substitution method in both studies. The Imax method shows better reliability and less variability than the substitution method. The Imax method can be applied for receptor occupancy study, and bring more reliability and accuracy to the occupancy study in patients with schizophrenia. </P>

Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [¹⁸F]DOPA PET Study

Kim, Euitae,Howes, Oliver D,Veronese, Mattia,Beck, Katherine,Seo, Seongho,Park, Jin Woo,Lee, Jae Sung,Lee, Yun-Sang,Kwon, Jun Soo Nature Publishing Group 2017 Neuropsychopharmacology Vol. No.

<P>Some patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment-resistant schizophrenia The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment-resistant schizophrenia However, in this study, the treatment-resistant patients were highly symptomatic, whereas the responsive patients showed no or minimal symptoms. The study could not distinguish whether this was a trait effect or reflected the difference in symptom levels. Thus, we aimed to test whether dopaminergic function is altered in patients with a history of treatment resistance to first-line drugs relative to treatment responders when both groups are matched for symptom severity levels by recruiting treatment-resistant patients currently showed low symptom severity with the clozapine treatment. Healthy controls (n = 12), patients treated with clozapine (n = 12) who had not responded to first-line antipsychotics, and patients who had responded to first-line antipsychotics (n = 12) were recruited. Participants were matched for age and sex and symptomatic severity level in patient groups. Participants' dopamine synthesis capacity was measured by using [F-18]DOPA PET. We found that patients treated with clozapine show lower dopamine synthesis capacity than patients who have responded to first-line treatment (Cohen's d=0.9191 (whole striatum), 0.7781 (associative striatum), 1.0344 (limbic striatum), and 1.0189 (sensorimotor striatum) in line with the hypothesis that the dopaminergic function is linked to treatment response. This suggests that a different neurobiology may underlie treatment-resistant schizophrenia and that dopamine synthesis capacity may be a useful biomarker to predict treatment responsiveness.</P>

Predicting Brain Occupancy from Plasma Levels using PET: Superiority of Combining Pharmacokinetics with Pharmacodynamics while Modeling the Relationship

Kim, Euitae,Howes, Oliver D,Kim, Bo-Hyung,Jeong, Jae Min,Lee, Jae Sung,Jang, In-Jin,Shin, Sang-Goo,Turkheimer, Federico E,Kapur, Shitij,Kwon, Jun Soo SAGE Publications 2012 Journal of cerebral blood flow and metabolism Vol.32 No.4

<P> Positron emission tomography (PET) studies of dopamine receptor occupancy can be used to assess dosing of antipsychotics. Typically, studies of antipsychotics have applied pharmacodynamic (PD) modeling alone to characterize the relationship between antipsychotic dose and its effect on the brain. However, a limitation of this approach is that it does not account for the discrepancy between the time courses of plasma concentration and receptor occupancy by antipsychotics. Combined pharmacokinetic-PD (PK-PD) modeling, by incorporating the time dependence of occupancy, is better suited for the reliable analysis of the concentration-occupancy relationship. To determine the effect of time on the concentration-occupancy relationship as a function of analysis approach, we measured dopamine receptor occupancy after the administration of aripiprazole using [<SUP>11</SUP>C]raclopride PET and obtained serial measurements of the plasma aripiprazole concentration in 18 volunteers. We then developed a PK-PD model for the relationship, and compared it with conventional approach (PD modeling alone). The hysteresis characteristics were observed in the competitor concentration-occupancy relationship and the value of EC50 was different according to the analysis approach ( EC50 derived from PD modeling alone = 11.1 ng/mL (95% confidence interval (CI) = 10.1 to 12.1); while that derived from combined PK-PD modeling = 8.63 ng/mL (95% CI = 7.75 to 9.51)). This finding suggests that PK-PD modeling is required to obtain reliable prediction of brain occupancy by antipsychotics. </P>

A "GAP-Model" based Framework for Online VVoIP QoE Measurement

Calyam, Prasad,Ekici, Eylem,Lee, Chang-Gun,Haffner, Mark,Howes, Nathan The Korea Institute of Information and Commucation 2007 Journal of communications and networks Vol.9 No.4

Increased access to broadband networks has led to a fast-growing demand for voice and video over IP(VVoIP) applications such as Internet telephony(VoIP), videoconferencing, and IP television(IPTV). For pro-active troubleshooting of VVoIP performance bottlenecks that manifest to end-users as performance impairments such as video frame freezing and voice dropouts, network operators cannot rely on actual end-users to report their subjective quality of experience(QoE). Hence, automated and objective techniques that provide real-time or online VVoIP QoE estimates are vital. Objective techniques developed to-date estimate VVoIP QoE by performing frame-to-frame peak-signal-to-noise ratio(PSNR) comparisons of the original video sequence and the reconstructed video sequence obtained from the sender-side and receiver-side, respectively. Since processing such video sequences is time consuming and computationally intensive, existing objective techniques cannot provide online VVoIP QoE. In this paper, we present a novel framework that can provide online estimates of VVoIP QoE on network paths without end-user involvement and without requiring any video sequences. The framework features the "GAP-model", which is an offline model of QoE expressed as a function of measurable network factors such as bandwidth, delay, jitter, and loss. Using the GAP-model, our online framework can produce VVoIP QoE estimates in terms of "Good", "Acceptable", or "Poor"(GAP) grades of perceptual quality solely from the online measured network conditions.

The Relationship Between Frontostriatal Connectivity and Striatal Dopamine Function in Schizophrenia: An 18F-DOPA PET and Diffusion Tensor Imaging Study in Treatment Responsive and Resistant Patients

신상호,Jung Wi Hoon,Robert McCutcheon,Mattia Veronese,Katherine Beck,Lee Jae Sung,Lee Yun-Sang,Oliver D. Howes,Kim Euitae,Kwon Jun Soo 대한신경정신의학회 2022 PSYCHIATRY INVESTIGATION Vol.19 No.7

Objective Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefrontal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connectivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We therefore investigated the relationship between frontostriatal connectivity and striatal dopamine synthesis in treatment-responsive schizophrenia (non-TRS) and compared them to treatment-resistant schizophrenia (TRS) and healthy controls (HC).Methods Twenty-four patients with schizophrenia and twelve HC underwent [¹⁸F] DOPA PET scans to measure dopamine synthesis capacity (the influx rate constant K_i^cer) and diffusion 3T MRI to measure structural connectivity (fractional anisotropy, FA). Connectivity was assessed in 2 major frontostriatal tracts. Associations between K_i^cer and FA in each group were evaluated using Spearman’s rho correlation coefficients.Results Non-TRS showed a negative correlation (r=-0.629, p=0.028) between connectivity of dorsolateral prefrontal cortex-associative striatum (DLPFC-AST) and dopamine synthesis capacity of associative striatum but this was not evident in TRS (r=-0.07, p=0.829) and HC (r=-0.277, p=0.384).Conclusion Our findings are consistent with the hypothesis of dysregulation of the striatal dopaminergic system being related to prefrontal cortex pathology localized to connectivity of DLPFC-AST in non-TRS, and also extend the hypothesis to suggest that different mechanisms underlie the pathophysiology of non-TRS and TRS.

A sample-in-digital-answer-out system for rapid detection and quantitation of infectious pathogens in bodily fluids

Yang, Haowen,Chen, Zhu,Cao, Xiaobao,Li, Zhiyang,Stavrakis, Stavros,Choo, Jaebum,deMello, Andrew J.,Howes, Philip D.,He, Nongyue Springer-Verlag 2018 Analytical and Bioanalytical Chemistry Vol.410 No.27