Higher serotonin transporter availability in early‐onset obsessive–compulsive disorder patients undergoing escitalopram treatment: A [11C]DASB PET study

Objective

Early‐onset obsessive–compulsive disorder (EOCD) and late‐onset obsessive–compulsive disorder (LOCD) are distinct subtypes of obsessive–compulsive disorder (OCD). OCD patients are treated with serotonin reuptake inhibitors, but the difference in serotonin transporter (SERT) availability between medicated EOCD and LOCD is unexplored yet.

Methods

Six EOCD and 6 LOCD patients were enrolled. They underwent serial [¹¹C]DASB positron emission tomography scans during maintenance therapy with escitalopram, and their plasma concentration of escitalopram was measured simultaneously with the scan. Then, the drug‐free binding potential of SERT was calculated by pharmacokinetic–pharmacodynamic modelling.

Results

In comparison with LOCD patients, SERT availability was significantly higher in the putamen of EOCD patients (U = 4, p = .026), but not in the caudate nucleus (U = 14, p = .589), thalamus (U = 16, p = .818), and dorsal raphe nucleus (U = 7, p = .093). Binding potential of putamen showed a negative correlation (r = ?.580, p = .048) with age of onset of the disease, but not with the Yale–Brown Obsessive Compulsive Scale scores.

Conclusions

These findings indicate that the earlier the age of onset of OCD, the less serotonergic pathology there is and that this difference remains even after long‐term serotonin reuptake inhibitor treatment. Clinically, it might suggest that nonserotonergic treatments would be a better option for EOCD patients.     

No significant effect of the <Emphasis Type="Italic">SLCO1B1</Emphasis> polymorphism on the pharmacokinetics of ursodeoxycholic acid

Purpose  

To investigate possible effects of the SLCO1B1 polymorphism on the pharmacokinetics of ursodeoxycholic acid (UDCA) and its metabolites in healthy volunteers.     

Group II mGluR agonist LY354740 and NAAG peptidase inhibitor effects on prepulse inhibition in PCP and <Emphasis Type="SmallCaps">d</Emphasis>-amphetamine models of schizophrenia

Rationale  

Group II metabotropic glutamate receptor (mGluR) agonists represent a novel approach to the treatment of schizophrenia. Inasmuch as the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) activates these receptors, NAAG peptidase inhibitors conceptually represent a parallel path toward development of new antipsychotic drugs. While group II agonists are effective in several animal models of schizophrenia, they are reported to lack efficacy in moderating the effects of phencyclidine (PCP) on prepulse inhibition of acoustic startle in animal models of sensory processing deficits found in this disorder.     

Comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of active gastric ulcer—a European multicentre study

Background:

Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active, benign gastric ulcers.

Methods:

In this randomized, double-blind, multicentre study, conducted at 25 European sites, rabeprazole and omeprazole were compared in patients with active gastric ulcers. Two hundred and twenty-seven patients with active benign gastric ulcer were randomized to receive either rabeprazole 20 mg (n = 113) or omeprazole 20 mg (n = 114) once daily for 3 or 6 weeks, with healing monitored by endoscopy.

Results:

After 3 weeks, complete healing (ITT analysis) was documented in 58% of patients given rabeprazole and 61% in patients given omeprazole (N.S.). After 6 weeks the healing rates were identical in both groups at 91%. Rabeprazole-treated patients had numerically greater symptom relief at all 12 points of comparison. The differences significantly favoured rabeprazole at week 3 for daytime pain improvement (P = 0.023) and at week 6 for pain frequency (P = 0.006) and complete resolution of night pain (P = 0.022). Both drugs were well-tolerated over the 6-week treatment course. Mean changes from baseline to end-point in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen.

Conclusion:

In this study, rabeprazole produced healing rates comparable to omeprazole at weeks 3 and 6, but provided more consistent and occasionally significantly superior symptom improvement. Both treatments were well-tolerated.

     

<Emphasis Type="BoldItalic">Leucine-Aspartic Acid-Valine</Emphasis> Sequence as Targeting Ligand and Drug Carrier for Doxorubicin Delivery to Melanoma Cells: <Emphasis Type="BoldItalic">In Vitro</Emphasis> Cellular Uptake and Cytotoxicity Studies

Purpose  

To study the feasibility of Leucine-Aspartic Acid-Valine (LDV) as targeting ligand and drug carrier for targeted delivery to integrin α₄β₁ over-expressing cancer cells.     

<Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Effects of Water Extract of White Cocoa Tea (<Emphasis Type="Italic">Camellia ptilophylla</Emphasis>) Against Human Prostate Cancer

Purpose  

We evaluated the chemotherapeutic effect of water extract of white cocoa tea (WCTE) against human prostate cancer (PCa) in vitro and in vivo.     

Enhanced Bioavailability of L-Carnitine After Painless Intradermal Delivery <Emphasis Type="BoldItalic">vs.</Emphasis> Oral Administration in Rats

Purpose  

In vitro and in vivo permeation studies were conducted to evaluate the characteristic of percutaneous administration of high hydrophilic drug L-carnitine (LC) by Functional MicroArray (FMA) painless intradermal delivery system.     

Role of Organic Cation Transporter 1, OCT1 in the Pharmacokinetics and Toxicity of <Emphasis Type="Italic">cis</Emphasis>-Diammine(pyridine)chloroplatinum(II) and Oxaliplatin in Mice

Purpose  

The goal of this study was to test the hypothesis that by controlling intracellular uptake, organic cation transporter 1, Oct1 is a key determinant of the disposition and toxicity of cis-diammine(pyridine)chloroplatinum(II)(CDPCP) and oxaliplatin.     

Effect of the <Emphasis Type="Italic">ADRB1</Emphasis> 1165C>G and 145A>G polymorphisms on hemodynamic response during dobutamine stress echocardiography

Purpose  

The aim of this study was to determine an association between the ADRB1 1165C>G and 145A>G polymorphisms and hemodynamic response [heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure] to dobutamine during dobutamine stress echocardiography (DSE).     

Fast Surface Crystallization of Amorphous Griseofulvin Below <Emphasis Type="Italic">T</Emphasis><Subscript>g</Subscript>

Purpose  

To study crystal growth rates of amorphous griseofulvin (GSF) below its glass transition temperature (T _g) and the effect of surface crystallization on the overall crystallization kinetics of amorphous GSF.     

Population <Emphasis Type="Italic">In Vitro</Emphasis>-<Emphasis Type="Italic">In Vivo</Emphasis> Correlation Model for Pramipexole Slow-Release Oral Formulations

Purpose  

To establish an in vitro-in vivo level A correlation (IVIVC) for pramipexole slow-release formulations.     

PEGylated PAMAM Dendrimer-Doxorubicin Conjugates: <Emphasis Type="BoldItalic">In Vitro</Emphasis> Evaluation and <Emphasis Type="BoldItalic">In Vivo</Emphasis> Tumor Accumulation

Purpose  

To investigate the effects of PEGylation degree and drug conjugation style on the in vitro and in vivo behavior of PEGylated polyamidoamine (PAMAM) dendrimers-based drug delivery system.     

<Emphasis Type="Italic">Linum usitatissimum</Emphasis> (linseed/flaxseed) fixed oil: antimicrobial activity and efficacy in bovine mastitis

Purpose  

In vitro antimicrobial activity and in vivo therapeutic efficacy of L. usitatissimum (linseed/flaxseed) fixed oil in bovine mastitis were investigated.     

Design and synthesis of 4′‐((5‐benzylidene‐2,4‐dioxothiazolidin‐3‐yl)methyl)biphenyl‐2‐carbonitrile analogs as bacterial peptide deformylase inhibitors

Herein, we report the synthesis and screening of 4′‐((5‐benzylidene‐2,4‐dioxothiazolidin‐3‐yl)methyl)biphenyl‐2‐carbonitrile analogs 11(a–j) as bacterial peptide deformylase (PDF) enzyme inhibitors. The compounds 11b (IC₅₀ value = 139.28 μm ), 11g (IC₅₀ value = 136.18 μm ), and 11h (IC₅₀ value = 131.65 μm ) had shown good PDF inhibition activity. The compounds 11b (MIC range = 103.36–167.26 μg/mL), 11g (MIC range = 93.75–145.67 μg/mL), and 11h (MIC range = 63.61–126.63 μg/mL) had also shown potent antibacterial activity when compared with standard ampicillin (MIC range = 100.00–250.00 μg/mL). Thus, the active derivatives were not only PDF inhibitors but also efficient antibacterial agents. To gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 11(a–j) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. The results suggest that this class of compounds has potential for development and use in future as antibacterial drugs.     

Multiclass mycotoxins in lotus seeds analysed by an isotope‐labelled internal standard‐based UPLC‐MS/MS

Objectives

This study aimed to explore the residue levels of multiclass mycotoxins in medicinal and edible lotus seeds.

Methods

A rapid and reliable isotope‐labelled internal standard‐based UPLC ‐MS /MS method was developed and validated for sensitive and accurate analysis of multiclass mycotoxins including aflatoxins (AFB ₁, AFB ₂, AFG ₁ and AFG ₂), ochratoxin A (OTA ), zearalenone (ZEN ), deoxynivalenol (DON ), fumonisins (FB ₁ and FB ₂), T‐2 and HT ‐2 toxins in lotus seeds. Some critical conditions such as extract solution with the addition of isotope‐labelled internal standard, type of mobile phase and the elution condition were scientifically optimized. The 11 mycotoxins obtained satisfactory resolution and sensitive detection in multiple reactions monitoring scanning mode combined with the ion switching technology in positive and negative ion switching mode.

Key findings

The developed isotope‐labelled internal standard‐based UPLC ‐MS /MS method exhibited an approving linearity (r  ≥  0.9984), high sensitivity (limit of detection in the range of 0.015–30.05 μg/kg), acceptable precision (RSD s ≤6.3%) and good recovery (76.0–116.0%) for 11 analytes, respectively. Ten batches of real lotus seed samples were tested, and three batches out of which were contaminated with AFB ₁, FB ₂, T‐2 and ZEN . AFB ₁ showed the highest occurrence rate (30%) with contents of 10.50 and 8.32 μg/kg in two samples over the official limit (5.0 μg/kg).

Conclusions

The monitoring of multiclass mycotoxins in Chinese herbal medicines is in great urgency to ensure the security of consumers. The proposed method could be further utilized for simple, sensitive and rapid detection of more mycotoxins in other complex matrices to compensate for matrix effects.

     

Characterization of a Microsphere Formulation Containing Glucose Oxidase and its <Emphasis Type="BoldItalic">In Vivo</Emphasis> Efficacy in a Murine Solid Tumor Model

Purpose  

This work focused on the characterization and in vitro/in vivo evaluation of an alginate/chitosan microsphere (ACMS) formulation of glucose oxidase (GOX) for the locoregional delivery of reactive oxygen species for the treatment of solid tumors.     

<Emphasis Type="Italic">In Vivo</Emphasis> Distribution of Polymeric Nanoparticles at the Whole-Body,Tumor, and Cellular Levels

Purpose  

Block copolymer micelles (BCMs) were functionalized with indium-111 and/or epidermal growth factor (EGF), which enabled investigation of the in vivo transport of passively and actively targeted BCMs. The integration of conventional and image-based techniques afforded novel quantitative means to achieve an in-depth insight into the fate of polymeric nanoparticles in vivo.     

Radioactive Holmium Acetylacetonate Microspheres for Interstitial Microbrachytherapy: An <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Stability Study

Purpose  

The clinical application of holmium acetylacetonate microspheres (HoAcAcMS) for the intratumoral radionuclide treatment of solid malignancies requires a thorough understanding of their stability. Therefore, an in vitro and an in vivo stability study with HoAcAcMS was conducted.     

<Emphasis Type="Italic">SLCO1B1</Emphasis> haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia

Purpose  

Recent studies reported the association of SLCO1B1 haplotypes with the development of musculoskeletal side effects during simvastatin use. The aim was to evaluate the pharmacogenetic association of SLCO1B1 haplotypes with atorvastatin-induced myalgia in a sample of individuals on high-dose atorvastatin regimens.